Rheumatology and Therapy最新文献

Introduction: Filgotinib is an oral Janus kinase 1 (JAK1) preferential inhibitor approved for adult patients with moderate-to-severe active rheumatoid arthritis (RA) who have responded inadequately to, or who are intolerant of, one or more disease-modifying antirheumatic drugs (DMARDs). While randomised trials have demonstrated its efficacy and tolerability, real-world data on very early treatment effects-particularly on pain relief, fatigue and function-remain scarce. The FIRST-RA study was initiated to address this evidence gap under routine care conditions.

Methods: FIRST-RA is a prospective, multicentre, non-interventional cohort study in Germany and Austria. Approximately 300 adult patients with RA newly starting filgotinib are enrolled and followed for 24 weeks. Patients are stratified into three groups based on prior use of advanced therapies (AT; biologic [b]DMARDs or targeted synthetic [ts]DMARDs): AT-naïve, one prior AT and ≥ 2 prior ATs. Clinical assessments are conducted at baseline and weeks 4, 12 and 24. Patient-reported outcomes (PROs), including the Rheumatoid Arthritis Impact of Disease (RAID) questionnaire, are captured electronically or on paper- daily during week 1 and at regular intervals thereafter.

Planned outcomes: The primary endpoint is the change in RAID pain score from baseline to week 4 (or earlier). Secondary endpoints include fatigue, disease activity, morning stiffness, treatment satisfaction and tolerability. Additional analyses will investigate very early symptom changes, drug utilisation patterns and treatment persistence, as well as effectiveness within AT exposure subgroups (AT-naïve and AT-experienced), summarised descriptively without formal subgroup testing. An exploratory, descriptive analysis will examine how the 2023 label update for JAK inhibitors may have influenced patient characteristics, prescribing patterns and safety outcomes, using the earlier-enrolled FILOSOPHY real-world cohort as an external reference. FIRST-RA is the first real-world study to capture very early symptomatic responses to filgotinib. By integrating PRO data with clinical outcomes, the study aims to support personalised RA management and clarify the use of filgotinib in today's clinical practice.

Study registration: German Clinical Trials Register, DRKS0003613.

Introduction: Although tumor necrosis factor inhibitors (TNFis) have improved management of psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA); many patients experience suboptimal disease control. We quantified achievement of varying degrees of disease activity in patients with PsA and axSpA who initiated and maintained TNFi treatment for 12 months.

Methods: Patients with PsA or axSpA enrolled in the PPD™ CorEvitas™ PsA/Spondyloarthritis Registry were included in the study. Varying degrees of disease control were quantified based on minimal disease activity (MDA) status for PsA and BASDAI50 (≥ 50% improvement in Bath Ankylosing Spondylitis Disease Activity Index) status for axSpA at 6 and 12 months. Patients were categorized into four groups: sustained (MDA/BASDAI50 at 6 and 12 months), improved (MDA/BASDAI50 at 12 months only), worsened (MDA/BASDAI50 at 6 months only), and never achieved (no MDA/BASDAI50 at 6 or 12 months).

Results: For PsA, 338 patients initiated and persisted on TNFis. At 6 months, the majority (65%, n = 221) did not achieve MDA status; of these, 86% (n = 189) still did not achieve MDA at 12 months. For axSpA, 152 patients initiated and persisted on TNFis. At 6 months, 80% (n = 121) did not achieve BASDAI50; among these patients, 91% (n = 110) still did not achieve BASDAI50 status at 12 months. For both PsA and axSpA initiators, the risk of not achieving clinical or quality of life outcomes was two- to threefold lower in patients who never achieved versus patients who achieved and sustained MDA/BASDAI50.

Conclusion: More than 80% of patients with PsA or axSpA who did not achieve low disease activity at 6 months still did not achieve low disease activity by 12 months even though they persisted on TNFi treatment. These findings underscore the importance for physicians to consider modifying therapy if treatment targets with TNFi have not been achieved in the first 6 months.

Introduction: We report an exploratory subgroup analysis of a Chinese phase 3 study to investigate the effect of baseline inflammation measured by magnetic resonance imaging (MRI) on ixekizumab efficacy in radiographic axial spondyloarthritis (r-axSpA).

Methods: Adults with r-axSpA were randomized (1:1) to receive ixekizumab 80 mg every 4 weeks (IXEQ4W) or placebo for 16 weeks. Endpoints analyzed by baseline Spondyloarthritis Research Consortium of Canada (SPARCC) MRI spine or sacroiliac joint (SIJ) inflammation score (< 2 or ≥ 2; elevated inflammation defined as score ≥ 2) were: Assessment of SpondyloArthritis International Society 40 (ASAS40); Bath Ankylosing Spondylitis Disease Activity Index 50 (BASDAI50); Ankylosing Spondylitis Disease Activity Score (ASDAS) < 2.1; ASDAS clinically important improvement (CII; change from baseline ≥ 1.1); Patient Global Assessment of Disease Activity (PtGA); spinal pain; nocturnal spinal pain; stiffness/inflammation; function; fatigue; Short Form-36 Physical Component Score (SF-36 PCS); European Quality of Life 5 Dimensions 5 Levels visual analog scale (EQ-5D-5L VAS).

Results: Overall, 145 patients were included. At Week 16, ASAS40 response rates were numerically improved with IXEQ4W versus placebo in the SPARCC MRI spine score < 2 subgroup (40.9% vs. 14.3%; p = 0.088) and significantly improved in the ≥ 2 subgroup (37.3% vs. 5.9%; p < 0.001). ASAS40 response rates were significantly improved in the SPARCC MRI SIJ score < 2 (34.4% vs. 8.6%; p < 0.05) and ≥ 2 (41.5% vs. 8.1%; p < 0.001) subgroups. Similar results were obtained on BASDAI50, ASDAS < 2.1, and ASDAS CII. IXEQ4W significantly improved PtGA, inflammation, and fatigue across all subgroups. Spinal and nocturnal spinal pain were significantly improved in the SPARCC MRI spine score ≥ 2 subgroup and both SPARCC MRI SIJ score subgroups. Function and SF-36 PCS were significantly improved in the SPARCC MRI spine score ≥ 2 subgroup. There were no significant differences in EQ-5D-5L VAS.

Conclusion: These findings support IXEQ4W as an effective treatment for Chinese patients with r-axSpA, irrespective of baseline MRI inflammation.

Trial registration: ClinicalTrials.gov identifier, NCT04285229.

Introduction: The ongoing KEEPsAKE 1 and 2 (KS1; KS2) trials evaluate the efficacy and safety of risankizumab in patients with psoriatic arthritis (PsA) who had an inadequate response to ≥ 1 conventional synthetic disease-modifying antirheumatic drug(s) (csDMARD-IR, KS1&2) and/or 1-2 biologic DMARDs (bDMARD-IR, KS2). Herein, we present week 196 efficacy and safety findings from KS1 and KS2.

Methods: Patients were randomized 1:1 in a double-blind fashion to receive subcutaneous risankizumab 150 mg or placebo (weeks 0, 4, 16, and 24). All patients received open-label risankizumab at week 28 and every 12 weeks thereafter (i.e., continuous risankizumab, placebo/risankizumab). Assessments included ≥ 20%/50%/70% improvement in PsA symptoms using American College of Rheumatology criteria (ACR20/50/70) and achievement of minimal disease activity (MDA).

Results: At week 196, 749 patients remained in KS1 and 289 in KS2. In KS1, 57.1% of patients receiving continuous risankizumab and 56.5% receiving placebo/risankizumab achieved ACR20, while 54.5% receiving continuous risankizumab and 50.2% receiving placebo/risankizumab achieved ACR20 in KS2 at week 196. Maintenance of ACR20 achievement in KS1 from week 52 to week 196 was observed for 71.0% of patients receiving continuous risankizumab and 72.7% receiving placebo/risankizumab. The same was observed in KS2 for 68.7% of patients receiving continuous risankizumab and 73.0% receiving placebo/risankizumab. The proportion of patients achieving MDA was 39.6% receiving continuous risankizumab and 35.2% receiving placebo/risankizumab in KS1, while 35.3% of patients receiving continuous risankizumab and 37.4% receiving placebo/risankizumab achieved MDA in KS2 at week 196. In KS1, maintenance of MDA at week 196 from week 52 was achieved by 72.8% of patients receiving continuous risankizumab and 72.2% receiving placebo/risankizumab. In KS2, 77.0% of patients receiving continuous risankizumab and 70.3% receiving placebo/risankizumab achieved the same. No new safety signals were reported.

Conclusions: Risankizumab demonstrated durable efficacy and safety at week 196 in KS1 and KS2.

Trial registration: KS1: ClinicalTrials.gov, NCT03675308; KS2: ClinicalTrials.gov, NCT03671148.

Introduction: Vagus nerve stimulation activates neuroimmune reflexes that modulate systemic inflammation and may represent a novel non-pharmacologic treatment modality for autoimmune diseases like rheumatoid arthritis (RA). In a 3-month first-in-human, double-blind trial, 50% of patients with drug-refractory RA improved clinically, two patients achieved remission, and pro-inflammatory cytokines declined by 30-50% with daily stimulation. The current study is a 36-month extension of that trial, designed to assess the sustained safety and efficacy of the neuroimmune modulation device in patients with multidrug-refractory RA.

Methods: Patients (N = 14) with active RA and prior insufficient response to at least two different biological or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) with at least two mechanisms of action were implanted with a novel neuroimmune modulation device that stimulates the cervical vagus nerve, treated for 12 weeks, and then assessed for safety and clinical effectiveness in an open-label 36-month extension.

Results: Eleven patients completed the extension study through month 36. Patients had previously failed an average of 4.8 different drugs, with 64% (9/14) having failed a tsDMARD before enrolling in the study. The median change in clinical disease activity index (CDAI) score from day 0 to month 36 was - 17.8 (SEM 4.9). At month 36, 64% (7/11) of patients achieved a CDAI response that met or exceeded the minimal clinically important difference. Two of these seven patients were treated with daily stimulation alone, while five patients combined stimulation with an adjunctive b/tsDMARD. No device-related infections, cardiac events, surgical revisions, or device explants were reported. Two adverse events related to the device occurred in a single patient: a mild sore throat and moderate tenderness near the implant site. These events were non-serious, anticipated, and resolved.

Conclusion: In this first-in-human long-term extension study, neuroimmune modulation was well tolerated among patients with multidrug-refractory RA, with reductions of clinical disease activity that were maintained through 36 months.

Introduction: Gout is an inflammatory arthritis that, when uncontrolled, can lead to chronic pain, disability, increased demand for healthcare, and poor health outcomes. This study sought to identify patients with gout and to describe the differences in epidemiology, pharmacotherapy, healthcare utilization, and outcomes for patients with controlled and uncontrolled gout in the United States (US) Veterans Affairs (VA) healthcare system.

Methods: This retrospective cohort study used electronic health record (EHR) data from VA patients from all US states and territories with gout from 1/1/2016 to 12/31/2022. The study included adult VA patients (18 +) with a diagnosis code for gout (ICD10 codes M10 or M1A) and two or more encounters 30 or more days apart. Uncontrolled gout was defined as one serum uric acid level (sUA) level > 8 mg/dl, tophi, or both in the study period.

Results: Of the 331,664 patients who met study criteria, 42% (138,068) were considered to have uncontrolled gout and 58% (193,596) were controlled. The uncontrolled group was younger (mean age 64 vs. 70 years, p < 0.01), and both groups were predominantly white non-Hispanic (58% and 70%) and male (99% and 99%). Specialist visits were more common in the uncontrolled group during follow-up: podiatry (38% vs. 30%, p < 0.01), rheumatology (24% vs. 9%, p < 0.01), and nephrology (24% vs. 12%, p < 0.01). Patients with uncontrolled gout were also significantly more likely to be seen in the emergency room (55% vs. 38%, p < 0.01) or admitted to the hospital (47% vs. 37%, p < 0.01) during follow-up.

Conclusions: Nearly half of VA patients with gout met criteria for uncontrolled gout, and these patients experienced greater healthcare utilization and worse health outcomes than patients with controlled gout. Patients with uncontrolled gout could benefit from additional/alternative approaches such as the adoption of a treat-to-target strategy and increasing referrals to a specialist.

Polymyalgia rheumatica (PMR) is a common inflammatory rheumatic disorder affecting those over 50 years of age. It is clinically heterogenous in both presentation and disease trajectory. Diagnostic complexity is heightened by the absence of a gold standard diagnostic test and the broad spectrum of disease mimics, posing challenges even for experienced rheumatologists. The primary goal of treatment is to restore health-related quality of life by achieving sustained symptom control, suppressing systemic inflammation, and minimising treatment-related toxicity. Despite advances in our understanding of PMR, glucocorticoids (GCs) remain the cornerstone of therapy. However, frequent relapses and prolonged treatment courses in many patients result in high cumulative GC exposure with associated adverse effects, which is of particular concern in this older, typically frailer and more vulnerable patient cohort. The urgent need for effective GC-sparing agents has resulted in pivotal developments over the past decade, notably the SAPHYR trial, which supported the US Food and Drug Administration (FDA) approval of sarilumab as the first biologic therapy for refractory PMR. This represents a major shift in the therapeutic landscape, with several biologic agents now under investigation. These advances, however, highlight gaps in the current management, including the need for rapid access pathways and specialist rheumatologist evaluation in all cases of suspected PMR to facilitate an early and accurate diagnosis, stratified treatment approaches and the accurate detection of a coexisting giant cell arteritis. Furthermore, standardised definitions of relapse and remission, alongside structured monitoring protocols, are lacking. This review explores current diagnostic and treatment strategies for isolated PMR. We also highlight unmet needs in PMR management, and discuss future directions aimed at improving outcomes and redefining the care pathway for PMR.

Introduction: Mental health status potentially influences treatment responses. The effect of probable anxiety and/or depressive disorder (pADD) on tofacitinib efficacy, patient-reported outcomes (PROs), and safety in psoriatic arthritis (PsA) was assessed.

Methods: This was a post hoc analysis of two phase 3 trials in patients with PsA receiving tofacitinib, adalimumab, or placebo, and an open-label extension study. Outcomes were stratified by presence/absence of baseline pADD (Short Form-36 Health Survey [SF-36] Mental Component Summary score ≤ 38/ > 38). American College of Rheumatology ≥ 20%, ≥ 50%, and ≥ 70% (ACR20/50/70) responses, remission and/or low disease activity based on Psoriatic Arthritis Disease Activity Score and Disease Activity Index for Psoriatic Arthritis score, minimal disease activity, and PROs (pain/Health Assessment Questionnaire-Disability Index/fatigue) were assessed through month 36. Safety was assessed through month 12.

Results: Overall, 323/706 (45.8%) patients had baseline pADD; of these, a higher proportion were female versus male (61.9% vs. 38.1%). Numerically higher proportions achieved efficacy/PRO responses with tofacitinib versus placebo, regardless of baseline pADD (month 3). Responses with tofacitinib were generally similar in patients with versus without baseline pADD (e.g., month 3 ACR20 responses: 54.0% vs. 58.5%); some differences were observed at later time points (e.g., month 9 minimal disease activity: 25.0% vs. 43.8%; p < 0.05). Baseline pADD did not appear to affect the incidence of treatment-emergent adverse events.

Conclusions: Baseline pADD was frequent in patients with PsA initiating tofacitinib and was higher in female patients. Tofacitinib-treated patients had generally similar efficacy/safety outcomes, regardless of baseline pADD. Some differences in efficacy outcomes were noted in the longer term (9-12 months). Limitations of this study include small numbers in some analyses and use of SF-36 as pADD proxy.

Trial registration: ClinicalTrials.gov: NCT01877668; NCT01882439; NCT01976364.

Introduction: This study assessed the real-world effectiveness of risankizumab (RZB) and treatment satisfaction in biologic-naïve patients with psoriatic arthritis (PsA) across the USA and Europe.

Methods: Data were drawn from the Adelphi Real World Spondyloarthritis Disease Specific Programme™, a cross-sectional survey of physicians and their adult patients with PsA receiving RZB 150 mg subcutaneous injections in Europe (France, Germany, Italy, Spain, UK) and the US, conducted from June 2023-June 2024. Physicians reported changes in body surface area (BSA), dactylitis, enthesitis, TJC68, and SJC66 and assessments of pain and fatigue on a 0-10 scale (higher scores indicating worse outcomes) from initiation to data collection, evaluated using McNemar or t-tests (p < 0.05 considered significant). Clinically meaningful improvements were complete resolution of dactylitis, enthesitis, TJC68, and SJC66 and pain (≥ 1.0-unit) and fatigue (≥ 3.0-unit) reductions. Physician and patient satisfaction with disease control was also reported. Outcomes were analyzed for the full cohort and stratified by prescription of a conventional synthetic disease-modifying antirheumatic drug (csDMARD) prior to the survey or at data collection vs csDMARD-naïve.

Results: Overall, 127 physicians reported on 192 patients with PsA (Europe 64%, US 36%). Mean ± SD patient age was 44.2 ± 10.7 years, and 45% were female. From RZB treatment initiation to time of data collection, resolution of dactylitis (82%) and enthesitis (90%), and improvements to TJC68 (- 3.7 ± 6.3), SJC66 (- 2.5 ± 5.1), pain (- 3.9 ± 2.4), fatigue (- 2.7 ± 2.6), and BSA (- 10 ± 10%) were observed (p < 0.001 for each) for the full cohort, with significant changes observed in both csDMARD subgroups. Patient and physician satisfaction with disease control was 95% and 98%, respectively.

Conclusion: Biologic-naïve patients with PsA starting RZB demonstrated significant and meaningful improvements in joint symptoms, pain, and fatigue in real-world settings. High levels of satisfaction with RZB for disease control were reported by both patients and physicians.