Modern Rheumatology最新文献

Objectives: To examine real-world clinical practices in the treatment of eosinophilic granulomatosis with polyangiitis (EGPA) across Japan and evaluate concordance with national treatment guidelines.

Methods: A cross-sectional, web-based survey was conducted between 14 and 19 February 2024. Physicians from rheumatology, pulmonology, and neurology departments who had treated EGPA within the past 24 months were invited to complete a 17-item questionnaire. The survey assessed actual prescribing behaviour, future treatment preferences, responses to two clinical scenarios, and the frequency of guideline use.

Results: Among 220 respondents (110 rheumatologists, 55 neurologists, and 55 pulmonologists), cyclophosphamide (77.3%) and mepolizumab (73.2%) were frequently used with glucocorticoids (GCs) for remission induction. GC monotherapy was the most commonly selected option overall (31.4%), but its use decreased to 14.8% for severe cases. GC + mepolizumab was the most frequently selected regimen for both maintenance and relapse. Responses to clinical scenarios revealed partial divergence from guideline-based recommendations, particularly regarding the limited use of immunosuppressants and the preferential use of mepolizumab.

Conclusions: This study identified a modest but clear evidence-practice gap in EGPA management in Japan. Broader dissemination of updated guidelines and enhanced interdisciplinary collaboration may help align clinical practice with evidence-based standards and improve patient care.

Objectives: To identify risk factors for myocardial involvement in idiopathic inflammatory myopathy (IIM) and evaluate their prognostic value.

Methods: We analysed 92 IIM patients with abnormal cardiac troponin T (cTnT). Myocardial involvement was diagnosed by late gadolinium enhancement on cardiovascular magnetic resonance. All-cause mortality was recorded during follow-up.

Results: Myocardial involvement occurred in 68.5% and was associated with higher cTnT/creatine kinase (CK) ratios and anti-Ro52 positivity. Anti-Ro52-positive patients exhibited higher rates of late gadolinium enhancement and increased E/e'. Both cTnT/CK [odds ratio (OR) = 1.030, P = .024] and anti-Ro52 (OR = 5.629, P = .003) independently predicted myocardial involvement. A cTnT/CK cutoff > 19.3% predicted myocardial involvement [area under the curve (AUC) = 0.660], rising to 0.780 when combined with anti-Ro52. Subgroup analysis showed cTnT/CK was discriminative only in anti-Ro52-negative individuals. During a 36-month follow-up, 18 deaths occurred. Adjusted Cox regression identified cTnI positivity [hazard ratio (HR) = 7.395, P = .001] and cTnT/CK (HR = 1.012, P = .037) as independent mortality predictors. Time-dependent receiver operating characteristic at 3 years showed AUCs of 0.68 (cTnI) and 0.64 (cTnT/CK). Kaplan-Meier analysis confirmed worse survival with positive cTnI or a high cTnT/CK.

Conclusions: The cTnT/CK ratio identifies myocardial involvement and predicts mortality in IIM patients with abnormal cTnT. Combining it with anti-Ro52 antibodies improves the detection of myocardial involvement.

Rheumatoid Arthritis (RA) is a progressive autoimmune disorder with substantial global health and economic impacts. Despite advancements in conventional therapies, biologics, and targeted drugs, challenges such as adverse effects, cost, and interindividual heterogeneity underscore the need for safer, precision-based treatments. Notably, emerging evidence highlights the pivotal role of the gut microbiota-immune axis in RA pathogenesis. Affected individuals typically exhibit gut dysbiosis, marked by increased pro-inflammatory taxa and reduced anti-inflammatory species, which disrupts immune homeostasis through Th17/Treg imbalance, molecular mimicry, and compromised gut barrier integrity. These processes drive systemic inflammation, exacerbating both articular destruction and extra-articular manifestations. Probiotics demonstrate therapeutic potential by modulating this axis via microbiota restoration, barrier reinforcement, and immune regulation. Strain-specific effects have been documented in both preclinical and clinical studies, although efficacy varies depending on host genetics, baseline microbiota composition, and intervention protocols-a variability underscoring the need for personalized probiotic selection. This review consolidates current knowledge on gut microbiota-immune crosstalk in RA and explores probiotics as precision therapeutics. Integrating multi-omics (metagenomics, metabolomics) with targeted probiotic strategies could enable the development of personalized interventions. While translational obstacles persist, including mechanistic complexity and limited clinical validation, the gut microbiota-immune axis offers a novel paradigm for RA management. Future priorities include large-scale trials, biomarker discovery, and combinatorial approaches to advancing microbiome-guided precision medicine in autoimmune diseases.

Objectives: To investigate the standardized mortality ratio (SMR), causes of death, and mortality risk factors in Japanese patients with rheumatoid arthritis (RA) between 2007 and 2021, representing the biological disease-modifying antirheumatic drug (bDMARD) era.

Methods: We analysed Japanese patients in the Institute of Rheumatology, Rheumatoid Arthritis cohort. The SMR was calculated using the Japanese General Population Life Table. Multiple imputation methods were used for sensitivity analysis of lost-to-follow-up cases. Risk factors were analysed using a time-dependent Cox proportional hazards model.

Results: Among 10,613 patients with RA, 915 deaths occurred for 99,364.8 patient-years. Major causes of death were malignancy (27.8%), respiratory disease (22.3%), and cardiovascular disease (16.3%). The SMR varied based on lost-to-follow-up assumptions: 0.92 [95% confidence interval (CI): 0.86-0.98] assuming all survived, 1.57 (95% CI: 1.47-1.68) assuming lost cases had equal mortality to followed cases, and 1.68 (95% CI: 1.58-1.79) assuming 1.65 times higher mortality than followed cases, respectively. Time-dependent analysis revealed protective associations with methotrexate (MTX) and bDMARDs, while even low-dose glucocorticoids showed increased mortality risk.

Conclusions: Japanese patients with RA show excess mortality despite bDMARD-era treatments. MTX and bDMARDs were protective, while glucocorticoids increased mortality risk.

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

Methods: We used data from a Japanese hospital claims database (2008-24).

Results: Of the 2000 sJIA patients in the database, 315 (15.8%) received one or more biologics. For the first biologic, the most common were anti-interleukin-6 (anti-IL-6) drugs (82.5%; tocilizumab, 82.2% [IV, 65.1%; SC, 17.1%]; others, <0.4%), followed by anti-tumour necrosis factor drugs (11.7%; adalimumab SC, 4.4%; infliximab IV, 4.1%; others, < 1.6% each), canakinumab SC (3.8%), and abatacept IV or SC (1.9%). Over 53% of patients received anti-IL-6 drugs for ≥1 year. The most common conventional synthetic disease-modifying antirheumatic drugs administered prior to anti-IL-6 drugs were cyclosporine (11.9%), methotrexate (11.5%), and tacrolimus (6.2%), and those most commonly administered concomitantly with anti-IL-6 drugs were methotrexate (22.7%), cyclosporine (16.9%), and tacrolimus (11.5%). Fifty patients switched from tocilizumab IV to a second biologic (tocilizumab SC, 50.0%; canakinumab SC, 36.0%; others ≤4.0% each).

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

Objectives: This study of telemedicine aims to clarify the needs and issues of patients with rheumatic diseases and the medical personnel involved in their care.

Methods: A questionnaire survey, targeting members of the Japan Rheumatology Association and pertinent patients/companions, was conducted on the use of telemedicine in this field.

Results: Questionnaires were collected from 351 internists, 133 orthopaedists, and 144 patients/their companions. According to the internists and orthopaedists, 77.5% and 58.6% of their patients require ≥1 h one-way travel to a medical institution, respectively. Among the patients treated, 28.5% and 19.5% were from remote areas or islands, and 52.1% and 38.3% were from areas with a shortage of specialized medical care. Meanwhile, a positive view of remote medical care was held by 67.2% of the internists, 54.9% of the orthopaedists, and 73.0% of the patients/their companions. Medical personnel who treat patients from remote islands and in areas with a shortage of specialized medical care were especially open to performing remote medical care via telemedicine systems. Medical personnel expressed concerns about the quality of medical care, while the patients expressed concerns about reduced communication.

Conclusions: This study reveals some of the concerns of medical personnel and patients with rheumatic diseases about telemedicine.

Objective: To clarify T/B cell-specific gene expression patterns using RNA-Seq in IgG4-related disease (IgG4-RD).

Methods: Pathologically confirmed submandibular gland (SMG) (n = 3) and peripheral blood mononuclear cells (PBMC) (n = 4) from four treatment-naïve patients with definite IgG4-RD, as well as PBMCs from primary Sjögren syndrome (pSS) (n = 3) and healthy controls (HCs) (n = 3), were collected, and subsequently Pan T and CD19+ B cells were sorted. We conducted RNA sequencing to compare the gene expressions of Pan T and CD19+ B cells in SMGs and PBMCs in IgG4-RD or IgG4-RD versus pSS and HCs in PBMCs. Ingenuity pathway analysis (IPA) and qPCR validation were performed for differentially expressed genes (DEGs).

Results: Principal component analysis (PCA) results showed the gene expression patterns of Pan T and CD19+ B cells derived from SMGs differed from those derived from PBMCs in IgG4-RD. However, the gene expression patterns of Pan T and CD19+ B cells derived from PBMCs were not clustered between groups. A total of 214 upregulated and 50 downregulated DEGs in Pan T cells and 630 upregulated and 109 downregulated DEGs in CD19+ B cells were identified in SMGs compared with PBMCs in IgG4-RD. The upregulated DEGs in SMGs of IgG4-RD included cytokines, chemokines, and transcription regulators. IPA for these DEGs clarified immune system-related pathways were positively regulated in SMGs compared with PBMCs in IgG4-RD. Quantitative PCR validated significantly increased mRNA expression of IL-21 and EGR2 by Pan T cells in SMGs compared with PBMCs of IgG4-RD.

Conclusion: RNA-Seq clarified the DEGs of Pan T and CD19+ B cells from SMGs in comparison with PBMCs, which might contribute to the pathogenesis of IgG4-RD.

Objectives: The 2023 EULAR guidelines for systemic sclerosis (SSc) recommend biologics (rituximab, tocilizumab), mycophenolate mofetil (MMF), and nintedanib in addition to cyclophosphamide for interstitial lung disease (ILD). This study investigated recent actual use of these drugs in Japan.

Methods: We analysed data from a Japanese hospital claims database (2020-3), identifying patients with SSc disease codes (ICD-10 M34.x) and/or ILD codes. Patients with coexisting autoimmune disease codes were also included.

Results: Of 14,522 SSc patients, 2080 (14.3%) received small-molecule drugs and 618 (4.3%) received biologics. For SSc, common first small-molecule drugs were methotrexate (24.2%), nintedanib (19.5%), tacrolimus (17.9%), and MMF (16.8%); common first biologics were rituximab (44.2%) and tocilizumab (29.1%). Of 4890 SSc-ILD patients, 1081 (22.1%) received small-molecule drugs and 282 (5.8%) received biologics. For SSc-ILD, common first small-molecule drugs were nintedanib (30.8%), tacrolimus (20.9%), and MMF (18.3%); common first biologics were rituximab (51.8%) and tocilizumab (25.2%). Rituximab showed the greatest increase in use for both SSc and SSc-ILD between 2020 and 2023. Common subsequent treatments following rituximab or intravenous cyclophosphamide (which are typically administered for a limited duration) were nintedanib, MMF, and rituximab.

Conclusions: Recent actual drug use in Japan has been aligning increasingly closely with the EULAR recommendations.

Objectives: This study assessed the needs, perceptions, and challenges associated with telemedicine in the treatment of oligoarticular/polyarticular juvenile idiopathic arthritis (oJIA/pJIA) and childhood-onset systemic lupus erythematosus (cSLE) in Japan.

Methods: A nationwide survey was conducted using Google Forms targeting members of the Japan College of Rheumatology, the Paediatric Rheumatology Association of Japan, and paediatricians affiliated with core paediatric specialty training facilities.

Results: Responses were received from 128 physicians, with 77%, 50%, 27%, and 21% of patients travelling for more than 1 hour, crossing prefectural borders, coming from areas with limited specialised care, and residing in remote islands and regions, respectively. JCR board-certified rheumatologists are more likely to treat these patients. Telemedicine was expected to reduce travel time (92.2%) and consultation time (92.2%), while concerns included patients' preference for in-person consultations (89.8%) and perceived differences in the quality of care (86.7%). Telemedicine was supported by 71.9% of respondents for stable oJIA/pJIA cases and 76.3% for stable cSLE cases.

Conclusions: Many physicians support telemedicine for patients with oJIA/pJIA or cSLE who travel long distances. Further studies should explore the quality differences between telemedicine and in-person consultations.