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1.	Chatzidionysiou, K., et al. (författare) Effectiveness of a Second Biologic After Failure of a Non-tumor Necrosis Factor Inhibitor As First Biologic in Rheumatoid Arthritis 2021 Ingår i: Journal of Rheumatology. - : The Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 48:10, s. 1512-1518 Tidskriftsartikel (refereegranskat)abstract Objective. In rheumatoid arthritis (RA), evidence regarding the effectiveness of a second biologic disease-modifying antirheumatic drug (bDMARD) in patients whose first-ever bDMARD was a non-tumor necrosis factor inhibitor (TNFi) bDMARD is limited. The objective of this study was therefore to assess the outcome of a second bDMARD (non-TNFi: rituximab [RTX], abatacept [ABA], or tocilizumab [TCZ], separately; and TNFi) after failure of a non-TNFi bDMARD as first bDMARD. Methods. We identified patients with RA from the 5 Nordic biologics registers who started treatment with a non-TNFi as first-ever bDMARD but switched to a second bDMARD. For the second bDMARD, we assessed drug survival (at 6 and 12 months) and primary response (at 6 months). Results. We included 620 patients starting a second bDMARD (ABA 86, RTX 40, TCZ 67, and TNFi 427) following failure of a first non-TNFi bDMARD. At 6 and 12 months after start of their second bDMARD, approximately 70% and 60%, respectively, remained on treatment, and at 6 months, less than one-third of patients were still on their second bDMARD and had reached low disease activity or remission according to the Disease Activity Score in 28 joints. For those patients whose second bMDARD was a TNFi, the corresponding proportion was slightly higher (40%). Conclusion. The drug survival and primary response of a second bDMARD in patients with RA switching due to failure of a non-TNFi bDMARD as first bDMARD is modest. Some patients may benefit from TNFi when used after failure of a non-TNFi as first bDMARD.
2.	Chatzidionysiou, K, et al. (författare) How do we use biologics in rheumatoid arthritis patients with a history of malignancy? An assessment of treatment patterns using Scandinavian registers 2020 Ingår i: RMD open. - : BMJ. - 2056-5933. ; 6:2 Tidskriftsartikel (refereegranskat)
3.	Courvoisier, DS, et al. (författare) The impact of seropositivity on the effectiveness of biologic anti-rheumatic agents: results from a collaboration of 16 registries 2021 Ingår i: RHEUMATOLOGY. - 1462-0324. ; 60:2, s. 820-828 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
4.	Sebbag, E, et al. (författare) EULAR POINTS TO CONSIDER ON THE INITIATION OF TARGETED THERAPIES IN PATIENTS WITH INFLAMMATORY ARTHRITIDES AND A HISTORY OF CANCER 2023 Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - 0003-4967. ; 82, s. 29-29 Konferensbidrag (övrigt vetenskapligt/konstnärligt)
5.	Sebbag, E, et al. (författare) SYSTEMATIC LITERATURE REVIEW INFORMING THE EULAR POINTS TO CONSIDER TASK FORCE ON THE INITIATION OF TARGETED THERAPIES IN PATIENTS WITH INFLAMMATORY ARTHRITIDES AND A HISTORY OF CANCER 2023 Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - 0003-4967. ; 82, s. 856-856 Konferensbidrag (övrigt vetenskapligt/konstnärligt)
6.	Smolen, JS, et al. (författare) EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2022 update 2023 Ingår i: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 82:1, s. 3-18 Tidskriftsartikel (refereegranskat)abstract To provide an update of the EULAR rheumatoid arthritis (RA) management recommendations addressing the most recent developments in the field.MethodsAn international task force was formed and solicited three systematic literature research activities on safety and efficacy of disease-modifying antirheumatic drugs (DMARDs) and glucocorticoids (GCs). The new evidence was discussed in light of the last update from 2019. A predefined voting process was applied to each overarching principle and recommendation. Levels of evidence and strengths of recommendation were assigned to and participants finally voted on the level of agreement with each item.ResultsThe task force agreed on 5 overarching principles and 11 recommendations concerning use of conventional synthetic (cs) DMARDs (methotrexate (MTX), leflunomide, sulfasalazine); GCs; biological (b) DMARDs (tumour necrosis factor inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab including biosimilars), abatacept, rituximab, tocilizumab, sarilumab and targeted synthetic (ts) DMARDs, namely the Janus kinase inhibitors tofacitinib, baricitinib, filgotinib, upadacitinib. Guidance on monotherapy, combination therapy, treatment strategies (treat-to-target) and tapering in sustained clinical remission is provided. Safety aspects, including risk of major cardiovascular events (MACEs) and malignancies, costs and sequencing of b/tsDMARDs were all considered. Initially, MTX plus GCs is recommended and on insufficient response to this therapy within 3–6 months, treatment should be based on stratification according to risk factors; With poor prognostic factors (presence of autoantibodies, high disease activity, early erosions or failure of two csDMARDs), any bDMARD should be added to the csDMARD; after careful consideration of risks of MACEs, malignancies and/or thromboembolic events tsDMARDs may also be considered in this phase. If the first bDMARD (or tsDMARD) fails, any other bDMARD (from another or the same class) or tsDMARD (considering risks) is recommended. With sustained remission, DMARDs may be tapered but should not be stopped. Levels of evidence and levels of agreement were high for most recommendations.ConclusionsThese updated EULAR recommendations provide consensus on RA management including safety, effectiveness and cost.
7.	Yang, C, et al. (författare) Development and external validation of prediction models for adverse health outcomes in rheumatoid arthritis: A multinational real-world cohort analysis 2022 Ingår i: Seminars in arthritis and rheumatism. - : Elsevier BV. - 1532-866X .- 0049-0172. ; 56, s. 152050- Tidskriftsartikel (refereegranskat)
8.	Adamichou, C, et al. (författare) Development and Implementation of a Pilot Registry for Monitoring the Efficacy and Safety of Novel Therapies in Patients with Systemic Lupus Erythematosus 2020 Ingår i: Mediterranean journal of rheumatology. - : Convin SA. - 2529-198X. ; 31:1, s. 87-91 Tidskriftsartikel (refereegranskat)
9.	Di Giuseppe, D., et al. (författare) The occurrence of multiple treatment switches in axial spondyloarthritis. Results from five Nordic rheumatology registries 2022 Ingår i: Rheumatology. - : Oxford University Press (OUP). - 1462-0324 .- 1462-0332. ; 61:9, s. 3647-3656 Tidskriftsartikel (refereegranskat)abstract Objectives In axial spondyloarthritis (axSpA), switching between multiple biologic or targeted synthetic (b/ts-) DMARDs might indicate difficult-to-treat disease. We aimed to explore the occurrence of multiple switching in routine care axSpA patients using various definitions, and to identify associated clinical characteristics upon start of first b/tsDMARD (baseline). Methods Observational cohort study including patients with axSpA starting a first-ever b/tsDMARD 2009-2018 based on data from five biologic registries (Denmark/Sweden/Finland/Norway/Iceland). Comorbidities and extra-articular manifestations were identified through linkage to national registries. Multi-switching was defined in overlapping categories according to b/tsDMARD treatment history: treatment with >= 3, >= 4 or >= 5 b/tsDMARDs during follow-up. We explored the cumulative incidence of patients becoming multi-switchers with >= 3 b/tsDMARDs stratified by calendar-period (2009-2011, 2012-2013, 2014-2015, 2016-2018). In the subgroup of patients starting a first b/tsDMARD 2009-2015, baseline characteristics associated with multi-switching (within 3 years' follow-up) were explored using multiple logistic regression analyses. Results Among 8398 patients included, 6056 patients (63% male, median age 42 years) started a first b/tsDMARD in 2009-2015, whereof proportions treated with >= 3, >= 4 or >= 5 b/tsDMARDs within 3 years' follow-up were 8%, 3% and 1%, respectively. Calendar-period did not affect the cumulative incidence of multi-switching. Baseline characteristics associated with multi-switching (>= 3 b/tsDMARDs) were female gender, shorter disease duration, higher patient global score, comorbidities and having psoriasis but not uveitis. Conclusion In this large Nordic observational cohort of axSpA patients, multiple switching was frequent with no apparent time-trend. Clinical associated factors included gender, but also previous comorbidities and extra-articular manifestations illustrating the ongoing challenge of treating this patient group.
10.	Duarte-Salles, T, et al. (författare) COMPARATIVE RISK OF CANCER ASSOCIATED WITH FIRST-LINE DMARDS USE IN RHEUMATOID ARTHRITIS: REAL WORLD EVIDENCE FROM THE OHDSI NETWORK 2020 Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 79, s. 1000-1000 Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract Conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) are recommended as first line treatment for rheumatoid arthritis (RA) patients, but limited information exists on the comparative risk of cancer associated with their use.Objectives:To compare the risk of incident overall (excluding non-melanoma skin) and site-specific cancers (colorectal, lung, lymphoma, leukaemia) associated with first-line use of csDMARDs in patients with RA.Methods:We conducted a multinational cohort study informed by data from 7 healthcare databases including claims and electronic medical records from 4 countries (SIDIAP-Spain, MDCR-US Optum-US, CCAE-US, IQVIA AMBEMR-US, IQVIA-Germany, THIN-UK) part of the Observational Health Data Sciences and Informatics (OHDSI) network. All patients aged ≥18 years who initiated methotrexate (MTX), hydroxychloroquine (HCQ), sulphasalazine (SSZ), or leflunomide (LEF) as first-line monotherapy after a diagnosis of RA between 2005 to 2018 were eligible. Individuals with a prior diagnosis of another inflammatory arthropathy or cancer, or <1 year of follow-up were excluded. Patients were followed from 1-year after treatment initiation to the earliest of incident cancer, loss to follow-up, or 5-years. Cox proportional-hazard models for MTX against each other csDMARD were performed after propensity score stratification. A large set of negative control outcomes were analysed to calibrate hazard ratios (cHRs). Estimates were pooled where homogeneity across sources was adequate (I2<0.4).Results:Across the databases, 127,547 RA patients initiating csDMARD therapy were included in the analyses (MTX: 73,996, HCL: 36,381 SSZ: 9,383 LEF: 7,787). The pooled incidence rate of overall cancer for MTX was 22.8 per 1,000 person years. The pooled summary and source-specific estimated cHRs for overall cancer are shown below in Figure 1. While little difference was seen for HCQ and SSZ compared to MTX, LEF was consistently associated with a reduced cancer risk: pooled cHR (95% CI) 0.67 (0.59 to 0.76) and cHRs ranged from 0.53 (0.36 to 0.80) in CCAE-US to 0.84 (0.58 to 1.22) in SIDIAP-Spain. There were insufficient cases to look site-specific cancers within data sources, although pooled results suggest little risk difference in leukemia, lymphoma, colorectal, or lung cancers.Figure 1.Calibrated hazard ratios (cHRs) of overall cancer risk with their respective confidence intervals (95%CI) by study database. Database estimates not reported where adequate covariate balance not attained. Meta-analysis results not reported where I2>0.4.Conclusion:Compared to MTX users, patients treated with LEF had a lower risk of overall cancer. Risk of four specific cancers did not differ by first line csDMARD exposure.Disclosure of Interests: :Talita Duarte-Salles: None declared, Martina Recalde: None declared, James Weaver Shareholder of: J&J Shares, Grant/research support from: Full-time employment salary from Janssen, Consultant of: Janssen employee, Employee of: Janssen, Paid instructor for: Janssen employee, have instructed at conferences, Speakers bureau: Janssen employee, have spoken at conferences, Edward Burn: None declared, Karine Marinier Employee of: Servier, Yesika Díaz: None declared, Ben Illingens: None declared, David Vizcaya Employee of: Bayer, Katerina Chatzidionysiou Consultant of: AbbVie, Pfizer, Lilly., Patrick Ryan: None declared, Daniel Prieto-Alhambra Grant/research support from: Professor Prieto-Alhambra has received research Grants from AMGEN, UCB Biopharma and Les Laboratoires Servier, Consultant of: DPA’s department has received fees for consultancy services from UCB Biopharma, Speakers bureau: DPA’s department has received fees for speaker and advisory board membership services from Amgen
11.	Flores-Chavez, A, et al. (författare) Using Autoantibodies to Diagnose Systemic Autoimmune Diseases Triggered by Immune Checkpoint Inhibitors: A Clinical Perspective 2022 Ingår i: Critical reviews in immunology. - 1040-8401. ; 42:4, s. 21-36 Tidskriftsartikel (refereegranskat)
12.	Fragoulis, GE, et al. (författare) Higher depression rates and similar cardiovascular comorbidity in psoriatic arthritis compared with rheumatoid arthritis and diabetes mellitus 2020 Ingår i: Therapeutic advances in musculoskeletal disease. - 1759-720X. ; 12, s. 1759720X20976975- Tidskriftsartikel (refereegranskat)
13.	Fragoulis, GE, et al. (författare) SIMILAR CARDIOVASCULAR COMORBIDITY AND HIGHER DEPRESSION RATES IN PSORIATIC ARTHRITIS COMPARED TO AGE- AND SEX-MATCHED RHEUMATOID ARTHRITIS AND DIABETES MELLITUS PATIENTS 2020 Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 79, s. 758-759 Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract Comorbidities are frequent in psoriatic arthritis (PsA) but it is not known how they differ from other high comorbidity burden diseases like rheumatoid arthritis (RA) and diabetes mellitus (DM).Objectives:To compare the prevalence of comorbidities in PsA vs. RA and DM patients.Methods:215 PsA patients were age/gender-matched with 215 RA and 215 DM patients from two tertiary hospitals. Prevalence of comorbidities (hypertension, current smoking, hyperlipidemia, obesity (BMI≥30), coronary disease [CD], stroke, MACE [combined CD and stroke], depression, osteoporosis, history of malignancies) were compared across the three groups. Within PsA group, associations between comorbidities and demographic and clinical features (e.g entheitis), including PsA phenotypes (RA-like vs oligoarthritis pattern and Axial-involvment vs Non-Axial-involvement) were assessed.Results:Hyperlipidaemia, obesity and depression were more frequent in PsA vs. RA. Depression and osteoporosis were more common in PsA vs DM. In contrast, hypertension was more frequent in DM. All other comorbidities, including frequency of stroke, CD and major adverse cardiovascular events did not differ between groups. Results remain unchanged after adjustments (Table 1).Table 1.Comparison of comorbidities between psoriatic arthritis (PsA), rheumatoid (RA) arthritis and Diabetes mellitus (DM) patients. OR: odds ratio, MACE: major adverse cardiovascular events. CI: Confidence IntervalsPsA vs RAPsA vs DMComorbidityPsAn=215n (%)RAn=215n (%)DMN=215n (%)Crude OR(95% CI)Adjusted OR(95% CI)Crude OR(95% CI)Adjusted OR(95% CI)Smoking76 (35.4)62 (28.8)85 (39.5)1.35(0.90-2.03)0.84(0.57-1.24)Obesity50 (29.4)24 (12.8)79 (36.7)2.83(1.65-4.86)0.72(0.47-1.10)Hyperlipidemia101 (47.0)67 (31.2)101 (47.0)1.96(1.32-2.90)-1-Hypertension62 (28.8)51 (23.8)97 (45.1)1.30(0.84-1.99)-0.49(0.33-0.74)-Coronary disease10 (4.7)10 (4.7)16 (7.4)1(0.41-2.45)0.97(0.34-2.79)0.61(0.27-1.37)0.66(0.23-1.91)Stroke8 (3.7)2 (0.9)7 (3.3)4.12(0.86-19.6)3.74(0.73-19.3)1.15(0.41-3.22)1.20(0.35-4.12)MACE12 (5.6)12 (5.6)22 (10.2)1(0.44-2.28)0.94(0.36-2.46)0.52(0.25-1.08)0.42(0.16-1.10)Osteoporosis9 (5.5)24 (11.2)2 (0.9)0.46(0.21-1.03)0.67(0.28-1.64)6.22(1.33-29.2)-Depression42 (19.5)15 (7.0)12 (5.6)3.24(1.74-6.04)3.02(1.57-5.81)4.11(2.10-8.05)4.85(2.37-9.93)Malignancy12 (5.6)7 (3.3)-1.76(0.68-4.55)1.60(0.60-4.26)*-- adjusted for age, gender, smoking, hypertension, dyslipidemia, body mass index, adjusted for steroids, * adjusted for age, gender, disease duration, smoking, **** adjusted for age, disease durationWithin PsA group, depression was associated with female gender (p=0.02), older age (p=0.03), higher disease duration (p=0.04) and current smoking (p=0.04). MACEs in PsA, were associated with male gender (p=0.03), older age (p=0.0002), dyslipidaemia (p=0.003) and hypertension (p<0.0001). No differences were found between different phenotypes of PsA.Conclusion:PsA patients had higher BMI and hyperlipidaemia compared to RA but not to DM. MACE is comparable between PsA and RA or DM, while depression is more common in PsA. Taking into account certain risk factors, screening for and management of comorbidities in PsA is important in the clinical setting.Disclosure of Interests:George E. Fragoulis: None declared, Gerasimos Evangelatos: None declared, Nikolaos Tentolouris: None declared, Kalliopi Fragkiadaki: None declared, Stylianos Panopoulos: None declared, George Konstantonis: None declared, Alexios Iliopoulos: None declared, Katerina Chatzidionysiou Consultant of: AbbVie, Pfizer, Lilly., Petros Sfikakis Grant/research support from: Grant/research support from Abvie, Novartis, MSD, Actelion, Amgen, Pfizer, Janssen Pharmaceutical, UCB, Maria Tektonidou Grant/research support from: AbbVie, MSD, Novartis and Pfizer, Consultant of: AbbVie, MSD, Novartis and Pfizer
14.	Karlsson, ML, et al. (författare) Evaluation of an individually tailored smoking-cessation intervention for patients with rheumatoid arthritis in an outpatient clinic 2023 Ingår i: Scandinavian journal of rheumatology. - 1502-7732. ; , s. 1-11 Tidskriftsartikel (refereegranskat)
15.	Karlsson, M-l, et al. (författare) Evaluation of an individually tailored smoking-cessation intervention for patients with rheumatoid arthritis in an outpatient clinic 2023 Ingår i: Scandinavian Journal of Rheumatology. - : Taylor & Francis. - 0300-9742 .- 1502-7732. ; 52:6, s. 591-600 Tidskriftsartikel (refereegranskat)abstract Objective: The aim of this study was to evaluate an individually tailored smoking-cessation intervention delivered in rheumatology care and compare the characteristics of patients who quit smoking with those who did not.Method: This was an open single-group prospective intervention study over 24 months, with assessments at baseline and at 6, 12, 18, and 24 months. Current smokers with rheumatoid arthritis (RA) were invited to a smoking-cessation programme including behavioural change support, with or without pharmacotherapy. Data on disease activity, medical treatment, and patient-reported outcomes were retrieved from the Swedish Rheumatology Quality Register. The primary outcome was the proportion of patients at month 24 who reported having quit smoking with self-reported 7 day smoking abstinence.Results: In total, 99 patients participated in the study. Median age was 58 years (interquartile range 50-64); 69% were female and 88% rheumatoid factor and/or anti-cyclic citrullinated peptide positive. At 24 months, 21% of the patients had quit smoking. At 6, 12, and 18 months, 12%, 12%, and 14% of patients, respectively, had quit smoking. For patients still smoking at 24 months, the median number of cigarettes per day was significantly reduced from 12 to 6 (p <= 0.001). Among patients who had quit smoking at 24 months, a smaller proportion reported anxiety at baseline compared to those still smoking (28% vs 58%, p = 0.02).Conclusion: A smoking-cessation intervention including behavioural change support with or without pharmacotherapy can be helpful for a substantial number of RA patients. Anxiety is associated with lower smoking-cessation success rates.
16.	Karlsson, ML, et al. (författare) THE EFFECT OF A PERSON-CENTERED SMOKING CESSATION PROGRAM IN RHEUMATOID ARTHRITIS PATIENTS IN A RHEUMATOLOGY OUTPATIENT CLINIC SETTING - RESULTS OF AN INTERVENTIONAL FEASIBILITY STUDY 2021 Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 80, s. 93-94 Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract Smoking is associated with worse treatment response1 and higher mortality2 in rheumatoid arthritis (RA).Objectives:To assess the effect of a smoking cessation intervention in a rheumatology setting.Methods:We designed a smoking cessation interventional feasibility study. RA patients who were active smokers were asked to participate. A nurse-delivered program consisting of behavioural changes techniques and voluntary pharmacotherapy was executed. The intervention was at baseline and at several time points during a 24 month period, based on the individual patient’s needs. Smoking status was collected at baseline, 6, 12, 18 and 24 months. Smoking cessation was verified by 7-days abstinence and carbon monoxide in expiratory air. The main outcome was the proportion of patients who quit smoking (QS) at 24 months.Results:A total of 99 patients were included in the study between 2011-2020. Median (IQR) age of patients was 58 (50 - 64), 69 % were female and 82% were RF and/or ACPA positive. 59% of patients had a newly diagnosed RA, (included from the early RA-track), with a median (IQR) symptom duration of 5 (2-9,5) months. Patients with established RA 41% (included from regular rheumatology department) had a median disease duration of 4 (2-8) years. After 24 months 21% quit smoking (QS) (Table 1). At months 6, 12, 18 and 24 the proportion of QS patients was 12, 13, 15 and 21, respectively. The proportion of QS patients at month 12 and continued being in the QS group throughout the study period was 10%. In the subgroup of patients who continued smoking (CS) the median number of cigarettes per day was significantly reduced at all follow-up time points (Table 1). No significant differences were observed at baseline between CS at 24 months and QS, apart from the proportion of patients who reported anxiety (extracted from EQ-5D and defined as absent or present), which was significantly fewer in the QS group (Table). In the QS group at month 24, the proportion of females was numerically lower compared to CS (52% vs. 73%, p=0.07).Table 1.Baseline demographical, clinical characteristics and number of cigarettes at specific time-points for patients who were non-smokers (QS) and smokers (CS) at month 24.QSN=21 (21%)CSN=78 (79%)Difference between QS and CS(p-value)Age(median, IQR)60 (53-62)57 (50-64)0.94Symptom duration in early RA patients (months) (median, IQR)6 (2-12)4.5 (2-8.5)0.49Disease duration of patients with established RA (years) (median, IQR)8 (3.5-16.5)3 (2-6)0.12% females52730.07% RF and/or ACPA positive85810.70DAS28 (median, IQR)4.24 (3.13-5.72)4.11 (2.88-5.36)0.69HAQ* (median, IQR)0.75 (0.25 -1.38)0.88 (0.38-1.25)0.74VAS pain* (median, IQR)46.0 (11-60)34.5 (12-70)0.90% of patients with reported anxiety* (part of EQ5D)28580.02Smoking duration (years)(median, IQR)40 (30-50)40 (34-49)0.92Median number of cigarettes per day-at baseline10 (7-15)12 (10-20)0.22-at 6 months0 (0-3)6 (3-10)0.006-at 12 months0 (0-5)6 (3-10)0.0003-at 18 months0 (0-0)6 (2-10)0.00-at 24 months0 (0-0)6 (3-10)0.00*=measured at baselineConclusion:Smoking cessation intervention in a rheumatology clinic setting may facilitate reduced smoking or complete cessation in patients with RA. Patient who did not report anxiety were more likely to quit smoking.References:[1]Saevarsdottir, S., et al (2011). Patients with early rheumatoid arthritis who smoke are less likely to respond to treatment with methotrexate and tumor necrosis factor inhibitors: observations from the Epidemiological Investigation of Rheumatoid Arthritis and the Swedish Rheumatology Register cohorts. Arthritis Rheum, 63(1), 26-36.[2]Joseph, R´., et al (2016) Smoking-Related Mortality in Patients With Early Rheumatoid Arthritis: A Retrospective Cohort Study Using the Clinical Practice Research Datalink Arthritis Care Res (Hoboken) 68 (11) 1598-1606Acknowledgements:This study was partly funded by grants from Swedish Reumatism Association.Disclosure of Interests:Marie-Louise Karlsson Speakers bureau: MLK has recivied fee form Novartis Sverige AB, Grant/research support from: MLK had recivied finical grants from Novartis Sverige. Abbvie has fincial support brochure wich was used in the study, Katarina Hertzberg-Nyquist: None declared, Saedis Saevarsdottir Employee of: S is a part-time employee of deCODE genetics Inc., unrelated to this work., Ingrid E. Lundberg Consultant of: I Lundberg har recieved consulting fees from Corbus Pharmaceutical, EMD Serono Research & Development Institute, Octapharma AG, Orphazyme, Janssen, Kezar Life Sciences Inc., Ingrid Demmelmaie: None declared, Susanne Pettersson: None declared, Katerina Chatzidionysiou Consultant of: KC has received consultancy fees from Eli Lilly, AbbVie and Pfizer.
17.	Sena, AG, et al. (författare) FIRST LINE TREATMENT WITH CONVENTIONAL SYNTHETIC DISEASE MODIFYING ANTIRHEUMATIC DRUGS IN RHEUMATOID ARTHRITIS: A MULTINATIONAL POPULATION-BASED COHORT FROM 14 REAL WORLD HEALTHCARE DATABASES AND 9 COUNTRIES - REALITY VERSUS GUIDELINES 2020 Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 79, s. 327-327 Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract Treatment guidelines recommend early initiation of csDMARDs following diagnosis of rheumatoid arthritis (RA), with methotrexate (MTX) as first-line therapy. Scarce evidence exists on adherence to this guidanceObjectives:To characterize first-line csDMARD treatment during the first year following an RA diagnosis.Methods:14 real world databases (3 Primary care, 6 primary/secondary care records, 5 claims) from 9 countries were included, all mapped to the OMOP common data model.Patients were included on the earliest event of: 1st diagnosis of RA or 1st DMARD prescription with an RA diagnosis within 30 days. Patients were >18 years-old, required 1+ year pre-index data, and at least 1-year follow-up. Study period covered 2000-2018. Previous users of DMARDs or non-RA inflammatory arthritis history were excluded. Only MTX, Hydroxychloroquine (HCQ), Sulfasalazine (SSZ) and Leflunomide (LEF) were available in all databases.Results:We identified 323,547 eligible participants. Large variation was observed internationally (Figure 1). MTX as first-line monotherapy ranged from 33.3% to 74.5%, and in combination with HCQ from 2.1% to 6.7%. Three additional csDMARDs were used as first-line: HCQ in 10.1% to 30.2%, SSZ in 0.9% to 28.7%, and LEF in 1.8% to 15.2%.Figure 1.First line csDMARD treatment during 1yr from first observed RA diagnosisConclusion:We report wide heterogeneity of first-line csDMARDs regimens internationally. Despite recommendations for MTX to be first line therapy, data suggest that a large proportion of patients receive alternative csDMARD.Disclosure of Interests: :Anthony G Sena Shareholder of: J&J shares, Grant/research support from: Full-time employment salary from Janssen, Consultant of: Full-time employment salary from Janssen, Employee of: Janssen employee, Paid instructor for: Janssen employee, Speakers bureau: Janssen employee, Denis Granados: None declared, Nigel Hughes Shareholder of: J&J shares, Grant/research support from: Full-time employment salary from Janssen, Consultant of: Janssen employee, Employee of: Janssen employee, Paid instructor for: Janssen employee, Speakers bureau: Janssen employee, WALID FAKHOURI Shareholder of: E Lilly Shares, Employee of: Eli Lilly and Company, Antje Hottgenroth Shareholder of: Eli Lilly shares, Employee of: Lilly Deutschland GmbH, Raivo Kolde: None declared, Sulev Reisberg: None declared, Carmen Olga Torre: None declared, Talita Duarte-Salles: None declared, Yesika Díaz: None declared, Jose Felipe Golib-Dzib Grant/research support from: Full-time employment salary from Janssen, Employee of: Yes, Janssen employee, Paid instructor for: Janssen Employee, Speakers bureau: Janssen Employee, Emily S. Brouwer Shareholder of: J&J shares, Takeda shares, Grant/research support from: Full-time employment salary from Janssen, Consultant of: Janssen employee, Employee of: Janssen employee, Paid instructor for: Janssen Employee, Speakers bureau: Janssen Employee, Edward Burn: None declared, Jennifer Lane: None declared, David Vizcaya Employee of: Bayer, Sara Bruce Wirta Employee of: Janssen-Cilag Sweden AB, Marcel de Wilde: None declared, Katia Verhamme: None declared, Peter Rijnbeek: None declared, Elke Theander Employee of: Janssen-Cilag Sweden AB, Katerina Chatzidionysiou Consultant of: AbbVie, Pfizer, Lilly., Daniel Prieto-Alhambra Grant/research support from: Professor Prieto-Alhambra has received research Grants from AMGEN, UCB Biopharma and Les Laboratoires Servier, Consultant of: DPA’s department has received fees for consultancy services from UCB Biopharma, Speakers bureau: DPA’s department has received fees for speaker and advisory board membership services from Amgen, Patrick Ryan: None declared
18.	Barbulescu, A, et al. (författare) COMPARATIVE EFFECTIVENESS OF JAKI VERSUS BDMARDS; A NATIONWIDE STUDY IN RA 2021 Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 80, s. 68-68 Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract The Janus kinase inhibitors (JAKi) have been increasingly used for the treatment of rheumatoid arthritis (RA) in Sweden, with baricitinib representing ~80% of prescriptions. Evidence regarding the comparative effectiveness of JAKis versus biologics (bDMARDs), and in particular non- tumour-necrosis-factor inhibitor (TNFi) bDMARDs, in real-life is limited.Objectives:To compare RA patients treated with bDMARDs and JAKi in Sweden, in terms of: (1) patient characteristics at treatment start; (2) proportions of patients remaining on therapy, and response rates, at 12 months.Methods:RA patients starting treatment in 2017 and 2018 with either a TNFi, rituximab, abatacept, interleukin 6 inhibitors (IL6i) or a JAKi as different lines of treatment were identified in the Swedish Rheumatology Quality Register. One patient could contribute with more than one treatment episode.Treatment response at 12 months was measured as EULAR good response, HAQ improvement >0.2 units, DAS28 and CDAI remission, and as 0 tender and swollen joint counts (28JC). Patients were classified as non-responders if they stopped treatment before evaluation due to safety or inefficacy. Responses for patients who stopped treatment due to pregnancy or death and patients on treatment but with missing response were imputed using multiple imputation.Proportions of responders and differences in proportions between treatment groups, adjusted using inverse probability of treatment weighting, were estimated using linear regression with robust standard errors.Results:JAKi were often used after bDMARDs, and less frequently prescribed in combination with methotrexate. Measured comorbidities were less frequent among JAKi initiators than among non-TNFi biologic initiators, but RA activity was similar (Table).Table 1.Patient characteristics at treatment initiationCharacteristicMedian (IQR) or N (%)AbataceptIL6iRituximabTNFiJAKiTreatment Starts6945346923497905Age63 (53-71)59 (48-70)65 (54-73)59 (47-68)60 (51-70)Female543 (78)441 (83)519 (75)2739 (78)759 (84)RA duration (years)13 (5-21)10 (5-18)12 (6-22)9 (3-17)13 (7-22)Rheum. factor535 (79)385 (73)588 (87)2405 (70)686 (77)DAS284.8 (3.9-5.6)4.9 (4.0-5.7)4.7 (3.8-5.5)4.4 (3.4-5.3)4.7 (3.9-5.7)HAQ1.3 (0.8-1.6)1.3 (0.8-1.8)1.3 (0.8-1.8)1.0 (0.5-1.4)1.3 (0.8-1.8)Tender joints5 (2-9)6 (3-10)5 (2-9)4 (2-8)6 (2-10)Swollen joints4 (2-6)4 (2-7)4 (2-7)3 (1-6)4 (2-7)ts/bDMARD line3 (2-4)3 (2-4)2 (1-4)1 (1-2)4 (2-6)At least one prev. TNFi539 (78)442 (83)457 (66)1448 (41)770 (85)At least one prev. non-TNFi271 (39)220 (41)243 (35)441 (13)584 (65)Methotrexate co-treatment264 (50)172 (40)286 (53)1708 (62)296 (40)Glucocorticoids co-treatment247 (47)186 (43)275 (51)1126 (41)389 (53)Cancer90 (2.8)64 (2.3)363 (7.7)410 (1.8)20 (2.2)Cardio-vascular dis.245 (7.5)123 (4.4)322 (6.8)749 (3.4)41 (4.4)Chronic respiratory dis.303 (9.3)140 (5.0)473 (10.0)721 (3.2)50 (5.4)Diabetes324 (9.9)216 (7.7)456 (9.7)1479 (6.7)69 (7.5)* any diagnosis within 5 years before start Adjusted differences in proportion with each response outcomeIn a crude comparison, 65% (61%-68%) of JAKi, 62% (59%-66%) of abatacept, 58% (53%-62%) of IL6i, 80% (77%-83%) of rituximab and 68% (67%-70%) of TNFi initiators remained on treatment at 12 months after start. Also, JAKi showed lower overall responder proportions than TNFi, rituximab and IL6i.After adjustment for demographic and socio-economic factors, RA disease activity, previous use of ts/bDMARDs, co-medication with glucocorticoids and methotrexate and comorbidities at baseline, no significant differences in responder proportions between JAKi and bDMARDs remained (Figure). Furthermore, the adjusted proportions of patients on treatment were higher for JAKi and rituximab than for the other bDMARDs.Conclusion:This preliminary analysis of patients treated in clinical practice found no statistically significant difference in effectiveness between JAKi and bDMARDs.Disclosure of Interests:Andrei Barbulescu: None declared, Johan Askling Grant/research support from: Abbvie, Astra-Zeneca, BMS, Eli Lilly, MSD, Pfizer, Roche, Samsung Bioepis, Sanofi, and UCB. These entities have entered into agreements with Karolinska Institutet with JA as principal investigator, mainly in the context of safety monitoring of biologics via the ARTIS national safety monitoring system, Katerina Chatzidionysiou Speakers bureau: Eli Lilly, Abbvie and Pfizer, Consultant of: Eli Lilly, Abbvie and Pfizer, Helena Forsblad-d’Elia: None declared, Alf Kastbom Employee of: Sanofi, Ulf Lindström: None declared, Carl Turesson Speakers bureau: Abbvie, Bristol-Myers Squibb, Medac, Pfizer, Roche, Consultant of: Roche, Grant/research support from: Bristol-Myers Squibb, Thomas Frisell: None declared
19.	Barbulescu, A., et al. (författare) Effectiveness of baricitinib and tofacitinib compared with bDMARDs in RA: results from a cohort study using nationwide Swedish register data 2022 Ingår i: Rheumatology. - : Oxford University Press (OUP). - 1462-0324 .- 1462-0332. ; 61:10, s. 3952-3962 Tidskriftsartikel (refereegranskat)abstract Objectives To describe the use of baricitinib and tofacitinib by Swedish RA patients and to compare their effectiveness with that of biologic DMARDs (bDMARDs). Methods RA patients who initiated baricitinib (n = 1420), tofacitinib (n = 316), abatacept (n = 1050), IL-6 inhibitors (IL-6is; n = 849), rituximab (n = 1101) or TNF inhibitors (TNFis; n = 6036) between January 2017 and November 2019 were followed for a minimum of 1 year using data from several linked Swedish national registers. Proportions reaching a good EULAR 28-joint DAS (DAS28) response, HAQ Disability Index (HAQ-DI) improvement >0.2 units and Clinical Disease Activity Index (CDAI) remission were compared at 1 year, imputing discontinued treatments as 'non-response'. Additionally, we compared drug retention and changes in DAS28, HAQ-DI and CDAI from baseline to 3 months after treatment initiation. Results On average, baricitinib, and particularly tofacitinib, were initiated as later lines of therapy and more frequently as monotherapy compared with rituximab and TNFi. Adjusted 1 year response proportions were consistently lower on TNFi compared with baricitinib, with differences of -4.3 percentage points (95% CI -8.7, 0.1) for good EULAR response, -9.9 (-14.4 to -5.4) for HAQ-DI improvement and -6.0 (-9.8 to -2.2) for CDAI remission. Comparisons with non-TNFi bDMARDs also favoured baricitinib, but not consistently. Treatment responses for tofacitinib were only marginally lower than those for baricitinib and generally similar to those of bDMARDs, with precision limited by low power. Comparisons of drug retention and changes in disease activity from baseline to 3 months supported the 1 year findings. Conclusions Baricitinib and tofacitinib showed at least equivalent effectiveness compared with bDMARDs after exploring several different effectiveness measures.
20.	Bolla, E, et al. (författare) Original research on Behçet's syndrome: a bibliometric analysis over 20 years (2000-2019) 2023 Ingår i: Clinical and experimental rheumatology. - : Clinical and Experimental Rheumatology. - 0392-856X .- 1593-098X. ; 41:10, s. 1985-1990 Tidskriftsartikel (refereegranskat)
21.	Bower, H., et al. (författare) Effects of the COVID-19 pandemic on patients with inflammatory joint diseases in Sweden: from infection severity to impact on care provision 2021 Ingår i: Rmd Open. - : BMJ. - 2056-5933. ; 7:3 Tidskriftsartikel (refereegranskat)abstract Objectives To compare risks for COVID-19-related outcomes in inflammatory joint diseases (IJDs) and across disease-modifying antirheumatic drugs (DMARDs) during the first two waves of the pandemic and to assess effects of the pandemic on rheumatology care provision. Methods Through nationwide multiregister linkages and cohort study design, we defined IJD and DMARD use annually in 2015-2020. We assessed absolute and relative risks of hospitalisation or death listing COVID-19. We also assessed the incidence of IJD and among individuals with IJD, rheumatologist visits, DMARD use and incidence of selected comorbidities. Results Based on 115 317 patients with IJD in 2020, crude risks of hospitalisation and death listing COVID-19 (0.94% and 0.33% across both waves, respectively) were similar during both waves (adjusted HR versus the general population 1.33, 95% CI 1.23 to 1.43, for hospitalisation listing COVID-19; 1.23, 95% CI 1.08 to 1.40 for death listing COVID-19). Overall, biological disease-modifying antirheumatic drugs (bDMARDs)/targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs) did not increase risks of COVID-19 related hospitalisation (with the exception of a potential signal for JAK inhibitors) or death. During the pandemic, decreases were observed for IJD incidence (-7%), visits to rheumatology units (-16%), DMARD dispensations (+6.5% for bDMARD/tsDMARDs and -8.5% for conventional synthetic DMARDs compared with previous years) and for new comorbid conditions, but several of these changes were part of underlying secular trends. Conclusions Patients with IJD are at increased risk of serious COVID-19 outcomes, which may partially be explained by medical conditions other than IJD per se. The SARS-CoV-2 pandemic has exerted measurable effects on aspects of rheumatology care provision demonstrated, the future impact of which will need to be assessed.
22.	Chatzidionysiou, K (författare) Beyond Methotrexate and Biologics in RA - Efficacy of JAK Inhibitors and their Place in the Current Treatment Armamentarium 2020 Ingår i: Mediterranean journal of rheumatology. - : Convin SA. - 2529-198X. ; 31:Suppl 1, s. 120-128 Tidskriftsartikel (refereegranskat)
23.	Chatzidionysiou, K, et al. (författare) Could severe COVID-19 be considered a complementopathy? 2020 Ingår i: Lupus science & medicine. - : BMJ. - 2053-8790. ; 7:1 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
24.	Chatzidionysiou, K, et al. (författare) Effect of belimumab treatment on antiphospholipid antibody levels: post-hoc analysis based on two randomised placebo-controlled trials in systemic lupus erythematosus 2020 Ingår i: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 79:2, s. 304- Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
25.	Chatzidionysiou, K (författare) Mediterranean Journal of Rheumatology March 2020 Highlights 2020 Ingår i: Mediterranean journal of rheumatology. - : Convin SA. - 2529-198X. ; 31:1, s. 1-2 Tidskriftsartikel (refereegranskat)
26.	Chatzidionysiou, K, et al. (författare) Response to: 'Association of subcutaneous belimumab and long-term antimalarial treatment reduces antiphospholipid antibodies levels in systemic lupus erythematosus: post-hoc analysis of a randomised placebo-controlled trial-comment on: 'Effect of belimumab treatment on antiphospholipid antibody levels: post-hoc analysis based on two randomised placebo-controlled trials in systemic lupus erythematosus' by Chatzidionysiou et al' by Bettiol et al 2022 Ingår i: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 81:8, s. e141- Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
27.	Chatzidionysiou, K, et al. (författare) Risk of lung cancer in rheumatoid arthritis and in relation to autoantibody positivity and smoking 2022 Ingår i: RMD open. - 2056-5933. ; 8:2 Tidskriftsartikel (refereegranskat)
28.	Chatzidionysiou, K, et al. (författare) Risk of lung cancer in rheumatoid arthritis and in relation to autoantibody positivity and smoking 2022 Ingår i: RMD open. - : BMJ. - 2056-5933. ; 8:2 Tidskriftsartikel (refereegranskat)abstract Lung cancer is a common malignancy in rheumatoid arthritis (RA). Since smoking is a risk factor for both (seropositive) RA and lung cancer, it remains unclear whether RA, in itself, increases lung cancer risk.MethodsWe performed a population-based cohort study of patients with RA and individually matched general population reference individuals identified in Swedish registers and from the Epidemiological Investigation of RA early RA study, prospectively followed for lung cancer occurrence 1995–2018. We calculated incidence rates and performed Cox regression to estimate HRs including 95% CIs of lung cancer, taking smoking and RA serostatus into account.ResultsOverall, we included 44 101 patients with RA (590 incident lung cancers, 56 per 100 000), and 216 495 matched general population individuals (1691 incident lung cancers, 33 per 100 000), corresponding to a crude HR (95% CI) of 1.76 (1.60 to 1.93). In subset analyses, this increased risk remained after adjustment for smoking (HR 1.77, 95% CI 1.06 to 2.97). Compared with general population subjects who were never smokers, patients with RA who were ever smokers had almost seven times higher risk of lung cancer. In RA, seropositivity was a significant lung cancer risk factor, even when adjusted for smoking, increasing the incidence 2–6 times. At 20 years, the risk in patients with RA was almost 3%, overall and over 4% for patients who were ever smokers and had at least one RA autoantibody.ConclusionsSeropositive RA is a risk factor for lung cancer over and above what can be explained by smoking, although residual confounding by smoking or other airway exposures cannot be formally excluded. There is a need for increased awareness and potentially for regular lung cancer screening, at least in a subset of patients with RA.
29.	Chatzidionysiou, K, et al. (författare) THE RISK OF LUNG CANCER IN RHEUMATOID ARTHRITIS AND IN RELATION TO AUTOANTIBODY POSITIVITY AND SMOKING 2022 Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 81, s. 247-247 Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract Lung cancer is a common malignancy in rheumatoid arthritis (RA)1,2. Since smoking is a risk factor for both (seropositive) RA and lung cancer, it remains unclear whether RA, in itself, increases lung cancer risk.ObjectivesThe aim of this study was to examine whether and to what extent the increased risk of lung cancer in RA may (or may not) be attributable to smoking, and to examine this association, both in terms of absolute and relative risks, specifically in relation to RA serostatus.MethodsWe performed a population-based cohort study of RA patients and individually matched general population reference individuals identified in Swedish registers and from the EIRA early RA study, prospectively followed for lung cancer occurrence 1995 through 2018. We calculated incidence rates and performed Cox regression to estimate hazard ratios (HR) including 95% confidence intervals (CI) of lung cancer, taking smoking and sero-status into account.ResultsOverall, we included 44,101 RA patients (590 incident lung cancers, 56 per 100,000), and 216,495 matched general population individuals (1,691 incident lung cancers, 33 per 100,000), corresponding to a crude HR (95% CI) of 1.76 (1.60-1.93). In subset analyses this increased risk remained after adjustment for smoking (HR=1.77, 95% CI 1.06-2.97). Compared to general population subjects who were never smokers, RA patients who were ever smokers had almost 7 times higher risk of lung cancer.Positive autoantibody status was associated with an at least doubled risk of lung cancer in ACPA positive patients (vs. ACPA negative patients) and double seropositive (vs. double seronegative) patients after adjusting for comorbidities and smoking (Table 1).Table 1.Number of events, person-years of follow-up, number of events per 100,000 person-years, and relative risk of lung cancer according to autoantibody status in the EIRA sub-cohort. Five Hazard ratios are presented: a) crude; b) adjusted for age, sex, index year, county of residency (model A); c) age, sex, index year, county of residency and comorbidities (renal failure, heart failure, ischemic heart disease, COPD, respiratory infections, hospitalization) (model B) c) all the above plus smoking (model C) and d) as model C with packet-years instead of smoking ever vs. never.No of events (person years of follow-up; No of events/100 000 person years)Crude Hazard ratio (95% CI)Model A Hazard ratio* (95% CI)Model BHazard ratio (95% CI)Model CHazard ratio (95% CI)Model D with smoking as pack-years instead of ever/neverPositiveNegativeRF (N=2060)30(49,440; 60.7)6(49,440; 12.1)2.78 (1.16-6.69)3.01 (1.25-7.26)2.82 (1.17-6.82)2.44 (1.01-5.89)2.16 (0.88-5.28)ACPA (N=2060)30(49,440; 60.7)6(49,440; 12.1)3.13 (1.30-7.51)3.43 (1.42-8.25)3.22 (1.33-7.77)2.88 (1.19-6.95)3.29 (1.26-8.58)RF and/or ACPA (N=2060)34(49,440; 68.8)2(49,440; 4.0)6.38 (1.53-26.56)7.62 (1.83-31.83)7.20 (1.72-30.11)6.29 (1.51-26.30)5.76 (1.37-24.21)RF and ACPA (positive vs. double negative)(N=1608)26(38,592; 67.4)2(38,592; 5.2)6.67 (1.58-28.08)7.92 (1.87-33.50)7.08 (1.67-29.98)6.21 (1.47-26.33)5.86 (1.37-25.01)The average absolute five-year risk of lung cancer counting from RA diagnosis was 1.3% in ever-smoking seropositive RA. At 20 years the risk was almost 3% in RA overall, and over 4% for patients who were ever smokers and had at least one autoantibody.ConclusionRA seropositivity is a strong and at least seemingly independent risk factor for lung cancer in RA. The absolute risks point to the potential for regular lung cancer screening, at least in seropositive RA.References[1]Simon TA, Thompson A, Gandhi KK, et al. Incidence of malignancy in adult patients with rheumatoid arthritis: A meta-analysis. Arthritis Res Ther Published Online First: 2015.[2]Khurana R, Wolf R, Berney S, et al. Risk of development of lung cancer is increased in patients with rheumatoid arthritis: A large case control study in US veterans. J Rheumatol 2008.Disclosure of InterestsKaterina Chatzidionysiou Consultant of: consultancy fees from Eli Lilly, AbbVie and Pfizer, Daniela Di Giuseppe: None declared, Jonas Söderling: None declared, Anca Catrina: None declared, Johan Askling Grant/research support from: Karolinska Institutet has entered into agreements between Karolinska Institutet (JA as principal investigator) with AbbVie, BMS, MSD, Eli Lilly, Pfizer, Roche, Samsung Bioepis, Sanofi and UCB, mainly regarding safety monitoring of anti-rheumatic therapies
30.	Chatzidionysiou, K, et al. (författare) Tocilizumab decreases T cells but not macrophages in the synovium of patients with rheumatoid arthritis while it increases the levels of serum interleukin-6 and RANKL 2021 Ingår i: RMD open. - : BMJ. - 2056-5933. ; 7:2 Tidskriftsartikel (refereegranskat)abstract Our knowledge about the effect of tocilizumab (TCZ) on the synovium in rheumatoid arthritis (RA) is limited. The aim of this study was to investigate the effect of TCZ on citrullination and on inflammation in the synovial tissue and in the peripheral blood.Methods15 patients with RA underwent synovial biopsy before and 8 weeks after TCZ initiation. Clinical evaluation was performed at baseline and at 8 weeks. Using immunohistochemistry, we evaluated the expression of CD68, CD3, CD20, osteoprotegerin (OPG) and receptor activator for nuclear factor-κB ligand (RANKL) before and after treatment with TCZ. We also analysed the expression of protein arginine deiminase (PAD)-2 and PAD-4 enzymes in the synovial tissue and protein citrullination patterns with the help of anticitrullinated protein antibody (ACPA) clones 1325:04C03 and 1325:01B09. Serum levels of interleukin-6 (IL-6), IL-8, RANKL, OPG and C-terminal crosslinked telopeptide type II collagen were measured by ELISA. Paired-wise Wilcoxon signed-rank test was used to compare median values before and after treatment.ResultsDisease activity in patients was reduced from baseline to 8 weeks. Although PAD-2 and PAD-4 expressions remained unchanged after TCZ treatment, the binding of one ACPA clone decreased in the synovial tissue. TCZ did not affect the number of CD68+ macrophages or CD20+ B cells but induced significant decrease in the number of CD3+ T cells. RANKL and OPG expression remained unchanged in the synovial tissue. A significant increase in the levels of IL-6 and RANKL was observed in the serum. This increase was statistically significant in patients who responded to TCZ (achieving Clinical Disease Activity Index low disease activity or remission) but not in non-responders.ConclusionsTCZ reduced synovial T-cell counts but not macrophages. A significant increase of serum IL-6 was observed in responders.
31.	Chatzidionysiou, K, et al. (författare) Treatment of rheumatic immune-related adverse events due to cancer immunotherapy with immune checkpoint inhibitors-is it time for a paradigm shift? 2021 Ingår i: Clinical rheumatology. - : Springer Science and Business Media LLC. - 1434-9949 .- 0770-3198. ; 40:45, s. 1687-1695 Tidskriftsartikel (refereegranskat)abstract Immunotherapy has revolutionized cancer treatment during the last years. Several monoclonal antibodies that are specific for regulatory checkpoint molecules, that is, immune checkpoint inhibitors (ICIs), have been approved and are currently in use for various types of cancer in different lines of treatment. Cancer immunotherapy aims for enhancing the immune response against cancer cells. Despite their high efficacy, ICIs are associated to a new spectrum of adverse events of autoimmune origin, often referred to as immune-related adverse events (irAEs), which limit the utility of these drugs. These irAEs are quite common and can affect almost every organ. The grade of toxicity varies from very mild to life-threatening. The pathophysiological mechanisms behind these events are not fully understood. In this review, we will summarize current evidence specifically regarding the rheumatic irAEs and we will focus on current and future treatment strategies. Treatment guidelines largely support the use of glucocorticoids as first-line therapy, when symptomatic therapy is not efficient, and for more persistent and/or moderate/severe degree of inflammation. Targeted therapies are higher up in the treatment pyramid, after inadequate response to glucocorticoids and conventional, broad immunosuppressive agents, and for severe forms of irAEs. However, preclinical data provide evidence that raise concerns regarding the potential risk of impaired antitumoral effect. This potential risk of glucocorticoids, together with the high efficacy and potential synergistic effect of newer, targeted immunomodulation, such as tumor necrosis factor and interleukin-6 blockade, could support a paradigm shift, where more targeted treatments are considered earlier in the treatment sequence.
32.	Di Giuseppe, D., et al. (författare) Comparison of treatment retention of originator vs biosimilar products in clinical rheumatology practice in Sweden 2021 Ingår i: Rheumatology. - : Oxford University Press (OUP). - 1462-0324 .- 1462-0332. ; 61:9, s. 3596-3605 Tidskriftsartikel (refereegranskat)abstract Objectives To compare treatment retention between biosimilars and their originator products among first starters (etanercept, infliximab, adalimumab and rituximab), as well as after non-medical switch. Methods Patients with rheumatic diseases starting, for the first time, an originator or biosimilar etanercept, infliximab, adalimumab or rituximab were identified in the national Swedish Rheumatology Quality Register. Moreover, patients switching from an originator to its biosimilar were identified and individually matched to patients continuing on the originator. One-year treatment retention was calculated and hazard ratios (HR) for discontinuation with 95% CIs were estimated, adjusting for comorbidities and socio-economic factors. Results In total, 21 443 first treatment courses were identified. The proportion of patients still on the drug at 1 year and the HR for discontinuation revealed no differences across adalimumab (Humira, Imraldi, Amgevita and Hyrimoz) nor across rituximab products (Mabthera, Ritemvia/Truxima and Rixathon). The proportions on the drug at 1 year were similar for Benepali (77%) and Enbrel (75%) and the adjusted HR for Benepali compared with Enbrel was 0.91 (95% CI 0.83, 0.99). For infliximab, the proportion still on the drug at 1 year was 67% for Remicade and 66% for Remsima/Inflectra and the HR compared with Remicade was 1.16 (95% CI 1.02, 1.33). Among 2925 patients switching from an originator drug to one of its biosimilars, we noted no statistically significant or clinically relevant differences in drug survival compared with those who remained on originator therapy. Conclusion This large observational study supports the equivalence of biologic DMARD biosimilar products and originators when used in routine rheumatology care.
33.	Di Giuseppe, D, et al. (författare) DIFFERENCES IN DRUG SURVIVAL BETWEEN ORIGINATOR AND BIOSIMILAR PRODUCTS AMONG FIRST USERS OF EACH MOLECULE 2021 Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 80, s. 535-535 Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract Biosimilar products of biological disease-modifying antirheumatic drugs (bDMARDs) entered the Swedish market in 2015, with regulatory approvals based on head to head trials of limited duration. Longer-term comparative drug survival, in clinical practice, remains less well documented.Objectives:To compare survival on drug between biosimilars and their originator products among first starters of etanercept, infliximab, adalimumab and rituximab.Methods:Data from the Swedish Rheumatology Quality register (SRQ) was used to identify and follow patients who started a first ever treatment with etanercept since April 2015 (originator=ETA,biosimilar= SB4), infliximab since March 2014 (originator=IFX,biosimilar= CT-P13), adalimumab since January 2018 (originator=ADA biosimilars=SB5, ABP501), or rituximab since January 2018 (originator=RIT,biosimilar= GP2013), through December 31st, 2019, date of first discontinuation of the drug, or death. Discontinuation was defined as lack of effectiveness or adverse events, while other reasons for interruption of the drug (including non-medical switch) were considered censoring events. Descriptive characteristics were collected from the SRQ and tabulated. Hazard ratios (HR) of discontinuation were estimated using Cox regression, with each drug analyzed separately, adjusted for age,sex,indication,line of treatment,disease duration,year of treatment start,region and concomitant use of csDMARD.Results:9274 patients started etanercept(49% SB4), 3609 started infliximab(64% CT-P13), 3117 started adalimumab(27% SB5, 14% ABP 501), and 763 started rituximab(39% GP2013), Table 1. Patients starting CT-P13 and GP2013 were less likely to be biologics-naïve compared to those starting the originator product. Initiators of SB5,ABP501 and GP2013 were more likely,and those starting CT-P13 were less likely,to be on concomitant csDMARDs compared to those starting the originator products. Patients characteristics of ETA and SB4 were similar.The introduction of a biosimilar was typically followed by a decrease in the uptake of the originator, but for ETA a change in pricing in 2018 later led to a reversal of this pattern (Figure 1).For IFX,ADA,and RIT, survival on drug was similar for the originator and its biosimilar(s). For ETA,risk of discontinuation was somewhat lower for the biosimilar than for the originator(adjusted HR:0.87,95% confidence interval:0.79-0.95), Table 1.Table 1.Hazard ratios of discontinuation and descriptive characteristics of biosimilar vs. originator among first starters of each molecule, until 31st December 2019.EtanerceptInfliximabAdalimumabRituximabOriginatorSB4OriginatorCT-P13OriginatorSB5ABP 501OriginatorGP2013N47214553130823011834852431465298Discontinuation12891236582878399139805726Adjusted hazard ratios*Ref0.87 (0.79-0.95)Ref1.14 (0.99-1.31)Ref1.02 (0.83-1.26)1.16 (0.88-1.52)Ref1.12 (0.68-1.85)Age, mean years (std)51 (16)51 (15)49 (16)49 (16)48 (15)52 (15)51 (15)59 (15)60 (15)Female, %67%65%61%64%62%64%65%75%76%RA, %46%48%39%35%33%42%43%61%76%Bionaïve, %72%72%76%69%45%52%43%53%38%Disease duration, mean years (std)11 (12)11 (11)11 (11)11 (11)12 (13)12 (11)14 (15)14 (19)15 (11)DAS28, mean4.0 (1.3)4.0 (1.4)4.1 (1.4)4.1 (1.4)3.7 (1.4)3.8 (1.3)4.0 (1.3)4.5 (1.4)4.7 (1.4)Concomitant csDMARDs, %45%47%57%48%37%49%42%36%43%Abbreviations: RA=rheumatoid arthritis. csDMARDs=conventional synthetic DMARD, std=standard deviation.Figure 1.Number of starts of biosimilars compared to the originator during the follow-up time, by moleculeConclusion:Despite their identical indications and therapeutic positioning, there are some differences in the baseline characteristics between patients who start ADA, IFX and RIT and their biosimilars. There are no differences in drug survival between originator and biosimilar with the possible exception of etanercept although the observed difference should be interpreted in light of possible unmeasured or residual channeling.Disclosure of Interests:Daniela Di Giuseppe: None declared, Hannah Bower: None declared, Bénédicte Delcoigne: None declared, Thomas Frisell: None declared, Katerina Chatzidionysiou Consultant of: Eli Lilly, AbbVie and Pfizer, Ulf Lindström: None declared, Christopher Sjowall: None declared, Elisabet Lindqvist: None declared, Johan Askling Grant/research support from: Abbvie, Astra-Zeneca, BMS, Eli Lilly, MSD, Pfizer, Roche, Samsung Bioepis, Sanofi, and UCB,
34.	Ekberg, NR, et al. (författare) Corrigendum to "Protective Effect of the HIF-1A Pro582Ser Polymorphism on Severe Diabetic Retinopathy" 2021 Ingår i: Journal of diabetes research. - : Hindawi Limited. - 2314-6753 .- 2314-6745. ; 2021, s. 9827150- Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
35.	Fragoulis, GE, et al. (författare) Lung cancer in rheumatoid arthritis. Is there a need for better risk assessment and screening? 2020 Ingår i: Clinical rheumatology. - : Springer Science and Business Media LLC. - 1434-9949 .- 0770-3198. ; 39:3, s. 957-961 Tidskriftsartikel (refereegranskat)
36.	Frodlund, M., et al. (författare) Predictors Of Antibody Response To Covid-19 Vaccine In Rituximab Treated Patients With Inflammatory Rheumatic Diseases. A Swedish Nationwide Study (Covid19-Reuma) 2022 Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 81, s. 368-369 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract In line with other reports, our group showed that patients treated with rituximab had significant impaired antibody response compared to patients treated with other biologic and targeted and synthetic disease modifying anti-rheumatic drugs (csDMARD).ObjectivesTo investigate predictors of response to COVID-19 vaccination (2 doses of mRNA vaccines, 2 doses of virus vector vaccines or combinations of these) in patients with inflammatory rheumatic diseases (IRD) treated with rituximab and controls.MethodsAntibody levels to three antigens: Spike protein full length, Spike S1 and Nucleocapsid C-terminal fragment (to confirm previous COVID-19 infection) were measured in sera collected before vaccination and 2-12 weeks after the second vaccine using a multiplex bead-based serology assay. The antigen-specific cut-off was defined as the median fluorescence intensity signal plus 6x standard deviations across 12 pre-pandemic controls. A good vaccine response was defined as having antibodies over the cut-off level for both spike antigens. Proportion (%) responders was compared between patients and controls (Chi2 test).Patients with IRD receiving last rituximab treatment within a mean (range) 193 (23-501) days before first vaccination participated. Individuals without IRD served as a control group. Predictors of a good vaccine response were explored using multivariate logistic regression analysis adjusted for age, sex, disease duration, diagnosis (systemic vasculitis/RA/JIA/other), concomitant csDMARD, rituximab dose and prednisolone dose. Hazard ratio (chanse) of a good antibody response in relation to time between the last rituximab treatment and vaccination was studied by Kaplan-Meier survival analysis.ResultsIn total, 145 patients receiving rituximab and 61 controls were inclyded. Of these, 82 received rituximab as monotherapy (67% women; mean age 66 years, mean disease duration 13 years; 33% had RA/JIA and 60% vasculitis) and 63 received rituximab+csDMARD (62% women; mean age 66 years; mean disease duration 17 years; 76% had RA/JIA and 10 % vasculitis). Controls (n=61) were 74% women and mean age 49 years. Compared to controls, rituximab patients had lower antibody levels for both spike proteins (p<0.001). Proportion (%) responders among patients receiving rituximab as monotherapy (40.2%) and rituximab+DMARDs (25.4%) was significantly lower than in controls (98.4%) (p<0.001, Chi2). Higher age, concomitant csDMARD at vaccination and shorter time from last rituximab treatment predicted impaired antibody response (multivariate logistic regression model) (Table 1). Longer time between the last rituximab course and vaccination was associated with better antibody response (Figure 1).Table 1.Predictors of good antibody response to two doses of COVID-19 vaccine defined as antibodies over the cut-off level for both spike antigensBp-valueOR95% CIAge at vaccination (years)-0.040.0090.960.93-0.99Sex (male/female)-9.550.2090.580.24-1.36csDMARD at vaccination (yes/no)-1.080.0260.340.13-0.88Prednisolone (mg/dag)-0.100.1030.900.80-1.02Rituximab dos (1000 mg vs 500 mg)-0.010.3700.990.99-1.00Time between the last rituximab and vaccination (months)0.200.0011.311.11-1.55Diagnosis at vaccination (systemic vasculitis vs others)-0.510.3150.600.21-1.64Figure 1.The chance of good antibody response following two doses of COVID-19 vaccine in relation to time between the last rituximab course and vaccination.ConclusionPatients with IRD getting vaccinated with two doses of COVID19 vaccine during the treatment with rituximab have the ability to develop antibody response although the response is impaired. For each month passed after the last rituximab course, the chance of good antibody response increases with 30%. Younger patients receiving rituximab as monotherapy and vaccinated preferably several months after the last rituximab treatment have the highest chance of achieving a good antibody response.AcknowledgementsUnrestricted research grants have been received from Roche and starting grants from The Swedish Rheumatism AssociationDisclosure of InterestsMartina Frodlund: None declared, Katerina Chatzidionysiou Consultant of: consultancy fees from Eli Lilly, AbbVie and Pfizer., Anna Södergren: None declared, Eva Klingberg: None declared, Monika Hansson: None declared, Elisa Pin: None declared, Sophie Olsson: None declared, Anders Bengtsson: None declared, Lars Klareskog Grant/research support from: has eceived research grants from Pfizer, BMS, Affibody, Sonoma Biotherapeutics, Meliha C Kapetanovic Consultant of: have received consultancy fees from Abbvie, Pfizer and GSK, Grant/research support from: have received unrestricted research grants from Roche and Pfizer
37.	Frodlund, M, et al. (författare) THE IMPACT OF IMMUNOMODULATING TREATMENT ON THE IMMUNOGENICITY OF COVID-19 VACCINES IN PATIENTS WITH IMMUNE-MEDIATED INFLAMMATORY RHEUMATIC DISEASES COMPARED TO HEALTHY CONTROLS. A SWEDISH NATIONWIDE STUDY (COVID19-REUMA) 2022 Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 81, s. 113-114 Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract Initial studies on the immunogenicity of COVID-19 vaccines in patients with immune-mediated inflammatory rheumatic diseases (IRD) reported diminished antibody response in general, and particularly when treated with rituximab or abatacept (1). Additional data are needed, especially for patients with IRD and immunomodulatory treatments.ObjectivesTo elucidate the antibody response after two doses of COVID-19 vaccine in patients with IRD treated with biologic or targeted synthetic disease modifying anti-rheumatic drugs (b/ts DMARDs) as monotherapy or combined with conventional synthetic DMARDS (csDMARDs).MethodsAntibodies against two antigens representing Spike full length protein and Spike S1 and a Nucleocapsid C-terminal fragment (used to confirm previously COVID-19 infection) were measured in serum obtained before and after the second vaccination using a multiplex bead-based serology assay (2). Patients with IRD receiving immunomodulating treatment, followed at a rheumatology department and healthy individuals (controls) were recruited from five Swedish regions. Antibody positivity was classified as the signal passing an antigen specific cutoff based on the mean intensity signal of 12 selected negative pre-pandemic controls plus 6SD for Spike/S1 and 12SD for Nucleocapsid-C. Good vaccine response was defined as having antibodies over cut-off level for both spike antigens. Percentage of responders in each treatment group was compared to controls (Chi2 test). Predictors of antibody response were determined using logistic regression analysis.ResultsIn total, 414 patients (320 RA/JIA/psoriatic arthritis/axial spondylarthritis, 60 systemic vasculitis and 32 other IRD) and 61 controls participated. Patients receiving rituximab (n=145; 65% female; mean age 65years), abatacept (n=21; 77% female; mean age 66 years), IL6 inhibitors (n=77; 74% female; mean age 64years), JAK-inhibitors (n=58; 75% female, mean age 53years), TNF-inhibitors (n=68; 66% female; mean age 44years;), IL17 inhibitors (n=42; 54% female; mean age 44years) and controls (n=61; 74% female, mean age 49years) were studied. Patients receiving IL6 inhibitor (81.0%), abatacept (43.8%) or rituximab (33.8%) had a significantly lower antibody response rate compared to controls (98.4%), further pronounced if combined with csDMARD (p<0.001) (Figure 1). In the adjusted logistic regression analysis, higher age, rituximab, abatacept, concomitant csDMARD but not IL6 inhibitors, concomitant prednisolone, or a vasculitis diagnosis, remained significant predictors of antibody response (Table 1). All vaccines were well tolerated. 14 (3.4%) patients reported an increased activity in their IRD following vaccination.ConclusionIn this nationwide study including IRD patients receiving b/ts DMARDs a decreased immunogenicity of COVID-19 vaccines was observed in patients receiving rituximab, abatacept and to some extent IL-6 inhibitors. Concomitant csDMARD gave further attenuation. Patients on rituximab and abatacept should be prioritized for booster doses of COVID19 vaccine.References[1]Jena, et al. Response to SARS-CoV-2 vaccination in immune mediated inflammatory diseases: Systematic rev./meta-analysis. Autoim. Rev: 2021;102927[2]Hober, et al. Systematic evaluation of SARS-CoV-2 antigens enables a highly specific and sensitive multiplex serol. C-19 assay. Clin Transl Im. 2021;10(7): e1312Table 1.Predictors of antibody response to COVID-19 vaccineRituximab-1.799<0.0010.170.07-0.42Abatacept-1.9710.0010.140.04-0.45IL6 inhibitor0.0230.9651.020.36-2.94Age (years)-0.0810.0000.920.89-0.96csDMARD-1.1270.0020.320.16-0.66Prednisolone (mg/day)-0.0640.2060.940.85-1.04Frequency (%) of individuals with good antibody response to COVID-19 vaccineAcknowledgementsUnrestricted research grants have been received från Roche and starting grants from the Swedish Rheumatism AssociationDisclosure of InterestsMartina Frodlund Consultant of: Consultancy fees from AstraZeneca and GSK, Katerina Chatzidionysiou Consultant of: Consultancy fees from Eli Lilly, AbbVie and Pfizer, Anna Södergren: None declared, Eva Klingberg: None declared, Anders Bengtsson: None declared, Lars Klareskog Grant/research support from: Research grants from Pfizer, BMS, Affibody, Sonoma Biotherapeutics, Meliha C Kapetanovic: None declared
38.	Frodlund, M, et al. (författare) The Impact of Immunomodulating Treatment on the Immunogenicity of COVID-19 Vaccines in Patients with Immune-mediated Inflammatory Rheumatic Diseases Compared to Healthy Controls. a Swedish Nationwide Study (COVID19-REUMA) 2022 Ingår i: ARTHRITIS & RHEUMATOLOGY. - 2326-5191. ; 74, s. 1525-1527 Konferensbidrag (övrigt vetenskapligt/konstnärligt)
39.	Frodlund, M., et al. (författare) The impact of immunomodulating treatment on the serological immunogenicity following three doses of covid-19 vaccine and persistence of immunogenicity of two vaccine doses in patients with inflammatory rheumatic diseases - a swedish study (covid19-reuma) 2023 Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 82, s. 533-533 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract Background Data on serological immunity after three doses and the long-term immunogenicity (persistence) of COVID-19 vaccine in patients with inflammatory rheumatic diseases (IRD) treated with different immunomodulating drugs are still limited.Objectives To elucidate if 1) a third dose COVID-19 vaccine improves antibody responses, compared to two doses, in patients with IRD treated with biologic or targeted synthetic DMARD (b/tsDMARDs) treatment given as monotherapy or in combination with conventional synthetic DMARDs (csDMARDs) compared to controls, and 2) the persistence of antibody response after two doses of COVID-19 vaccine in IRD patients.Methods Antibody levels to two antigens representing Spike full length protein and Spike S1 and a Nucleocapsid C-terminal fragment (used to confirm previous COVID-19 infection) were measured in serum samples collected 2-12 and 21-40 weeks after the second vaccine dose and 2-12 weeks after the third dose using a multiplex bead-based serology assay. A sufficient antibody response (seropositivity) was defined as having antibodies over the cut-off level for both spike antigens (1). WT (wild type) anti-Spike IgG and omicron BA.1 and BA.2 variants were measured. Patients with IRD receiving immunomodulating treatment, regularly followed at a rheumatology department and a group of controls were recruited from five Swedish region.Results In total, 323 of 414 patients with IRD and 36 controls who received three vaccine doses participated in this part of the study. Following treatment groups were included: rituximab (n=118; 68% female; mean age 67 years), abatacept (n=18; 72% female; mean age 64 years), IL6r inhibitors (n=60; 73% female; mean age 64 years), JAK-inhibitors (n=44; 80% female, mean age 52 years), TNF-inhibitors (n=59; 70% female; mean age 47 years;), IL12/23/17 inhibitors (n=24; 46% female; mean age 54 years) and controls (n=36; 75% female, mean age 51 years). b/ts DMARD treatment was given as monotherapy or in combination with csDMARD, methotrexate (MTX) being the most frequently used csDMARD (32.5%). Compared to results after two vaccine doses, proportion (%) of seropositivity after three vaccine doses increased significantly in groups rituximab +/- DMARD (p=0.003 and p=0.004, respectively), IL6r inhibitors +DMARD (p=0.02), and abatacept+DMARD (p=0.01). However, the proportion of seropositivity after three vaccine doses was still significantly lower in rituximab treated patients (52%) compared to other treatment groups or controls (p<0.001) (Figure 1A/B). Antibody response to WT, omicron sBA.1 and sBA.2 showed similar pattern with the lowest levels among patients treated with rituximab.When antibody response was compared between 2-12 weeks and 21-40 weeks after second dose, the proportion of seropositive rituximab treated patients decreased from 34.9 % to 32.6%. All patients with JAK inhibitors and with JAK-inhibitors and IL6r-inhibitors seropositive 21-40 weeks after the second vaccine dose. Patients treated with other bDMARDs were not included in this analysis due to limited number participants.Conclusion In this Swedish study including IRD patients receiving different b/t DMARDs, a sufficient immunogenicity of the third dose of COVID-19 vaccine was observed in all treatments with exception for rituximab. However, the increased proportion of seropositivity after the third COVID-19 vaccine doses in rituximab and other patients with insufficient response to two doses including response to the omicron variants, supports the current recommendations on additional booster doses. The immunogenicity of two vaccine doses was preserved to 40 weeks in majority of patients treated with different immunomodulating treatment with exception for rituximab.
40.	Galindo-Feria, AS, et al. (författare) AN UNUSUAL INITIAL PRESENTATION OF VEXAS SYNDROME 2023 Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - 0003-4967. ; 82, s. 1164-1165 Konferensbidrag (övrigt vetenskapligt/konstnärligt)
41.	Gomez, A, et al. (författare) Use of Antimalarial Agents is Associated with Favourable Physical Functioning in Patients with Systemic Lupus Erythematosus 2020 Ingår i: Journal of clinical medicine. - : MDPI AG. - 2077-0383. ; 9:6 Tidskriftsartikel (refereegranskat)abstract Impaired health-related quality of life (HRQoL) is a major problem in patients with systemic lupus erythematosus (SLE). Antimalarial agents (AMA) are the cornerstone of SLE therapy, but data on their impact on HRQoL are scarce. We investigated this impact using baseline data from the BLISS-52 (NCT00424476) and BLISS-76 (NCT00410384) trials (n = 1684). HRQoL was self-reported using the Medical Outcomes Study short-form 36 (SF-36), functional assessment of chronic illness therapy (FACIT)-Fatigue and 3-level EuroQoL 5-Dimension (EQ-5D) questionnaires. Patients on AMA (n = 1098/1684) performed better with regard to SF-36 physical component summary, physical functioning, role physical, bodily pain, FACIT-Fatigue, EQ-5D utility index and EQ-5D visual analogue scale scores. The difference in SF-36 physical functioning (mean ± standard deviation (SD): 61.1 ± 24.9 versus 55.0 ± 26.5; p < 0.001) exceeded the minimal clinically important difference (≥5.0). This association remained significant after adjustment for potential confounding factors in linear regression models (standardised coefficient, β = 0.07; p = 0.002). Greater proportions of AMA users than non-users reported no problems in the mobility, self-care, usual activities and anxiety/depression EQ-5D dimensions. AMA use was particularly associated with favourable HRQoL in physical aspects among patients with active mucocutaneous and musculoskeletal disease, and mental aspects among patients with active renal SLE. These results provide support in motivating adherence to AMA therapy. Exploration of causality in the relationship between AMA use and favourable HRQoL in SLE has merit.
42.	Helgadottir, H, et al. (författare) [Overview of immune-related side effects from immune checkpoint inhibitors. Part 2: Endocrine, rheumatologic and skin toxicity] 2021 Ingår i: Lakartidningen. - 1652-7518. ; 118 Tidskriftsartikel (refereegranskat)
43.	Jani, M, et al. (författare) Comparative risk of infection for first line csDMARD therapy in rheumatoid arthritis: A multinational cohort analysis of real world data 2020 Ingår i: PHARMACOEPIDEMIOLOGY AND DRUG SAFETY. - 1053-8569. ; 29, s. 610-611 Konferensbidrag (övrigt vetenskapligt/konstnärligt)
44.	Jani, M, et al. (författare) COMPARATIVE RISK OF INFECTION FOR FIRST-LINE CSDMARD THERAPY IN RHEUMATOID ARTHRITIS: A MULTINATIONAL COHORT ANALYSIS OF REAL WORLD DATA 2022 Ingår i: RHEUMATOLOGY. - 1462-0324. ; 61, s. I72-I72 Konferensbidrag (övrigt vetenskapligt/konstnärligt)
45.	Jensen, AK, et al. (författare) Comparison of immune checkpoint inhibitor-induced arthritis and reactive arthritis to inform therapeutic strategy 2022 Ingår i: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. - : Elsevier BV. - 1950-6007. ; 148, s. 112687- Tidskriftsartikel (refereegranskat)
46.	Joshua, V, et al. (författare) Association between number and type of different ACPA fine specificities with lung abnormalities in early, untreated rheumatoid arthritis 2020 Ingår i: RMD open. - : BMJ. - 2056-5933. ; 6:2 Tidskriftsartikel (refereegranskat)abstract Rheumatoid arthritis (RA)-associated anticitrullinated protein/peptide antibodies (ACPA) might originate at mucosal sites such as the lungs. We aimed to examine the relationship between the ACPA repertoire and lung abnormalities on high-resolution CT (HRCT) in patients with earlyuntreated RA.Methods106 patients with newly diagnosed untreated RA were examined with HRCT of the lungs. Blood samples were analysed for presence of rheumatoid factor (RF) and ACPA using either a CCP2 detection kit or an immunochip containing 10 different citrullinated peptides. Association between HRCT findings and the antibody repertoire was assessed by logistic regression analysis.ResultsThe number (%) of patients with HRCT abnormalities was 58 (54.7%) for parenchymal abnormalities and 68 (64.2%) for airway abnormalities. CCP2 IgG, RF IgA and antibodies against citrullinated fibrinogen were associated with the presence of parenchymal lung abnormalities. Interestingly, a high number of ACPA fine specificities gave a high risk of having parenchymal lung abnormalities at the time of RA diagnosis. No significant signals were identified between ACPA specificities and risk for airway abnormalities.ConclusionsThe presence of RF and ACPAs (especially against citrullinated fibrinogen peptides) as well as high number of ACPAs fine specificities are associated with parenchymal lung abnormalities in patients with early, untreated RA. This provides further support for an important pathogenic link between the lung and systemic autoimmunity, contributing to RA development.
47.	Koutsianas, C, et al. (författare) The Rheumatologist's Role in the Battle Against COVID-19: Insights from the Front Line and Challenges for the Future 2020 Ingår i: Mediterranean journal of rheumatology. - : Convin SA. - 2529-198X. ; 31:Suppl 2, s. 247-252 Tidskriftsartikel (refereegranskat)
48.	Li, R, et al. (författare) Validation of new classification criteria of rheumatoid arthritis in an international multicentre study 2020 Ingår i: Clinical and experimental rheumatology. - 0392-856X. ; 38:5, s. 841-847 Tidskriftsartikel (refereegranskat)
49.	Liapi, M, et al. (författare) RISK FACTORS FOR DEVELOPING RHEUMATIC IMMUNE-RELATED ADVERSE EVENTS AFTER IMMUNOTHERAPY WITH IMMUNE CHECKPOINT INHIBITORS 2023 Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - 0003-4967. ; 82, s. 2053-2054 Konferensbidrag (övrigt vetenskapligt/konstnärligt)
50.	Liapi, M, et al. (författare) TREATMENT OF IMMUNE CHECKPOINT INHIBITOR-INDUCED INFLAMMATORY ARTHRITIS AND POLYMYALGIA RHEUMATICA 2022 Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 81, s. 1017-1017 Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract Therapy with immune check point inhibitors (ICIs) has revolutionized cancer treatment during the last years. Despite their high efficacy, ICIs are associated to a new spectrum of adverse events, the immune-related adverse events (irAEs). Inflammatory arthritis and polymyalgia rheumatica (PMR) are two of the most common rheumatic irAEs. The optimal management of irAEs remains unclear. Treatment guidelines largely support the use of glucocorticoids (GCs) as first line therapy [1]. Preclinical data raise concerns regarding the potential risk of impaired antitumoral effect with use of GCs. The high efficacy and potential synergistic effect (according to recent findings) [2] of targeted immunomodulation, such as interleukin 6 (IL-6) blockade, could support a paradigm shift, where targeted treatments are considered earlier in the treatment sequence.ObjectivesTo assess how frequently a disease modifying anti-rheumatic drug (DMARD) treatment in patients with ICI induced arthritis and/or PMR, after inadequate response to GCs, is initiated and to assess its effectiveness.MethodsWe retrospectively identified patients who were diagnosed with inflammatory arthritis and/or PMR at the rheumatology department at Karolinska University Hospital, after referral from the oncology department due to suspicion of a rheumatic irAE, between Jan 2020 and Dec 2021. Treatment response was defined as sustained low disease activity or remission according to the rheumatologist evaluation at 6 months (+/- 1 month) after initiation of DMARD.ResultsA total of 20 patients were identified, who were diagnosed with arthritis (N=11), PMR (N=6) or both (N=3). The median (IQR) age was 70 (46-76) years; 50% of patients were females. The type of cancer was urogenital (N=8), melanoma (N=6), lung cancer (N=2), and other (N=4). 14 patients received a PD-1 inhibitor (9 nivolumab, 4 pembrolizumab, 1 cemiplimab), 3 received a PDL-1 inhibitor (2 atezolizumab, 1 avelumab), 2 received a combination of nivolumab and the CTLA-4 inhibitor ipilimumab and one patient combination of nivolumab and pembrolizumab. The median time from start of ICI treatment to symptom debut was 2 (1.25-3.75) months.83% of patients with PMR and/or arthritis responded well to GCs without the need for treatment escalation. On the contrary,11 out of 14 patients (79%) with inflammatory arthritis (with or without PMR) responded inadequately to GC treatment, despite receiving moderate-high doses (median 20mg/day Prednisolone or equivalent), or flared when the dose was reduced below 10mg/day. A conventional synthetic DMARD was initiated in 7 patients (methotrexate N=6, hydroxychloroquine N=1), with a response rate of 71%. 3 patients received a biologic DMARD as first-line DMARD, either because of contraindication for methotrexate and/or high disease activity, and 2 patients after methotrexate failure. All 5 patients tocilizumab, with a response rate of 100%. Subsequently 1 of these patients discontinued tocilizumab due to suspected side effects, and started with a TNF inhibitor. After initiation of tocilizumab all patients were able to reduce the dose of GCs to less than 5mg/day.ConclusionThe majority of patients developing ICI-induced arthritis are refractory to GCs and need a DMARD treatment, although selection bias cannot be formally excluded, since the most severe forms of arthritis might be referred to the rheumatology department. csDMARDs are effective in a significant proportion of patients. Tocilizumab is highly effective and well tolerated in ICI-induced arthritis. ICI-induced PMR seems to respond adequately to GCs.References[1]Kostine M, et al. EULAR points to consider for the diagnosis and management of rheumatic immune-related adverse events due to cancer immunotherapy with checkpoint inhibitors. Annals of the Rheumatic Diseases 2021;80:36-48.[2]J.S. Weber, et al. Phase II trial of ipilimumab, nivolumab and tocilizumab for unresectable metastatic melanoma. Annals of Oncology (2021) 32 (suppl_5): S867-S905. 10.1016/annonc/annonc706Disclosure of InterestsMatina Liapi: None declared, Katerina Chatzidionysiou Consultant of: consultancy fees from Eli Lilly, AbbVie and Pfizer

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