Rheumatology and Therapy最新文献

Introduction: 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.

Methods: 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.

Results: 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.

Conclusions: Data from this interim analysis support the long-term effectiveness and safety of canakinumab for the treatment of TRAPS.

Introduction: 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.

Methods: 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).

Primary outcome: 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.

Results: 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.

Conclusions: 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.

Introduction: 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.

Methods: 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.

Outcomes: 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.

Results: 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.

Conclusion: 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.

Trial registration: ClinicalTrials.gov identifier, NCT05195814.

Introduction: 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.

Methods: 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).

Results: 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.

Conclusions: 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.

Introduction: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Trial registration: NCT04758117 (ClinicalTrials.gov).

Introduction: The primary objective was to describe the therapeutic approach to methotrexate (MTX) use at the initiation of the first biologic or targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD) in the treatment of rheumatoid arthritis (RA). Secondary objectives included characterising participants initiating b/tsDMARD treatment, examining treatment strategies over time, monitoring disease progression, and identifying factors influencing treatment choices.

Methods: This longitudinal, prospective, non-interventional, multicentre study (STRATEGE2) enrolled adult participants with RA who had been treated with MTX for at least 3 months and required b/tsDMARD treatment due to persistent disease activity. Outcomes were assessed at 12 months (M12) and 24 months (M24) after initiating b/tsDMARD treatment.

Results: At baseline, 173 participants with RA had a mean (SD) disease duration of 5.6 (7.3) years and a mean Disease Activity Score in 28 joints (DAS28) score of 4.3 (1.2). Approximately two-thirds had been on MTX for over a year, with a mean weekly dose of 18.8 (4.2) mg (median 20.0), and 72.3% received it subcutaneously. MTX was continued at the initiation of b/tsDMARD therapy in 97.7% of participants. By M12, 83.2% of participants remained on MTX, with 39.9% (95% CI 32.5-47.6) maintaining the same dosage and route of administration. Discontinuation of MTX was primarily due to participant choice or adverse events. At M24, the mean change in DAS28 score was - 2.0 (1.3), with 66.0% of participants achieving remission. On the basis of European Alliance of Associations for Rheumatology (EULAR) classification criteria, 65.2% had a good response, 19.1% a moderate response, and 15.6% an inadequate response.

Conclusion: The STRATEGE2 study investigators adhered to current clinical guidelines by continuing MTX in combination with b/tsDMARD initiation for the management of RA.

Trial registration: ClinicalTrials.gov: Therapeutic Strategy Associated with bDMARDs or tsDMARDs in Rheumatoid Arthritis and Psoriatic Arthritis (STRATEGE2), NCT05082805.

Introduction: Psoriatic arthritis (PsA) is a heterogeneous, progressive inflammatory disease that often arises in patients with psoriasis. Increasing evidence highlights potential critical windows of opportunity during which early recognition and appropriate therapeutic intervention can alter long-term outcomes.

Methods: This review summarizes evolving treatment strategies for PsA across the disease continuum-from psoriasis and very early PsA through to established disease-focusing on the rationale for rapid intervention and risk-stratified use of biologics and emerging therapies.

Results: Data from many recent trials support the principle that earlier use of effective targeted therapy can improve outcomes, including controlling psoriasis and arthritis, inducing remission and even drug-free remission. Treat-to-target strategies, with close monitoring and timely escalation, are central to optimizing outcomes. In this recent literature, biologics targeting TNF, IL-17, and IL-23 have reshaped our understanding of the treatment landscape. Novel oral cytokine-signaling inhibitors, such as TYK2 and IL-23 receptor antagonists, represent promising future options but require long-term safety and head-to-head data in PsA. Comorbidities, patient preference, and safety considerations remain essential in tailoring therapy.

Conclusions: PsA management is shifting from reactive to proactive care. Aligning clinical practice toward early detection of skin and joint disease, rapid access to appropriate biologics, and disciplined treat-to-target approaches offer the best prospect for durable remission and improved quality of life. The next challenge lies in defining early PsA, predicting progression from psoriasis, and integrating new therapeutic classes into evidence-based treatment algorithms.

Introduction: Psoriatic arthritis (PsA) is a heterogeneous disease, and clinical manifestations can differ between sexes. Sex-disaggregated baseline characteristics, guselkumab efficacy, and radiographic progression were assessed in a pooled cohort of randomized controlled trial (RCT) participants with active PsA.

Methods: Post hoc analyses of DISCOVER-1 (N = 381), DISCOVER-2 (N = 739), and COSMOS (N = 285) assessed sex-related baseline characteristics differences. Week (W) 24 clinical response rates with guselkumab 100 mg at W0/W4/every 8W (Q8W) were compared between sexes using multivariate logistic regression. In DISCOVER-2, multivariate repeated-measures mixed models evaluated associations between sex and radiographic progression with guselkumab Q4W + Q8W through W100, and between early (W8) response in joint disease activity with guselkumab Q4W + Q8W and radiographic progression, stratifying by sex.

Results: Females were older; had higher body mass index; longer PsA duration; less severe psoriasis; more prevalent enthesitis; and reported more fatigue, pain, and functional impairment. Analyses adjusting for sex-specific differences in baseline characteristics showed no significant sex impact on guselkumab clinical response. Through W100, males exhibited significantly greater radiographic progression than females in unadjusted and adjusted models. Early clinical improvement in joint disease activity with guselkumab afforded significantly less radiographic progression through W100 in males (p = 0.0288) and numerically less in females.

Conclusions: Despite being associated with significant differences in characteristics at baseline, sex had no independent effect on guselkumab clinical efficacy in this RCT cohort. The known independent association between male sex and radiographic progression was confirmed; males exhibited a stronger relationship between early improvement in joint disease activity and lower long-term rates of radiographic progression.

Trial registration: ClinicalTrials.gov identifier NCT03162796, NCT03158285, NCT03796858.

Introduction: The human leukocyte antigen (HLA)-B27 is associated with axial spondyloarthritis (axSpA) and is a predictor of response to tumor necrosis factor inhibitors. However, limited data are available on HLA-B27 and interleukin-17 inhibitors. We evaluated the influence of HLA-B27 status on ixekizumab response through 52 weeks in patients with axSpA.

Methods: Data were analyzed from three randomized placebo-controlled trials: COAST-V (NCT02696785), COAST-W (NCT02696798), and COAST-X (NCT02757352). Patients fulfilled the Assessment of SpondyloArthritis international Society (ASAS) criteria for radiographic (r)-axSpA or non-radiographic (nr)-axSpA. Patients were randomized to receive 80 mg ixekizumab every 2 weeks, 80 mg ixekizumab every 4 weeks, or placebo. This post hoc analysis assessed the intent-to-treat population. The magnitude of benefit was calculated as the value for ixekizumab minus placebo.

Results: Among ixekizumab-treated patients with r-axSpA at week 16, ASAS ≥ 40% improvement (ASAS40) was achieved by 39.6% (n = 118/298) of HLA-B27-positive and 29.3% (n = 12/41) of HLA-B27-negative patients. The magnitude of benefit (ixekizumab-placebo) was 23.5% for HLA-B27-positive and 15.2% for HLA-B27-negative patients. At week 52, 44% of HLA-B27-positive and 31.7% of HLA-B27-negative patients achieved ASAS40. Similar trends were seen for Axial Spondyloarthritis Disease Activity Score low disease activity (ASDAS LDA; < 2.1) and Bath Ankylosing Spondylitis Disease Activity Index ≥ 50% improvement (BASDAI50). In ixekizumab-treated patients with nr-axSpA at week 16, ASAS40 response was achieved by 41.7% (n = 55/132) of HLA-B27-positive and 28.0% (n = 14/50) of HLA-B27-negative patients. The magnitude of benefit was 19.2% for HLA-B27-positive and 16.0% for HLA-B27-negative patients. At week 52, 52.3% of HLA-B27-positive and 32.0% of HLA-B27-negative patients achieved ASAS40. Similar trends were seen among patients with nr-axSpA for ASDAS LDA and BASDAI50.

Conclusions: In patients with r-axSpA and nr-axSpA, ixekizumab improved response through 52 weeks for both HLA-B27-positive and HLA-B27-negative patients. However, the magnitude of benefit for ixekizumab versus placebo was numerically greater for HLA-B27-positive patients.

Trial registration: ClinicalTrials.gov identifiers, NCT02696785, NCT02696798, and NCT02757352.

Introduction: The "Ustekinumab Pediatric Opportunistic Pharmacokinetics Study" (U-POPS) was conducted to evaluate the pharmacokinetics (PK) and safety of ustekinumab, an interleukin-12/23p40 antagonist, in patients with juvenile psoriatic arthritis (jPsA) who were already receiving ustekinumab via an opportunistic study design. U-POPS was based on the clinical hypothesis that PK should be similar in jPsA and pediatric psoriasis (PsO) populations to further strengthen the extrapolation paradigm between the two populations.

Methods: This real-world, open-label study enrolled participants 5 to < 18 years old with jPsA or 6 to < 18 years with PsO (internal control) who were on ustekinumab for ≥ 16 weeks and received ≥ 3 doses to ensure steady-state concentrations. Ustekinumab was prescribed by the treating physician and supplied outside of the study; PK samples were collected at intervals during a maximum of 16 weeks. The primary endpoint was the observed serum ustekinumab concentrations, which were compared to model-predicted values from prior PsO PK data.

Results: The study included 11 patients with jPsA (mean age, 15.1 years) and 20 with pediatric PsO (mean age, 12.6 years), yielding 100 PK samples. The median ustekinumab dose was 45 mg every 12 weeks. Observed serum ustekinumab concentration-time profiles aligned well with model-predicted concentration-time profiles from pediatric PsO patients. Treatment-emergent adverse events (TEAEs) occurred in 25.8% of patients (jPsA, n = 1; PsO, n = 7) and were consistent with those observed in other ustekinumab studies, with no serious TEAEs reported.

Conclusions: The opportunistic U-POPS study confirmed the existing population PK model for ustekinumab and suggests that ustekinumab exposure and time course are similar between jPsA and pediatric PsO populations, with no new safety concerns.

Trial registration: ClinicalTrials.gov identifier, NCT05252533 (registration date: 02-16-2022); EudraCT Number, 2021-005085-18.