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BACKGROUND/AIM: The purpose of this review is to provide an overview of the contraindications, special warnings, and boxed warnings with the aim to establish a framework to create a prescription safety checklist for a class of drugs or disease indication. This study covers biologic disease modifying antirheumatic drugs (bDMARDs) and targeted synthetic DMARDs (tsDMARDs). METHODS: We identified contraindications, boxed warnings, and special warnings provided by the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA). The study included b/tsDMARDs approved for treating rheumatoid arthritis (RA), psoriatic arthritis (PsA), axial spondyloarthritis (SpA), and juvenile idiopathic arthritis (JIA) within the drug-classes anti-CD20, tumor necrosis factor inhibitors (TNFi), interleukin-1 inhibitors (IL-1i), cytotoxic T-lymphocyte-associated protein (CTLA) 4, interleukin-12/23 inhibitors (IL-12/23i), interleukin 6 receptor inhibitors (IL-6Ri), Janus kinase inhibitors (JAKi), phosphodiesterase 4 inhibitors (PDE4i), interleukin-17 inhibitors (IL-17i), and interleukin-23 inhibitors (IL-23i). RESULTS: All drug classes, except PDE4i, had contraindications and/or warnings related to infections, including tuberculosis. A warning about herpes zoster was listed for anti-CD20, IL-1i, IL-6Ri, and JAKi, while a warning about hepatitis reactivation was listed for anti-CD20, TNFi, IL-1i, CTLA4-Ig, IL-6Ri, and JAKi. Malignancy risk was mentioned for all drug classes except PDE4i, IL-17i, and IL-23i. Other warnings included demyelinating disease (TNFi, CTLA4-Ig, and IL-6Ri), heart failure (anti-CD20 and TNFi), major adverse cardiac events (JAKi and IL-12/23) and venous thromboembolism (JAKi), hyperlipidemia (IL-6Ri and JAKi), liver impairment (TNFi, IL-1i, IL-6Ri, and JAKi), kidney impairment (IL-1i, JAKi, and PDE4i), inflammatory bowel disease (IL-17i), gastrointestinal perforation (IL-6Ri, JAKi), cytopenia (anti-CD20, TNFi, IL-1i, IL-6Ri, JAKi), and depression (PDE4i). Contraindications and warnings appeared to increase with the passage of time since the drug's approval. CONCLUSION: This review provides an overview to establish the framework to create an easily accessible and actionable prescription safety checklist from individual medical product prescription information provided by regulatory medical authorities.
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OBJECTIVE: European Alliance of Associations for Rheumatology (EULAR) task forces (TF) requires participation of ≥2 junior members, a health professional in rheumatology (HPR) and two patient research partners for the development of recommendations or points to consider. In this study, participation of these junior and representative members was compared with the one of traditional TF members (convenor, methodologist, fellow and expert TF members). METHODS: An online survey was developed and emailed to previous EULAR TF members. The survey comprised multiple-choice, open-ended and 0-100 rating scale (fully disagree to fully agree) questions. RESULTS: In total, 77 responded, 48 (62%) women. In total, 46 (60%) had participated as a junior or representative TF member. Most junior/representative members reported they felt unprepared for their first TF (10/14, 71%). Compared with traditional members, junior/representative members expressed a significantly higher level of uncertainty about their roles within the TF (median score 23 (IQR 7.0-52.0) vs 7 (IQR 0.0-21.0)), and junior/representative members felt less engaged by the convenor (54% vs 71%). Primary factors that facilitated interaction within a TF were experience, expertise and preparation (54%), a supportive atmosphere (42%) and a clear role (12%). CONCLUSION: Juniors, patients and HPR experience various challenges when participating in a EULAR TF. These challenges differ from and are generally less pronounced than those experienced by traditional TF members. The convenor should introduce the participants to the tasks, emphasise the value of their contributions and how to prepare accordingly for the TF meeting.
Subject(s)
Advisory Committees , Health Personnel , Rheumatology , Humans , Female , Surveys and Questionnaires , Male , Health Personnel/psychology , Adult , Europe , Middle AgedABSTRACT
OBJECTIVE: To develop an automatic gout register from electronic health records (EHRs) data. METHODS: We analysed the EHR of all patients >18 years old from a tertiary academic hospital (2013-2022) based on six criteria: International Classification of Diseases 10 gout diagnosis, urate-lowering therapy prescription, monosodium urate crystals in joint aspiration and gout-related terms in problem lists, clinical or imaging reports. We assessed the positive and negative predictive value (PPV and NPV) of the query by chart reviews. RESULTS: Of 2 110 902 outpatients and inpatients, 10 289 had at least one criterion for gout. The combination of joint aspiration OR diagnostic in the problem list OR≥2 other criteria created a register of 5138 patients, with a PPV of 92.4% (95% CI 88.5% to 95.0%) and an NPV of 94.3% (95% CI 91.9% to 96.0%). PPV and NPV were similar among outpatients and inpatients. Incidence was 2.9 per 1000 person-year and dropped by 30% from the COVID-19 pandemic onward. Patients with gout were on average 71.2 years old (SD 14.9), mainly male (76.5%), overweight (69.5%) and polymorbid (mean number of comorbidities of 3, IQR 1-5). More than half (57.4%) had received a urate-lowering treatment, 6.7% had a gout that led to a hospitalisation or ≥2 flares within a year and 32.9% received a rheumatology consultation. CONCLUSION: An automatic EHR-based gout register is feasible, valid and could be used to evaluate and improve gout management. Interestingly, the register uncovered a marked underdiagnosis or under-reporting of gout since the COVID-19 pandemic.
Subject(s)
COVID-19 , Electronic Health Records , Gout , Registries , Humans , Gout/epidemiology , Gout/diagnosis , Gout/drug therapy , Male , Female , Aged , Middle Aged , COVID-19/epidemiology , Aged, 80 and over , SARS-CoV-2ABSTRACT
OBJECTIVES: This observational study compares the effectiveness of baricitinib (BARI), a targeted synthetic disease-modifying antirheumatic drug (tsDMARD), with alternative biological DMARDs (bDMARDs) in patients with rheumatoid arthritis (RA), from a prospective, longitudinal cohort. METHODS: We compared patients initiating a treatment course (TC) of BARI, tumour necrosis factor inhibitors (TNFi) or bDMARDs with other modes of action (OMA), during a period when all these DMARDs were available in Switzerland. The primary outcome was drug maintenance; secondary outcomes included discontinuation rates related specifically to ineffectiveness and adverse events. We further analysed rates of low disease activity (LDA) and remission (REM) at 12 months and drug maintenance in bDMARD-naïve and tsDMARD-naïve population. RESULTS: A total of 1053 TCs were included: 273 on BARI, 473 on TNFi and 307 on OMA. BARI was prescribed to older patients with longer disease duration and more previous treatment failures than TNFi. Compared with BARI, the adjusted drug maintenance was significantly shorter for TNFi (HR for discontinuation: 1.76; 95% CI, 1.32 to 2.35) but not compared with OMA (HR 1.27; 95% CI, 0.93 to 1.72). These results were similar in the b/tsDMARD-naïve population. The higher discontinuation of TNFi was mostly due to increased discontinuation for ineffectiveness (HR 1.49; 95% CI, 1.03 to 2.15), with no significant differences in drug discontinuation for adverse events (HR 1.46; 95% CI, 0.83 to 2.57). The LDA and REM rates at 12 months did not differ significantly between the three groups. CONCLUSIONS: BARI demonstrated a significantly higher drug maintenance compared with TNFi, mainly due to lower drug discontinuations for ineffectiveness. We found no difference in drug maintenance between BARI and OMA. Clinical outcomes did not differ between the three groups. Our results suggest that BARI is an appropriate therapeutic alternative to bDMARDs in the management of RA.
Subject(s)
Antirheumatic Agents , Arthritis, Rheumatoid , Azetidines , Biological Products , Purines , Pyrazoles , Sulfonamides , Humans , Cohort Studies , Prospective Studies , Switzerland , Antirheumatic Agents/therapeutic use , Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/chemically induced , Biological Products/therapeutic use , Treatment OutcomeABSTRACT
Musculoskeletal diseases, on the rise, pose a major challenge in French-speaking Switzerland where the shortage of rheumatologists is worsening, due to the aging of practitioners, a scarcity of emerging professionals, and a trend towards part-time work among young doctors. To address this, increasing rheumatology training positions and enhancing general practitioners' training in these pathologies are essential. The adoption of alternative care models, such as monitoring by specialized nurses and greater involvement of physiotherapists, should be considered. This evolution is crucial for patients, whose quality of life and health depend on the accessibility and effectiveness of adequate care. Therefore, concerted action is indispensable to ensure a sustainable and effective future for rheumatology in French-speaking Switzerland.
Les maladies musculosquelettiques, en augmentation, posent un défi majeur en Romandie, où la pénurie de rhumatologues s'aggrave en raison du vieillissement des praticiens, du manque de relève et de la tendance au travail partiel chez les jeunes médecins. Pour y faire face, augmenter les postes de formation en rhumatologie et renforcer la formation des généralistes dans les pathologies concernées est essentiel. L'adoption de modèles de soins alternatifs, comme le suivi par des infirmiers spécialisés, et une plus grande implication des physiothérapeutes sont à envisager. Cette évolution est cruciale pour les patients, dont la qualité de vie et la santé dépendent de l'efficacité et de l'accessibilité à des soins adéquats. Une action concertée est donc indispensable pour assurer un avenir durable et efficace de la rhumatologie en Romandie.
Subject(s)
Musculoskeletal Diseases , Rheumatology , Humans , Quality of Life , Rheumatologists , Musculoskeletal Diseases/epidemiology , Musculoskeletal Diseases/therapy , ForecastingABSTRACT
In rheumatology, this year has been characterized by a broader knowledge of the pathogenesis of rheumatoid arthritis and mechanisms involved in the onset and persistence of low back pain. Studies relevant to the management of of gout, axial spondyloarthritis, autoinflammatory diseases and systemic vasculitides were published. New data on the safety of JAK inhibitors have been published. The ASAS-EULAR recommendations for the treatment of axial spondyloarthritis were updated, and the 2023 EULAR/PReS guidelines for the diagnosis and treatment of systemic juvenile idiopathic arthritis and adult-onset Still's disease are now available. New molecules and different glucocorticoid sparing strategies were introduced for giant cell arteritis.
En 2023, en rhumatologie, une avancée des connaissances sur la pathogenèse de la polyarthrite rhumatoïde et des mécanismes impliqués dans l'apparition et la persistance des lombalgies a été notée. Des études relevantes pour le traitement de la goutte, de la spondylarthrite axiale, des maladies auto-inflammatoires et des vascularites systémiques ont été publiées. De nouvelles données concernant la sécurité des inhibiteurs de Janus kinase sont disponibles. Les directives ASAS-EULAR pour le traitement de la spondylarthrite axiale ont été actualisées et les recommandations EULAR/PReS 2023 pour le diagnostic et le traitement de l'arthrite juvénile idiopathique systémique et de la maladie de Still de l'adulte sont désormais disponibles. De nouvelles molécules et différentes stratégies d'épargne des glucocorticoïdes ont été proposées pour l'artérite à cellules géantes.
Subject(s)
Arthritis, Juvenile , Arthritis, Rheumatoid , Axial Spondyloarthritis , Giant Cell Arteritis , Rheumatology , Adult , Humans , Giant Cell Arteritis/diagnosis , Giant Cell Arteritis/therapyABSTRACT
OBJECTIVE: To evaluate and compare the use of oral glucocorticoids with three classes of bDMARDs in patients with rheumatoid arthritis (RA). METHODS: We included patients from 13 observational registries treated with a TNF-inhibitor, abatacept or tocilizumab and with available information on the use of oral glucocorticoids. The main outcome was oral glucocorticoid withdrawal. A McNemar test was used to analyse the change in the use of glucocorticoids after 1 year. Kaplan-Meier estimates and Cox regressions, adjusted for patient, treatment, and disease characteristics, were used to evaluate glucocorticoid discontinuation in patients with glucocorticoids at baseline. Because of heterogeneity, analyses were done by registers and pooled using random-effects meta-analysis. RESULTS: A total of 12,334 participants treated with TNF-inhibitors, 2100 with tocilizumab and 3229 with abatacept were included. At one-year, oral glucocorticoid use decreased in all treatment groups (odds ratio for stopping vs. starting of 2.19 [95% CI 1.58; 3.04] for TNF-inhibitors, 2.46 [1.39; 4.35] for tocilizumab; 1.73 [1.25; 2.21] for abatacept). Median time to glucocorticoid withdrawal was ≈2 years or more in most countries, with a gradual decrease over time. Compared to TNF-inhibitors, crude hazard ratios of glucocorticoid discontinuation were 0.65[0.48-0.87] for abatacept, and 1.04 [0.76-1.43] for tocilizumab, and adjusted hazard ratios were 1.1 [0.83-1.47] for abatacept, and 1.30 [0.96-1.78] for tocilizumab. CONCLUSION: After initiation of a bDMARD, glucocorticoid use decreased similarly in all treatment groups. However, glucocorticoid withdrawal was much slower than advocated by current international guidelines. More effort should be devoted to glucocorticoid tapering when low disease activity is achieved.
Subject(s)
Antibodies, Monoclonal, Humanized , Antirheumatic Agents , Arthritis, Rheumatoid , Humans , Abatacept/adverse effects , Glucocorticoids/adverse effects , Antirheumatic Agents/adverse effects , Tumor Necrosis Factor Inhibitors/therapeutic use , Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/chemically inducedABSTRACT
BACKGROUND: In a clinical trial setting, patients with rheumatoid arthritis (RA) taking the Janus kinase inhibitor (JAKi) tofacitinib demonstrated higher adverse events rates compared with those taking the tumour necrosis factor inhibitors (TNFi) adalimumab or etanercept. OBJECTIVE: Compare treatment discontinuations for adverse events (AEs) among second-line therapies in an international real-world RA population. METHODS: Patients initiating JAKi, TNFi or a biological with another mode of action (OMA) from 17 registers participating in the 'JAK-pot' collaboration were included. The primary outcome was the rate of treatment discontinuation due to AEs. We used unadjusted and adjusted cause-specific Cox proportional hazard models to compare treatment discontinuations for AEs among treatment groups by class, but also evaluating separately the specific type of JAKi. RESULTS: Of the 46 913 treatment courses included, 12 523 were JAKi (43% baricitinib, 40% tofacitinib, 15% upadacitinib, 2% filgotinib), 23 391 TNFi and 10 999 OMA. The adjusted cause-specific hazard rate of treatment discontinuation for AEs was similar for TNFi versus JAKi (1.00, 95% CI 0.92 to 1.10) and higher for OMA versus JAKi (1.11, 95% CI 1.01 to 1.23), lower with TNFi compared with tofacitinib (0.81, 95% CI 0.71 to 0.90), but higher for TNFi versus baricitinib (1.15, 95% CI 1.01 to 1.30) and lower for TNFi versus JAKi in patients 65 or older with at least one cardiovascular risk factor (0.79, 95% CI 0.65 to 0.97). CONCLUSION: While JAKi overall were not associated with more treatment discontinuations for AEs, subgroup analyses suggest varying patterns with specific JAKi, such as tofacitinib, compared with TNFi. However, these observations should be interpreted cautiously, given the observational study design.
Subject(s)
Antirheumatic Agents , Arthritis, Rheumatoid , Azetidines , Janus Kinase Inhibitors , Purines , Pyrazoles , Sulfonamides , Humans , Antirheumatic Agents/therapeutic use , Janus Kinase Inhibitors/therapeutic use , Treatment Outcome , Tumor Necrosis Factor-alpha , Arthritis, Rheumatoid/drug therapy , Tumor Necrosis Factor Inhibitors/therapeutic useABSTRACT
OBJECTIVES: To assess the relationship between self-reported and serologic evidence of prior chlamydial infection, rheumatoid arthritis (RA)-related autoantibodies and risk of RA-development. METHODS: This is a nested study within a prospective Swiss-based cohort including all first-degree relatives of RA patients (RA-FDR) who answered a question on past chlamydial infections. Primary outcome was systemic autoimmunity associated with RA (RA-autoimmunity) defined as positivity for anti-citrullinated peptide antibodies (ACPA) and/or rheumatoid factor (RF). Secondary outcomes were high levels of RA-autoimmunity, RA-associated symptoms and RA-autoimmunity, and subsequent seropositive RA diagnosis. We conducted a nested case-control analysis by measuring the serological status against Chlamydia trachomatis' major outer membrane protein. We replicated our analysis in an independent United States-based RA-FDR cohort. RESULTS: Among 1231 RA-FDRs, 168 (13.6%) developed RA-autoimmunity. Prevalence of self-reported chlamydial infection was significantly higher in individuals with RA-autoimmunity compared with controls (17.9% vs 9.8%, OR = 2.00, 95%CI: 1.27-3.09, p < 0.01). This association remained significant after adjustments (OR = 1.91, 95%CI: 1.20-2.95). Stronger effect sizes were observed in later stages of RA development. There was a similar trend between a positive C. trachomatis serology and high levels of RA-autoimmunity (OR = 3.05, 95% CI: 1.10-8.46, p= 0.032). In the replication cohort, there were significant associations between chlamydial infection and RF positivity and incident RA, but not anti-CCP positivity. CONCLUSIONS: Self-reported chlamydial infections are associated with elevated RA-autoimmunity in at risk individuals. The differing association of chlamydial infections and ACPA/RF between cohorts will need to be explored in future studies but is consistent with a role of mucosal origin of RA-related autoimmunity.
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To develop EULAR recommendations for screening and prophylaxis of chronic and opportunistic infections in patients with autoimmune inflammatory rheumatic diseases (AIIRD). An international Task Force (TF) (22 members/15 countries) formulated recommendations, supported by systematic literature review findings. Level of evidence and grade of recommendation were assigned for each recommendation. Level of agreement was provided anonymously by each TF member. Four overarching principles (OAP) and eight recommendations were developed. The OAPs highlight the need for infections to be discussed with patients and with other medical specialties, in accordance with national regulations. In addition to biologic/ targeted synthetic disease-modifying antirheumatic drugs (DMARDs) for which screening for latent tuberculosis (TB) should be performed, screening could be considered also before conventional synthetic DMARDs, glucocorticoids and immunosuppressants. Interferon gamma release assay should be preferred over tuberculin skin test, where available. Hepatitis B (HBV) antiviral treatment should be guided by HBV status defined prior to starting antirheumatic drugs. All patients positive for hepatitis-C-RNA should be referred for antiviral treatment. Also, patients who are non-immune to varicella zoster virus should be informed about the availability of postexposure prophylaxis should they have contact with this pathogen. Prophylaxis against Pneumocystis jirovecii seems to be beneficial in patients treated with daily doses >1530mg of prednisolone or equivalent for >24 weeks. These recommendations provide guidance on the screening and prevention of chronic and opportunistic infections. Their adoption in clinical practice is recommended to standardise and optimise care to reduce the burden of opportunistic infections in people living with AIIRD.
Subject(s)
Humans , Autoimmune Diseases/complications , Opportunistic Infections/etiology , Rheumatic Diseases/complications , Triage/standards , Disease Prevention , Antiviral Agents/therapeutic use , Tuberculosis/prevention & control , Hepatitis C/prevention & control , Herpesvirus 3, Human , Pneumocystis carinii/immunology , Post-Exposure Prophylaxis , Hepatitis B/prevention & controlABSTRACT
Gout is a common complication occurring among inpatients, as factors affecting urate levels in blood and tissues are often modified by acute conditions. The control of chronic uricemia within recommended target values helps reduce the risk of flares. Joint aspiration is the gold standard for diagnosis, but ultrasound and dual-energy CT scan are reasonable alternatives. Acute and chronic treatments do not differ from those provided in outpatient care, although the increased prevalence of organ failures often require treatment adjustments. Active patient engagement, including therapeutic education during hospitalization, is essential for long-term disease control.
Lors d'un séjour hospitalier, les facteurs impactant la concentration sanguine et tissulaire d'urate sont souvent modifiés, augmentant le risque d'une crise de goutte. Le maintien de l'uricémie dans les cibles reconnues grâce à la poursuite des traitements contribue à réduire ce risque. La ponction articulaire est la méthode de référence pour établir le diagnostic, mais l'ultrason et le scanner à double énergie sont des alternatives fiables pour diagnostiquer une goutte. Les traitements aigu et chronique ne diffèrent pas de ceux pratiqués en ambulatoire, mais la fréquence augmentée d'insuffisances d'organes peut nécessiter l'adaptation des traitements. Pour assurer un contrôle de la maladie sur le long terme, il est essentiel d'impliquer le patient dans sa prise en charge, notamment par l'éducation thérapeutique dispensée pendant l'hospitalisation.
Subject(s)
Gout , Inpatients , Humans , Gout/diagnosis , Gout/therapy , Ambulatory Care , Hospitalization , Patient ParticipationABSTRACT
OBJECTIVES: Treatment response is worse in obese patients with rheumatoid arthritis (RA), including patients on weight-adjusted therapies like infliximab. We aimed to assess the association between body mass index (BMI) and changes in RA disease activity and radiographic progression over time. METHODS: We included infliximab users with an RA diagnosis in the Swiss Clinical Quality Management in Rheumatic Diseases registry (1997-2020). Two cohorts were defined: (1) starting from their first BMI measurement or disease activity score (DAS28-esr), and (2) from their first BMI measurement or radiographic assessment (Rau score). We evaluated the coefficient and 95% CI of BMI with changes in mean DAS28-esr (cohort 1) and mean Rau scores (a structural joint damage score, cohort 2) using generalised estimation equations, overall and stratified by BMI categories. RESULTS: Cohort 1 comprised 412 patients (74% women, mean age 53 years, mean BMI 25). We observed no change in mean DAS28-esr with increasing BMI overall (adjusted coefficient: 0.00, 95% CI -0.02 to 0.02), or in BMI categories. Cohort 2 comprised 187 patients highly alike to those in cohort 1. We observed a significant decrease of 1.05 in mean Rau scores for every increase in BMI unit (adjusted coefficient: -1.05, 95% CI -1.92 to -0.19). Results remained statistically non-significant across BMI categories. CONCLUSIONS: Our longitudinal investigation suggests that BMI increase may not lead to changes in DAS28-esr in patients receiving infliximab, despite the weight-adapted dose. Yet, there may be a decrease in erosions with increasing weight non-limited to obese patients.
Subject(s)
Antirheumatic Agents , Arthritis, Rheumatoid , Humans , Female , Middle Aged , Male , Infliximab/therapeutic use , Body Mass Index , Antirheumatic Agents/therapeutic use , Arthritis, Rheumatoid/complications , Arthritis, Rheumatoid/diagnostic imaging , Arthritis, Rheumatoid/drug therapy , Obesity/complicationsABSTRACT
OBJECTIVES: This study aimed to evaluate if and how the incidence of serious infection (SI) and active tuberculosis (TB) differ among seven biological disease-modifying antirheumatic drugs (bDMARDs) in patients with rheumatoid arthritis (RA) considering the line of therapy. METHODS: Patients with RA from the British Society for Rheumatology Biologics Register-RA cohort who initiated etanercept, certolizumab, infliximab, adalimumab, abatacept, rituximab, or tocilizumab from the first to fifth line of therapy were included. Follow-up extended up to three years. Primary outcome was SI, secondary outcome was TB. Event rates were calculated and compared using Cox proportional-hazards, controlling for confounding with inverse probability of treatment weights. Comparisons were made overall and stratified by line of therapy. Sensitivity analysis restricted to all treatment courses from 2009 (tocilizumab availability) until end of study (2018). RESULTS: Among 33 897 treatment courses (62 513 patient-years) the incidence of SI was 4.4/100 patient-years (95%CI 4.2-4.5). After adjustment, hazards ratios (HR) of SI were slightly higher with adalimumab and infliximab compared with etanercept. However, no clear pattern was observed when stratifying by line of therapy, in terms of incidence rate or hazards ratio. Sensitivity analyses showed similar HR among these treatments. Regarding TB, all 49 cases occurred during the first three lines of treatment and rarely since 2009. CONCLUSION: The risk of serious infections does not appear to be influenced by the line of therapy in patients with RA. However, the risk of tuberculosis seems to be more frequent during the initial lines of treatment or prior to 2009.
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Objectives: To investigate the association between severe acute respiratory syndrome-associated coronavirus-2 (SARS-CoV-2) infection and subsequent development of autoimmunity or pre-clinical manifestations associated with rheumatoid arthritis (RA) in at risk population. Methods: This is a nested study within a prospective cohort of first-degree relatives of RA patients (RA-FDR). Participants are tested for RA-associated autoantibodies (anti-citrullinated peptide antibodies (ACPA)/rheumatoid factor (RF)) and clinical signs and symptoms suggestive of early disease. SARS-CoV-2 infections were self-reported between March 2020 and January 2023. All individuals with a pre-pandemic (sample 1) and a post-pandemic sample (sample 2) were included in the analysis. The exposure of interest was self-reported SARS-CoV-2 infection. The primary outcome was a clinically significant change in RA-associated autoantibody serum titers. Secondary outcomes included: becoming seropositive, becoming symptomatic, developing classifiable RA. Results: Among 168 RA-FDRs, 109 reported a SARS-CoV-2 infection between sample 1 and sample 2. During this period, 2 RA-FDRs (1.2%) became anti-CCP2 seropositive, none became anti-CCP3 IgG positive, 6 (3.6%) became RF IgM seropositive, 1 became (0.6%) RF IgA seropositive, 19 (11.3%) became symptomatic and none developed classifiable RA. SARS-CoV-2 infection was not significantly associated with increases in RA autoantibody titers or with secondary outcomes. Conclusion: We could not detect an association between SARS-CoV-2 infection and subsequent development of RA-associated autoimmunity, nor signs or symptoms of RA in an at risk population. These findings do not support the hypothesis that SARS-CoV-2 infections triggers the immune onset of RA.
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Rheumatoid arthritis (RA) is a common chronic autoimmune inflammatory disease, primarily affecting the joints. Its activity is subject to exacerbations called flares. These RA flares are linked to cardiovascular, functional and radiological complications. The mechanisms behind these flares are still poorly understood. There is currently no reliable biomarker for the diagnosis of the flares. Diagnostic scores have been developed for research purposes but their application in clinical practice is not yet clear. The therapeutic approach includes acute treatment of the flare with corticosteroids and evaluation of the need for intensification of background therapy.
La polyarthrite rhumatoïde (PR) est une maladie inflammatoire chronique auto-immune fréquente, touchant principalement les articulations, dont l'activité peut être sujette à des exacerbations appelées « poussées ¼. Ces dernières sont liées à des complications cardiovasculaires, fonctionnelles et radiologiques. Les mécanismes à l'origine de ces poussées sont encore mal compris. Il n'existe pas à l'heure actuelle de biomarqueur fiable permettant de diagnostiquer les poussées. Des scores à but diagnostic ont été développés pour la recherche, mais leur application en clinique n'est pas encore claire. L'attitude thérapeutique comprend un traitement aigu de la poussée par une corticothérapie ainsi qu'une évaluation systématique de l'indication à une intensification du traitement de fond.
Subject(s)
Arthritis, Rheumatoid , Humans , Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/diagnostic imaging , RadiographyABSTRACT
In rheumatology, this year has seen an expansion of knowledge about the treatment of rheumatoid arthritis, with the availability of results from randomized trials evaluating a new molecule targeting IL-6, and regarding the safety profile of tofacitinib compared to TNF-alpha inhibitors. Interesting data on the outcome of pregnancy in patients with spondylarthritis have also been published. New molecules and different treatment strategies have shown promising results in psoriatic arthritis and systemic lupus erythematosus. The utility of botulinum toxin A injections for Raynaud's phenomenon and the efficacy of transplantation of autologous adipose-derived regenerative cells for the treatment of hand dysfunctions have been questioned by 2 randomized controlled trials of patients with systemic sclerosis.
Cette année a vu un approfondissement des connaissances sur le traitement de la polyarthrite rhumatoïde, avec la publication de résultats d'essais randomisés évaluant une nouvelle molécule ciblant l'IL-6 et le profil de sécurité du tofacitinib par rapport aux inhibiteurs du TNF-alpha. Des données intéressantes sur l'issue de la grossesse chez les patientes atteintes de spondylarthrite ont également été publiées. De nouvelles stratégies de traitement ont donné des résultats prometteurs dans le rhumatisme psoriasique et le lupus érythémateux systémique. L'utilité des injections de toxine botulique A pour le phénomène de Raynaud et l'efficacité de la transplantation de cellules régénératrices adipeuses autologues pour le traitement de dysfonctions de la main ont été remises en question par deux études dans la sclérose systémique.
Subject(s)
Arthritis, Rheumatoid , Botulinum Toxins, Type A , Lupus Erythematosus, Systemic , Rheumatology , Scleroderma, Systemic , Humans , Arthritis, Rheumatoid/drug therapy , Scleroderma, Systemic/therapyABSTRACT
OBJECTIVES: The expanded therapeutic arsenal in rheumatoid arthritis (RA) raises new clinical questions. The objective of this study is to compare the effectiveness of cycling Janus kinase inhibitors (JAKi) with switching to biologic disease-modifying antirheumatic drug (bDMARD) in patients with RA after failure to the first JAKi. METHODS: This is a nested cohort study within data pooled from an international collaboration of 17 national registries (JAK-pot collaboration). Data from patients with RA with JAKi treatment failure and who were subsequently treated with either a second JAKi or with a bDMARD were prospectively collected. Differences in drug retention rates after second treatment initiation were assessed by log-rank test and Cox regression analysis adjusting for potential confounders. Change in Clinical Disease Activity Index (CDAI) over time was estimated using a linear regression model, adjusting for confounders. RESULTS: 365 cycling and 1635 switching patients were studied. Cyclers were older and received a higher number of previous bDMARDs. Both strategies showed similar observed retention rates after 2 years of follow-up. However, adjusted analysis revealed that cycling was associated with higher retention (p=0.04). Among cyclers, when the first JAKi was discontinued due to an adverse event (AE), it was more likely that the second JAKi would also be stopped due to an AE. Improvement in CDAI over time was similar in both strategies. CONCLUSIONS: After failing the first JAKi, cycling JAKi and switching to a bDMARD appear to have similar effectiveness. Caution is advised if an AE was the reason to stop the first JAKi.
Subject(s)
Antirheumatic Agents , Arthritis, Rheumatoid , Janus Kinase Inhibitors , Humans , Janus Kinase Inhibitors/therapeutic use , Cohort Studies , Antirheumatic Agents/therapeutic use , Arthritis, Rheumatoid/drug therapy , RegistriesABSTRACT
OBJECTIVES: To develop EULAR recommendations for screening and prophylaxis of chronic and opportunistic infections in patients with autoimmune inflammatory rheumatic diseases (AIIRD). METHODS: An international Task Force (TF) (22 members/15 countries) formulated recommendations, supported by systematic literature review findings. Level of evidence and grade of recommendation were assigned for each recommendation. Level of agreement was provided anonymously by each TF member. RESULTS: Four overarching principles (OAP) and eight recommendations were developed. The OAPs highlight the need for infections to be discussed with patients and with other medical specialties, in accordance with national regulations. In addition to biologic/targeted synthetic disease-modifying antirheumatic drugs (DMARDs) for which screening for latent tuberculosis (TB) should be performed, screening could be considered also before conventional synthetic DMARDs, glucocorticoids and immunosuppressants. Interferon gamma release assay should be preferred over tuberculin skin test, where available. Hepatitis B (HBV) antiviral treatment should be guided by HBV status defined prior to starting antirheumatic drugs. All patients positive for hepatitis-C-RNA should be referred for antiviral treatment. Also, patients who are non-immune to varicella zoster virus should be informed about the availability of postexposure prophylaxis should they have contact with this pathogen. Prophylaxis against Pneumocystis jirovecii seems to be beneficial in patients treated with daily doses >15-30 mg of prednisolone or equivalent for >2-4 weeks. CONCLUSIONS: These recommendations provide guidance on the screening and prevention of chronic and opportunistic infections. Their adoption in clinical practice is recommended to standardise and optimise care to reduce the burden of opportunistic infections in people living with AIIRD.
Subject(s)
Antirheumatic Agents , Opportunistic Infections , Rheumatic Diseases , Humans , Adult , Antirheumatic Agents/therapeutic use , Immunosuppressive Agents/therapeutic use , Opportunistic Infections/diagnosis , Opportunistic Infections/prevention & control , Rheumatic Diseases/complications , Rheumatic Diseases/drug therapy , Antiviral Agents/therapeutic useABSTRACT
OBJECTIVES: To provide an update of the EULAR rheumatoid arthritis (RA) management recommendations addressing the most recent developments in the field. METHODS: An 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. RESULTS: The 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. CONCLUSIONS: These updated EULAR recommendations provide consensus on RA management including safety, effectiveness and cost.