Modern Rheumatology最新文献

Objectives: To evaluate the efficacy and safety of canakinumab 4 mg/kg every 4 weeks administered subcutaneously in Japanese AOSD patients.

Methods: Fourteen participants were included in this open-label, single-arm active-treatment study. The primary endpoint was adapted ACR30 response, with a pre-defined 95% CI lower limit requirement of 40% at week 8. Secondary endpoints included glucocorticoid tapering from weeks 8 to 28; adapted ACR30/50/70/90/100 responses over time; systemic feature score (SFS) over time.

Results: The primary endpoint was not met (6/11 patients [54.5%]; 95% CI: 20.6-88.5; one-sided P = 0.249). From weeks 8 to 28, 6/11 patients (54.5%) successfully tapered oral glucocorticoids. At week 28, among the 11 patients assessed, 70% achieved adapted ACR30 and adapted ACR50, 60% achieved adapted ACR70 and adapted ACR90, and 40% achieved adapted ACR100. At week 28, mean (SD) change from baseline in SFS was -4.3 (2.06). All 14 patients had at least one treatment-emergent adverse event. Six participants (42.9%) had SAEs. Three patients had serious infections; all were considered treatment-related and all recovered.

Conclusion: Although the primary endpoint was not met, week 28 analysis showed that canakinumab treatment led to improvements in various efficacy outcome measures in Japanese patients with AOSD, with no unexpected safety signals.

Telemedicine is a promising solution for addressing regional disparities and improving access to specialized care for patients with rheumatic diseases in Japan. This review provides a comprehensive overview of the current challenges, proposed clinical models, and future directions for implementing telemedicine for these conditions. Drawing from the European Alliance of Associations for Rheumatology (EULAR) points to consider and national surveys, we highlight the potential of hybrid care models, the importance of digital literacy, and the need for interdisciplinary collaboration in this field. We introduce innovative remote care systems currently being piloted in island regions to deliver high-quality care in underserved settings. Additionally, we discuss the outcomes of a health economic simulation, revealing the benefits and financial concerns regarding the current reimbursement structures. Key barriers-technical, clinical, patient-related, organizational, and legal-are analysed alongside proposed countermeasures. Finally, we outline a research agenda to evaluate the effectiveness, safety, and sustainability of telemedicine. With appropriate policy support and system development, telemedicine could play a pivotal role in enhancing the quality and equity of rheumatologic care in Japan.

Objectives: This real-world study evaluated the effectiveness of baricitinib on activities of daily living (ADL) and health-related quality of life (HRQoL) in patients with rheumatoid arthritis (RA) in Japan and explored the association between early pain and fatigue improvements and 12-month remission.

Methods: The study involved patients with RA aged ≥20 who initiated baricitinib and were followed for 12 months. Patient-reported outcomes (PROs) were assessed using visual analogue scale, Locomo 5, EQ-5D-5L, and SF-36 subscales.

Results: The study included 353 patients (mean age 63.4 years). Baricitinib substantially reduced pain levels from a mean (SD) of 48.4 (26.5) mm, fatigue levels from 42.3 (28.3) mm, and morning stiffness from 51.8 (126.9) min at baseline, to 25.2 (21.4) mm, 24.3 (22.7) mm, and 15.8 (38.7) min, respectively, at 12 months. Clinically meaningful improvements were observed in ADL (Locomo 5 scores: 6.9 [5.7] to 4.7 [5.3]) and HRQoL (EQ-5D-5L index scores: 0.700 [0.217] to 0.829 [0.166]) over 12 months. Logistic regression analysis revealed that early improvements in pain and fatigue were predictive of disease remission at 12 months.

Conclusion: Baricitinib improved PROs in patients with RA in Japan, with early symptom relief predicting mid-term disease remission.

Objective: To evaluate long-term safety of filgotinib as treatment of moderately to severely active rheumatoid arthritis (RA) for up to 5 years in Japanese patients.

Methods: Safety was assessed in Japanese patients receiving filgotinib 200 mg (FIL200) or filgotinib 100 mg (FIL100) in three Phase 3, multinational trials (NCT02889796, NCT02873936, NCT02886728) and a long-term extension trial (NCT03025308) through May 2022.

Results: The pooled Japanese population included 124 patients receiving FIL200 and 107 receiving FIL100, with 413.6 and 352.9 patient-years of exposure (median [maximum] of 3.9 [5.0] and 3.7 [5.1] years), respectively. Overall, 97% experienced treatment-emergent adverse events (EAIR 29.1 [95% CI 25.5-33.2]), and 73% experienced treatment-related adverse events (21.8 [18.7-25.4]); rates were similar between FIL200 and FIL100. In the FIL200 and FIL100 groups, EAIRs (95% CIs) were 2.7 (1.5-4.8) and 2.0 (0.9-4.2) for serious infections and 3.1 (1.8-5.4) and 2.6 (1.3-4.9) for herpes zoster. No venous or arterial systemic thromboembolism occurred. There were 0 and 2 incidents of all-cause mortality in the FIL200 and FIL100 groups, respectively.

Conclusions: Long-term filgotinib treatment was well tolerated at 200 mg and 100 mg in Japanese patients with RA over up to 5 years, confirming previous global analyses.

Objective: To evaluate the effectiveness of sarilumab in patients with polymyalgia rheumatica (PMR) who were clinically assessed as having coexisting rheumatoid arthritis (RA).

Methods: Using data from the FIRST registry, a cohort of patients initiating molecular targeted therapy for RA, we identified cases from 2003 to April 2024 in which sarilumab was introduced as the first biologic agent and PMR was concurrently diagnosed. As a control group, we selected patients hospitalized for PMR flare during the same period who received standard of care (SoC) without biologic therapy. The primary outcome was the clinical Polymyalgia Rheumatica Activity Score (clin-PMR-AS) at 52 weeks post-treatment initiation.

Results: Among 5,645 registered cases, 67 patients were identified as having PMR with coexisting RA and received sarilumab as their initial biologic therapy. The control group comprised 76 patients treated with conventional therapy alone. The 52-weeks continuation rate of sarilumab was 77.5%, indicating high treatment persistence. At 52 weeks, clin-PMR-AS scores decreased in both groups. Logistic regression analysis using low disease activity at 52 weeks as the outcome revealed sarilumab use as a significant predictor. After adjusting for baseline differences using inverse probability weighting based on propensity scores, the sarilumab group showed a significantly greater reduction in clin-PMR-AS compared to the SoC group.

Conclusion: These findings suggest that sarilumab may have the potential to improve disease activity in polymyalgia rheumatica compared to conventional therapy.

Objective: This study aimed to determine whether interferon regulatory factor 5 (IRF5) activation and its temporal dynamics in immune cells correlate with disease activity and flares in patients with systemic lupus erythematosus (SLE).

Methods: Patients with SLE were prospectively enrolled and followed up for 52 weeks. The IRF5 nuclear translocation rate (NTR) was assessed in monocytes, dendritic cells, and B cells during baseline and follow-ups. Associations among IRF5 NTR, disease activity, and flares were statistically analyzed.

Results: Of 40 patients enrolled, 27 were included in the analysis after meeting all inclusion criteria. Baseline IRF5 NTR in B cells was correlated with SLE disease activity index scores (r = 0.529, p = 0.005). Nineteen patients developed flares, and high baseline IRF5 NTR showed good predictive accuracy (AUC = 0.763) and an increased flare risk (OR = 25.5, p = 0.003). In survival analysis, patients with high IRF5 NTR had significantly shorter flare-free survival (log-rank p = 0.030) and higher hazard of flare (HR = 7.43, p = 0.010). IRF5 NTR further increased during the 12 weeks preceding flares (p = 0.040).

Conclusion: The IRF5 NTR in B cells is a potential biomarker for disease activity and flare prediction in SLE.

Objectives: Low-dose aspirin (LDA) is widely recommended to prevent hypertensive disorders of pregnancy (HDP). However, the evidence of its effectiveness in pregnancies with systemic lupus erythematosus (SLE) remains limited. This study evaluated the efficacy of LDA in preventing HDP in women with SLE.

Methods: We conducted a retrospective cohort study of 124 pregnancies with SLE managed at our hospital. Pregnancy outcomes were compared between women treated with LDA and those not treated, using propensity score and inverse probability weighting analyses to adjust for confounders.

Results: LDA was used in 65 pregnancies and not used in 59. HDP occurred in 7/65 (10.8%) and 8/59 (13.6%), respectively. After adjusting for potential confounders, including antiphospholipid antibodies, lupus nephritis, chronic hypertension, chronic kidney disease, history of HDP, and hydroxychloroquine use, the risk ratio for HDP with LDA was 0.76 (95% confidence interval: 0.25-2.33; p=0.64). Sensitivity analysis was consistent.

Conclusions: LDA did not significantly reduce the incidence of HDP in women with SLE. This lack of effect may reflect the low event rate in a well-controlled cohort. These findings underscore the need for individualized risk assessment and careful monitoring, beyond reliance on LDA alone, in the management of pregnancies with SLE.

Objectives: Limited information is available on patients with non-systemic juvenile idiopathic arthritis (nsJIA) receiving biologics in Japan. The types of biologics, treatment duration, prior and concomitant treatments, administration route (intravenous [IV] or subcutaneous [SC] injection), and patient characteristics were investigated.

Methods: We investigated nsJIA, excluding psoriatic arthritis and ankylosing spondylitis, using data from a Japanese hospital claims database (2008-2024).

Results: Of the 4191 nsJIA patients in the database, 965 (23.0%) received one or more biologics. For the first biologic, the most common were anti-tumour necrosis factor (anti-TNF) drugs (55.3% overall; adalimumab SC, 32.1%; etanercept SC, 9.8%; infliximab IV, 9.2%; others, <2.1% each), followed by anti-interleukin-6 (anti-IL-6) drugs (39.9% overall; tocilizumab, 39.1% [IV, 32.4%; SC, 6.6%]; others, ≤0.7%), abatacept IV or SC (3.7%), and canakinumab SC (1.0%). Of patients receiving anti-TNF and anti-IL-6 drugs, 40% and 58% continued treatment for ≥1 year, respectively. The most common conventional synthetic disease-modifying antirheumatic drugs (csDMARD) administered prior to anti-TNF and anti-IL-6 drugs was methotrexate (39.0% [anti-TNF] and 33.5% [anti-IL-6]), with others ≤3.6%. The most common csDMARD used concomitantly was also methotrexate (66.9% [anti-TNF] and 50.4% [anti-IL-6]), with others <8.6%.

Conclusions: Our study described the real-world usage of biologics for nsJIA in Japan.

Objectives: Although clinical remission is the primary treatment goal in rheumatoid arthritis (RA), many patients continue to experience residual symptoms that impair quality of life. This study examined whether the complete absence of residual symptoms, assessed using the Okomarigoto Sheet (OS), is associated with achieving the Patient Acceptable Symptom State (PASS), including among patients in Simplified Disease Activity Index (SDAI)-defined remission.

Methods: This cross-sectional, single-center study included 260 consecutive patients with RA. Residual symptoms were evaluated using the OS, with particular emphasis on whether an OS score of zero was associated with PASS achievement. Clinical characteristics were compared between groups, and factors associated with PASS non-achievement were analyzed using univariate and multivariate logistic regression analyses.

Results: Of the 260 patients, 196 achieved PASS. An OS score of zero was strongly associated with PASS achievement (odds ratio [OR], 11.02; 95% confidence interval [CI], 4.06-29.2; p < 0.001). Among patients in SDAI remission, none of the PASS nonachievers had an OS score of zero. PASS nonachievement was associated with higher disease activity, greater functional impairment, and persistent residual symptoms. Multivariate analysis identified Steinbrocker class, C-reactive protein, and total OS score (OR, 1.27; 95% CI, 1.13-1.43; p < 0.001) as independent predictors of PASS nonachievement. In patients in SDAI remission, OS-assessed pain independently predicted PASS nonachievement.

Conclusions: The complete absence of residual symptoms, as measured by the OS, was strongly associated with achieving PASS, even among patients in SDAI-defined remission. Systematic evaluation and targeted management of residual symptoms may improve patient satisfaction and facilitate shared decision-making in RA care.

Objectives: To translate and culturally adapt the Japanese version of the Paediatric Quality of Life Questionnaire (PedsQL) 3.0 Rheumatology Module (PedsQL-RM3.0JA) for children with paediatric rheumatic diseases, as well as to evaluate its reliability and validity.

Methods: This study included 76 patients aged 2-18 years and their parents who completed the Japanese PedsQL 4.0 Generic Core Scale (PedsQL-GCS4.0JA) and PedsQL-RM3.0JA. Internal consistency (Cronbach's α), intraclass correlation coefficients (ICC), and validity were analysed using SPSS 29.

Results: Child self-reports and parent proxy reports had Cronbach's α coefficients ranging from 0.781-0.938 and 0.722-0.915, respectively, indicating good to excellent reliability. ICCs exceeded 0.7 for most subscales. Physical Functioning and Emotional Functioning had moderate to strong correlations with Pain and Daily Living subscales (r = 0.442-0.749), confirming concurrent and convergent validity. The sample size of infants (2-4 years) was insufficient for evaluation. The evaluation had limited reliability in young children (5-7 years) due to a small sample size and developmental considerations.

Conclusions: The PedsQL-RM3.0JA demonstrated high reliability and validity in children aged 8 years and older, supporting its utility for evaluating health-related quality of life in paediatric rheumatic diseases in Japan.