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5. |
- Andreoli, L., et al.
(author)
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COVID-19 VACCINE SAFETY DURING PREGNANCY AND BREASTFEEDING IN WOMEN WITH AUTOIMMUNE DISEASES : RESULTS FROM THE COVAD STUDY
- 2023
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In: Annals of the Rheumatic Diseases. - : HighWire Press. - 0003-4967 .- 1468-2060. ; 82:Suppl. 1, s. 56-57
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Journal article (other academic/artistic)abstract
- Background: COVID-19 vaccine hesitancy among pregnant and breastfeeding women with autoimmune diseases (AID) is often attributed to the fear of adverse events (AE) and disease flares (DF). No data are available regarding COVID-19 vaccine safety in this population.Objectives: We aimed at describing delayed-onset (>7 days) vaccine-related AE (minor and major), DF, and related AID treatment modifications from the COVID-19 Vaccination in Autoimmune Diseases (COVAD) study.Methods: Among complete responses from 9201 participants as of June 21, 2022, 6787 (73.8%) were women. Six subgroups were identified upon diagnosis of AID vs healthy controls (HC) and their pregnancy/breastfeeding status at the time of any dose of vaccine (Figure 1).Results: Forty pregnant and 52 breastfeeding AID patients were identified and their vaccination rates (at least one dose) was 100% and 96.2%, respectively (Table 1). Overall AE, minor AE, and major AE were reported significantly more frequently by pregnant than non-pregnant patients (45% vs. 26%, p=0.01; 40% vs. 25.9%, p=0.03; 17.5% vs. 4.6%, p<0.01), but no difference was found in comparison with pregnant HC. No difference was observed between breastfeeding patients and HC. Post-vaccination DF were reported by 17.5% of pregnant and 20% of breastfeeding patients, and by 18% of age- and disease-matched control patients (n=2315). All DF in pregnant/breastfeeding patients were managed with glucocorticoids and a fifth of them required initiation or change in immunosuppressive treatment.Conclusion: This study provides the first insights into the safety of COVID-19 vaccination during the antenatal period in women with AID. While AEs were more commonly reported by pregnant patients with AID, these were no higher than among pregnant healthy controls without AID. These observations are reassuring, likely to strengthen physician-patient communication and overcome hesitancy as the benefits for the mother and fetus by passive immunization are likely to overweigh the potential risks of AE and DF.Reference: [1]Fazal ZZ, et al; COVAD Study Group. COVAD survey 2 long-term outcomes: unmet need and protocol. Rheumatol Int 2022; 42:2151-2158.
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- Aoude, M., et al.
(author)
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TREATMENT PATTERNS OF IDIOPATHIC INFLAMMATORY MYOPATHIES : RESULTS FROM AN INTERNATIONAL COHORT OF OVER 1,400 PATIENTS
- 2022
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In: Annals of the Rheumatic Diseases. - : HighWire Press. - 0003-4967 .- 1468-2060. ; 81:Suppl. 1, s. 105-106
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Journal article (other academic/artistic)abstract
- Idiopathic inflammatory myopathies (IIM) are a group of heterogeneous autoimmune disorders with limited standardization of treatment protocols.ObjectivesTo evaluate frequency and patterns of various treatments used for IIM based on disease subtype, world region, and organ involvement.MethodsCross-sectional data from the international CoVAD self-report e-survey1 was extracted on Sep 14th, 2021. Patient details included demographics, IIM subtypes (dermatomyositis (DM), polymyositis (PM), inclusion body myositis (IBM), antisynthetase syndrome (ASSD), necrotizing myositis (NM) and overlap myositis (OM)), clinical symptoms, disease duration and activity, and current treatments. Treatments were categorized in corticosteroids (CS), antimalarials, immunosuppressants (IS), intravenous immunoglobulins (IVIG), biologics, and others. Typical clinical symptoms (dyspnea, dysphagia) were used as surrogate for organ involvement. Factors associated with IS were analyzed using multivariable logistic regression, adjusting for IIM subtype, demographics, world region, disease activity, and prevalent clinical symptoms (>10%).ResultsIn 1418 patients with IIM, median age was 61 years [IQR 49-70], 62.5% were females, median disease duration was 6 years [IQR 3-11], most common subset was DM (32.4%).The most used treatments were IS (49.4%, including Methotrexate 19.6%, Mycophenolate Mofetil 18.2%, Azathioprine 8.8%, Cyclosporine 2.7%, Tacrolimus 2%, Leflunomide 1.6%, Sulfasalazine 1%, and Cyclophosphamide 0.6%), followed by CS (40.8%), antimalarials (13.8%) and IVIG (9.4%). Biologics were used in 4.3% of patients.Treatment patterns differed significantly by IIM subtypes with a higher frequency of IS (77.7%) and CS (63.4%) use in ASSD; antimalarials (28.6%) and biologics (9.8%) use in OM and IVIG use in NM (24.6%) (Table 1). Also, treatment patterns were different in regions of the world (Figure 1), with a higher frequency of CS use in Europe (60.5%) and IS use in South America (77.2%). Antimalarials were most used in Asia (19.4%), while IVIG use was most common in Oceania (16.9%). Dyspnea was associated with higher use of IS (69.9%) and CS (65.8%) (p<0.001), whereas dysphagia was negatively associated with IS (39.7%) and CS (32.7%) likely due to a higher proportion in IBM patients reporting dysphagia.Table 1.Current Treatments for IIM, Stratified by Disease SubtypesDermatomyositisPolymyositisInclusion Body MyositisAnti-synthetase syndromeNecrotizing myositisOverlap syndromeAll IIMp-valueNumber of patients459182348148572241418Immunosuppressants*269 (58.6)107 (58.8)39 (11.2)115 (77.7)40 (70.2)130 (58.0)700 (49.4)<0.001Corticosteroids208 (48.0)81 (46.8)32 (9.7)90 (63.4)32 (59.3)103 (50.0)546 (40.8)<0.001Antimalarials99 (21.6)7 (3.8)0 (0.0)25 (16.9)1 (1.8)64 (28.6)196 (13.8)<0.001Intravenous Immunoglobulins54 (11.8)16 (8.8)19 (5.5)10 (6.8)14 (24.6)20 (8.9)133 (9.4)<0.001Biologics**17 (3.7)7 (3.8)0 (0.0)13 (8.8)2 (3.5)22 (9.8)61 (4.3)<0.001Others***6 (1.3)0 (0.0)0 (0.0)1 (0.7)0 (0.0)5 (2,2)12 (0.8)0.098*Methotrexate (278), Mycophenolate Mofetil (258), Azathioprine (125), Cyclosporine (38), Tacrolimus (28), Leflunomide (23), Sulfasalazine (14), Cyclophosphamide (9). **Rituximab (44), Abatacept (5), TNF inhibitors (4), Tocilizumab (3), Belimumab (3), Secukinumab (1). ***JAK(10) and PDE4 inhibitors (2)Multivariable logistic regression analysis showed an association of IS with the IIM subtype (least used in IBM (OR 0.07 [95%CI 0.04-0.13] compared to DM), world region (most used in South America (OR 2.35 [1.12-4.91] compared to North America), active and worsening disease activity (OR 3.49 [1.76-6.91] compared to remission), and some clinical features (dyspnea, fatigue, and muscle weakness).ConclusionIIM treatment patterns differ significantly by disease subtypes, world regions and organ involvement, highlighting the need for unified international consensus-driven guidelines.References[1]Parikshit S. et al. Rheumatol Int. 2022 Jan;42(1):23–9.Disclosure of InterestsNone declared
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8. |
- Blaess, Julien, et al.
(author)
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Recommendations for physical activity and exercise in persons living with Systemic Lupus Erythematosus (SLE) : consensus by an international task force
- 2024
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In: RMD Open. - : BMJ Publishing Group Ltd. - 2056-5933. ; 10:2
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Research review (peer-reviewed)abstract
- OBJECTIVE: This international task force aimed to provide healthcare professionals and persons living with systemic lupus erythematosus (SLE) with consensus-based recommendations for physical activity and exercise in SLE.METHODS: Based on evidence from a systematic literature review and expert opinion, 3 overarching principles and 15 recommendations were agreed on by Delphi consensus.RESULTS: The overarching principles highlight the importance of shared decision-making and the need to explain the benefits of physical activity to persons living with SLE and other healthcare providers. The 15 specific recommendations state that physical activity is generally recommended for all people with SLE, but in some instances, a medical evaluation may be needed to rule out contraindications. Pertaining to outdoor activity, photoprotection is necessary. Both aerobic and resistance training programmes are recommended, with a gradual increase in frequency and intensity, which should be adapted for each individual, and ideally supervised by qualified professionals.CONCLUSION: In summary, the consensus reached by the international task force provides a valuable framework for the integration of physical activity and exercise into the management of SLE, offering a tailored evidence-based and eminence-based approach to enhance the well-being of individuals living with this challenging autoimmune condition.
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9. |
- Borg, Alexander, et al.
(author)
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Obesity is associated with pain and impaired mobility despite therapy in systemic lupus erythematosus
- 2023
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In: Frontiers in Medicine. - : Frontiers Media S.A.. - 2296-858X. ; 10
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To investigate whether abnormal BMI is associated with health-related quality of life (HRQoL) impairments, defined as patient-reported problems within the different dimensions of the three-level EQ-5D (EQ-5D-3L), before and after treatment for active systemic lupus erythematosus (SLE).PATIENTS AND METHODS: We conducted a post-hoc analysis of data from two phase III clinical trials of belimumab in SLE, i.e., BLISS-52 (n = 865) and BLISS-76 (n = 819). Underweight was defined as BMI <18.5 kg/m2, normal weight as BMI ≥18.5 but <25 kg/m2, pre-obesity as BMI ≥25 but <30 kg/m2, and obesity as BMI ≥30 kg/m2. We investigated associations between BMI groups and problems (level 2 or 3) within each one of the five EQ-5D dimensions before treatment initiation and at week 52, using logistic regression analysis adjusting for age, ethnicity, disease activity, and glucocorticoid dose, and for the post-treatment analysis also for belimumab treatment and baseline EQ-5D-3L responses.RESULTS: Of 1,684 patients included, 73 (4%) were classified as underweight, 850 (50%) as normal weight, 438 (26%) as pre-obese, and 323 (19%) as obese. At baseline, obesity was associated with mild to severe problems in all EQ-5D dimensions (p < 0.05 for all), yielding the strongest association with problems in mobility (adjusted odds ratio, aOR: 2.1; 95% confidence interval, CI: 1.6-2.8; p < 0.001). Pre-obesity was also associated with problems in mobility (aOR: 1.4; 95% CI: 1.1-1.8; p = 0.005). Post-intervention, obesity was associated with problems in mobility and pain/discomfort, and pre-obesity with problems in mobility and self-care (p < 0.05 for all).CONCLUSION: Our study adds to the evidence that high BMI negatively affects SLE patients' HRQoL, with obesity being associated with pain and impaired mobility despite therapy.
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- Chatterjee, Tulika, et al.
(author)
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Type 1 diabetes, COVID-19 vaccines and short-term safety : Subgroup analysis from the global COVAD study
- 2024
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In: Journal of Diabetes Investigation. - : John Wiley & Sons. - 2040-1116 .- 2040-1124. ; 15:1, s. 131-138
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Journal article (peer-reviewed)abstract
- AIMS/INTRODUCTION: Coronavirus disease 2019 (COVID-19) vaccinations have been proven to be generally safe in healthy populations. However, the data on vaccine safety in patients with type 1 diabetes are scarce. This study aimed to evaluate the frequency and severity of short-term (<7-day) adverse vaccination events (AEs) and their risk factors among type 1 diabetes patients. MATERIALS AND METHODS: This study analyzed data from the COVID-19 vaccination in Autoimmune Diseases (COVAD) survey database (May to December 2021; 110 collaborators, 94 countries), comparing <7-day COVID-19 vaccine AE among type 1 diabetes patients and healthy controls (HCs). Descriptive statistics; propensity score matching (1:4) using the variables age, sex and ethnicity; and multivariate analyses were carried out.RESULTS: This study analyzed 5,480 completed survey responses. Of all responses, 5,408 were HCs, 72 were type 1 diabetes patients (43 females, 48.0% white European ancestry) and Pfizer was the most administered vaccine (39%). A total of 4,052 (73.9%) respondents had received two vaccine doses. Patients with type 1 diabetes had a comparable risk of injection site pain, minor and major vaccine AEs, as well as associated hospitalizations to HCs. However, type 1 diabetes patients had a higher risk of severe rashes (3% vs 0.4%, OR 8.0, 95% confidence interval 1.7-36), P = 0.007), although reassuringly, these were rare (n = 2 among type 1 diabetes patients).CONCLUSIONS: COVID-19 vaccination was safe and well tolerated in patients with type 1 diabetes with similar AE profiles compared with HCs, although severe rashes were more common in type 1 diabetes patients.
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11. |
- Da Mutten, Raffaele, et al.
(author)
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Intracardiac Thrombi in Morbus Adamantiades-Behçet in Two Swedish Patients
- 2023
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In: Journal of Clinical Medicine. - : MDPI. - 2077-0383. ; 12:16
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Journal article (peer-reviewed)abstract
- Morbus Adamantiades-Behçet (MAB) is an inflammatory disease typically manifesting with oral and genital aphthosis, erythema nodosum, and vasculopathy, and in only around 2%, cardiac involvement. Its prevalence is usually higher along the historic Silk Road, but rarer in Scandinavia where 0.64-4.9 in 100,000 people are affected. We herein present two Swedish patients with cardiac manifestations of Morbus Adamantiades-Behçet. Along with the intracardial thrombi, which both patients presented with, one patient also had cerebrovascular insults leading to visual field deficits as well as involvement of peripheral nerves. Being of Scandinavian origin and showing uncommon symptoms as their initial manifestations of MAB, the 62- and 35-year-old patients presenting herein constitute rare cases.
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12. |
- Dey, Mrinalini, et al.
(author)
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COVID-19 Vaccination-Related Delayed Adverse Events among Patients with Systemic Lupus Erythematosus
- 2023
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In: Journal of Clinical Medicine. - : MDPI. - 2077-0383. ; 12:24
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Journal article (peer-reviewed)abstract
- BACKGROUND: The safety profile of COVID-19 vaccination is well documented, but hesitancy among people with immune-mediated inflammatory diseases, often immunocompromised, remains high, partially due to a scarcity of data on safety over a longer term. We herein aimed to assess delayed adverse events (DAEs) occurring >7 days after COVID-19 vaccination in systemic lupus erythematosus (SLE) versus other rheumatic autoimmune diseases (rAIDs), non-rheumatic AIDs (nrAIDs), and healthy controls (HCs).METHODS: Self-reported data were captured within the COVID-19 Vaccination in Autoimmune Diseases (COVAD)-2 online survey, which comprised >150 centres and responses from 106 countries, between February and June 2022. Logistic regression analysis adjusting for important confounders (age, sex, ethnicity) was used to compare groups.RESULTS: Of 7203 eligible individuals, 882 (12.2%) patients had SLE, 3161 (43.9%) patients had rAIDs, 426 (5.9%) patients had nrAIDs, and 2734 (38.0%) were HCs. SLE patients had a median age of 39 years (IQR: 31-50); 93.7% were women. SLE patients reported, more frequently, major DAEs (OR: 1.6; 95% CI: 1.2-2.0; p = 0.001) and hospitalisation (OR: 2.2; 95% CI: 1.4-3.4; p < 0.001) compared to HCs, severe rashes (OR: 2.4; 95% CI: 1.3-4.2; p = 0.004) compared to people with rAIDS, and hospitalisation (OR: 2.3; 95% CI: 1.1-4.9; p = 0.029) as well as several minor DAEs compared to people with nrAIDs. Differences were observed between vaccines in terms of frequency of major DAEs and hospitalisations, with the latter seen more frequently in patients receiving the Moderna vaccine. People with SLE with no autoimmune multimorbidity less frequently reported overall minor DAEs compared to SLE patients with comorbid nrAIDs (OR: 0.5; 95% CI: 0.3-1.0; p = 0.036).CONCLUSION: Hospitalisations post-vaccination were more frequent in SLE patients than in HCs. Monitoring of SLE patients following COVID-19 vaccination can help in identifying DAEs early, informing patients about expected DAEs, and supporting patients, especially those with autoimmune multimorbidity.
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13. |
- Dey, Mrinalini, et al.
(author)
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Fatigue in Systemic Lupus Erythematosus and Rheumatoid Arthritis : A Comparison of Mechanisms, Measures and Management
- 2021
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In: Journal of clinical medicine. - : MDPI. - 2077-0383. ; 10:16
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Research review (peer-reviewed)abstract
- Fatigue is a common constitutional feature of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). While the two diseases share a common mechanism of autoimmunity, they differ in their clinical manifestations and treatment. Fatigue is one of the most commonly reported symptoms in both groups, associated with pain, depression and anxiety, and affecting function, work and quality of life. Fatigue is not easy to assess or conceptualise. It can be linked to disease activity, although it is not always, and is challenging to treat. Several measures have been trialled in RA and SLE; however, none have been adopted into mainstream practice. Despite being a common symptom, fatigue remains poorly managed in both RA and SLE-more so in the latter, where there have been relatively fewer studies. Additionally, comorbidities contribute to fatigue, further complicating its management. Pain, depression and anxiety also need to be addressed, not as separate entities, but together with fatigue in a holistic manner. Here, we describe the similarities and differences between fatigue in patients with RA and SLE, discuss concepts and practices applicable to both conditions and identify areas for further research. Through this review, we aim to highlight the importance of the holistic management of fatigue in SLE.
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15. |
- Emamikia, S., et al.
(author)
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CAN WE ENHANCE ADHERENCE TO MEDICATIONS IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS? RESULTS FROM A QUALITATIVE STUDY
- 2022
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In: Annals of the Rheumatic Diseases. - : HighWire Press. - 0003-4967 .- 1468-2060. ; 81:Suppl. 1, s. 439-439
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Journal article (other academic/artistic)abstract
- Medication non-adherence is common among patients with systemic lupus erythematosus (SLE) [1] and may lead to poor clinical outcomes [2,3].ObjectivesOur aim was to identify influenceable contributors to medication non-adherence to suggest interventions that could increase adherence.MethodsPatients with SLE from two Swedish tertiary referral centres (N=205) participated in a survey assessing self-reported adherence to medications. Medication adherence was self-reported and measured using the generic instrument Medication Adherence Self-Report Inventory (MASRI) and the rheumatic disease-specific instrument Compliance Questionnaire Rheumatology (CQR). Responses were used to select patients for qualitative interviews (N=15). Verbatim interview transcripts were analysed by two researchers using content analysis methodology.ResultsThe mean age of the interviewees was 39 years, 87% were women, and their mean SLE duration was 11.6 years. Patients’ medications and adherence levels are detailed in Table 1. We categorised reasons for non-adherence thematically into (i) patient-related e.g., unintentional non-adherence due to forgetfulness or intentional non-adherence due to disbelief in medications, (ii) healthcare-related e.g., untrustworthy relationship with the treating physician, authority fear, and poor information about the prescribed medications or the disease, (iii) medication-related e.g., fear of side-effects, and (iv) disease-related reasons e.g., lacking acceptance of a chronic illness or perceived disease quiescence. Interventions identified that healthcare could implement to improve patients’ adherence to medications included (i) increased communication between healthcare professionals and patients, (ii) patient education, (iii) accessible healthcare, preferably with the same personnel, (iv) smooth transition from paediatric to adult care, (v) regularity in addressing adherence to medications, (vi) psychological support, and (vii) involvement of family members or people who are close to the patient.Table 1.Characteristics of the fifteen interviewees.PatientPrescribed medicationsOverall medication adherence according to:Intentional non-adherence (Y/N)MASRI (0–100%)CQR (0–100%)Direct question (Y/N) *1PRED9661NYHCQ96AZA962PRED10077YNAHCQ100MTX (pills)1003PRED10081YNA4HCQ9058NY5HCQ10054NY6PRED7065NNHCQ70AZA697PRED6747NYHCQ50AZA208HCQ8872NN9PRED9574NYHCQ96MMF RTX (iv)9910PRED10066NNHCQ100AZA BEL (sc)8011PRED9654NNHCQ100MMF RTX9812PRED8958NNHCQ9213PRED10084YNACYS10014HCQ10074YNAMTX (pills)10015PRED9067NNHCQ90MMF801 MASRI: Medications Adherence Self Report Inventory; CQR: Compliance Questionnaire Rheumatology; F/M: female/male; Y/N: yes/no; NA: not applicable; iv: intravenous; sc: subcutaneous; PRED: prednisolone; HCQ: hydroxychloroquine; AZA: azathioprine; MTX: methotrexate; MMF: mycophenolate mofetil; RTX: rituximab; BEL: belimumab; CYS: cyclosporine; * Y= Adherence assent to direct question; N= Non-adherence assent to direct question.ConclusionThe reasons for medication non-adherence are complex and multifaceted. From the patients’ perspective, multiple different strategies could be implemented in healthcare with the goal of improving adherence, including increased communication, patient education and psychological support.References[1]Mehat, P et al. Arthritis Care & Research 2017, 69, 1706-1713.[2]Feldman, C.H. et al. Arthritis Care & Research 2015, 67, 1712-1721.[3]Julian, L.J. et al. Arthritis and rheumatism 2009, 61, 240-246.AcknowledgementsAll authors would like to express our gratitude to the individuals who participated in the interviews and shared their thoughts, views, and opinions.Disclosure of InterestsSharzad Emamikia: None declared, Cidem Gentline: None declared, Yvonne Enman: None declared, Ioannis Parodis Grant/research support from: Amgen, AstraZeneca, Aurinia Pharmaceuticals, Elli Lilly and Company, Gilead Sciences, GlaxoSmithKline, Janssen Pharmaceuticals, Novartis and F. Hoffmann-La Roche AG.
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16. |
- Emamikia, Sharzad, et al.
(author)
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Factors associated with non-adherence to medications in systemic lupus erythematosus : Results from a Swedish survey
- 2024
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In: Lupus. - : Sage Publications. - 0961-2033 .- 1477-0962. ; 33:6, s. 615-628
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To identify determinants of medication non-adherence in a Swedish population of systemic lupus erythematosus (SLE).METHODS: Patients with SLE from Karolinska and Örebro University Hospitals participated in a survey-based cross-sectional study. Demographics, disease activity, organ damage, HRQoL (LupusQol, EQ-5D-5 L), medication non-adherence (<80% on CQR-19 or MASRI) and beliefs about medicines (BMQ) were registered. MASRI was used to report adherence to different drugs/drug classes, categorised into (i) antimalarial agents (AMA), (ii) glucocorticoids and (iii) other SLE medications. Multivariable logistic regression adjusted for age, sex, disease activity and organ damage.RESULTS: Among 205 respondents, the median age was 52.0 years (IQR: 34.0-70.0), 86.3% were women, 66.8% were non-adherent to their medications according to CQR-19, and 6.6% and 6.3% were non-adherent to AMA and glucocorticoids, respectively, according to MASRI. Positive beliefs about glucocorticoids (OR; 95% CI: 0.77; 0.59-0.99; p = .039) and medications overall (0.71; 0.52-0.97; p = .029) were protective against non-adherence to glucocorticoids. Anxiety/depression (3.09; 1.12-8.54; p = .029), medication concerns (1.12; 1.05-1.20; p < .001) and belief that medications are overused (1.30; 1.15-1.46; p < .001) or harmful (1.36; 1.19-1.56; p < .001) were associated with medication non-adherence (CQR-19); beliefs in the necessity of medications (0.73; 0.65-0.82; p < .001) and positive beliefs in medications were protective (0.72; 0.60-0.86; p < .001). No associations were found between other investigated factors and medication non-adherence.CONCLUSIONS: Beliefs about medications were a major determinant of medication non-adherence. Patient education may help alleviate the negative impact of misinformation/unawareness on adherence.
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17. |
- Emamikia, Sharzad, et al.
(author)
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How Can We Enhance Adherence to Medications in Patients with Systemic Lupus Erythematosus? Results from a Qualitative Study
- 2022
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In: Journal of Clinical Medicine. - : MDPI. - 2077-0383. ; 11:7
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Journal article (peer-reviewed)abstract
- Medication non-adherence is common among patients with systemic lupus erythematosus (SLE) and may lead to poor clinical outcomes. Our aim was to identify influenceable contributors to medication non-adherence and suggest interventions that could increase adherence. Patients with SLE from two Swedish tertiary referral centres (n = 205) participated in a survey assessing self-reported adherence to medications. Responses were used to select patients for qualitative interviews (n = 15). Verbatim interview transcripts were analysed by two researchers using content analysis methodology. The median age of the interviewees was 32 years, 87% were women, and their median SLE duration was nine years. Reasons for non-adherence were complex and multifaceted; we categorised them thematically into (i) patient-related (e.g., unintentional non-adherence due to forgetfulness or intentional non-adherence due to disbelief in medications); (ii) healthcare-related (e.g., untrustworthy relationship with the treating physician, authority fear, and poor information about the prescribed medications or the disease); (iii) medication-related (e.g., fear of side-effects); and (iv) disease-related reasons (e.g., lacking acceptance of a chronic illness or perceived disease quiescence). Interventions identified that healthcare could implement to improve patient adherence to medications included (i) increased communication between healthcare professionals and patients; (ii) patient education; (iii) accessible healthcare, preferably with the same personnel; (iv) well-coordinated transition from paediatric to adult care; (v) regularity in addressing adherence to medications; (vi) psychological support; and (vii) involvement of family members or people who are close to the patient.
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18. |
- Emamikia, Sharzad, et al.
(author)
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Impact of remission and low disease activity on health-related quality of life in patients with systemic lupus erythematosus
- 2022
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In: Rheumatology. - : Oxford University Press. - 1462-0324 .- 1462-0332. ; 61:12, s. 4752-4762
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Journal article (peer-reviewed)abstract
- OBJECTIVES: To investigate the impact of remission and lupus low disease activity state (LLDAS) on health-related quality of life (HRQoL) in systemic lupus erythematosus.METHODS: SF-36, EQ-5D-3L and FACIT-Fatigue data from the BLISS-52 (NCT00424476) and BLISS-76 (NCT00410384) trials were used. Duration in remission/LLDAS required to reach a HRQoL benefit ≥ minimal clinically important differences (MCIDs) during and post-treatment was determined using quantile regression and generalised estimating equations.RESULTS: Patients (N = 1684) were assessed every 4th week (15 visits). Four cumulative (β = 0.60) or four consecutive (β = 0.66) visits in remission were required to achieve a benefit ≥MCID in SF-36 physical component summary (PCS) scores, and six cumulative (β = 0.44) or five consecutive (β = 0.49) for a benefit ≥MCID in mental component summary (MCS) scores. Eight cumulative (β = 0.30 for both) or eight consecutive (β = 0.32 for both) visits in LLDAS were required for a benefit in PCS/MCS ≥MCID, respectively.For EQ-5D-3L index scores ≥MCID, six cumulative (β = 0.007) or five consecutive (β = 0.008) visits in remission were required, and eight cumulative (β = 0.005) or six consecutive (β = 0.006) visits in LLDAS. For FACIT-Fatigue scores ≥MCID, 12 cumulative (β = 0.34) or 10 consecutive (β = 0.39) visits in remission were required, and 17 cumulative (β = 0.24) or 16 consecutive (β = 0.25) visits in LLDAS.CONCLUSION: Remission and LLDAS contribute to a HRQoL benefit in a time-dependent manner. Shorter time in remission than in LLDAS was required for a clinically important benefit in HRQoL, and longer time in remission for a benefit in mental compared with physical HRQoL aspects. When remission/LLDAS was sustained, the same benefit was achieved in a shorter time.
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19. |
- Emamikia, Sharzad, et al.
(author)
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The Impact of Remission and Low Disease Activity Attainment on Health-related Quality of Life in Two Phase III Clinical Trials of Belimumab in Systemic Lupus Erythematosus
- 2021
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In: Arthritis & Rheumatology. - : John Wiley & Sons. - 2326-5191 .- 2326-5205. ; 73:Suppl. 9, s. 2604-2606
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Journal article (other academic/artistic)abstract
- Background/Purpose: Health- related quality of life (HRQoL) is considered one of the most important outcomes in clinical trials of systemic lupus erythematosus (SLE), along with reduction in disease activity and safety. We studied the duration and consecutiveness of remission or low disease activity throughout a 52- week long period on standard therapy plus belimumab or placebo in relation to HRQoL outcome.Methods: We analysed pooled 52- week data from the BLISS- 52 (N=865) and BLISS- 76 (N=819) phase III trials. We determined remission using the prevailing Definitions of Remission in SLE (DORIS) definition (1) and low disease activity using the Lupus Low Disease Activity State (LLDAS) (2). Remission required clinical (c)SLEDAI- 2K=0, PhGA (0– 3) <0.5, and prednisone ≤5 mg/day. LLDAS required SLEDAI- 2K ≤4, PhGA (0– 3) ≤1, and prednisone ≤7.5 mg/day. HRQoL was measured with the SF- 36 physical and mental component summary (PCS and MCS), and EQ- 5D- 3L. Minimal clinically important difference (MCID) at week 52 for PCS and MCS was set to 2.5, and for EQ- 5D- 3L utility index to 0.040. Associations were assessed using quantile regression analysis. Adjustments for demographics, disease duration, organ damage and baseline status were incorporated.Results: The minimum cumulative attainment of remission to achieve a benefit in PCS ≥MCID at week 52 was four visits (corresponding to 16 weeks) (β=0.63), while 7 visits (28 weeks) were required for MCS differences ≥MCID (β=0.37). Correspondingly, 9 visits in LLDAS (36 weeks) were required for achieving differences ≥MCID in both PCS (b=0.28) and MCS (β=0.29). Table 1 shows 95% confidence intervals and p values. When analysing the impact of sustained remission and LLDAS, four consecutive visits in remission (16 weeks) were required for PCS ≥MCID (b=0.70), whereas six visits (24 weeks) were required for MCS ≥MCID (b=0.46). Sustained LLDAS for nine consecutive visits (36 weeks) was needed for PCS and MCS ≥MCID (b=0.31 and 0.31, respectively). For EQ- 5D ≥MCID to be reached, a cumulative total of seven visits (28 weeks) in remission (b=0.006), or eight visits (32 weeks) in LLDAS (b=0.005) was required, whereas if sustained, remission for six visits (24 weeks; b=0.008) or LLDAS for seven visits (28 weeks; b=0.006) were sufficient.Conclusion: Attainment of remission or LLDAS in the BLISS- 52 and BLISS- 76 trials of belimumab was associated with improved HRQoL. Less time was required in remission than in LLDAS to achieve clinically important differences in multiple HRQoL aspects. Clinically important differences in HRQoL required shorter total time if the remission or LLDAS was sustained. Clinically important differences in mental aspects of HRQoL required longer time in remission than physical aspects. The impact of cumulative and sustained remission or LLDAS on HRQoL adds evidence on the clinical importance of these treat- to- target endpoints.References:1) van Vollenhoven R. et al. Ann Rheum Dis. 20172) Franklyn K. et al. Ann Rheum Dis. 2016
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20. |
- Fanouriakis, Antonis, et al.
(author)
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EULAR recommendations for the management of systemic lupus erythematosus : 2023 update
- 2024
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In: Annals of the Rheumatic Diseases. - : HighWire Press. - 0003-4967 .- 1468-2060. ; 83:1, s. 15-29
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Journal article (peer-reviewed)abstract
- OBJECTIVES: To update the EULAR recommendations for the management of systemic lupus erythematosus (SLE) based on emerging new evidence.METHODS: An international Task Force formed the questions for the systematic literature reviews (January 2018-December 2022), followed by formulation and finalisation of the statements after a series of meetings. A predefined voting process was applied to each overarching principle and recommendation. Levels of evidence and strengths of recommendation were assigned, and participants finally provided their level of agreement with each item.RESULTS: The Task Force agreed on 5 overarching principles and 13 recommendations, concerning the use of hydroxychloroquine (HCQ), glucocorticoids (GC), immunosuppressive drugs (ISDs) (including methotrexate, mycophenolate, azathioprine, cyclophosphamide (CYC)), calcineurin inhibitors (CNIs, cyclosporine, tacrolimus, voclosporin) and biologics (belimumab, anifrolumab, rituximab). Advice is also provided on treatment strategies and targets of therapy, assessment of response, combination and sequential therapies, and tapering of therapy. HCQ is recommended for all patients with lupus at a target dose 5 mg/kg real body weight/day, considering the individual's risk for flares and retinal toxicity. GC are used as 'bridging therapy' during periods of disease activity; for maintenance treatment, they should be minimised to equal or less than 5 mg/day (prednisone equivalent) and, when possible, withdrawn. Prompt initiation of ISDs (methotrexate, azathioprine, mycophenolate) and/or biological agents (anifrolumab, belimumab) should be considered to control the disease and facilitate GC tapering/discontinuation. CYC and rituximab should be considered in organ-threatening and refractory disease, respectively. For active lupus nephritis, GC, mycophenolate or low-dose intravenous CYC are recommended as anchor drugs, and add-on therapy with belimumab or CNIs (voclosporin or tacrolimus) should be considered. Updated specific recommendations are also provided for cutaneous, neuropsychiatric and haematological disease, SLE-associated antiphospholipid syndrome, kidney protection, as well as preventative measures for infections, osteoporosis, cardiovascular disease.CONCLUSION: The updated recommendations provide consensus guidance on the management of SLE, combining evidence and expert opinion.
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21. |
- Fazal, Zoha Zahid, et al.
(author)
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COVAD survey 2 long-term outcomes : unmet need and protocol
- 2022
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In: Rheumatology International. - : Springer. - 0172-8172 .- 1437-160X. ; 42:12, s. 2151-2158
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Journal article (peer-reviewed)abstract
- Vaccine hesitancy is considered a major barrier to achieving herd immunity against COVID-19. While multiple alternative and synergistic approaches including heterologous vaccination, booster doses, and antiviral drugs have been developed, equitable vaccine uptake remains the foremost strategy to manage pandemic. Although none of the currently approved vaccines are live-attenuated, several reports of disease flares, waning protection, and acute-onset syndromes have emerged as short-term adverse events after vaccination. Hence, scientific literature falls short when discussing potential long-term effects in vulnerable cohorts. The COVAD-2 survey follows on from the baseline COVAD-1 survey with the aim to collect patient-reported data on the long-term safety and tolerability of COVID-19 vaccines in immune modulation. The e-survey has been extensively pilot-tested and validated with translations into multiple languages. Anticipated results will help improve vaccination efforts and reduce the imminent risks of COVID-19 infection, especially in understudied vulnerable groups.
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22. |
- Fornaro, M., et al.
(author)
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MULTIMORBIDITY AND PROMIS HEALTH OUTCOMES IN PATIENTS WITH IDIOPATHIC INFLAMMATORY MYOPATHIES : DATA FROM A LARGE, GLOBAL E-SURVEY (COVAD STUDY)
- 2023
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In: Annals of the Rheumatic Diseases. - : HighWire Press. - 0003-4967 .- 1468-2060. ; 82:Suppl. 1, s. 942-943
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Journal article (other academic/artistic)abstract
- Background: Prevalence of comorbidities and their impact on health outcomes in Idiopathic inflammatory myopathies (IIMs) is limited.Objectives: This study aimed to explore the prevalence of multimorbidity in patients with IIMs, other autoimmune rheumatic diseases (AIRDs) and Healthy controls (HCs). We further explore the impact of comorbidities on patients’ physical, mental, and social health assessed by the Patient-Reported Outcome Measurement Information System (PROMIS instruments).Methods: Data for this study were acquired from the COVAD 2 e-survey hosted by a study group consisting of 167 collaborators in 110 countries. Basic multimorbidity (BM) was defined as the co-occurrence of two or more comorbidities in an individual, while complex multimorbidity (CM) signified the co-occurrence of 3 or more chronic conditions affecting 3 or more different organ systems. PROMIS global physical health (PGP), mental health (PGM), fatigue 4a (F4a) and physical function short form (SF10) were analysed using descriptive statistics and linear regression models. Hierarchical Clustering on Principal Components was performed to outline the grouping.Results: Of 10740 complete respondents, 1558 IIMs, 4591 AIRDs and 3652 HCs were analysed. Individuals with IIMs exhibited high burden of any comorbidity (OR: 1.62 vs AIRDs and 2.95 vs HCs,p<0.01), BM (OR 1.66 vs AIRDs and 3.52 vs HCs,p<0.01), CM (OR: 1.69 vs AIRDs and 6.23 vs HCs,p<0.01), and mental health disorders (MHDs) (OR 1.33 vs AIRDs and 2.63 vs HCs,p<0.01).IIM patients with comorbidities (and MHDs) had worse physical function (low PGP, PGM, SF10 and higher F4a scores, all p<0.001). Worse physical function (PGP) was predicted by age (0.35; 0.030), active disease (-1.51; <0.001), BM (-1.11; <0.001), and MHDs (-1.47; <0.001). PGM was impacted by age (0.51; 0.004), active disease (-1.34, <0.001), BM (-0.75; 0.001) and MHDs (-2.22; <0.001). Determinants of SF10a were age (-3.86; <0.001), active disease (-7.03, <0.001), female (2.85, <0.001), BM (-2.95; <0.001) and MHDs (-2.37; <0.001). Fatigue (F4a) was impacted by age (-0.96, <0.001), active disease (1.45, <0.001), country human development index (0.95; 0.036), BM (1.11; <0.001); and MHDs (2.17; <0.001).Four distinct clusters (Figure 1A, Table 1) were identified i.e., cluster 0: lower burden of comorbidities and good health status; cluster 1: older patients, whit higher burden of comorbidities and poor health status, cluster 2: patients with higher prevalence of MHDs, lower PGP and PGM; and higher F4a scores; and lastly Cluster 3 that comprised older patients with an average burden of comorbidities and overall good health status according to PROMIS scores.Dermatomyositis, anti-synthetase syndrome, necrotizing autoimmune myopathy were similarly represented in all clusters, whilst inclusion body myositis and polymyositis were more predominant in clusters 1 (40.6% and 17.2%) and 3 (32 % and 17.5%), while overlap myositis was more represented in cluster 2 (25.6%) and 0 (32.7%) (Figure 1B).Conclusion: Patients with IIMs have a higher burden of comorbidities that adversely impact physical and mental health, calling for optimized approaches for holistic patient management.
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23. |
- Giannopoulou, Nefeli, et al.
(author)
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COVID-19 vaccine safety during pregnancy in women with systemic lupus erythematosus
- 2023
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In: Autoimmunity Reviews. - : Elsevier. - 1568-9972 .- 1873-0183. ; 22:4
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Journal article (peer-reviewed)abstract
- COVID-19 vaccination has been shown to be safe in patients with systemic lupus erythematosus (SLE), but data on vaccine-associated adverse events (AEs) during the antenatal and lactation period are scarce or lacking. We investigated COVID-19 vaccination-related AEs in pregnant SLE patients from the COVAD study, a global esurvey involving 157 collaborators from 106 countries. A total of 9201 complete responses were extracted. Among 6787 (73.8%) women, we identified 70 (1.1%) who were exposed to at least one COVID-19 vaccine dose during pregnancy, 11 with SLE. Delayed onset (>7 days) vaccine-related AEs were triangulated with disease activity, treatment changes due to flare after vaccination, and COVID-19 infections in vaccinated pregnant women. Health-related quality of life and physical function was recorded using PROMIS. Age of patients ranged from 28 to 39 years; 5/11 women were of Asian origin. None of these patients reported major vaccine AEs or change in the status of their autoimmune disease. Although minor AEs were common, they did not impair daily functioning, and the symptoms resolved after a median of 3 (IQR: 2.5-5.0) days. All patients reported good to excellent health status. No adverse pregnancy outcomes were reported. Importantly, none of the patients reported thrombotic events post-vaccination, which provides reassurance in a patient population with a high risk for cardiovascular comorbidity and thrombosis, especially in the presence of antiphospholipid antibodies or the antiphospholipid syndrome, a considerable portion of SLE patients. Our findings provide reassurance and can contribute to informed decisions regarding vaccination in patients with SLE and highrisk pregnancies due to their background autoimmune disease. The risk/benefit ration of COVID-19 vaccination appears favourable, with vaccines both providing passive immunisation to the fetus and active immunisation to the mother with no signals of exacerbation of the mother's autoimmune disease.
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24. |
- Giannopoulou, N., et al.
(author)
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COVID-19 VACCINE SAFETY DURING PREGNANCY IN WOMEN WITH SYSTEMIC LUPUS ERYTHEMATOSUS
- 2023
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In: Annals of the Rheumatic Diseases. - : HighWire Press. - 0003-4967 .- 1468-2060. ; 82:Suppl. 1, s. 1495-1496
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Journal article (other academic/artistic)abstract
- Background: Vaccinations comprise a part of the antenatal care of pregnant women, including patients with systemic lupus erythematosus (SLE) who are at increased risk of adverse pregnancy outcomes (APOs). While COVID-19 vaccination has been shown to be safe in patients with SLE, data on vaccine-associated adverse events (AEs) during the antenatal and lactation period are scarce or lacking.Objectives: To investigate the association between COVID-19 vaccination and AEs in pregnant SLE patients.Methods: A total of 9201 complete responses were extracted on June 21st, 2022 from the COVID-19 Vaccination in Autoimmune Diseases (COVAD) 2 database, a global e-survey involving 157 collaborators from 106 countries. Among respondents, 6787 (73.8%) were women. We identified 70 (1.1%) women who were exposed to at least one COVID-19 vaccine dose during pregnancy, among those 11 with SLE. Delayed onset (>7 days) vaccine-related AEs were extracted and triangulated with disease activity, treatment changes due to flare after vaccination, and COVID-19 infections in vaccinated pregnant women with SLE. Additionally, information on health-related quality of life and physical function was recorded using PROMIS at the time of survey completion.Results: The age of patients ranged from 28 to 39 years; 5/11 women were of Asian origin. None of these patients reported major vaccine AEs, including four patients with self-reported active SLE prior to the vaccination. None of them reported any change in the status of their autoimmune disease, and no hospitalisation or special treatment was recorded. Six women experienced minor vaccine AEs; two of them had active disease prior to vaccination. Four patients reported COVID-19 infection; two of them while they were pregnant and post-vaccination and two prior to pregnancy and vaccination. All four patients experienced symptoms of their disease, but no overt SLE flare was reported. At the time of survey completion, all patients reported their general health as being good to excellent in all aspects evaluated. Importantly, no APOs were reported.None of the patients reported thrombotic events post-vaccination, which provides some reassurance regarding COVID-19 vaccination in a patient population with a high risk for cardiovascular comorbidity and thrombosis, especially in the presence of antiphospholipid antibodies or in patients diagnosed with the antiphospholipid syndrome, a considerable portion within SLE populations. Moreover, it was reassuring to note an absence of association between experienced vaccine AEs and active disease prior to vaccination. Although minor AEs were common, they did not impair daily functioning, and the symptoms resolved in all patients after a median of 3 (IQR: 2.5–5.0) days.Conclusion: Our report adds relevant evidence concerning the sensitive issue of COVID-19 vaccine AEs and flares in SLE patients during the antenatal and lactation period. Despite the small sample size, the findings provide some reassurance and can contribute to informed decisions regarding vaccination in patients with SLE and high-risk pregnancies due to their background autoimmune disease. Based on the present data, the risk/benefit ration of COVID-19 vaccination appears favourable, with vaccines both providing passive immunisation to the fetus and active immunisation to the mother with no signals of exacerbation of the mother’s autoimmune disease.
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25. |
- Gil-Vila, Albert, et al.
(author)
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COVID-19 Vaccination In Autoimmune Diseases (COVAD) Study : Vaccine Safety In Idiopathic Inflammatory Myopathies
- 2022
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In: Muscle and Nerve. - : John Wiley & Sons. - 0148-639X .- 1097-4598. ; 66:4, s. 426-437
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Journal article (peer-reviewed)abstract
- INTRODUCTION/AIMS: We studied COVID-19 vaccination-related adverse events (ADEs) 7-days post-vaccination in patients with idiopathic inflammatory myopathies (IIMs) and other systemic autoimmune and inflammatory disorders (SAIDs).METHODS: 7-day vaccine ADEs were collected in an international patient self-reported e-survey. Descriptive statistics and multivariable regression were performed.RESULTS: 10,900 respondents [1227 IIMs; 4640 SAIDs; 5033 healthy controls (HCs), median age 42 (IQR 30-55) years, 74% female, 45% Caucasian, 69% completely vaccinated] were analysed. 76.3% IIMs patients reported minor and 4.6% major ADEs. Patients with active IIMs reported more frequent major [OR 2.7 (1.04-7.3)] and minor [OR 1.5 (1.1-2.2)] ADEs than inactive IIMs. Rashes were more frequent in IIMs [OR-2.3(1.2-4.2)] than HCs. ADEs were not impacted by steroid dose, although hydroxychloroquine and intravenous/subcutaneous immunoglobulins were associated with a higher risk of minor ADEs [OR 1.9 (1.1-3.3), OR 2.2 (1.1-4.3)]. Overall, ADEs were less frequent in inclusion body myositis (IBM) and BNT162b2 (Pfizer) vaccine recipients DISCUSSION: 7-day post-vaccination ADEs were comparable in patients with IIMs, SAIDs, and HCs, except for a higher risk of rashes in IIMs. Patients with DM, active disease may be at higher risk, and IBM patients at lower risk of specific ADEs. Overall, the benefit of preventing severe COVID-19 through vaccination likely outweighs the risk of vaccine-related ADEs Our results may inform future guidelines regarding COVID-19 vaccination in patients with SAIDs, and specifically in IIMs. Studies to evaluate long-term outcomes and disease flares are needed to shed more light on developing future COVID-19 vaccination guidelines.
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26. |
- Gomez, Alvaro, et al.
(author)
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Belimumab and antimalarials combined against renal flares in patients treated for extra-renal systemic lupus erythematosus : results from 4 phase III clinical trials
- 2024
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In: Rheumatology. - : Oxford University Press. - 1462-0324 .- 1462-0332. ; 63:2, s. 338-348
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Journal article (peer-reviewed)abstract
- OBJECTIVES: To determine the effect of antimalarial agents (AMA) and different doses and pharmaceutical forms of belimumab on preventing renal flares in patients with systemic lupus erythematosus (SLE) treated for extra-renal disease.METHODS: We pooled data from the BLISS-52, BLISS-76, BLISS-SC and BLISS-Northeast Asia trials of belimumab (N = 3225), that included patients with active SLE yet no severe ongoing nephritis. Participants were allocated to receive intravenous belimumab 1 mg/kg, intravenous belimumab 10 mg/kg, subcutaneous belimumab 200 mg, or placebo in addition to standard therapy. We estimated hazards of renal flare development throughout the study follow-up (52-76 weeks) using Cox regression analysis.RESULTS: In total, 192 patients developed a renal flare after a median of 197 days. Compared with placebo, the risk of renal flares was lower among patients receiving intravenous belimumab 10 mg/kg (HR: 0.62; 95% CI: 0.41-0.92; p = 0.018) and intravenous belimumab 1 mg/kg (HR: 0.42; 95% CI: 0.22-0.79; p = 0.007), while no significant association was found for subcutaneous belimumab 200 mg. AMA use yielded a lower hazard of renal flares (HR: 0.66; 95% CI: 0.55-0.78; p < 0.001). The protection conferred was enhanced when belimumab and AMA were co-administered; the lowest flare rate was observed for the combination intravenous belimumab 1 mg/kg and AMA (18.5 cases per 1000 person-years).CONCLUSIONS: The protection conferred from belimumab against renal flare development in patients treated for extra-renal SLE appears enhanced when belimumab is administered along with AMA. The prominent effect of low-dose belimumab warrants investigation of the efficacy of intermediate doses.
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27. |
- Gomez, Alvaro, et al.
(author)
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Do biological agents improve health-related quality of life in patients with systemic lupus erythematosus? Results from a systematic search of the literature
- 2022
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In: Autoimmunity Reviews. - : Elsevier. - 1568-9972 .- 1873-0183. ; 21:11
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Research review (peer-reviewed)abstract
- Despite an unprecedented rise in the number of biological therapies developed for systemic lupus erythematosus (SLE) during the last decades, most randomised clinical trials (RCTs) have failed to reach their primary efficacy endpoint. These endpoints mainly constitute composite outcomes that encompass disease activity indices derived from clinician-reported and laboratory data and do not necessarily reflect the patient perspective, as symptoms that represent major concerns to patients, such as fatigue, are seldom part of the evaluation. To overcome this limitation, patient-reported outcomes (PROs) constitute useful tools for evaluating the effect of an intervention on facets that are particularly relevant for the patients. In the present review, we performed a systematic literature search aiming to examine the effect of biological therapies on SLE patients' health-related quality of life (HRQoL) and fatigue in RCT and real-life settings. We summarised results concerning 14 different biological agents, the majority of which targeting B cells or type I interferons, and discuss strategies that have been used to analyse HRQoL data, putting emphasis on minimal clinically important differences and the potential use of PROs as distinct targets in treat-to-target approaches. Lastly, we discuss differences between generic and disease-specific PRO measures and highlight the need of using a combination thereof aiming to capture the patient perspective in a comprehensive manner.
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28. |
- Gomez, Alvaro, et al.
(author)
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Impact of Belimumab on Patient-Reported Outcomes in Systemic Lupus Erythematosus : Insights from Clinical Trials and Real-World Evidence
- 2023
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In: Patient Related Outcome Measures. - : Dove Medical Press Ltd.. - 1179-271X. ; 14, s. 1-13
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Research review (peer-reviewed)abstract
- Systemic lupus erythematosus (SLE) is a chronic, autoimmune disease, characterised by a relapsing-remitting pattern of inflammatory activity, with each relapse contributing to irreversible end-organ damage with detrimental effects on patients' course, adding up to morbidity burden and shortening life-length. Along with several other demographic, socioeconomic, and life-style factors, high inflammatory activity and accrued organ damage have been coupled with adverse health-related quality of life (HRQoL) within physical, mental, and psychosocial aspects. The management of SLE has improved substantially during the last decades, owing to a technological explosion that has advanced drug development towards more targeted options. Being the first drug to be approved for SLE in more than half a century and the first in history biological agent for SLE, the introduction in 2011 of the monoclonal antibody belimumab that specifically binds to the soluble counterpart of B cell activating factor (BAFF) was a breakthrough in SLE drug development. The efficacy and favourable safety profile of belimumab has been demonstrated across several clinical trials and observational studies. Herein, we reviewed the literature and provide a summary on the effects of belimumab on SLE patients' HRQoL based on 23 studies. Belimumab has been shown to induce clinically important improvements in physical aspects of HRQoL and in fatigue, the latter being a common and major complaint within the SLE population. People with SLE overall benefit more from belimumab within physical compared with mental aspects of HRQoL. However, despite improvements of clinical and immunological features upon therapy with belimumab, HRQoL perception remains unsatisfactory for a substantial percentage of the patients. Finally, our review made apparent an urgent need for optimisation of the use of patient-reported outcome measures, both in research and clinical practice.
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29. |
- Gomez, A., et al.
(author)
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LOW-DOSE BELIMUMAB AND ANTIMALARIAL AGENTS PREVENT RENAL FLARES IN SYSTEMIC LUPUS ERYTHEMATOSUS : RESULTS FROM FOUR RANDOMISED CLINICAL TRIALS
- 2023
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In: Annals of the Rheumatic Diseases. - : HighWire Press. - 0003-4967 .- 1468-2060. ; 82:Suppl. 1, s. 1467-1468
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Journal article (other academic/artistic)abstract
- Background: Lupus nephritis (LN) is one of the most severe manifestations in systemic lupus erythematosus (SLE), constituting a substantial cause of end-stage kidney disease, dialysis, and mortality. Prompt and adequate treatment of LN, and prevention of renal flares are key components of disease management towards improved outcomes in patients with SLE.Objectives: We aimed to determine the effect of the use of antimalarial agents (AMA) and different doses and pharmaceutical forms of belimumab on preventing renal flares in patients with active SLE.Methods: We pooled data from the BLISS-52, BLISS-76, BLISS-SC and BLISS-Northeast Asia randomised clinical trials of belimumab (N=3225), that included patients with seropositive (antinuclear antibody titres ≥1:80 and/or anti-dsDNA levels ≥30 IU/mL), active SLE yet no severe ongoing renal disease. Participants were allocated to receive intravenous (IV) belimumab 1 mg/kg (N=559), IV belimumab 10 mg/kg (N=1033), subcutaneous (SC) belimumab 200 mg (N=556) or placebo (N=1077) in addition to standard therapy. Additionally, we classified patients as AMA users if they had received hydroxychloroquine, chloroquine, mepacrine, or quinine sulphate in stable doses for at least 30 days prior to the trial commencement. The outcome of the present post-hoc analysis was development of renal flares, defined according to the analysis plan within the BLISS programme. The hazard of renal flare was assessed with Cox proportional hazards regression models, adjusted for age, sex, ethnicity, previous renal involvement, baseline proteinuria and glomerular filtration rate, and use of glucocorticoids and immunosuppressants.Results: In total, 192 patients developed a renal flare after a median of 197 days. In multivariable Cox regression analysis, use of AMA was associated with a lower risk of renal flares (HR: 0.64; 95% CI: 0.54–0.96; p=0.026). Compared with placebo, the risk of renal flares was lower among patients receiving IV belimumab 1 mg/kg (HR: 0.44; 95% CI: 0.25–0.79; p=0.006) and IV belimumab 10 mg/kg (HR: 0.63; 95% CI: 0.45–0.87; p=0.005), but not SC belimumab 200 mg (HR: 0.90; 95% CI: 0.57–1.42; p=0.648). When analysing all study arms with and without antimalarials separately, patients receiving IV belimumab 1 mg/kg along with AMA experienced the lowest rate of renal flares (18.5 (7.4–38.1) cases per 1000 person-years). Using patients who received placebo but not AMA as the reference comparator, patients receiving IV belimumab 1 mg/kg (OR: 0.30; 95% CI: 0.13–0.70; p=0.005) and patients receiving IV belimumab 10 mg (OR: 0.45; 95% CI: 0.27–0.75; p=0.002) were protected against renal flares only when belimumab use was combined with AMA.Conclusion: In this RCT setting, belimumab and AMA protected against renal flares in patients with active seropositive SLE yet no ongoing severe renal involvement. The protective effect of IV belimumab against renal flares appeared optimal when belimumab was combined with AMA. The prominent effect of low-dose belimumab motivates investigation of the efficacy of intermediate doses of belimumab.
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30. |
- Gomez, A., et al.
(author)
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OBESITY AND TOBACCO SMOKING ARE INDEPENDENTLY ASSOCIATED WITH POOR PATIENT-REPORTED OUTCOMES IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS FROM A SWEDISH TERTIARY REFERRAL CENTRE
- 2022
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In: Annals of the Rheumatic Diseases. - : HighWire Press. - 0003-4967 .- 1468-2060. ; 81:Suppl. 1, s. 1402-1402
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Journal article (other academic/artistic)abstract
- Patients with systemic lupus erythematosus (SLE) experience impaired health-related quality of life (HRQoL), pain, fatigue and functional disability. The effect of pharmacotherapy on these aspects has been inconclusive in literature. In light of this, investigation of the impact of lifestyle facets is needed to support complementary non-pharmacological interventions such as weight control strategies and tobacco smoking cessation.ObjectivesTo evaluate associations of obesity and tobacco smoking with SLE patients’ HRQoL, pain, fatigue and functional disability.MethodsPatients from the Linköping University Hospital with an SLE diagnosis according to the 1982 American College of Rheumatology (ACR) and/or the 2012 Systemic Lupus International Collaborating Clinics (SLICC) criteria (n=325) were included in the present cross-sectional analysis of data captured at visits between January 2008 and September 2021. Among consecutive visits, the first visit with complete demographic, clinical and patient-reported data was selected for the present analysis.Body mass index (BMI) categories were based on the World Health Organization classification: underweight (BMI <18.5 kg/m2), normal weight (18.5≤ BMI <25 kg/m2), pre-obesity (25≤ BMI <30 kg/m2) and obesity (BMI ≥30 kg/m2). Smoking status was self-reported and categorised into never, prior and current smoking.HRQoL was self-reported using the 3-level EuroQoL 5-Dimension (EQ-5D-3L) index scores. Visual analogue scales (VAS; 0–100) were used to self-report fatigue, pain and well-being within the preceding 7 days. Functional disability was evaluated using the Swedish version of the Health Assessment Questionnaires Disability Index (HAQ-DI). Disease activity was evaluated using the clinical (c)SLEDAI-2K (serology excluded).Comparisons of continuous data between different BMI and smoking categories were performed using the Mann-Whitney U test and Kruskal-Wallis test. Multivariable linear regression analysis was employed to assess independence and priority of contributors to HRQoL and functional impairment.ResultsCompared with normal weight, obese individuals reported lower EQ-5D-3L index score [0.73 (0.36–0.80) versus 0.78 (0.68–0.85); P=0.014], as well as higher VAS fatigue [50.0 (27.0–72.5) versus 32.0 (6.5–59.5); P=0.008], VAS pain [40.0 (11.0–67.0) versus 20.5 (5.3–46.5); P=0.011] and HAQ scores [0.63 (0.13–1.13) versus 0.13 (0.0–0.63); P<0.001]. Similarly, ongoing smokers reported higher VAS fatigue [56.0 (28.0–78.0) versus 32.0 (8.0–58.0); P=0.001], VAS pain [45.0 (18.0–62.0) versus 18.0 (5.0–39.8); P=0.001] and HAQ scores [0.63 (0.13–1.13) versus 0.13 (0.0–0.63); P=0.001] compared with individuals who were never exposed to regular tobacco smoking. There were no differences across groups regarding cSLEDAI-2K scores.In multivariable linear regression models, obesity and current tobacco smoking were independently associated with lower EQ-5D-3L index scores (β=-0.12; P=0.021 and β=-0.11; P=0.029, respectively), and higher VAS fatigue (β=12.8; P=0.007 and β=17.5; P<0.001), VAS pain (β=12.1; P=0.004 and β=15.5; P<0.001), VAS well-being (β=9.6; P=0.028 and β=9.8; P=0.035) and HAQ scores (β=0.30; P=0.001 and β=0.27; P=0.007), but not with cSLEDAI-2K (β=-0.73; P=0.189 and β=0.34; P=0.572).ConclusionIn a Swedish SLE population, obesity and ongoing tobacco smoking were independently associated with worse outcomes - compared with normal weight and individuals who never smoked, respectively - regarding HRQoL, fatigue, pain and functional disability but were not associated with clinical disease activity.Disclosure of InterestsNone declared
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31. |
- Gomez, Alvaro, et al.
(author)
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Obesity and tobacco smoking are independently associated with poor patient-reported outcomes in SLE : a cross-sectional study
- 2024
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In: Rheumatology International. - : Springer. - 0172-8172 .- 1437-160X. ; 44:5, s. 851-861
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Journal article (peer-reviewed)abstract
- We investigated associations of obesity and tobacco smoking with health-related quality of life (HRQoL), pain, fatigue, and functional impairment in systemic lupus erythematosus (SLE). Furthermore, we explored whether there was an effect modification between these two factors. We included adult SLE patients from the Linköping University Hospital (n = 325) in the present cross-sectional analysis. We further included population-based controls and performed cardinality matching to balance age and sex distributions with cases (n = 224). HRQoL was assessed with the EQ-5D index score; pain, fatigue, and overall SLE-related health state with visual analogue scales (VAS; 0 [best] to 100 [worst]); and functional impairment with the HAQ-DI. Unacceptable outcomes were defined as VAS scores corresponding to the 90th percentile derived from the matched controls. SLE patients reported worse scores than controls in all measures, and approximately 30% experienced unacceptable outcomes. When compared with normal-weight, obese SLE patients reported lower HRQoL, and greater functional impairment and risk of unacceptable pain (OR: 3.2; 95% CI 1.6-6.7) and fatigue (OR: 2.1; 95% CI 1.0-4.3). Similarly, the current smokers reported higher levels of functional impairment and a greater risk of unacceptable pain (OR: 3.8; 95% CI 1.8-8.2) and fatigue (OR: 2.8; 95% CI 1.3-5.9) than never smokers. The associations were independent of age, sex, disease duration, disease activity, and organ damage. There was no evidence of a synergistic effect between increased BMI and smoking on any outcome. In summary, obesity and smoking are risk factors for unacceptable patient-reported outcomes in SLE, regardless of clinical activity.
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32. |
- Grignaschi, S., et al.
(author)
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HIGH FATIGUE SCORES IN PATIENTS WITH IDIOPATHIC INFLAMMATORY MYOPATHIES : A MULTIGROUP COMPARATIVE STUDY FROM THE COVAD E-SURVEY
- 2022
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In: Annals of the Rheumatic Diseases. - : HighWire Press. - 0003-4967 .- 1468-2060. ; 81:Suppl. 1, s. 748-748
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Journal article (other academic/artistic)abstract
- Idiopathic inflammatory myopathies (IIM) are a rare, multisystem, heterogeneous diseases, and contribute to high psychological burden. The patients’ perception of physical health, deteriorating independence and social and environmental relationships may not always be a direct function of disease activity. To face with these aspects, several worldwide specialized organization have recommended the use of patient reported outcome measures (PROMs) both in clinical trials and observational studies to highlight patient’s perception of the disease (1). Unfortunately, data on fatigue scores in IIM is limited.ObjectivesWe compared fatigue VAS scores in patients with IIM, autoimmune diseases (AIDs) and healthy controls (HCs) and triangulated them with PROMIS physical function in a large international cohort made up of answers from the e-survey regarding the COVID-19 Vaccination in Autoimmune Diseases (COVAD) study.MethodsData of 16327 respondents was extracted from the COVAD database on August 31th 2021. VAS fatigue scores were compared between AID, HC and IIM using univariate followed by multivariate analysis after adjusting for baseline differences. We further performed a propensity score matched analysis on 1827 subjects after adjusting for age, gender and ethnicity. The Kruskal-Wallis test was used for continuous variables and chi-square test for categorical variables, and Bonferroni’s correction was applied for the post hoc analyses considering IIMs as a reference group.ResultsWe analyzed answers from 6988 patients, with a mean age of 43.8 years (SD 16.2). The overall percentage of female was 72% and the population ethnicity was mainly composed of White (55.1%), followed by Asian (24.6%), and Hispanic (13.8%). The overall fatigue VAS was 3.6 mm (SD 2.7). IIMs VAS was 4.8 mm (SD 2.6), AIDs 4.5 mm (SD 2.6), and HC 2.8 mm (SD 2.6) (P <0,001). VAS fatigue scores of IIMs were comparable with AIDs (P 0.084), albeit significantly higher than the HCs (P <0,001). Notably, fatigue VAS was lower in IIMs than AIDs in two distinct subsets: inactive disease as defined by the patient’s perception and the “excellent” general health condition group, where IIMs had worse scores (P <0,05). Interestingly, fatigue VAS was comparable in active disease defined by physician assessment, patient perception, based on general functional status, or when defined by steroid dose being prescribed. Notably, after propensity matched analysis of patients adjusting for gender, age and ethnicity (1.827 answers, i.e. 609 subjects per group, P =1) the differences disappeared and IIMs and AIDs had comparable fatigue levels across all levels of disease activity, although the fatigue discrepancies with HCs were substantially confirmed.After application of a multivariate linear regression analysis we found that lower fatigue VAS scores were related to HC (P <0,001), male gender (P <0,001), Asian and Hispanic ethnicities (P <0,001 and 0,003).ConclusionOur study confirms that there is a higher prevalence of fatigue in all the AIDs patients, with comparable VAS scores between IIMs and other AIDs. We can also read our data commenting that females and/or Caucasians patients suffer a higher impact of this manifestation of chronic autoimmune diseases upon their lives. This is why these subjects, to our judgement, should be carefully evaluated during outpatients visits and to whom we should spend some extra time to discuss health related issues and how to improve them.References[1]Regardt, M. et al. OMERACT 2018 Modified Patient-reported Outcome Domain Core Set in the Life Impact Area for Adult Idiopathic Inflammatory Myopathies. J. Rheumatol.46, 1351–1354 (2019).Figure 1.distribution of Fatigue VAS scores in the three population evaluated. IIM idiopathic inflammatory myositis; AID autoimmune diseases; HC healthy controls; * P < 0,05.Disclosure of InterestsNone declared
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33. |
- Grignaschi, Silvia, et al.
(author)
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High fatigue scores in patients with idiopathic inflammatory myopathies : a multigroup comparative study from the COVAD e-survey
- 2023
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In: Rheumatology International. - : Springer. - 0172-8172 .- 1437-160X. ; 43:9, s. 1637-1649
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Journal article (peer-reviewed)abstract
- Idiopathic inflammatory myopathies (IIMs) confer a significant risk of disability and poor quality of life, though fatigue, an important contributing factor, remains under-reported in these individuals. We aimed to compare and analyze differences in visual analog scale (VAS) scores (0-10 cm) for fatigue (VAS-F) in patients with IIMs, non-IIM systemic autoimmune diseases (SAIDs), and healthy controls (HCs). We performed a cross-sectional analysis of the data from the COVID-19 Vaccination in Autoimmune Diseases (COVAD) international patient self-reported e-survey. The COVAD survey was circulated from December 2020 to August 2021, and details including demographics, COVID-19 history, vaccination details, SAID details, global health, and functional status were collected from adult patients having received at least one COVID-19 vaccine dose. Fatigue experienced 1 week prior to survey completion was assessed using a single-item 10 cm VAS. Determinants of fatigue were analyzed in regression models. Six thousand nine hundred and eighty-eight respondents (mean age 43.8 years, 72% female; 55% White) were included in the analysis. The overall VAS-F score was 3 (IQR 1-6). Patients with IIMs had similar fatigue scores (5, IQR 3-7) to non-IIM SAIDs [5 (IQR 2-7)], but higher compared to HCs (2, IQR 1-5; P < 0.001), regardless of disease activity. In adjusted analysis, higher VAS-F scores were seen in females (reference female; coefficient -0.17; 95%CI -0.21 to -13; P < 0.001) and Caucasians (reference Caucasians; coefficient -0.22; 95%CI -0.30 to -0.14; P < 0.001 for Asians and coefficient -0.08; 95%CI -0.13 to 0.30; P = 0.003 for Hispanics) in our cohort. Our study found that patients with IIMs exhibit considerable fatigue, similar to other SAIDs and higher than healthy individuals. Women and Caucasians experience greater fatigue scores, allowing identification of stratified groups for optimized multidisciplinary care and improve outcomes such as quality of life.
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34. |
- Gupta, L., et al.
(author)
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COMORBIDITIES, COMPLEX MULTIMORBIDITY AND PROMIS HEALTH OUTCOMES AMONGAUTOIMMUNE RHEUMATIC DISEASES : DATA FROM THE COVAD STUDY
- 2023
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In: Annals of the Rheumatic Diseases. - : HighWire Press. - 0003-4967 .- 1468-2060. ; 82:Suppl. 1, s. 555-556
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Journal article (other academic/artistic)abstract
- Background: Comorbidities have a profound impact on the QoL of patients living with autoimmune rheumatic diseases (AIRDs). Unfortunately, global data on the burden of comorbidities and its impact on health outcomes in this vulnerable group is scarce.Objectives: We studied the prevalence, distribution and clustering of comorbidities and multimorbidity among patients with AIRDs and healthy controls (HCs) and its impact on health outcomes, utilizing data from the ongoing 2nd COVAD study.Methods: The COVAD study is a global e-survey that embodies patient voice while empowering collaborators and young researchers. The study group of 157 physicians across 106 countries from February-June 2022 captured details of AIRDs, autoimmune and non-autoimmune comorbidities, and validated patient reported outcomes. Human Development Index (UNDP 2021-22) of country of residence was taken as a surrogate marker for socioeconomic status (SES).Basic multimorbidity (BM), Complex multimorbidity (CM), Autoimmune multimorbidity (AM) are defined as the co-occurrence of ≥2 non-rheumatic comorbidities, ≥3 non-rheumatic chronic conditions affecting ≥3 different organ systems [1] and ≥3 autoimmune diseases (AIDs) in an individual respectively.PROMIS global physical health (PGP), mental health (PGM), fatigue 4a (F4a) and physical function short form (SF10) scores were calculated for the different groups and compared using descriptive statistics, linear regression and cluster analysis (hierarchical followed by K means).Results: Of 17,612 total respondents, 6149 (62.7%) had underlying AIRDs and 3652 (37.3%) were HCs, with female (80.8%) and Caucasian (53.9%) predominance in the former.All types of multimorbidity were more frequent in AIRDs than HCs, including any comorbidity (77.1% versus 25.0%; OR: 2.9; 2.7-3.2), BM (21.0% vs 6.2%; 4.0; 3.4-4.6), and CM (3.1% vs 0.5%; 6.4; 3.9-10.4), and with prevalence increasing with age (p<0.001) (Figure 1A, B). Comorbidity prevalence was the highest among Americans and Australians (72% each).Patients with AIRDs had poorer health outcomes than HCs, including lower PGP, PGM, SF10, F4a scores (all p<0.001). Among AIRDs, those with comorbidities had lower physical function and PROMIS scores (PGP, PGM, and SF10), and reported fatigue more often (all p<0.001).Female gender, and underlying BM and AM particularly predisposed patients to worse physical health (lower PGP, lower SF10a) and mental health outcomes (lower PGM). While advanced age (-1.815; <0.001), and lower SES (0.871; 0.027) specifically predicted poorer physical function (lower SF10a). Fatigue (higher F4a) was seen more frequently among women (1.711; <0.001), and those with BM (1.142; 0.002); AM (1.768; 0.011), and higher SEC (0.478; 0.016).Cluster analysis of patients with AIRDs revealed 2 clusters (Figure 1C 1D); cluster 1 with low PGP, PGM, SF10 and high F4a; cluster 2 with high PGP, PGM, SF10 and low F4a. The clusters differed predominantly based on the frequency of comorbidities; any comorbidity (59.7% vs 41.8%; p<0.001), BM (28.5% vs 14.7%; 0.001); CM (4.5% vs 1.9%; <0.001), and AM (10.0% vs 4.0%; <0.001).Conclusion: Comorbidities complicate three-quarters of individuals living with AIRDs, and have an outsized impact on self-reported physical function, perceived fatigue, and QoL. Substantial regional differences call for further exploration of key drivers of this important aspect to allow optimized multidisciplinary and holistic care in anticipation of poorer outcomes.Reference: [1]Harrison C, Britt H, Miller G, Henderson J. Examining different measures of multimorbidity, using a large prospective cross-sectional study in Australian general practice. BMJ Open. 2014 Jul 1;4(7):e004694.
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35. |
- Gupta, L., et al.
(author)
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COVID-19 SEVERITY AND VACCINE BREAKTHROUGH INFECTIONS IN IDIOPATHIC INFLAMMATORY MYOPATHIES, OTHER SYSTEMIC AUTOIMMUNE AND INFLAMMATORY DISEASES, AND HEALTHY INDIVIDUALS : RESULTS FROM THE COVID-19 VACCINATION IN AUTOIMMUNE DISEASES (COVAD) STUDY.
- 2022
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In: Annals of the Rheumatic Diseases. - : HighWire Press. - 0003-4967 .- 1468-2060. ; 81:Suppl. 1, s. 334-336
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Journal article (other academic/artistic)abstract
- Significant gaps are present in the evidence of the spectrum and severity of COVID-19 infection in idiopathic inflammatory myopathies (IIM). IIM patients typically require immunosuppressive therapy, may have multiple disease sequelae, and frequent comorbidities, and thus may be more susceptible to severe COVID-19 infection and complications (1). The possibility of attenuated immunogenicity and reduced efficacy of COVID-19 vaccines due to concomitant immunosuppressive medication is a major concern in these patients, and there is little data available on COVID-19 vaccine breakthrough infections (BI) in IIM (2).ObjectivesThis study aimed to compare disease spectrum and severity and COVID-19 BI in patients with IIM, other systemic autoimmune and inflammatory diseases (SAIDs) and healthy controls (HCs).MethodsWe developed an extensive self-reporting electronic-survey (COVAD survey) featuring 36 questions to collect respondent demographics, SAID details, COVID-19 infection history, COVID-19 vaccination details, 7-day post vaccination adverse events and patient reported outcome measures using the PROMIS tool. After pilot testing, validation, translation into 18 languages on the online platform surveymonkey.com, and vetting by international experts, the COVAD survey was circulated in early 2021 by a multicenter study group of >110 collaborators in 94 countries. BI was defined as COVID-19 infection occurring more than 2 weeks after receiving 1st or 2nd dose of a COVID-19 vaccine. We analyzed data from the baseline survey for descriptive and intergroup comparative statistics based on data distribution and variable type.Results10900 respondents [mean age 42 (30-55) years, 74% females and 45% Caucasians] were analyzed. 1,227 (11.2%) had IIM, 4,640 (42.6%) had other SAIDs, and 5,033 (46.2%) were HC. All respondents included in the final analysis had received a single dose of the vaccine and 69% had received 2 primary doses. Pfizer (39.8%) was the most common vaccine received, followed by Oxford/AstraZeneca (13.4%), and Covishield (10.9%). IIM patients were older, had a higher Caucasian representation and higher Pfizer uptake than other SAIDs, and HC. A higher proportion of IIM patients received immunosuppressants than other SAIDs.IIMs were at a lower risk of symptomatic pre-vaccination COVID-19 infection compared to SAIDs [multivariate OR 0.6 (0.4-0.8)] and HCs [multivariate OR 0.39 (0.28-0.54)], yet at a higher risk of hospitalization due to COVID-19 compared to SAIDs [univariate OR 2.3 (1.2-3.5)] and HCs [multivariate OR 2.5 (1.1-5.8)]. BIs were very uncommon in IIM patients, with only 17 (1.4%) reporting BI. IIM patients were at a higher risk of contracting COVID-19 prior to vaccination than ≤2 weeks of vaccination [univariate OR 8 (4.1-15)] or BI [univariate OR 4.6 (2.7-8.0)]. BIs were equally severe compared to when they occurred prior to vaccination in IIMs, and were comparable between IIM, SAIDs, and HC (Figure 1), though BI disease duration was shorter in IIMs than SAIDs (7 vs 11 days, p 0.027). 13/17 IIM patients with BI were on immunosuppressants.ConclusionIIM patients experienced COVID-19 infection less frequently prior to vaccination but were at a higher risk of hospitalization and requirement for oxygen therapy compared with patients with HC. Breakthrough COVID-19 infections were rare (1.4%) in vaccinated IIM patients, and were similar to HC and SAIDs, except for shorter disease duration in IIM.References[1]Brito-Zerón P, Sisó-Almirall A, Flores-Chavez A, Retamozo S, Ramos-Casals M. SARS-CoV-2 infection in patients with systemic autoimmune diseases. Clin Exp Rheumatol. 2021 Jun;39(3):676–87.[2]Wack S, Patton T, Ferris LK. COVID-19 vaccine safety and efficacy in patients with immune-mediated inflammatory disease: Review of available evidence. J Am Acad Dermatol. 2021 Nov;85(5):1274–84.AcknowledgementsThe authors thank all members of the COVAD study group for their invaluable role in the collection of data. The authors thank all respondents for filling the questionnaire. The authors thank The Myositis Association, Myositis India, Myositis UK, the Myositis Global Network, Cure JM, Cure IBM, Sjögren’s India Foundation, EULAR PARE, and various other patient support groups and organizations for their invaluable contribution in the dissemination of this survey among patients which made the data collection possible. The authors also thank all members of the COVAD study group.Disclosure of InterestsLatika Gupta: None declared, Leonardo Santos Hoff: None declared, Naveen R: None declared, Parikshit Sen: None declared, Samuel Katsuyuki Shinjo: None declared, Jessica Day Grant/research support from: JD has received research funding from CSL Limited, James B. Lilleker: None declared, Vishwesh Agarwal: None declared, Sinan Kardes: None declared, Minchul Kim: None declared, Ashima Makol: None declared, Marcin Milchert: None declared, Tamer A Gheita: None declared, Babur Salim: None declared, Tsvetelina Velikova: None declared, Abraham Edgar Gracia-Ramos: None declared, Ioannis Parodis Speakers bureau: IP has received research funding and/or honoraria from Amgen, AstraZeneca, Aurinia Pharmaceuticals, Elli Lilly and Company, Gilead Sciences, GlaxoSmithKline, Janssen Pharmaceuticals, Novartis and F. Hoffmann-La Roche AG., Consultant of: IP has received research funding and/or honoraria from Amgen, AstraZeneca, Aurinia Pharmaceuticals, Elli Lilly and Company, Gilead Sciences, GlaxoSmithKline, Janssen Pharmaceuticals, Novartis and F. Hoffmann-La Roche AG., Grant/research support from: IP has received research funding and/or honoraria from Amgen, AstraZeneca, Aurinia Pharmaceuticals, Elli Lilly and Company, Gilead Sciences, GlaxoSmithKline, Janssen Pharmaceuticals, Novartis and F. Hoffmann-La Roche AG., Albert Selva-O’Callaghan: None declared, Elena Nikiphorou Speakers bureau: EN has received speaker honoraria/participated in advisory boards for Celltrion, Pfizer, Sanofi, Gilead, Galapagos, AbbVie, Lilly, Consultant of: EN has received speaker honoraria/participated in advisory boards for Celltrion, Pfizer, Sanofi, Gilead, Galapagos, AbbVie, Lilly, Grant/research support from: EN holds research grants from Pfizer and Lilly., Tulika Chatterjee: None declared, Ai Lyn Tan Speakers bureau: ALT has received honoraria for advisory boards and speaking for Abbvie, Gilead, Janssen, Lilly, Novartis, Pfizer, UCB., Consultant of: ALT has received honoraria for advisory boards and speaking for Abbvie, Gilead, Janssen, Lilly, Novartis, Pfizer, UCB., Arvind Nune: None declared, Lorenzo Cavagna: None declared, Miguel A Saavedra: None declared, Nelly Ziade Speakers bureau: NZ has received speaker fees, advisory board fees and research grants from Pfizer, Roche, Abbvie, Eli Lilly, NewBridge, Sanofi-Aventis, Boehringer Ingelheim, Janssen, Pierre Fabre; none is related to this manuscript, Consultant of: NZ has received speaker fees, advisory board fees and research grants from Pfizer, Roche, Abbvie, Eli Lilly, NewBridge, Sanofi-Aventis, Boehringer Ingelheim, Janssen, Pierre Fabre; none is related to this manuscript, Grant/research support from: NZ has received speaker fees, advisory board fees and research grants from Pfizer, Roche, Abbvie, Eli Lilly, NewBridge, Sanofi-Aventis, Boehringer Ingelheim, Janssen, Pierre Fabre; none is related to this manuscript, Johannes Knitza: None declared, Masataka Kuwana: None declared, Oliver Distler Speakers bureau: OD has/had consultancy relationship with and/or has received research funding from or has served as a speaker for the following companies in the area of potential treatments for systemic sclerosis and its complications in the last three years: Abbvie, Acceleron, Alcimed, Amgen, AnaMar, Arxx, Baecon, Blade, Bayer, Boehringer Ingelheim, ChemomAb, Corbus, CSL Behring, Galapagos, Glenmark, GSK, Horizon (Curzion), Inventiva, iQvia, Kymera, Lupin, Medac, Medscape, Mitsubishi Tanabe, Novartis, Roche, Roivant, Sanofi, Serodapharm, Topadur and UCB. Patent issued “mir-29 for the treatment of systemic sclerosis” (US8247389, EP2331143)., Consultant of: OD has/had consultancy relationship with and/or has received research funding from or has served as a speaker for the following companies in the area of potential treatments for systemic sclerosis and its complications in the last three years: Abbvie, Acceleron, Alcimed, Amgen, AnaMar, Arxx, Baecon, Blade, Bayer, Boehringer Ingelheim, ChemomAb, Corbus, CSL Behring, Galapagos, Glenmark, GSK, Horizon (Curzion), Inventiva, iQvia, Kymera, Lupin, Medac, Medscape, Mitsubishi Tanabe, Novartis, Roche, Roivant, Sanofi, Serodapharm, Topadur and UCB. Patent issued “mir-29 for the treatment of systemic sclerosis” (US8247389, EP2331143)., Grant/research support from: OD has/had consultancy relationship with and/or has received research funding from or has served as a speaker for the following companies in the area of potential treatments for systemic sclerosis and its complications in the last three years: Abbvie, Acceleron, Alcimed, Amgen, AnaMar, Arxx, Baecon, Blade, Bayer, Boehringer Ingelheim, ChemomAb, Corbus, CSL Behring, Galapagos, Glenmark, GSK, Horizon (Curzion), Inventiva, iQvia, Kymera, Lupin, Medac, Medscape, Mitsubishi Tanabe, Novartis, Roche, Roivant, Sanofi, Serodapharm, Topadur and UCB. Patent issued “mir-29 for the treatment of systemic sclerosis” (US8247389, EP2331143)., Hector Chinoy Speakers bureau: HC has been a speaker for UCB, Biogen., Consultant of: HC has received consulting fees from Novartis, Eli Lilly, Orphazyme, Astra Zeneca, Grant/research support from: HC has received grant support from Eli Lilly and UCB, Vikas Agarwal: None declared, Rohit Aggarwal Consultant of: RA has/had a consultancy relationship with and/or has received research funding from the following companies-Bristol Myers-Squibb, Pfizer, Genentech, Octapharma, CSL Behring, Mallinckrodt, AstraZeneca, Corbus, Kezar, and Abbvie, Janssen, Alexion, Argenx, Q32
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36. |
- Gupta, Latika, et al.
(author)
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FLARES FOLLOWING COVID-19 VACCINATION IN PATIENTS WITH IDIOPATHIC INFLAMMATORY MYOPATHIES : COMBINED ANALYSIS FROM THE COVID-19 VACCINATION IN AUTOIMMUNE DISEASES (COVAD) STUDIES
- 2023
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In: Rheumatology. - : Oxford University Press. - 1462-0324 .- 1462-0332. ; 62:Suppl. 2
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Journal article (other academic/artistic)abstract
- Background/Aims: Flares following COVID-19 vaccination are an emerging concern among patients with rare rheumatic disease like idiopathic inflammatory myositis (IIMs), whereas data and understanding of this is rather limited. We aimed to study the prevalence, characteristics and determinants of IIM flares following COVID-19 vaccination.Methods: CoVAD (COVID-19 Vaccination In Autoimmune Diseases) surveys are global patient self-reported e-surveys from 109 countries conducted in 2021 and 2022. Flares of IIM were defined by 4 definitions; a. patient self-reported, b. physician and immunosuppression (IS) denoted, c. sign directed (new erythematous rash, or worsening myositis or arthritis), d. MCID worsening of PROMISPF10a score between the patients who had taken both surveys. Descriptive statistics and multivariate regression were used to describe the predictors of flare. Cox-regression analysis was used to differentiate flares by IIM subtypes.Results: Among the 1,278 IIM patients, aged 63 (50-71) years, 276 (21.5%) were dermatomyositis, 237 (18.5%) IBM, 899 (70.3%) were female and most were Caucasian (80.8%). Flares of IIM were seen in 123/1278 (9.6%), 163/1278 (12.7%), 112/1278 (8.7%), and 16/96 (19.6%) by definitions a-d respectively with median time to flare being 71.5 (10.7-235) days. Muscle weakness (69.1%), and fatigue (56.9%) were the most common symptoms of flare. The predictors of self-reported flare were: inactive/disease in remission prior to first dose of vaccine (OR ¼ 4.3, 95%CI¼2.4-7.6), and anxiety disorder (OR ¼ 2.2, 95%CI¼1.1-4.7). Rituximab use (OR ¼ 0.3, 95%CI¼0.1-0.7) and IBM (OR ¼ 0.3, 95%CI¼0.1-0.7) were protective. Physician defined flares were seen more often in females, mixed ethnicity, and those with asthma, ILD, and anxiety disorder (OR ranging 1.6-7.0, all p < 0.05). Notably, overlap myositis (OM) had higher HR for flare compared to polymyositis (HR ¼ 2.3, 95%CI¼1.2-4.4, p ¼ 0.010).Conclusion: Nearly one in ten individuals with IIM develop flares after vaccination, more so among women, those with overlap myositis, and inactive disease prior to vaccination. Formal definition of flares in IIM is needed.
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37. |
- Gupta, Latika, et al.
(author)
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POST COVID-19 SYNDROME IN PATIENTS WITH AUTOIMMUNE RHEUMATIC DISEASES : RESULTS FROM THE COVID-19 VACCINATION IN AUTOIMMUNE DISEASES (COVAD) STUDY
- 2023
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In: Rheumatology. - : Oxford University Press. - 1462-0324 .- 1462-0332. ; 62:Suppl. 2
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Journal article (other academic/artistic)abstract
- Background/Aims: Post COVID-19 syndrome (PCS) is an emerging cause of morbidity and poor quality of life in COVID-19 survivors. We aimed to assess the prevalence, risk factors, outcomes, and association with disease flaresof PCS in patients with autoimmune rheumatic diseases (AIRDs) and non-rheumatic autoimmune diseases (nrAIDs), both vulnerable groups understudied in the current literature using data from the 2nd COVID-19 Vaccination in Autoimmune Diseases (COVAD) global multicentre patient self-reported e-survey.Methods: The survey was circulated from February to July 2022 by the international COVAD Study Group (157 collaborators from 106 countries), and demographics, comorbidities, AIRD/nrAID status, COVID-19 history, vaccination details, and PROMIS physical and mental function were recorded. PCS was defined as symptom resolution time >90 days following acute COVID-19. Predictors of PCS were analysed using regression models for the different groups.Results: 7666 total respondents completed the survey. Of these, 2650 respondents with complete responses had positive COVID-19 infection, and 1677 (45.0% AIRDs, 12.5% nrAIDs, 42.5% HCs) completed the survey >90 days post acute COVID-19. Of these, 136 (8.1%) had PCS. Prevalence of PCS was higher in AIRDs (10.8%) than healthy controls HCs (5.3%) (OR: 2.1; 95%CI: 1.4-3.1, p ¼ 0.002).Across the entire cohort, a higher risk of PCS was seen in women (OR: 2.9; 95%CI: 1.1-7.7, p ¼ 0.037), patients with long duration of AIRDs/nrAIDs (OR 1.01; 95%CI: 1.0-1.02, p ¼ 0.016), those with comorbidities (OR: 2.8; 95%CI: 1.4-5.7, p ¼ 0.005), and patients requiring oxygen supplementation for severe acute COVID-19 (OR: 3.8; 95%CI: 1.1-13.6, p ¼ 0.039).Among patients with AIRDs, comorbidities (OR 2.0; 95%CI: 1.08-3.6, p ¼ 0.026), and advanced treatment (OR: 1.9; 95%CI: 1.08-3.3, p ¼ 0.024), or intensive care (OR: 3.8; 95%CI: 1.01-14.4, p ¼ 0.047) for severe COVID-19 were risk factors for PCS.Notably, patients who developed PCS had poorer PROMIS global physical [15 (12-17) vs 12 (9-15)] and mental health [14 (11-16) vs 11 (8-14)] scores than those without PCS.Conclusion: Individuals with AIRDs have a greater risk of PCS than HCs. Associated comorbid conditions, and advanced treatment or intensive care unit admission for severe COVID-19 confer a higher risk of PCS. It is imperative to identify risk factors for PCS for immediate multidisciplinary management in anticipation of poor physical and mental health.
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38. |
- Hege, Inga, et al.
(author)
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Developing a European longitudinal and interprofessional curriculum for clinical reasoning
- 2023
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In: Diagnosis. - : Walter de Gruyter GmbH. - 2194-8011 .- 2194-802X.
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Journal article (peer-reviewed)abstract
- Clinical reasoning is a complex and crucial ability health professions students need to acquire during their education. Despite its importance, explicit clinical reasoning teaching is not yet implemented in most health professions educational programs. Therefore, we carried out an international and interprofessional project to plan and develop a clinical reasoning curriculum with a train-the-trainer course to support educators in teaching this curriculum to students. We developed a framework and curricular blueprint. Then we created 25 student and 7 train-the-trainer learning units and we piloted 11 of these learning units at our institutions. Learners and faculty reported high satisfaction and they also provided helpful suggestions for improvements. One of the main challenges we faced was the heterogeneous understanding of clinical reasoning within and across professions. However, we learned from each other while discussing these different views and perspectives on clinical reasoning and were able to come to a shared understanding as the basis for developing the curriculum. Our curriculum fills an important gap in the availability of explicit clinical reasoning educational materials both for students and faculty and is unique with having specialists from different countries, schools, and professions. Faculty time and time for teaching clinical reasoning in existing curricula remain important barriers for implementation of clinical reasoning teaching.
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39. |
- Hernández-Breijo, Borja, et al.
(author)
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BAFF predicts immunogenicity in older patients with rheumatoid arthritis treated with TNF inhibitors
- 2021
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In: Scientific Reports. - : Springer Nature. - 2045-2322. ; 11:1
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Journal article (peer-reviewed)abstract
- Immunogenicity related to treatment with TNF inhibitors (TNFi) is one of the causes for the decreased attainment of clinical response in patients with rheumatoid arthritis (RA). The B-cell activating factor (BAFF) may be playing a role in the development of immunogenicity. The objective of this study was to analyse the association of baseline concentration of serum B-cell activating factor (BAFF) with immunogenicity after 6 months of TNFi treatment. A total of 127 patients with RA starting a TNFi (infliximab, adalimumab, certolizumab pegol or golimumab) were followed-up for 6 months. Serum samples were obtained at baseline and at 6 months and anti-drug antibody (ADA) and BAFF concentrations were measured. Logistic regression models were employed in order to analyse the association between BAFF concentrations and immunogenicity. Receiver operating characteristic analysis was performed to determine the BAFF concentrations with a greater likelihood of showing immunogenicity association. At 6 months, 31 patients (24%) developed ADA. A significant interaction between the age and baseline BAFF concentration was found for the development of ADA (Wald chi-square value = 5.30; p = 0.02); therefore, subsequent results were stratified according to mean age (≤ / > 55 years). Baseline serum BAFF concentration was independently associated with ADA development only in patients over 55 years (OR = 1.51; 95% CI 1.03-2.21). Baseline serum BAFF ≥ 1034 pg/mL predicted the presence of ADA at 6 months (AUC = 0.81; 95% confidence interval (CI) 0.69-0.93; p = 0.001; positive likelihood ratio = 3.7). In conclusion, our results suggest that the association of BAFF concentration and immunogenicity depends on the patient's age. Baseline serum BAFF concentration predicts the presence of ADA within 6 months of TNFi therapy in older patients with RA.
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40. |
- Hernández-Breijo, Borja, et al.
(author)
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Low Serum BAFF Concentration Is Associated with Response to TNF Inhibitors in Seropositive Patients with Rheumatoid Arthritis
- 2022
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In: Journal of Clinical Medicine. - : MDPI. - 2077-0383. ; 11:17
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Journal article (peer-reviewed)abstract
- We investigated B-cell-activating factor (BAFF) in relation to response to treatment with TNF inhibitors (TNFis) in rheumatoid arthritis (RA). This was a longitudinal study including 158 patients with RA treated with TNFis and followed up for 6 months. Clinical response at 6 months of treatment was defined according to the EULAR criteria for good responders (GRs). BAFF concentration was measured in serum samples, collected at baseline and at 6 months. Associations with EULAR response were evaluated using univariable and multivariable logistic regression models. ROC analysis was performed to determine the optimal threshold of serum BAFF concentration associated with good EULAR response to treatment. After 6 months of TNFi treatment, 24% of patients were GRs. They had a lower BMI, lower baseline DAS28 and lower baseline serum BAFF concentration than non-responders. After 6 months of TNFi treatment, autoantibody-positive patients who attained GR had significantly lower serum BAFF concentrations compared with patients who did not. Serum BAFF < 968 pg/mL at 6 months represented the concentration likely to best discriminate between GR and non-GR at 6 months of TNFi treatment. Autoantibody-seropositive patients who had serum BAFF < 968 pg/mL at 6 months demonstrated a more than four-fold increased probability to be GRs compared with patients with higher BAFF concentrations. In conclusion, serum BAFF concentrations were associated with response to TNFis in seropositive RA patients, corroborating the importance of the B-cell compartment in RA.
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41. |
- Hernandez-Breijo, Borja, et al.
(author)
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Serum B Cell Activating Factor Reflects Good EULAR Response to TNF Inhibition in Patients with Rheumatoid Arthritis
- 2021
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In: Arthritis & Rheumatology. - : John Wiley & Sons. - 2326-5191 .- 2326-5205. ; 73:Suppl. 9, s. 2586-2588
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Journal article (other academic/artistic)abstract
- Background/Purpose: The latest breakthroughs in the pathophysiology of rheumatoid arthritis (RA) highlighted the activation of B cells as a trigger of the joint flare initiation and therefore, implicated a central role for B cells in RA pathogenesis. B cell activating factor (BAFF) is essential for B cell activation, differentiation and survival. The main objective of this study was to investigate the role of BAFF in the progression of rheumatoid arthritis during treatment with TNF inhibitors (TNFi) and its association with treatment response.Methods: This was a prospective study including 158 patients with RA initiated at the first TNFi and followed- up for 6 months (m). Disease activity was assessed using the Disease Activity Score 28 (DAS28) at baseline and 6m of treatment. Clinical response at 6m of treatment was defined according to the EULAR criteria for good responders. BAFF concentration was measured in serum samples collected at baseline and 6m. Associations between the EULAR response at 6m and clinical/serological variables were evaluated using univariable and multivariable logistic regression models. Receiver operating characteristic (ROC) analysis was performed to determine the optimal threshold of serum BAFF concentration portending EULAR response at 6m of TNFi treatment, determined as the highest Youden index.Results: After 6m of TNFi treatment, 38/158 (24%) of patients attained good EULAR response (GR). These patients had lower body mass index (BMI) (p=0.02), lower baseline DAS28 (p=0.02) and lower serum BAFF concentration at baseline and at 6m compared with patients who did not attain GR. To further investigate the role of BAFF, the cohort was stratified by anti- citrullinated protein antibody (ACPA) seropositivity. 134 (85%) patients were ACPA positive and 24 (15%) were seronegative. After 6m of TNFi treatment, seropositive patients who attained GR had lower serum BAFF concentration compared with patients who did not attain GR (median [IQR]: 793 [712- 956] pg/mL vs. 955 [808- 1176] pg/mL; p=0.006) (Figure 1). However, there were no differences in ACPA negative patients (Table 1). Therefore, the optimal threshold value for serum BAFF concentration associated with GR at 6m of TNFi treatment was evaluated in seropositive patients. Serum BAFF< 968 pg/mL at 6m represented the concentration likely to best discriminate between GR and non- GR at 6m of TNFi treatment (AUC: 0.67; 95% CI: 0.56- 0.78; p=0.009; sensitivity: 50%, specificity: 81%; PPV: 89%, NPV: 35%), yielding a positive likelihood | 2587ratio of 2.7 (Figure 2). Then, a logistic regression analysis adjusted by patient characteristics with p- value≤0.1 in univariable analysis (disease duration, BMI and baseline DAS28) was performed. We found that a serum BAFF< 968 pg/mL at 6m was significantly and independently associated with GR attainment in seropositive patients (OR: 5.28; 95% CI: 1.72- 16.17; p=0.004).Conclusion: Our results show that serum BAFF concentrations reflect clinical response to TNFi after 6m of treament, mainly in ACPA positive patients. These results suggest that BAFF may be considered a biomarker of clinical re-sponse to TNFi in patients with RA.
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42. |
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43. |
- Hoff, Leonardo Santos, et al.
(author)
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COVID-19 severity and vaccine breakthrough infections in idiopathic inflammatory myopathies, other systemic autoimmune and inflammatory diseases, and healthy controls : a multicenter cross-sectional study from the COVID-19 Vaccination in Autoimmune Diseases (COVAD) survey
- 2023
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In: Rheumatology International. - : Springer. - 0172-8172 .- 1437-160X. ; 43:1, s. 47-58
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Journal article (peer-reviewed)abstract
- OBJECTIVES: We aimed to compare the spectrum and severity of COVID-19 and vaccine breakthrough infections (BIs) among patients with IIMs, other systemic autoimmune and inflammatory diseases (SAIDs), and healthy controls (HCs).METHODS: This is a cross-sectional study with data from the COVAD study, a self-reported online global survey that collected demographics, COVID-19 history, and vaccination details from April to September 2021. Adult patients with at least one COVID-19 vaccine dose were included. BIs were defined as infections occurring > 2 weeks after any dose of vaccine. Characteristics associated with BI were analyzed with a multivariate regression analysis.RESULTS: Among 10,900 respondents [42 (30-55) years, 74%-females, 45%-Caucasians] HCs were (47%), SAIDs (42%) and IIMs (11%). Patients with IIMs reported fewer COVID-19 cases before vaccination (6.2%-IIM vs 10.5%-SAIDs vs 14.6%-HC; OR = 0.6, 95% CI 0.4-0.8, and OR = 0.3, 95% CI 0.2-0.5, respectively). BIs were uncommon (1.4%-IIM; 1.9%-SAIDs; 3.2%-HC) and occurred in 17 IIM patients, 13 of whom were on immunosuppressants, and 3(18%) required hospitalization. All-cause hospitalization was higher in patients with IIM compared to HCs [23 (30%) vs 59 (8%), OR = 2.5, 95% CI 1.2-5.1 before vaccination, and 3 (18%) vs 9 (5%), OR = 2.6, 95% CI 1.3-5.3 in BI]. In a multivariate regression analysis, age 30-60 years was associated with a lower odds of BI (OR = 0.7, 95% CI 0.5-1.0), while the use of immunosuppressants had a higher odds of BI (OR = 1.6, 95% CI 1.1-2.7).CONCLUSIONS: Patients with IIMs reported fewer COVID-19 cases than HCs and other SAIDs, but had higher odds of all-cause hospitalization from COVID-19 than HCs. BIs were associated with the use of immunosuppressants and were uncommon in IIMs.
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44. |
- Holloway, A., et al.
(author)
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EVALUATING GLOBAL PATTERNS IN TREATMENT AND PREVALENCE OF COMORBIDITIES IN SYSTEMIC LUPUS ERYTHEMATOSUS
- 2023
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In: Annals of the Rheumatic Diseases. - : HighWire Press. - 0003-4967 .- 1468-2060. ; 82:Suppl. 1, s. 1456-1458
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Journal article (other academic/artistic)abstract
- Background: Regional disparities in the management of systemic lupus erythematosus (SLE) are frequently described. Governance, funding, logistic barriers, and physician choice may be important determinants though scarce data from underrepresented regions limits our understanding.Objectives: To evaluate global patterns in treatment of SLE and identify the prevalence of comorbidities.Methods: We identified SLE patients from the COVAD 2 database, consisting of over 20,000 respondents worldwide. Healthy controls (HC) were included to assess population comorbidity levels. Demographics, treatment i.e., corticosteroids (CS), antimalarials, immunosuppressants (IS), cyclophosphamide and biologics plus comorbidity data was recorded. Country Human Development Index (HDI) classification, a composite index formulated by the United Nations to rank countries into tiers of development, was utilised.Results: 3323 HCs and 1167 SLE patients were included in analysis. Patients from low/medium HDI (lmHDI) countries were younger than those from high/very high HDI (hvhHDI) countries (median age 32, IQR 27-41 vs 41, IQR 32-52 years, p<0.0001). Disease duration was shorter in lmHDI countries (median 5, IQR 3-10 vs 10, IQR 5-19 years, p<0.0001).A higher proportion of SLE patients from lmHDI countries were on CS (73% vs 59%, p=0.0002), antimalarials (81% vs 68%, p=0.0002) and IS (66% vs 53%, p=0.0009) compared with patients from hvhHDI countries. Choice of IS varied with azathioprine prescribed more frequently in lmHDI countries (p=0.049). Biologics use was more common in hvhHDI countries (7% vs 2%, p=0.0055). Comorbidity prevalence was similar between groups, however when adjusted for age, patients with chronic kidney disease were significantly younger in lmHDI countries (36.67 vs 44.64 years, p=0.015), as were patients with coronary artery disease (35.7 vs. 44.6 years, p=0.015) and hypertension (41.5 vs 49.8 years, p=0.003). Results are detailed in Table 1.Conclusion: To our knowledge, this is the largest study evaluating treatment and comorbidity incidence in SLE populations based on country HDI. We identified striking differences in pharmacological management globally. Cardiovascular comorbidities were seen in younger patients and earlier in the disease course in lmHDI countries, suggestive of premature organ damage. This could be due to limited global access to high-cost medication and increasing access may improve outcomes. Our results call for review of cardiovascular risk guidelines and regional approaches to preventive action as well as pharmacological and non-pharmacological management of patients with established cardiovascular comorbidity.
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45. |
- Hua, Nicole, et al.
(author)
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Sensitivity analysis of EQ-5D-3L index scores in terms of discriminative and known-groups validity in SLE : introducing Adequate Health State
- 2023
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In: Rheumatology. - : Oxford University Press. - 1462-0324 .- 1462-0332. ; 62:12, s. 3916-3923
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Journal article (peer-reviewed)abstract
- OBJECTIVES: To investigate the ability of different EQ-5D-3L index scores to discriminate between verum drug and placebo (discriminant validity) as well as between responders and non-responders (known-groups validity) in the SLE patient population of two phase III clinical trials of belimumab.METHODS: Data from the BLISS-52 (NCT00424476) and BLISS-76 (NCT00410384) trials (N = 1684), which both showed superiority of belimumab to placebo, were utilised. Responders were defined as SLE Responder Index 4 (SRI-4) achievers at week 52. The Pearson's χ2 and Mann-Whitney U tests were used for comparisons, and logistic regression analysis was used for adjustments for confounders and assessment of independence.RESULTS: While full health state (FHS; EQ-5D index score 1) showed the best ability to discriminate between belimumab and placebo (adjusted OR: 1.47; 95% CI: 1.11-1.96; P = 0.008) and between SRI-4 responders and non-responders (adjusted OR: 3.47; 95% CI: 1.29-10.98; P = 0.020), the discriminative ability of EQ-5D index scores 0.800 or more reached statistical significance for both discriminant validity (adjusted OR: 1.29; 95% CI: 1.02-1.63; P = 0.036) and known-groups validity (adjusted OR: 3.08; 95% CI: 1.16-9.69; P = 0.034).CONCLUSION: Overall, higher EQ-5D index scores were associated with increasing ability to discriminate between belimumab and placebo, and between responders and non-responders. EQ-5D index scores less stringent than FHS may be clinically relevant HRQoL goals of treatment in patients with SLE, introducing the concept of EQ-5D adequate health state when FHS is not achievable.
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46. |
- Joshi, Mrudula, et al.
(author)
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Listening to patients, for the patients : The COVAD Study-Vision, organizational structure, and challenges
- 2024
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In: International Journal of Rheumatic Diseases. - : John Wiley & Sons. - 1756-1841 .- 1756-185X. ; 27:5
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Journal article (peer-reviewed)abstract
- Background: The pandemic presented unique challenges for individuals with autoimmune and rheumatic diseases (AIRDs) due to their underlying condition, the effects of immunosuppressive treatments, and increased vaccine hesitancy.Objectives: The COVID-19 vaccination in autoimmune diseases (COVAD) study, a series of ongoing, patient self-reported surveys were conceived with the vision of being a unique tool to gather patient perspectives on AIRDs. It involved a multinational, multicenter collaborative effort amidst a global lockdown.Methods: Leveraging social media as a research tool, COVAD collected data using validated patient-reported outcomes (PROs). The study, comprising a core team, steering committee, and global collaborators, facilitated data collection and analysis. A pilot-tested, validated survey, featuring questions regarding COVID-19 infection, vaccination and outcomes, patient demographics, and PROs was circulated to patients with AIRDs and healthy controls (HCs).Discussion: We present the challenges encountered during this international collaborative project, including coordination, data management, funding constraints, language barriers, and authorship concerns, while highlighting the measures taken to address them.Conclusion: Collaborative virtual models offer a dynamic new frontier in medical research and are vital to studying rare diseases. The COVAD study demonstrates the potential of online platforms for conducting large-scale, patient-focused research and underscores the importance of integrating patient perspective into clinical care. Care of patients is our central motivation, and it is essential to recognize their voices as equal stakeholders and valued partners in the study of the conditions that affect them.
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47. |
- Jägerback, Sandra, et al.
(author)
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Predictors of renal flares in systemic lupus erythematosus : a post-hoc analysis of four phase III clinical trials of belimumab
- 2024
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In: Rheumatology. - : Oxford University Press. - 1462-0324 .- 1462-0332.
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Journal article (peer-reviewed)abstract
- OBJECTIVES: To identify predictors of renal flares in patients with SLE treated for active extra-renal disease.METHODS: Data from four clinical trials of belimumab in SLE (BLISS-52, NCT00424476; BLISS-76, NCT00410384; BLISS-NEA, NCT01345253; BLISS-SC, NCT01484496) were used. Patients were assigned to belimumab or placebo on top of standard therapy. We investigated the performance of predictors of renal flares through 52-76 weeks using proportional hazards regression analysis.RESULTS: Of 3225 participants, 192 developed at least one renal flare during follow-up, with the first occurring after a median time of 197 days. Current/former renal involvement (HR: 15.4; 95% CI: 8.3-28.2; p< 0.001), low serum albumin levels (HR 0.9; 95% CI: 0.8-0.9; p< 0.001), proteinuria (HR: 1.6; 95% CI: 1.5-1.7; p< 0.001), and low C3 levels (HR: 2.9; 95% CI: 2.1-4.1; p< 0.001) at baseline appeared robust determinants of renal flares. Anti-dsDNA positivity yielded an increased hazard for renal flares (HR: 2.1; 95% CI: 1.4-3.2; p< 0.001), which attenuated after adjustments. Anti-Sm positivity was associated with renal flares in the placebo (HR: 3.7; 95% CI: 2.0-6.9; p< 0.001) but not in the belimumab subgroup, whereas anti-ribosomal P positivity was associated with renal flares in the belimumab subgroup only (HR: 2.8; 95% CI: 1.5-5.0; p= 0.001).CONCLUSION: A history of renal involvement, high baseline proteinuria, hypoalbuminaemia, and C3 consumption were robust determinants of impending renal flares. Beyond anti-dsDNA, anti-Sm and anti-ribosomal P protein antibody positivity may have value in surveillance of renal SLE.
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48. |
- Jägerback, S., et al.
(author)
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PREDICTORS OF RENAL FLARES IN SYSTEMIC LUPUS ERYTHEMATOSUS : A POST-HOC ANALYSIS OF FOUR PHASE III CLINICAL TRIALS OF BELIMUMAB
- 2023
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In: Annals of the Rheumatic Diseases. - : HighWire Press. - 0003-4967 .- 1468-2060. ; 82:Suppl. 1, s. 34-34
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Journal article (other academic/artistic)abstract
- Background: In patients with systemic lupus erythematosus (SLE), renal involvement is associated with high morbidity, and renal flares are major contributors to poor long-term prognosis. Identification of patients at risk of developing renal flares despite immunosuppressant therapy is imperative to optimise management.Objectives: To identify predictors of renal flares in patients receiving treatment for active extra-renal SLE.Methods: Data from BLISS-52 (NCT00424476), BLISS-76 (NCT00410384), BLISS Northeast Asia (NEA; NCT01345253), and BLISS-SC (NCT01484496) were used (N=3225). The trials included patients with active, seropositive SLE and excluded active severe renal SLE. Participants were assigned to belimumab or placebo, on top of non-biologic standard therapy. We investigated anti-dsDNA, anti-Sm, anti-ribosomal P, and anti-cardiolipin (aCL) antibodies, low C3 and low C4 levels, B cell activating factor (BAFF), serum albumin, serum creatinine, and proteinuria at baseline as potential predictors of renal flares during a 52-week follow-up. We used Cox regression models to evaluate traditional disease features as predictors of renal flares in the pooled trial population. We also performed subgroup analysis of belimumab and placebo recipients. Covariates in the adjusted models included age, sex, ethnicity, body mass index, organ damage, baseline extra-renal activity (SLEDAI-2K score excluding renal and immunological descriptors), current or former renal SLE history (renal BILAG A–D), baseline use of glucocorticoids, antimalarials, and immunosuppressants, and use of belimumab.Results: The mean age of the study population was 36.7 years, 94% were women, 54.6% had current or former renal involvement at baseline, and 192 developed a renal flare after a median follow-up time of 197 (IQR: 85–330) days from baseline. Patients with current or former renal involvement at baseline displayed a >9-fold increased hazard to develop a new renal flare (HR: 9.4; 95% CI: 5.0–17.7; P<0.001). In the pooled study population, baseline serum albumin (adjusted HR 0.9; 95% CI: 0.9–0.9; P<0.001), proteinuria (adjusted HR: 1.3; 95% CI: 1.2–1.4; P<0.001), and low C3 levels (adjusted HR: 1.8; 95% CI: 1.3–2.5; P<0.001) were robust determinants of subsequent renal flare occurrence; similar associations were found in the belimumab and placebo subgroups. Furthermore, we observed an association between anti-dsDNA positivity and renal flare development in univariable models (HR: 2.1; 95% CI: 1.4–3.2; P<0.001 in the pooled population), which attenuated in multivariable models (Figure 1). Positive levels of anti-Sm antibodies were associated with renal flare occurrence in the placebo (adjusted HR: 2.9; 95% CI: 1.5–5.6; P=0.002) but not in the belimumab subgroup, whereas anti-ribosomal P antibodies were associated with renal flare development in belimumab-treated (HR: 2.8; 95% CI: 1.5–5.0; P<0.001) but not in placebo-treated patients. Finally, positive levels of aCL antibodies (any isotype) predicted renal flare development in the belimumab group (adjusted HR: 1.8; 95% CI: 1.1–2.8; P=0.020) but yielded a negative association in the placebo group (adjusted HR: 0.4; 95% CI: 0.2–0.9; P=0.028).Conclusion: Current or former renal involvement, high baseline proteinuria levels, hypoalbuminaemia, and C3 consumption were robust determinants of imminent renal flares. Beyond anti-dsDNA, anti-ribosomal P and aCL antibody positivity may prove valuable early signals of imminent renal flares in patients treated with belimumab. Anti-Sm positivity predicted imminent renal flares in patients treated with non-biological standard therapy, but not in belimumab-treated patients, assumably due to benefit conferred from belimumab in anti-Sm positive individuals, as shown previously [1].Reference: [1]Parodis I, et al. Int J Mol Sci. 2020; 21(10):3463
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49. |
- Kadam, Esha, et al.
(author)
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Collating the voice of people with autoimmune diseases : Methodology for the Third Phase of the COVAD Studies
- 2024
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In: Rheumatology International. - : Springer. - 0172-8172 .- 1437-160X. ; 44:7, s. 1233-1244
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Journal article (peer-reviewed)abstract
- INTRODUCTION: The growing recognition of holistic patient care highlights the various factors shaping the quality of life of individuals with autoimmune and rheumatic diseases (AIRDs). Beyond the traditional disease measures, there is an emerging acknowledgment of the less-explored aspects, including subjective well-being, social determinants of health, comorbidities, mental health, and medication adherence. Moreover, digital health services have empowered patients to engage actively in decision-making alongside clinicians. To explore these domains within the context of AIRDs, the "Collating the Voice of People with Autoimmune Diseases" COVAD survey was conceived, a successor of the previous two COVAD surveys. In this document, we present the study protocol in comprehensive detail.METHODS: The COVAD-3 survey is a cross-sectional patient self-reported e-survey incorporating multiple widely accepted scales/scores to assess various aspects of patients' lifestyles objectively. To ensure the survey's accuracy and usability across diverse regions, it will be translated into multiple languages and subjected to rigorous vetting and pilot testing. It will be distributed by collaborators via online platforms and data will be collected from patients with AIRDs, and healthy individuals over eight months. Data analysis will focus on outcome measures related to various social, demographic, economic, and psychological factors.CONCLUSION: With the increasing awareness to adopt a holistic treatment approach encompassing all avenues of life, the COVAD-3 survey aims to gain valuable insights into the impact of social, demographic, economic, and psychological determinants of health on the subjective well-being in patients with AIRDs, which will contribute to a better understanding of their overall health and well-being.
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50. |
- Lee, S. Y., et al.
(author)
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IDENTIFYING DETERMINANTS OF FAVOURABLE AND POOR PHYSICAL FUNCTION IN SYSTEMIC LUPUS ERYTHEMATOSUS : RESULTS FROM AN INTERNATIONAL COLLABORATIVE STUDY
- 2023
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In: Annals of the Rheumatic Diseases. - : HighWire Press. - 0003-4967 .- 1468-2060. ; 82:Suppl. 1, s. 1110-1112
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Journal article (other academic/artistic)abstract
- Background: Systemic lupus erythematosus (SLE) can result in impaired daily physical function through various mechanisms including active disease, chronic damage, and mental health symptoms that are common in the disease. However, the key drivers of reduced physical function are poorly understood, and no large-scale global studies investigating this have been conducted to date.Objectives: To investigate key factors that contribute to impaired physical function in SLE globally.Methods: SLE patients were identified from the COVAD 2 database, a global register of more than 20,000 respondents. Healthy controls (HC) were included to compare differences in physical function using the Patient Reported Outcome Measurement Information System (PROMIS) questionnaire. Demographics, medication, comorbidities, disease activity, Global Physical Health (GPH) and Global Mental Health (GMH) were collected. Multivariable regression analysis was used to identify contributing factors to favourable or poor physical function (measured by PROMIS Physical Function shortform PF-10a score).Results: 979 SLE patients and 3358 HCs were included in analysis. Patients with SLE had significantly lower PF-10a score as compared to HCs (median 42, IQR 36-47 vs median 49, IQR 45-50, p<0.0001). Determinants of physical function status in patients with SLE are summarised in Table 1. Briefly, factors associated with poor physical function included increasing age (-0.042, 95% CI -0.069 to -0.015, p=0.002) and methotrexate use (-0.928, 95% CI -1.844 to -0.012, p=0.047). Diabetes (-1.862, 95% CI -3.481 to -0.243, p=0.024) and interstitial lung disease (ILD) (-2.441, 95% CI -4.366 to -0.517, p=0.013), but not asthma or COPD, also contributed to lower PF-10a score. From a mental health perspective, anxiety (-0.970, 95% CI -1.853 to -0.087, p=0.031) but not depression contributed to a lower physical function score. Higher Pain Visual Analogue Scales (VAS) (-2.889, 95% CI -3.107 to -2.671, p<0.001) and Fatigue VAS (-1.459, 95% CI -1.974 to -0.945, p<0.001) also contributed to lower PF-10 scores. Hydroxychloroquine use (0.844, 95% CI 0.190 to 1.498, p=0.012) and higher GPH score (2.287, 95% CI 2.079 to 2.494, p<0.001) were associated with favourable physical function.Conclusion: Patients with SLE show significantly reduced physical function compared with HCs. Key contributors to poor physical function include intercurrent diabetes and ILD. Screening for, and aggressive early treatment of these conditions may confer improved long-term function. As expected, higher levels of pain and fatigue were associated with poor physical function. Methotrexate use was also identified as a contributing factor to reduced function, which could represent its use in articular manifestations that limit physical function. Importantly, use of hydroxychloroquine was associated with favourable physical function, adding to the well-recognised benefits of this drug in SLE.
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