Rheumatology and Therapy最新文献

{"title":"Efficacy of Ixekizumab in Chinese Patients with Radiographic-Axial Spondyloarthritis by Baseline Inflammation Status on Magnetic Resonance Imaging.","authors":"Xiaoxia Zhu, Jiankang Hu, Dongzhou Liu, Jingyang Li, Huaxiang Wu, Lingyun Sun, Lie Dai, Chunyu Tan, Zhijun Li, Zhengyu Xiao, Yongfu Wang, Lingli Dong, Yan Yan, Hongying Li, Hejian Zou","doi":"10.1007/s40744-025-00819-w","DOIUrl":"10.1007/s40744-025-00819-w","url":null,"abstract":"<p><strong>Introduction: </strong>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).</p><p><strong>Methods: </strong>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).</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>These findings support IXEQ4W as an effective treatment for Chinese patients with r-axSpA, irrespective of baseline MRI inflammation.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov identifier, NCT04285229.</p>","PeriodicalId":21267,"journal":{"name":"Rheumatology and Therapy","volume":" ","pages":"313-327"},"PeriodicalIF":3.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12996569/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145912707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unravelling Fibromyalgia in Psoriatic Arthritis.","authors":"Kate E Findeisen, Emma K Guymer, Geoffrey O Littlejohn","doi":"10.1007/s40744-026-00825-6","DOIUrl":"10.1007/s40744-026-00825-6","url":null,"abstract":"<p><p>Fibromyalgia is a common condition causing widespread pain, fatigue, sleep disturbance, and cognitive dysfunction. It frequently coexists with chronic rheumatic diseases, including psoriatic arthritis (PsA), complicating diagnosis and management. This narrative review explores the interaction between fibromyalgia and PsA, highlighting recent studies that demonstrate that between 18% and 64% of patients with PsA have fibromyalgia with significant impact on disease assessment and quality of life. Patients with fibromyalgia have markedly higher scores for pain, tenderness, fatigue, poor sleep, and standard PsA disease activity measures. Where this overlap occurs \"disease activity\" indices often reflect fibromyalgia symptoms rather than true inflammation, leading to potential overtreatment with disease-modifying drugs rather than appropriate pain-modulating or lifestyle interventions. Additionally, fibromyalgia symptoms exist along a continuum, with many patients showing subthreshold manifestations that still affect function and well-being. Tools such as the Fibromyalgia Impact Questionnaire and Polysymptomatic Distress Scale help distinguish the central sensitization symptoms that characterize fibromyalgia from inflammatory activity and damage in joints and tendon sheaths that characterize PsA. Both peripheral and central pain-related neural mechanisms, including comorbid factors such as obesity and disease burden, contribute to fibromyalgia in PsA. Activation of the stress response likely contributes significantly to fibromyalgia in this setting. Fibromyalgia itself is seen not simply as a comorbidity but as part of the body's neurobiological stress response to chronic illness. Recognizing fibromyalgia within PsA is crucial to tailor management, improve outcomes, and avoid unnecessary treatments. This complex clinical picture requires nuanced management beyond that of inflammation alone.</p>","PeriodicalId":21267,"journal":{"name":"Rheumatology and Therapy","volume":" ","pages":"299-311"},"PeriodicalIF":3.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12996466/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147309623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum SCUBE1 and SCUBE2 Levels in Children with Immunoglobulin A Vasculitis: An Exploratory Study.","authors":"Gulbahar Kurt Bayir, Ferhat Demir, Suleyman Caner Karahan, Mukaddes Kalyoncu","doi":"10.1007/s40744-026-00836-3","DOIUrl":"10.1007/s40744-026-00836-3","url":null,"abstract":"<p><strong>Introduction: </strong>SCUBE1 and SCUBE2 are vascular-associated proteins involved in endothelial processes. Although these molecules have been investigated in several vascular and inflammatory disorders, their potential involvement in pediatric immunoglobulin A vasculitis (IgAV) has not yet been elucidated. IgAV is the most common systemic vasculitis of childhood, characterized by leukocytoclastic vasculitis and immune complex deposition, yet its biomarker profile remains incompletely understood. We explored the association of SCUBE proteins with inflammatory markers in pediatric IgAV.</p><p><strong>Methods: </strong>Twenty-six children diagnosed with IgAV according to the Ankara 2008 criteria were prospectively included. Serum SCUBE1, SCUBE2, interleukin (IL)-1, IL-6, and tumor necrosis factor alpha (TNFα) levels were measured during both the active and recovery phases of the disease. Findings were compared with age- and sex-matched healthy controls using enzyme-linked immunosorbent assay (ELISA) methods.</p><p><strong>Results: </strong>IL-1 and IL-6 levels were significantly elevated in patients during the active phase compared with healthy controls (p = 0.006 and p = 0.01, respectively), supporting their role in acute inflammation. SCUBE1 and SCUBE2 levels did not significantly differ between active and recovery phases. However, SCUBE2 levels were significantly lower in the recovery phase than in controls (p = 0.008), suggesting potential downregulation following acute inflammation.</p><p><strong>Conclusions: </strong>Our findings indicate that SCUBE2 may be more closely related to late-stage vascular stabilization or tissue repair mechanisms rather than acute inflammatory activity in IgAV. This preliminary finding suggests that SCUBE2 may be associated with post-inflammatory processes; however, further studies are required to clarify its clinical relevance.</p>","PeriodicalId":21267,"journal":{"name":"Rheumatology and Therapy","volume":" ","pages":"389-402"},"PeriodicalIF":3.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12996460/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147370036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Guselkumab Improves Patient-Reported Outcomes Among Participants with Psoriatic Arthritis and Inadequate Response to Tumor Necrosis Factor Inhibitors in the COSMOS Study.","authors":"Laure Gossec, Xenofon Baraliakos, James Galloway, Vilija Oke, Petros Sfikakis, Emmanouil Rampakakis, Mohamed Sharaf, Frederic Lavie, Iain B McInnes","doi":"10.1007/s40744-025-00821-2","DOIUrl":"10.1007/s40744-025-00821-2","url":null,"abstract":"<p><strong>Introduction: </strong>The aim of this work was to evaluate the achievement of minimal clinically important improvement (MCII) in patient-reported outcomes (PROs) with guselkumab among participants with active psoriatic arthritis (PsA) and inadequate response to tumor necrosis factor inhibitors (TNFi-IR).</p><p><strong>Methods: </strong>Post hoc analysis of phase 3b COSMOS study of participants with PsA and TNFi-IR randomized to guselkumab (N = 189) or placebo (N = 96) at week (W)0, W4 then every 8W through W44, with W16 (early escape) or W24 placebo-to-guselkumab transition. Time to MCII achievement (> 15-point) in patient global assessment of arthritis (PtGA Arthritis), PtGA Psoriasis, PtGA Arthritis + Psoriasis, and Patient Pain, Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue, ≥ 4-point), Health Assessment Questionnaire-Disability Index (HAQ-DI, ≥ 0.35-point), 36-item Short-Form Health Survey physical component summary score (≥ 5-point), Dermatology Life Quality Index (DLQI, ≥ 5-point), and DLQI 0/1 with guselkumab vs. placebo was determined using Cox regression adjusting for baseline factors. Logistic regression compared MCII achievement rates between treatment groups. All p values are nominal.</p><p><strong>Results: </strong>Time to MCII achievement across PROs through W24 was significantly faster with guselkumab vs. placebo (hazard ratio [HR] range 1.59 for PtGA Arthritis to 5.89 for DLQI), except for FACIT-Fatigue (HR 1.29, 95% confidence interval 0.93-1.81). Guselkumab treatment delivered significant improvements in PROs vs. placebo as early as W8 and through W24. Across all measures, odds of achieving MCII were higher with guselkumab vs. placebo at W8 (odds ratio [OR] range 1.43 for FACIT-Fatigue to 9.33 for DLQI) and W24 (OR range 3.12 for HAQ-DI to 19.42 for DLQI 0/1). MCII achievement rates for all PROs increased through W48 of guselkumab treatment, with consistent patterns following placebo-to-guselkumab transition.</p><p><strong>Conclusions: </strong>In these hypothesis-generating analyses of a TNFi-IR PsA population, guselkumab demonstrated rapid (W8) MCII achievement in patient-reported skin and joint symptoms, and pain, followed by improvements in fatigue, functional status, and quality of life, with response rates increasing further through W48.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov identifier, NCT03796858.</p>","PeriodicalId":21267,"journal":{"name":"Rheumatology and Therapy","volume":" ","pages":"347-360"},"PeriodicalIF":3.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12996573/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146030732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rationale, Design and Methods of the Filgotinib Initial Response Study in Rheumatoid Arthritis (FIRST-RA).","authors":"Georg Pongratz, Rieke Alten, Torsten Witte, Christine Pausch, Robert Reinhold, David Pittrow, Gerd R Burmester","doi":"10.1007/s40744-025-00814-1","DOIUrl":"10.1007/s40744-025-00814-1","url":null,"abstract":"<p><strong>Introduction: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Planned outcomes: </strong>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.</p><p><strong>Study registration: </strong>German Clinical Trials Register, DRKS0003613.</p>","PeriodicalId":21267,"journal":{"name":"Rheumatology and Therapy","volume":" ","pages":"435-449"},"PeriodicalIF":3.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12996454/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145952768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-term Effectiveness and Safety of Canakinumab in Patients with TRAPS: Analysis of the RELIANCE Non-Interventional Study.","authors":"Norbert Blank, Catharina Schuetz, Markus Hufnagel, Gerd Horneff, Michael Borte, Tilmann Kallinich, Prasad T Oommen, Ales Janda, Joerg Henes, Julia Weber-Arden, Michael Stock, Jasmin B Kuemmerle-Deschner","doi":"10.1007/s40744-025-00809-y","DOIUrl":"10.1007/s40744-025-00809-y","url":null,"abstract":"<p><strong>Introduction: </strong>This is an interim analysis of the long-term effectiveness and safety of canakinumab in the tumor necrosis factor receptor-associated periodic syndrome (TRAPS) cohort of the RELIANCE non-interventional study.</p><p><strong>Methods: </strong>From June 2018, the RELIANCE non-interventional study enrolled paediatric (aged ≥ 2 - < 18 years) and adult patients (aged ≥ 18 years) with TRAPS who were receiving canakinumab as part of their routine medical care. Physician- and patient-reported measures of disease activity, dosing patterns and safety were evaluated at baseline and every 6 months until the end-of-study visit.</p><p><strong>Results: </strong>A total of 21 patients with TRAPS were enrolled by the analysis cut-off date of December 2022, of which 61.9% (13/21) were paediatric patients (< 18 years) and 66.7% (14/21) were female. All patients were pre-treated with canakinumab prior to enrolment (median duration of canakinumab treatment prior to study inclusion: 1.2 years). Disease activity, evaluated by physician-reported (physician's global assessment, disease remission, C-reactive protein, serum amyloid A) and patient-reported (disease activity, fatigue, impact on social life, autoinflammatory disease activity index diary) measures, was generally well controlled throughout the study. At baseline, the majority of patients (71.4%) were receiving the recommended starting dose (SD) of canakinumab, with a more even distribution between the < SD, SD, and > SD dosing schedules observed from month 6. No serious adverse drug reactions were reported. Patients continued to receive vaccinations during long-term treatment with canakinumab. In total, 85.7% (18/21) of patients met the Eurofever/PRINTO classification criteria for TRAPS, 42.9% (9/21) with the presence of a confirmative TNFRSF1A genotype and 42.9% (9/21) without. In total, 14.3% (3/21) of patients did not meet the classification criteria.</p><p><strong>Conclusions: </strong>Data from this interim analysis support the long-term effectiveness and safety of canakinumab for the treatment of TRAPS.</p>","PeriodicalId":21267,"journal":{"name":"Rheumatology and Therapy","volume":" ","pages":"135-155"},"PeriodicalIF":2.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12816457/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145605537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-World Analysis of Initial Clinical Response and Future Outcomes Among Patients with Rheumatoid Arthritis Initiating and Remaining on a First-Line Tumor Necrosis Factor Inhibitor in the United States.","authors":"Christina Charles-Schoeman, Patrick Zueger, Erin McDearmon-Blondell, Siran Fang, Yi Peng, Tanjinatus Oishi, Manish Jain, John Tesser","doi":"10.1007/s40744-025-00808-z","DOIUrl":"10.1007/s40744-025-00808-z","url":null,"abstract":"<p><strong>Introduction: </strong>This study aimed to evaluate a subsequent treatment response among patients with rheumatoid arthritis (RA) who initiated and remained on a first-line tumor necrosis factor inhibitor (TNFi) after achieving or not achieving an initial response.</p><p><strong>Methods: </strong>This real-world, retrospective cohort study included patients with RA in moderate/high disease activity (MDA/HDA), defined by Clinical Disease Activity Index (CDAI) score > 10, who initiated a first-line TNFi and remained on therapy for ≥ 12 months. Data were analyzed according to the time of initial evaluation: 3 months (N = 1215) or 6 months (N = 1318).</p><p><strong>Primary outcome: </strong>proportion of patients achieving low disease activity (LDA)/remission in CDAI (≤ 10) at the initial evaluation; secondary outcome: proportion of patients achieving minimal clinically important difference (MCID) in CDAI. Patients were categorized as responders or nonresponders according to outcome achievement, then analyzed for subsequent response at 12 months and maintenance of initial response through 12 months.</p><p><strong>Results: </strong>After 3 months, 65.9% of patients were in MDA/HDA. Among these nonresponders, 73.5% remained in MDA/HDA at 12 months and 64.2% failed to improve through 12 months. Of patients in LDA/remission at 3 months, 27.0% lost their response at 12 months. Among the 59.2% of nonresponders at 6 months, 80.1% were in MDA/HDA at 12 months and 74.5% never improved through 12 months. For patients in LDA/remission at 6 months (40.8%), 23.4% subsequently lost their response at 12 months. Similar trends were observed for achievement of MCID in CDAI.</p><p><strong>Conclusions: </strong>In patients with RA treated with a first-line TNFi, most patients who did not achieve a treatment target at an initial evaluation also failed to achieve the treatment target at 12 months. Therefore, evaluating treatment as early as 3 months after initiation may help indicate future clinical improvements and could serve as a reasonable timepoint to consider changing therapy for patients with an inadequate response.</p>","PeriodicalId":21267,"journal":{"name":"Rheumatology and Therapy","volume":" ","pages":"95-114"},"PeriodicalIF":2.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12816474/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145524231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effectiveness of Tofacitinib in Patients with Psoriatic Arthritis Initiating Monotherapy Versus Combination Therapy: Results from the CorEvitas Psoriatic Arthritis/Spondyloarthritis Registry.","authors":"Alexis Ogdie, Nicole Middaugh, Taylor Blachley, Tran Bourgeois, You-Li Ling, Rajiv Mundayat, Lara Fallon, Karim R Masri, Philip J Mease","doi":"10.1007/s40744-025-00811-4","DOIUrl":"10.1007/s40744-025-00811-4","url":null,"abstract":"<p><strong>Introduction: </strong>This study evaluated the real-world effectiveness of tofacitinib monotherapy versus combination therapy in patients with psoriatic arthritis (PsA) enrolled in the CorEvitas PsA/Spondyloarthritis Registry.</p><p><strong>Methods: </strong>This study (NCT05195814) included adult patients with PsA initiating tofacitinib (from December 14, 2017 to October 1, 2023) as monotherapy, or in combination with oral small molecules (OSMs: methotrexate, leflunomide, sulfasalazine, hydroxychloroquine, and apremilast). Patients with baseline and 6-month follow-up visits (± 3 months) were included.</p><p><strong>Outcomes: </strong>mean change from baseline (∆) in/proportions achieving, disease activity measures (including body surface area [BSA] = 0%), and patient-reported outcomes. Continuous endpoints at month 6 were analyzed as ∆ with an analysis of covariance model including treatment and baseline value as covariates. ∆ in least squares (LS) means and adjusted LS means/odds ratios are presented.</p><p><strong>Results: </strong>The study included 141 patients (66/141 monotherapy; 75/141 combination therapy). Patients were predominantly female (61.0%) and white (94.3%), and average age was 56.7 years. More monotherapy initiators were OSM treatment-naïve and had higher mean Patient Global Assessment of Arthritis, compared with combination therapy initiators. By 6 ± 3 months, 28.8% and 25.3% of monotherapy and combination therapy initiators, respectively, discontinued tofacitinib. At 6 ± 3 months, 15.0% of monotherapy initiators achieved minimal disease activity, and 27.1% had BSA = 0%. Corresponding data for combination therapy initiators were 20.7%, and 22.0%, respectively. Differences between groups were not significant. LS mean differences from baseline in overall work impairment/activity impairment were - 13.0/- 21.8 and 1.4/- 2.9 for monotherapy and combination therapy initiators, respectively.</p><p><strong>Conclusion: </strong>Monotherapy and combination therapy initiators demonstrated improvements across effectiveness outcomes. Tofacitinib monotherapy initiators experienced numerical improvements in overall work impairment/activity impairment. This highlights tofacitinib effectiveness as monotherapy/combination therapy for a diverse PsA population. However, the small sample size limited the statistical power, and so results should be interpreted cautiously.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov identifier, NCT05195814.</p>","PeriodicalId":21267,"journal":{"name":"Rheumatology and Therapy","volume":" ","pages":"195-212"},"PeriodicalIF":2.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12816449/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145669794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Is a Functional Cure Possible in Autoimmune Diseases? Evidence from Trigger Eradication, Transplantation, and Cellular Therapies.","authors":"Jozélio Freire de Carvalho, Carlos Ewerton Maia Rodrigues","doi":"10.1007/s40744-025-00816-z","DOIUrl":"10.1007/s40744-025-00816-z","url":null,"abstract":"<p><strong>Introduction: </strong>Traditionally considered incurable, autoimmune diseases (AIDs) may-in specific circumstances-achieve sustained remission or even a \"functional cure,\" defined as durable clinical and laboratory remission without immunosuppression. This review evaluates evidence across five therapeutic axes: infectious trigger eradication, immune reset via autologous hematopoietic stem cell transplantation (HSCT), cellular therapies (CAR-T, extracorporeal photopheresis), environmental/nutritional strategies, and paraneoplastic syndromes.</p><p><strong>Methods: </strong>Systematic review according to PRISMA guidelines in PubMed/MEDLINE, Embase, Scopus, Web of Science, and Cochrane (up to September 2025). Eligible studies included trials, meta-analyses, cohorts, case series, and reports describing sustained or drug-free remission. Definitions applied were clinical remission, complete remission, sustained remission ≥ 12 months, drug-free remission, and functional cure (complete, off-therapy remission with stable biomarkers and no new organ damage).</p><p><strong>Results: </strong>Strong evidence supports Helicobacter pylori eradication in immune thrombocytopenic purpura, with signals in dermatoses and urticaria. In systemic sclerosis, HSCT outperformed cyclophosphamide in randomized trials, improving survival and reducing prolonged immunosuppression; lupus series reported extended drug-free remissions. Anti-CD19 CAR-T therapies induced deep remission in B-cell-mediated AIDs, normalizing autoantibodies over 12-24 months. Photopheresis showed safety but heterogeneous efficacy. Environmental interventions (vitamin D, plant-based diet, microbiota modulation) suggested benefit, though with limited evidence for cure. In paraneoplastic syndromes, tumor control often coincided with autoimmune remission.</p><p><strong>Conclusions: </strong>Functional cure in AIDs appears achievable in selected cases through trigger removal, immune reset, or profound immune depletion. Advancing this paradigm requires standardized definitions, predictive biomarkers, and long-term controlled trials to integrate these strategies into routine care.</p>","PeriodicalId":21267,"journal":{"name":"Rheumatology and Therapy","volume":" ","pages":"1-25"},"PeriodicalIF":2.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12816497/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145820583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effectiveness and Safety of Upadacitinib in Treating Oligoarticular and Polyarticular Psoriatic Arthritis: Primary Analysis from the UPJOINT-Study.","authors":"Stephanie Gabriele Werner, Ilka Schwarze, Xenofon Baraliakos, Michael Fiene, Jochen Walter, Tanya Girard, Marie-Claude Laliberté, Katharina Jeromin, Nikola Baschuk, Hugues Allard-Charmard, Louis Bessette, Axel J Hueber","doi":"10.1007/s40744-025-00802-5","DOIUrl":"10.1007/s40744-025-00802-5","url":null,"abstract":"<p><strong>Introduction: </strong>This study aimed to investigate the effectiveness and safety of upadacitinib in patients with either oligo- or polyarticular active psoriatic arthritis (oPsA/pPsA) in routine clinical practice.</p><p><strong>Methods: </strong>UPJOINT is a post-marketing, multicenter observational study in patients with active psoriatic arthritis (PsA), treated with upadacitinib according to local label over a period of 48 weeks. The decision for treatment initiation with upadacitinib was independent of the study participation. The study's denominated primary endpoint was the proportion of patients achieving minimal disease activity (MDA) at week 24 under continuous treatment with upadacitinib. Furthermore, maintenance of MDA response at week 48 among those who achieved response at week 24 was evaluated. Also, very low disease activity (VLDA), and improvement of the Disease Activity Index for Psoriatic Arthritis (DAPSA) in oPsA/pPsA were further composite outcomes of interest evaluated at baseline and weeks 4, 12, 24, 36, and 48 after treatment initiation. Safety data were collected in a separate dataset using standardized operating procedures regarding the documentation of adverse events, followed by MedDRA hierarchy categorization using system organ classes.</p><p><strong>Results: </strong>A total of 364 patients were included in the effectiveness dataset for an as-observed analysis. The proportion of patients achieving MDA increased from 3.6% (overall) at baseline, 7.1% (oPsA), and 1.3% (pPsA) to 41.5% (overall), 55.8% (oPsA), and 32.0% (pPsA) at week 24, respectively. At week 48, 47.5% of the patients with oPsA and 35.1% of the patients with pPsA achieved MDA. The proportion of MDA responders increased noticeably as early as week 4 in both subgroups (oPsA 38.4%, pPsA 16.3%). The proportion of patients achieving VLDA and DAPSA remission increased from 0% for both outcomes at baseline in patients with oPsA and pPsA to 22.2% and 14.3% and 24.2% and 14.9%, respectively, at week 48. Altogether 127 (33.3%) patients experienced 213 adverse events (AEs) with a reasonable possibility of being related to the study drug. Forty-one serious AEs were reported in 26 patients (6.8%). From the categorized AEs of particular interest, infections were most common. However, in line with previous clinical studies, no new safety signals were identified.</p><p><strong>Conclusion: </strong>Our data confirm that the effectiveness of upadacitinib in routine clinical practice is consistent with previous phase 3 trials for the treatment of active PsA, independent of the disease phenotype. Fast treatment effects reflected MDA achievement after 4 weeks of treatment in both PsA subgroups, similar to what is known from clinical studies.</p><p><strong>Trial registration: </strong>NCT04758117 (ClinicalTrials.gov).</p>","PeriodicalId":21267,"journal":{"name":"Rheumatology and Therapy","volume":" ","pages":"45-64"},"PeriodicalIF":2.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12816421/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145445742","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}