Rheumatology and Therapy最新文献

A Bayesian network meta-analysis was conducted to examine the radiographic and clinical efficacy of the Janus kinase (JAK) inhibitors tofacitinib, baricitinib, upadacitinib, and filgotinib and the biologic disease-modifying antirheumatic drug (bDMARD) adalimumab (all given with methotrexate [MTX]) in patients with rheumatoid arthritis (RA) and an inadequate response to MTX (MTX-IR). The PubMed database was systematically searched to identify relevant randomized controlled trials. Efficacy outcomes included the modified total Sharp score (mTSS), erosion, joint space narrowing, 70% improvement in American College of Rheumatology criteria (ACR70), Boolean remission, Clinical Disease Activity Index (CDAI) score ≤ 2.8, and Simplified Disease Activity Index (SDAI) score ≤ 3.3. Five studies were identified using the inclusion criteria, and two additional publications presented further results from one of the five studies, with the total meta-analysis population comprising 6933 patients. Among all JAK inhibitors analyzed and the bDMARD adalimumab, filgotinib 200 mg had the highest probability of being the treatment with the greatest improvement in mTSS versus placebo at 48/52 weeks, followed by filgotinib 100 mg, adalimumab 40 mg, baricitinib 4 mg, and upadacitinib 15 mg. Filgotinib 200 mg also had the highest probability of being the treatment with the greatest improvement in erosion and joint space narrowing at 48/52 weeks versus the same comparators. At 12 weeks, filgotinib 200 mg had the highest probability versus other JAK inhibitors and adalimumab of achieving clinical remission (CDAI ≤ 2.8 and SDAI ≤ 3.3). Varying treatments had the highest probability of achieving other efficacy outcomes of interest at 12, 24/26, and 48/52 weeks. In the absence of head-to-head comparisons, this analysis provides valuable evidence for the role of filgotinib in the treatment of patients with MTX-IR RA.

Introduction: Psoriatic arthritis (PsA) is a complex inflammatory disease often associated with metabolic syndrome (MetS). It has been demonstrated that pain catastrophizing (PC), characterized by an exaggerated negative cognitive and emotional response to actual or anticipated pain, impacts the achievement of remission and therapy discontinuation in patients with PsA. In this study, we evaluate the potential role of MetS, the most prevalent comorbidity in PsA, in influencing PC in patients with PsA.

Methods: We conducted a cross-sectional, observational study on 170 patients with PsA who met the Classification Criteria for PsA and MetS criteria. Data on disease activity, PC, and comorbidities were collected and analyzed using univariable and multivariable regressions.

Results: Our results indicate a significant association between MetS and elevated PC levels in patients with PsA. Univariable analysis identified female gender, fibromyalgia, and higher Disease Activity for Psoriatic Arthritis (DAPSA) scores as factors associated with increased PC. Multivariable analysis, adjusted for age, sex, fibromyalgia, and DAPSA, confirmed that MetS independently correlates with higher PC levels (b = 8.84, 95% CI 4.66-13.02, p < 0.0001) and its domains (helplessness, rumination, magnification).

Conclusions: These findings suggest that MetS significantly impacts PC in PsA, underscoring the need for a multidisciplinary approach to patient management. This study highlights the importance of addressing MetS to reduce pain catastrophizing and enhance disease management in PsA.

Introduction: Long-term treatment of psoriatic arthritis (PsA) is required to prevent progression. However, persistence with current treatments is challenging due to tolerability and acceptability issues. The objective of this study was to estimate 1-year persistence with secukinumab in patients with PsA treated with secukinumab, to compare persistence rates between secukinumab and adalimumab, to estimate usefulness rates, and to document adverse events.

Methods: This retrospective study used data from the Japanese Medical Data Vision database. A total of 182 patients with PsA initiating secukinumab were identified between February 1, 2015 and September 30, 2020. Of these, 171 could be matched to 171 patients initiating adalimumab over the same period using a propensity score. Patients were followed until death, treatment discontinuation, or until the end of the study period. Persistence rates were analyzed using Kaplan-Meier survival analysis. Usefulness was evaluated using a published algorithm. Selected adverse events were documented.

Results: Twelve-month persistence with secukinumab was 68.3%. The median persistence duration was significantly higher (p = 0.002) for secukinumab (27.8 months) than for adalimumab (12.5 months). After 12 months, the treatment was found to be useful in 47.0% of the secukinumab cohort and 22.2% of the adalimumab cohort (p < 0.001). Fourteen patients (7.7%) in the unmatched secukinumab cohort and 32 (9.1%) in the unmatched adalimumab cohort presented an adverse event of interest.

Conclusions: Patients with PsA showed higher persistence with secukinumab than with adalimumab. Since PsA is a chronic disease that requires long-term treatment, long-term persistence and usefulness should be considered for the treatment choice. Infographic available for this article. INFOGRAPHIC.

Introduction: Glucocorticoids are commonly used to treat immunoglobulin G4-related disease (IgG4-RD), but there is limited real-world evidence describing glucocorticoid-related toxicities in this population. This study assessed glucocorticoid use and toxicities during the first year after diagnosis among patients with IgG4-RD.

Methods: The IQVIA PharMetrics® Plus database was used to identify adults with IgG4-RD using a validated algorithm. Patients were stratified according to glucocorticoid use during the 12-month study period following the first observed IgG4-RD-related diagnosis (index date): low glucocorticoid use (prednisone equivalent daily dose [PEDD] < 5 mg/day) or high glucocorticoid use (PEDD ≥ 5 mg/day). Incident glucocorticoid-related toxicities were assessed during the study period and incidence was compared between groups using Chi-square tests.

Results: Among 295 patients with IgG4-RD, 150 (50.8%) had low glucocorticoid use, and 145 (49.2%) had high glucocorticoid use during the study period. In each glucocorticoid group, mean PEDD was highest in the 3 months post-index and subsequently decreased. At 12 months post-index, 24.7% of the low glucocorticoid use group and 60.7% of the high glucocorticoid use group were receiving glucocorticoids. The high glucocorticoid use group had a significantly higher mean (± standard deviation) number of incident glucocorticoid-related toxicities (1.8 ± 1.7 vs. 1.2 ± 1.3) and more frequently had ≥ 3 glucocorticoid-related toxicities (29.0% vs. 13.3%; both p < 0.01) compared to the low glucocorticoid use group. Specifically, cardiovascular- (29.0% vs. 18.7%), gastrointestinal- (29.7% vs. 16.0%), and infection-related (31.0% vs. 17.3%) toxicities were significantly more common in the high glucocorticoid use group than the low glucocorticoid use group (all p < 0.05).

Conclusions: In this retrospective, claims-based analysis, high glucocorticoid use was seen in half of patients with IgG4-RD during the first year following diagnosis. Patients with high glucocorticoid use experienced significantly more incident glucocorticoid-related toxicities than those with low use during this first year.

As more lupus nephritis (LN) medications become available, identifying treatments that are disease-modifying is critical in making treatment decisions. Based on our 2022 published working definition of LN disease modification as 'minimizing disease activity with the fewest treatment-associated toxicities and slowing progression to end-stage kidney disease' (ESKD), the objective of this review was to classify current LN treatments according to the proposed kidney disease modification criteria, excluding toxicities. Based upon a selection of LN clinical trial (n = 27) and observational study (n = 20) publications, as well as the authors' clinical experiences, we evaluated the disease modification potential for 16 LN treatments (inclusive of antimalarials, glucocorticoids, immunosuppressants, calcineurin inhibitors and biologics) according to the proposed kidney disease activity and organ damage criteria at year 1, years 2-5, and > 5-year time points. Fulfilling criteria at year 1 and years 2-5 was considered evidence for disease modification potential. Satisfying criteria at > 5 years (slowing or preventing progression in SLICC/ACR Damage Index [SDI] and ESKD, and/or doubling of serum creatinine) was used to confirm disease modification. Each treatment was designated as one of the following at each time point: (a) criterion met; (b) inconclusive; (c) no available supportive data. This review excluded an assessment of potential toxicities. All LN treatments met at least one of the potential kidney disease-modification criteria at any time point, but limited relevant data in the literature meant disease modification > 5 years could only be confirmed for cyclophosphamide. Belimumab met more criteria across the three time points than any other biologic treatment but lacked > 5-year data to confirm disease modification. Further research is needed to support the classification of LN treatments as disease modifiers, particularly for > 5 years. We discuss considerations for future studies, challenges to the classification, and possible updates to published criteria.

Interleukin-17A (IL-17A) plays a pivotal role in many rheumatic immune-mediated inflammatory diseases. Targeting the IL-17 pathway has transformed the way psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA) are managed, with a number of IL-17A inhibitors now available for treating rheumatic and musculoskeletal diseases. This narrative review will describe the opportunities presented by novel imaging techniques in understanding the metabolic and mechanical changes that characterize the pathogenesis of PsA and axSpA. It will look at the current consensus definitions of early disease in PsA and axSpA, present evidence for the benefit of early treatment, and highlight the gaps in current knowledge. Finally, it will describe novel treatment targets to address the unmet needs in giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) and discuss the potential role of IL-17A inhibition in treating GCA and PMR.

Introduction: This work aims to illustrate the evolution and ongoing challenges of rheumatoid arthritis (RA) management with targeted therapy over 20 years, using a cohort study from the world's oldest society.

Methods: Data were obtained from FIRST registry, a multicenter cohort of patients with RA treated with biologic/targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs). Patients were followed for 60 months and assessed for drug efficacy, retention, and reasons for discontinuation.

Results: Analysis of 5130 treatments over 16,616 person-years revealed shifts in strategies and demographics. Despite an aging population (51.9-64.3 years) with increasing comorbidities (lung disease: 11.1-36.2%, malignancy: 2.2-13.1%), b/tsDMARD use expanded to include patients with lower disease activity. With better disease control, discontinuations due to adverse events decreased, and particularly infections fell from 2.1 to 0.7 per 100 person-years. Remission rates improved over time in the naïve group but remained largely unchanged in the prior b/tsDMARDs group. Retention rates varied by bDMARD class, with TNF inhibitors (TNFi) showing a decrease over time and IL-6 receptor inhibitors (IL-6Ri) and CTLA4-Ig showing an increase in retention. TNFi had high remission rates but low retention, whereas CTLA4-Ig and IL-6Ri had lower remission rates and higher retention. Changes in functional improvement were modest overall, and in patients aged 75 years and older, functional gains remained limited.

Conclusions: The study highlights the evolving landscape of RA management in an aging society, noting gains in efficacy and safety. However, unmet needs persist, particularly for patients not fully achieving treat-to-target goals and those with limited functional improvement.

Introduction: Biosimilars have provided additional treatment options for patients with immune-mediated inflammatory diseases. This study evaluated the real-world use of adalimumab biosimilar ABP 501 in European patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriatic arthritis (PsA), or psoriasis (PsO).

Methods: Data were drawn from the RA, spondyloarthritis, and PsO Adelphi Disease Specific Programmes (DSP)™, cross-sectional surveys conducted in France, Germany, Italy, Spain, and the UK between January 2020 and February 2022. Physicians completed patient record forms which collected data on demographics, treatment history, and clinical outcomes. Patients voluntarily completed questionnaires self-reporting health-related quality of life. Outcome measures were assessed for patients who initiated ABP 501 as the first advanced therapy (AT, "ABP 501 initiators") and patients who switched to ABP 501 from the first-line AT with reference product (RP) ("RP-ABP 501 switchers") in each indication.

Results: Across disease cohorts, 868 initiators and 428 switchers were analyzed. At time of consultation, physicians reported that 77.1%, 63.2%, 67.8%, and 83.0% of initiators with RA, AS, PsA, and PsO, respectively, presented with mild disease after receiving ABP 501 for a median of 10.4-12.3 months. Among switchers, the most common reasons for switching were related to formulary or financial reasons and insurance restrictions. Most switching patients were assessed by physicians to have mild disease (75.0-87.5% across indications) at time of consultation having received ABP 501 for a median of 11.2-15.3 months. Patients' self-assessment, including EQ-5D and work productivity scores, indicated an overall good state of health while using ABP 501, regardless of indication and prior RP exposure. Overall, more than 89% of physicians and more than 86% patients reported being satisfied with the disease control provided by ABP 501.

Conclusion: Across indications, both physicians and patients reported positive clinical outcomes and high levels of satisfaction with ABP 501 treatment, regardless of prior use of RP.