| 1. |
- Borg, Alexander, et al.
(författare)
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Obesity is associated with pain and impaired mobility despite therapy in systemic lupus erythematosus
- 2023
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Ingår i: Frontiers in Medicine. - : Frontiers Media S.A.. - 2296-858X. ; 10
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Tidskriftsartikel (refereegranskat)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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| 2. |
- Emamikia, Sharzad, et al.
(författare)
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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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Ingår i: Lupus. - : Sage Publications. - 0961-2033 .- 1477-0962. ; 33:6, s. 615-628
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Tidskriftsartikel (refereegranskat)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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| 3. |
- Emamikia, Sharzad, et al.
(författare)
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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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Ingår i: Journal of Clinical Medicine. - : MDPI. - 2077-0383. ; 11:7
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Tidskriftsartikel (refereegranskat)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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| 4. |
- Emamikia, Sharzad, et al.
(författare)
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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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Ingår i: Rheumatology. - : Oxford University Press. - 1462-0324 .- 1462-0332. ; 61:12, s. 4752-4762
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Tidskriftsartikel (refereegranskat)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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| 5. |
- Emamikia, Sharzad, et al.
(författare)
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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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Ingår i: Arthritis & Rheumatology. - : John Wiley & Sons. - 2326-5191 .- 2326-5205. ; 73:Suppl. 9, s. 2604-2606
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)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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| 6. |
- Hua, Nicole, et al.
(författare)
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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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Ingår i: Rheumatology. - : Oxford University Press. - 1462-0324 .- 1462-0332. ; 62:12, s. 3916-3923
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Tidskriftsartikel (refereegranskat)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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| 7. |
- Lindblom, Julius, et al.
(författare)
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EQ-5D full health state after therapy heralds reduced hazard to accrue subsequent organ damage in systemic lupus erythematosus
- 2022
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Ingår i: Frontiers in Medicine. - : Frontiers Media S.A.. - 2296-858X. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To investigate whether self-reported EQ-5D full health state (FHS) after therapeutic intervention for active systemic lupus erythematosus (SLE) is associated with a reduced risk to accrue organ damage. In a separate analysis, we sought to investigate associations between experience of "no problems" in each one of the five dimensions of EQ-5D and the risk to accrue damage.METHODS: Data from the open-label extension periods of the BLISS-52 and BLISS-76 trials of belimumab in SLE (NCT00724867; NCT00712933) were used (N = 973). FHS was defined as an experience of "no problems" in all five EQ-5D dimensions. Organ damage was assessed annually using the Systemic Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology (ACR) Damage Index (SDI). Associations between the three-level version of the EQ-5D (EQ-5D-3L) responses at open-label baseline and the first documented increase in organ damage were investigated using Cox regression accounting for age, sex, ancestry, SDI at baseline, and background therapy, and associations with SDI items were investigated using phi (φ) correlation analyses.RESULTS: A total of 147 patients (15.1%) accrued organ damage during follow-up, with the first increase in their SDI score occurring after a mean time of 29.1 ± 19.6 months. Lower proportions of FHS respondents accrued damage over a course of up to 7.9 years of open-label follow-up compared with no FHS respondents (p = 0.004; derived from the logrank test). FHS was associated with a reduced hazard to accrue subsequent organ damage (HR: 0.60; 95% CI: 0.38-0.96; p = 0.033) after adjustments, as was experience of "no problems" in mobility (HR: 0.61; 95% CI: 0.43-0.87; p = 0.006). "No problems" in mobility was negatively correlated with musculoskeletal damage accrual (φ = -0.08; p = 0.008) and associated with a lower hazard to accrue musculoskeletal damage in Cox regression analysis (HR: 0.38; 95% CI: 0.19-0.76; p = 0.006).CONCLUSION: Experience of EQ-5D-3L FHS and "no problems" in mobility after therapeutic intervention heralded reduced hazard to accrue subsequent organ damage, especially musculoskeletal damage, suggesting that optimisation of these health-related quality of life aspects constitutes a clinically relevant treatment target in patients with SLE, along with clinical and laboratory parameters.
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| 8. |
- Parodis, Ioannis, 1981-, et al.
(författare)
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Associations Between Early Changes in Circulating B Cell Subsets and Severe Flare in Systemic Lupus Erythematosus : Results from Three Phase III Trials of Belimumab
- 2021
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Ingår i: Arthritis & Rheumatology. - : John Wiley & Sons. - 2326-5191 .- 2326-5205. ; 73:Suppl. 9, s. 2699-2700
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background/Purpose: Belimumab is the only approved targeted treatment for systemic lupus erythematosus (SLE). Identification of early predictors of response or non- response to therapy is imperative to optimize surveillance and decision- making. We studied early changes in B cell subsets in relation to flare during standard therapy plus belimumab or placebo given to patients with active SLE within the frame of three phase III clinical trials of belimumab.Methods: We analyzed pooled 52- week data from BLISS- 76 (N=819), BLISS- SC (N=836), and BLISS North- East Asia (N=60). B cell subsets were determined with flow cytometry. Severe flare was evaluated according to the SELENA-SLEDAI Flare Index every fourth week. We investigated B cell changes relative to baseline using proportional hazards regression analysis.Results: Early decreases in CD19+CD20- CD138+ long- lived (HR: 0.7; 95% CI: 0.56– 0.98; P=0.034) and CD19+CD-38brightCD27bright SLE- associated plasma cells (HR: 0.7; 95% CI: 0.50– 0.87; P=0.003) from baseline through week 24 were negatively associated with the development of a severe flare during the study period, i.e. through week 52 from treatment initiation. A similar trend was seen for decreases in naïve CD19+CD20+CD27- B cells (HR: 0.7; 95% CI: 0.56– 1.00; P=0.051). No such association was observed for early changes in the total CD19+CD20+ B cell pool, or in CD19+CD20+CD27+ memory B cells, CD19+CD20+CD69+ activated B cells, CD19+CD20+CD138+ cells or CD19+CD20- CD27bright short- lived plasma cells. The association with CD19+CD38brightCD27bright SLE- associated plasma cells held true for patients treated with belimumab (any dose) (HR: 0.7; 95% CI: 0.47– 0.97; P=0.032) but not placebo, while placebo receivers showing reductions in CD19+CD20- CD138+ long- lived plasma cells displayed a lower probability to flare (HR: 0.6; 95% CI: 0.38– 0.87; P=0.009).Conclusion: Early decreases in long- lived circulating plasma cells were negatively associated with severe flares in patients with active SLE treated with standard immunosuppression with or without add- on belimumab, while reductions in circulating CD19+CD38brightCD27bright SLE- associated plasma cells may prove a useful early biological marker of favorable response to belimumab therapy.
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| 9. |
- Parodis, Ioannis, 1981-, et al.
(författare)
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Early Increase in Circulating Memory B Cells Portends Clinical Response to Treatment in Pooled Data from Three Phase III Trials of Belimumab
- 2021
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Ingår i: Arthritis & Rheumatology. - : John Wiley & Sons. - 2326-5191 .- 2326-5205. ; 73:Suppl. 9, s. 2695-2696
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background/Purpose: Belimumab blocks soluble B cell activating factor (BAFF) and is the only to date approved targeted treatment for systemic lupus erythematosus (SLE). Identification of biological predictors of response occurring earlier upon treatment would provide measurable tools to improve patient monitoring and stratification according to likelihood of response. We investigated early changes in B lymphocyte subsets in relation to response to standard therapy plus belimumab or placebo given to patients with active SLE and mainly musculoskeletal and mucocutaneous symptoms.Methods: We analyzed pooled data from belimumab phase III clinical trials including BLISS-76 (N=819) and BLISS-SC (N=836); in addition, 60 patients from the BLISS North- East Asia trial were included in the analysis. B lymphocyte subsets were determined with flow cytometry. Treatment response was assessed using the composite measure SLE Responder Index 4 (SRI- 4), defined as decrease in SLEDAI by ≥4 points, no worsening in the physician’s global assessment by >30% and no new British Lupus Isles Assessment Group (BILAG) index (≥1 A or ≥2 B), at week 52. Additionally, persistence of SRI- 4 through week 52 was evaluated. We investigated B cell changes relative to baseline using logistic or proportional hazards regression analysis, as appropriate.Results: We found an association between an early expansion of CD19+CD20+CD27+ memory B cells from baseline through week 8 and attainment of SRI- 4 response at week 52 (OR: 1.5; 95% CI: 1.18– 1.89; P=0.001), or for relative increases >10% (OR: 1.5; 95% CI: 1.17– 1.83; P=0.001). Expansion above this threshold of 10% was also associated with increased probability or shorter time to achieve SRI- 4 response that was maintained through week 52 (HR: 1.4; 95% CI: 1.15– 1.61; P< 0.001). Notably, belimumab treatment (any dose) yielded an 11.5- fold increased probability of memory B cell expansion through week 8 compared with placebo (95% CI: 8.74– 15.02; P< 0.001). No association with SRI- 4 response was observed for early changes in CD19+CD20+ B cells, CD19+CD20+CD27- naïve B cells, CD19+CD20+CD69+ activated B cells, CD19+CD20- CD27bright short- lived plasma cells, CD19+CD20- CD138+ long- lived plasma cells, or CD19+CD38brightCD27bright SLE- associated plasma cells.Conclusion: Early increases in memory B cells through the first 8 weeks of therapy, mainly driven by belimumab, portended good and sustained clinical response within one year from treatment initiation. Early immunological changes preceding the clinical outcome and may prove useful in early evaluation of belimumab therapy.
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