In this review, we summarized the current evidence on the risks of incident malignancy and cancer recurrence in patients with rheumatoid arthritis (RA) treated with methotrexate (MTX). Before considering the effect of MTX, it is important to recognize the malignancy risk associated with RA itself. The overall risk of malignancy in patients with RA modestly increased, as per two meta-analyses, although Japanese studies report inconsistent findings, with one showing a slightly decrease and another a slight increase. The risk of malignant lymphoma has increased, whereas the risk of colorectal cancer appears reduced. Additionally, there are concerns regarding the increased risk of lung and skin cancers. However, there is limited evidence specific to patients with RA treated with MTX. According to an Australian report, patients have a higher risk of overall malignancy, with an increased risk of malignant lymphoma, lung cancer, and melanoma. Studies comparing MTX with tumor necrosis factor inhibitors have reported no significant difference in the overall malignancy risk or increased malignancy risk. In White patients, MTX has been associated with an increased risk of recurrence in patients with RA and a history of non-melanoma skin cancer. There is insufficient evidence regarding the risks of MTX use in patients with RA and malignancy. Therefore, decisions regarding MTX use should be made individually based on shared decision-making, and careful follow-up is necessary.
OBJECTIVES:Enthesitis-related arthritis (ERA), characterized by chronic arthritis and/or enthesitis, is a relatively rare subtype of juvenile idiopathic arthritis (JIA). Achieving sustained disease control can be challenging. We aimed to characterize ERA and to evaluate the efficacy of salazosulfapyridine (SASP) treatment. METHODS:We retrospectively reviewed 23 patients with ERA treated in our institute between 2015 and 2025. Clinical characteristics, laboratory findings, and treatment courses were analyzed descriptively. Patients were categorized into three groups based on treatment escalation following NSAID therapy. RESULTS:The median age at onset was 10 years, and median disease duration before diagnosis was 11 months; 47.8% were females. Axial involvement was present in 65.2%, and psychological comorbidities in 52.2%. Nineteen patients received SASP; four who were younger at onset and had lower CRP levels at diagnosis were maintained on SASP monotherapy without treatment escalation. Active joint and enthesitis counts generally improved during follow-up, although some patients had persistent disease activity at 12 months. No severe adverse events were observed. CONCLUSIONS:Diagnostic delay and psychological comorbidities were characteristic of ERA. SASP may be beneficial in selected patients with lower inflammatory activity at diagnosis; prospective studies are needed to better define its role in ERA management.
OBJECTIVES:This study aimed to evaluate real-world effectiveness and long-term retention of baricitinib in Japanese patients with rheumatoid arthritis (RA), including those classified as difficult-to-treat (D2T). METHODS:This 24-month observational study enrolled patients initiating baricitinib, stratified by prior use of biological/targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) and baseline Clinical Disease Activity Index (CDAI) scores. Key endpoints included time-to-discontinuation, achievement of and time to low disease activity (LDA) or remission. Data were analysed using logistic regression models adjusted for demographic and clinical variables. RESULTS:Baricitinib demonstrated sustained effectiveness, with 58.2% of overall patients (N=353) and 42.0% of patients with D2T RA (N=88) remaining on treatment at 24 months. CDAI remission was achieved in 36.4% of overall patients and 22.9% patients with D2T RA. Discontinuation was mainly due to primary non-response (11.0%). Mean (SD) changes in patient-reported outcomes (PROs) from baseline scores were: patient global assessment of disease activity (-21.7 [28.4] mm), Health Assessment Questionnaire-Disability Index (-0.360 [0.601]), and pain visual analogue scale (-24.9 [26.8] mm). Among baseline glucocorticoid users retained on baricitinib at 24 months, 55.9% discontinued glucocorticoids. CONCLUSION:Baricitinib showed sustained effectiveness and retention, including in patients with D2T RA; early improvements in pain and fatigue were predictive of CDAI disease remission during the 24-month follow-up.
OBJECTIVES:Total elbow arthroplasty is a common treatment for elbow stiffness due to rheumatoid arthritis. Although linked prostheses are often preferred, unlinked implants may reduce prosthetic stress and loosening risk. This study evaluated the clinical outcomes of unlinked total elbow arthroplasty in patients with rheumatoid arthritis presenting with stiff elbows. METHODS:This retrospective study included 9 women with 10 stiff elbows due to rheumatoid arthritis who underwent primary total elbow arthroplasty using an unlinked implant. Stiffness was defined as a range of motion of less than 60°. Mean age was 58 years and mean follow-up was 59 months. Outcomes included range of motion, Mayo Elbow Performance Score, pain during movement assessed with a visual analogue scale, complications, and implant loosening. RESULTS:Extension improved from -59° to -38°, flexion from 101° to 123° and arc of motion from 42° to 85°. Mayo Elbow Performance Score improved from 53 to 93, and pain score from 36 to 1. Two cases of transient ulnar neuropathy resolved without treatment. No implant loosening, dislocation, or revision surgery occurred. CONCLUSIONS:Unlinked total elbow arthroplasty improved clinical outcomes without major complications and may be a viable option for stiff elbows in patients with rheumatoid arthritis.
OBJECTIVES:To investigate the achievement of complete remission (CR) and the management for relapsed cases in the treatment of idiopathic inflammatory myopathies (IIM). METHODS:A total of 132 patients were retrospectively analysed. CR was defined as no evidence of disease activity in all involved organs for a continuous period of six months. Relapse was defined as a dose increase of glucocorticoid (GC) more than 50% and an increase in prednisolone (PSL) equivalent to more than 0.4 mg/kg/day. Clinical data were collected by electrical chart review. RESULTS:Eighty-eight (66.7%) patients achieved CR with an initial treatment. Forty-three patients experienced at least one relapse. Anti-ARS antibody was positively and achieving CR was negatively associated with relapse (HR 3.02 and OR 0.17, respectively). Re-induction therapies were classified into three groups: high-dose GC plus one immunosuppressant (IS)/biologics (H+1IS, n=12), moderate-dose GC plus two IS/biologics (M+2IS, n=12), and moderate-dose GC plus one IS/biologics (M+1IS, n=19). The frequency of second relapse was least in M+2IS regimen. Concomitant use of two IS/biologics did not increase the incidence of severe adverse events. CONCLUSIONS:CR was achieved in two-thirds of IIM patients. Achieving CR was protective for relapse. Combination therapy with two IS/biologics might be preferable in relapsed cases.
OBJECTIVES:Epidemiological studies consistently report an increased risk of lung cancer among rheumatoid arthritis patients. Proposed risk factors include male sex, smoking, and rheumatoid arthritis-associated interstitial lung disease. However, whether a direct genetic causal link exists between rheumatoid arthritis-associated interstitial lung disease and lung cancer remains unexplored. We used Mendelian randomization with East Asian genetic instruments to evaluate this relationship. METHODS:We conducted a two-sample Mendelian randomization in which genetic instruments for rheumatoid arthritis-associated interstitial lung disease were derived from an East Asian GWAS (358 RA-ILD cases, 4 550 RA controls), and lung cancer associations were obtained from a cross-ancestry GWAS meta-analysis (20 378 cases, 18 696 controls). Causal effects were estimated using inverse-variance weighted, Mendelian randomization-Egger, and weighted median methods. RESULTS:Ten single nucleotide polymorphisms were identified as genetic instruments. Inverse-variance weighted analysis revealed no significant causal association between genetically predicted rheumatoid arthritis-associated interstitial lung disease and lung cancer (odds ratio = 1.00; 95% confidence interval: 0.99-1.01; p-value = 0.78). Sensitivity analyses showed no horizontal pleiotropy or heterogeneity. CONCLUSIONS:Our findings suggest that the severe lung complications of rheumatic arthritis do not inherently share a direct, genetically driven pathway with malignancy. The observed clinical risk may be explained by shared environmental factors, such as smoking, or chronic immune dysregulation, rather than inherent genetic pleiotropy, although further investigation is needed to clarify these mechanisms.
OBJECTIVES:This study examined whether adopting the Boolean 2.0 remission criteria results in the inclusion of patients with a higher burden of residual symptoms (RS) in rheumatoid arthritis (RA). It also aimed to characterize differences in RS burden across remission definitions. METHODS:This cross-sectional, single-center study included 400 consecutive patients with RA. RSs were assessed using the Okomarigoto Sheet (OS), which evaluates pain, morning stiffness, and fatigue. Clinical remission was defined using the Disease Activity Score in 28 joints with C-reactive protein (DAS28-CRP), Clinical Disease Activity Index (CDAI), Simplified Disease Activity Index (SDAI), and Boolean 1.0 and 2.0 criteria. The primary outcome was the proportion of patients achieving OS = 0. Mixed-effects logistic regression and subgroup analyses were conducted to compare RS burden across remission definitions. RESULTS:The proportion of patients achieving complete absence of RSs differed across remission definitions, with the highest rate observed in Boolean 1.0 remission (52.7%), followed by Boolean 2.0 (45.0%) and DAS28-CRP (37.5%). Compared with Boolean 1.0 remission, patients meeting Boolean 2.0 but not Boolean 1.0 criteria had significantly higher total and domain-specific OS scores (all p < 0.001). Similar findings were observed among patients achieving DAS28-CRP remission but not Boolean 1.0 remission. Mixed-effects logistic regression indicated no significant difference between Boolean 1.0 and Boolean 2.0 remission in achieving OS = 0. CONCLUSIONS:RS burden in RA varies depending on the remission definition. Boolean 2.0 remission expands the classification of remission and is associated with higher multidimensional residual symptom scores than Boolean 1.0 remission.
Methotrexate (MTX) remains the anchor drug in the management of rheumatoid arthritis (RA). However, its clinical use is frequently limited by intolerance, leading to dose reduction or discontinuation. In addition, oral MTX exhibits pharmacokinetic limitations, including dose-dependent absorption and reduced bioavailability at higher doses, which may compromise therapeutic efficacy. Subcutaneous (SC) MTX has emerged as a strategy to overcome these limitations by providing more consistent bioavailability and potentially improved tolerability. Evidence suggests that switching from oral-to-SC MTX may improve gastrointestinal (GI) intolerance and support treatment persistence, whereas evidence for improved disease control or reduction of serious MTX-related toxicity remains limited. Recent Japanese studies suggest the potential utility of this approach at MTX doses commonly used in Japan, although evidence for the superiority of SC MTX over oral MTX in low-dose settings remains limited. This narrative review summarizes current evidence on MTX intolerance and oral-to-SC route switching in RA, with a focus on practical strategies for treatment optimization. Overall, oral-to-SC MTX switching may represent an important option to improve GI intolerance and support treatment persistence in patients with RA.
Dysphagia is a common and clinically significant complication in idiopathic inflammatory myopathies (IIM), contributing to aspiration pneumonia, malnutrition, and reduced quality of life. However, its prognostic significance in terms of survival and swallowing outcomes remains unclear. A narrative review was conducted using PubMed to identify relevant studies published between January 2000 and April 2026. Dysphagia in IIM is associated with increased mortality, primarily due to aspiration-related complications and underlying disease severity. Emerging evidence indicates that this association may be modified by the presence of malignancy, particularly in dermatomyositis. Swallowing outcomes are heterogeneous: some patients show improvement with immunosuppressive therapy or intravenous immunoglobulin, whereas others experience persistent or progressive dysfunction, especially those with inclusion body myositis. Key prognostic factors include age, disease subtype, autoantibody status, and baseline severity of dysphagia. Dysphagia in IIM should be recognized as a clinically important manifestation associated with both survival and functional outcomes. Early identification and appropriate management are essential to improve patient prognosis. Further prospective studies are needed to establish standardized assessment and risk stratification strategies.
OBJECTIVES:To examine the rate of glucocorticoid (GC) discontinuation and to identify factors associated with successful GC withdrawal in patients with systemic lupus erythematosus (SLE). METHODS:This multicentre retrospective study used data from the ANSWER-SLE cohort. Patients fulfilling the 2019 ACR/EULAR classification criteria and registered between October 2023 and May 2025 were included. Patients were classified by GC status at enrolment as follows: discontinued GCs (Group 1), GC-naïve (Group 2), or continuing GC therapy (Group 3). RESULTS:Among 1,689 patients, 107 (6.3%) were in Group 1, 130 (7.7%) in Group 2, and 1,452 (86.0%) in Group 3. Disease duration was longest in Group 3 (P<0.001). Group 2 had lower total 2019 classification scores (P=0.008), higher LLDAS attainment (P<0.001), and lower SLICC Damage Index scores (P<0.001). Group 1 had the highest concomitant use of hydroxychloroquine (HCQ) (P<0.001), mycophenolate mofetil (MMF) (P<0.001), and belimumab (P=0.001). In multivariable Cox regression analysis, older age at disease onset (HR=1.049, P<0.001), HCQ (HR=5.75, P<0.001), MMF (HR=1.82, P=0.009), and belimumab (HR=1.72, P=0.041) were independently associated with GC discontinuation. CONCLUSION:GC withdrawal may be achievable in selected patients with SLE, particularly those receiving HCQ, MMF, and belimumab, and in patients with an older age at disease onset.
OBJECTIVES:To examine factors affecting the apparent clearance (CL/F) of total methotrexate polyglutamates (MTX-PGs) in red blood cells (RBCs) in Japanese patients with rheumatoid arthritis (RA) using population pharmacokinetic analysis. METHODS:A total of 268 Japanese RA patients receiving low-dose MTX therapy were included. RBC MTX-PGs concentrations were measured using LC-MS/MS. Patient characteristics, including genetic polymorphisms in transporters (RFC1, ABCB1, ABCC2, ABCG2) and enzymes (FPGS, GGH) related to MTX metabolism, were evaluated as covariates. Population pharmacokinetic analysis was performed using Phoenix NLME software. RESULTS:The final population pharmacokinetic model identified body weight (BW), estimated glomerular filtration rate (eGFR), and proton pump inhibitor (PPI) co-administration as covariates for CL/F of total RBC MTX-PGs. Lower BW, lower eGFR, and PPI use were associated with decreased CL/F. Genetic polymorphisms were not identified as significant covariates for CL/F in this study. CONCLUSIONS:BW, eGFR, and PPI co-administration may influence the CL/F of total RBC MTX-PGs in Japanese patients with RA. These findings may support model-informed interpretation of RBC MTX-PGs concentrations, although further studies are needed to confirm the clinical applicability of the model.
OBJECTIVES:To investigate the impact of switching to benralizumab on flare risk in patients with eosinophilic granulomatosis with polyangiitis (EGPA) previously treated with mepolizumab. METHODS:We conducted a single-centre retrospective cohort study including 26 patients with EGPA who received mepolizumab. A landmark analysis was performed at 910 days after mepolizumab initiation (median time to switching), and patients were grouped according to treatment. The primary outcome was disease flares requiring treatment intensification. We used a Cox model with treatment switching as a time-dependent covariate. RESULTS:In the landmark analysis, the benralizumab group (n=4) had a higher flare rate than the mepolizumab group (n=10) (log-rank test, P = 0.002). However, the Cox model did not converge and the time-dependent analysis yielded an imprecise estimate (hazard ratio 3.14, 95% confidence interval 0.31-32.02). The 1-year flare-free rate after switching to benralizumab (n=19) was 94.1%, and no severe flares occurred. Most patients had low disease activity at switching, and switching was primarily driven by patient preference. CONCLUSIONS:Short-term flare-free survival after switching to benralizumab was high despite a small number of minor flares. Further evidence is warranted to assess long-term outcomes.
OBJECTIVES:Anti-citrullinated protein antibodies (ACPA) predict rheumatoid arthritis (RA) and radiographic joint destruction. However, data on long-term outcomes in ACPA-positive individuals without RA are limited. This study aimed to investigate the six-year cumulative incidence of RA and radiographic progression among ACPA-positive individuals without RA at baseline in a population-based cohort. METHOD:A total of 1,541 participants without RA at baseline were enrolled from the population-based cohort, of whom 28 tested positive for ACPA. Incident cases of RA were identified based on participants' self-reported physician diagnosis and medication history over a six-year follow-up period. Radiographic progression in the hands was assessed using the van der Heijde modified Sharp score. RESULTS:Five participants developed RA within the first three years, including three who were ACPA-positive at baseline (all with high ACPA titers). After 3 years, additional RA cases were identified only among participants who were ACPA-negative at baseline, whereas no further cases occurred among those who were ACPA-positive at baseline. The positive predictive value (PPV) of ACPA for RA within three years was 15.0%, rising to 30.0% among those with high ACPA titers. When combined with rheumatoid factor or matrix metalloproteinase-3, the PPV further increased. Radiographic progression occurred in all participants with high-titer ACPA who developed RA (n =3) and in one ACPA-positive individual without RA, but not in ACPA-negative individuals who developed RA. CONCLUSIONS:ACPA positivity, particularly at high titers, may be associated with an increased risk of incident RA and with radiographic bone destruction, even in the absence of clinical symptoms or RA diagnosis.
Fibromyalgia remains a contested clinical entity, characterized by persistent uncertainty regarding its definition, diagnostic boundaries, and underlying mechanisms. Over the past three decades, diagnostic frameworks have evolved from the 1990 American College of Rheumatology (ACR) classification criteria, based on widespread pain and tender point examination, to symptom-based models emphasizing patient-reported outcomes, such as the 2010 and 2016 ACR criteria. While these developments have improved feasibility and expanded clinical recognition, they have largely remained confined to biomedical and neuropsychological domains. This narrative review critically examines the historical evolution, conceptual foundations, and methodological limitations of fibromyalgia diagnostic criteria, integrating evidence from major classification systems, including ACR frameworks and the ACTTION-American Pain Society (APS) Pain Taxonomy (AAPT). Across these models, fibromyalgia is predominantly operationalized through symptom aggregation, with limited incorporation of social and contextual determinants of health. The analysis highlights persistent epistemological tensions, including diagnostic inflation, the continuum of polysymptomatic distress, and debates regarding disease legitimacy. In response, emerging proposals advocate for a biopsychosocial diagnostic framework that formally integrates biological, psychological, and social dimensions into the diagnostic core. This review also critically evaluates alternative dual-framework approaches that separate biological diagnosis from psychosocial severity assessment, emphasizing potential limitations such as fragmentation of patient experience and underestimation of psychosocial mechanisms in symptom generation. The findings suggest that future diagnostic models should move beyond static, symptom-based thresholds toward dynamic, integrative, and context-sensitive approaches. Such models may improve patient stratification, clinical decision-making, and research validity, while aligning diagnostic practice with contemporary understandings of chronic pain as a multidimensional and interactive condition.
OBJECTIVES:Adenosine deaminase acting on RNA 1 (ADAR1) is an interferon (IFN)-inducible RNA-editing enzyme involved in the regulation of IFN signaling pathways. Although increased ADAR1 expression has been reported in systemic lupus erythematosus (SLE), the presence and clinical significance of anti-ADAR1 antibodies remain unclear. METHODS:Serum samples from patients with SLE, idiopathic inflammatory myopathy (IIM), and rheumatoid arthritis (RA) were analyzed. Anti-ADAR1 antibodies were quantified using a newly developed ELISA, and specificity was confirmed by inhibition testing. Clinical and serological features were compared between antibody-positive and -negative patients. Hierarchical clustering and logistic regression analyses were performed to identify patient subsets and associated clinical features. RESULTS:Anti-ADAR1 antibodies were detected in 38 of 76 patients with SLE (50.0%), 29 of 130 with IIM (22.3%), and 2 of 22 with RA (9.0%). In SLE, patients with anti-ADAR1 antibodies more frequently exhibited pericarditis, myocarditis, splenomegaly, elevated immunoglobulin G levels, and positivity for anti-U1RNP, anti-Sm, and anti-SSA antibodies. Cluster analysis identified three subgroups, with anti-ADAR1 antibodies enriched in a subset characterized by co-occurrence of autoantibodies against RNA-binding proteins. Exploratory analyses suggested that some clinical features showed different patterns of association with anti-ADAR1 antibody positivity and Cluster 3 membership. CONCLUSIONS:Anti-ADAR1 antibodies are frequently detected in SLE and IIM, but are rare in RA. These antibodies are enriched in a subset of SLE cases characterized by coordinated production of antibodies against RNA-binding proteins within an IFN-related immunological context. These findings suggest that anti-ADAR1 antibodies may contribute to immunological stratification of SLE.
OBJECTIVES:IgG4-related disease (IgG4-RD) is a systemic fibroinflammatory disorder affecting multiple organs, but the extent to which immune microenvironments differ across tissues remains unclear. We compared immune cell compositions between submandibular gland and pancreatic lesions using transcriptome-based deconvolution analysis. METHODS:Bulk RNA sequencing data were obtained from patients with IgG4-related submandibular sialadenitis (n = 40) and autoimmune pancreatitis (n = 8). Immune cell fractions were estimated using CIBERSORTx with the LM22 immune signature matrix. Relative immune cell compositions were compared descriptively, and exploratory Mann-Whitney U tests with false discovery rate (FDR) adjustment were performed. RESULTS:Both tissues shared broad immune cell repertoires, including B cells, T cells, macrophages, dendritic cells, mast cells, and natural killer cells, indicating a common immune framework across IgG4-RD lesions. However, organ-specific differences in relative immune cell abundance were observed. Pancreatic lesions showed a tendency toward increased macrophage populations, particularly M1-like macrophages, together with relatively reduced naïve B-cell fractions. In contrast, submandibular gland lesions demonstrated relatively enriched B-cell populations, including naïve and memory B cells, with a more balanced macrophage distribution. These patterns were consistently observed across samples and supported by deconvolution confidence metrics. CONCLUSIONS:IgG4-RD lesions share common immunological features while exhibiting differences in relative immune cell composition across tissues. Pancreatic lesions tended to show relatively increased macrophage fractions, whereas submandibular gland lesions demonstrated a more lymphocyte-rich immune profile. These findings suggest that local tissue context may shape immune composition and contribute to clinical heterogeneity in IgG4-RD.
OBJECTIVES:To identify factors associated with flare after glucocorticoid (GC) reduction in systemic lupus erythematosus (SLE) and determine whether belimumab influences this risk. METHODS:Using the ANSWER-SLE cohort, this retrospective multicentre study enrolled 388 patients with GC reduction from ≤5 mg/day. The primary outcome was time to overall flare (SLE Disease Activity Index 2000 [SLEDAI-2K] increase ≥3 or GC escalation). Multivariable Cox models identified factors associated with overall flare. Propensity score-based matching weights were applied, and weighted Cox models assessed the association between belimumab and flare risk. RESULTS:During one-year follow-up, 133 overall flares occurred (1-year cumulative incidence 39.9%). Higher clinical SLEDAI (hazard ratio [HR] 1.10, 95% confidence interval [CI] 1.03-1.17), SDI (HR 1.11, 95% CI 1.01-1.22), and GC dose reduction (HR 1.40, 95% CI 1.15-1.70) were associated with increased overall flare risk. GC reductions >1 mg were associated with flare (HR 2.53, 95% CI 1.54-4.15). In weighted analyses, belimumab was not associated with overall flare (HR 0.83, 95% CI 0.51-1.34). CONCLUSIONS:In patients with SLE, carefully tapering GC doses from ≤5 mg/day according to disease activity and organ damage may be important, whereas belimumab was not associated with reduced flare risk.
OBJECTIVE:To determine the prevalence of radiographic sacroiliitis-a classification feature of spondyloarthritis-and to identify associated factors in Japanese patients with inflammatory bowel disease. METHODS:This retrospective study included 880 patients with ulcerative colitis or Crohn's disease who underwent abdominopelvic computed tomography at an inflammatory bowel disease centre. Sacroiliac joints were evaluated using a validated scoring system. Radiographic sacroiliitis was defined as a total erosion score ≥3 or the presence of sacroiliac joint ankylosis. Multivariate logistic regression analysis identified factors associated with radiographic sacroiliitis. RESULTS:Radiographic sacroiliitis was identified in 98 patients (11%), including 41 patients (5%) with complete ankylosis. Crohn's disease (vs. ulcerative colitis; odds ratio [OR] 2.14; 95% confidence interval [CI], 1.17-3.89), male sex (OR 3.85; 95% CI 1.96-7.56), and older age (OR 1.07 per year; 95% CI 1.05-1.09) were independently associated with radiographic sacroiliitis. In subgroup analysis, obesity was associated with radiographic sacroiliitis in Crohn's disease (OR 2.15; 95% CI 1.01-4.59). CONCLUSIONS:Radiographic sacroiliitis was present in approximately 10% of Japanese patients with inflammatory bowel disease. Evaluation of sacroiliac joints on routine abdominopelvic computed tomography may help identify patients warranting further evaluation for coexisting spondyloarthritis, particularly in older men with Crohn's disease.
OBJECTIVE:This study aims to describe the clinical characteristics of nervous system involvement in a cohort of patients from the SjögrenSER registry. METHODS:All patients included in the SjögrenSER study, a Spanish multicenter randomized cohort containing demographic, clinical, and histologic data, were retrospectively analyzed. Patients were classified based on the presence of neurological involvement (central and peripheral nervous systems). We performed descriptive statistical analyses, clinical associations, Student's t test or χ2 test, and uni- and multivariate logistic regression. RESULTS:The registry included 437 patients, with peripheral nervous system involvement observed in 39 patients (8.9%) and central nervous system involvement in 34 patients (7.8%). Stroke and ischemic cardiovascular disease were common comorbidities in patients with Sjögren's disease (SjD) and neurological involvement (p < 0.05). Neurological involvement was also frequently associated with other systemic manifestations, including renal involvement (p = 0.015), particularly glomerulonephritis with cryoglobulinemia (p = 0.021), and myositis (p = 0.002). Fatigue was significantly associated with neurological involvement (p = 0.012).Patients with nervous system involvement more frequently received glucocorticoids, antimalarials, immunosuppressants, intravenous immunoglobulins, and biologic therapies. Notably, steroids and cyclophosphamide were used more often than other medications (OR = 3.33; 1.54-7.18 and OR = 6.80; 1.49-30.96, respectively). CONCLUSIONS:In this cohort, neurological involvement was commonly associated with other systemic manifestations of SjD, such as myositis, suggesting a more severe disease phenotype that often requires immunosuppressants and biologic therapy.
