Barrera-Hernández S, Mendoza-Pinto C, Munguía-Realpozo P
… +7 more, Etchegaray-Morales I, Baez-Duarte BG, Zamora-Ginez I, Ramírez-Lara E, Montiel-Jarquin ÁJ, García-Flores MA, Méndez-Martínez S
BACKGROUND: Systemic lupus erythematosus (SLE) still lacks highly specific biomarkers; high-throughput metabolomics offers a route to elucidate disease-defining metabolic perturbations. OBJECTIVE: This systematic review...BACKGROUND: Systemic lupus erythematosus (SLE) still lacks highly specific biomarkers; high-throughput metabolomics offers a route to elucidate disease-defining metabolic perturbations. OBJECTIVE: This systematic review aims to identify common metabolite changes related to SLE. METHODS: PubMed, Web of Science, Scopus, and the Cochrane Library were searched through November 2024 for human observational studies comparing the metabolomic profiles of adult SLE patients with those of healthy controls. Random-effects meta-analyses used the ratio of means (RoM); heterogeneity was assessed using the I² statistic. RESULTS: Forty-six studies comprising 2,238 SLE patients and 1,761 healthy controls (total n = 3,999) were included. Ten metabolites, each reported in ≥2 of the five eligible studies, were quantitatively synthesized. Compared with controls, isoleucine (RoM = 0.73, 95 % CI = 0.72-0.74, I² = 0 %), leucine (RoM = 0.81, 95 % CI = 0.80-0.81, I² = 0 %), and tryptophan (RoM = 0.73, 95 % CI = 0.64-0.84, I² = 75 %) were significantly lower in SLE, whereas methionine was significantly higher (RoM = 1.54, 95 % CI = 1.26-1.88, I² = 88 %). Lipid remodeling included elevated oleic acid (RoM = 1.42, 95 % CI = 1.19-1.69, I² = 0 %) and reduced capric acid (RoM = 0.80, 95 % CI = 0.67-0.95, I² = 31 %). Qualitative synthesis revealed consistent reduction of tricarboxylic acid intermediates, accumulation of acylcarnitines, and an oxidized-lipid signature (e.g., 9-hydroxyoctadecadienoic acid, leukotriene B4), implying mitochondrial stress and redox imbalance. CONCLUSIONS: Metabolomic profiling identifies a reproducible SLE signature: relative to controls, branched-chain (isoleucine, leucine) and aromatic (tryptophan) amino acids are lower, methionine is higher, and lipid profiles show higher oleic and lower capric acids, patterns consistent with impaired mitochondrial energetics and altered one-carbon flux.
BACKGROUND/OBJECTIVE: Real-world experience with standardized assessments of longitudinally-followed patients on glucocorticoids (GCs) is limited. We aimed to assess the impact of GC use on GC-related toxicity and qualit...BACKGROUND/OBJECTIVE: Real-world experience with standardized assessments of longitudinally-followed patients on glucocorticoids (GCs) is limited. We aimed to assess the impact of GC use on GC-related toxicity and quality-of-life in a prospective cohort. METHODS: We established a prospective cohort of adults with rheumatic diseases receiving GCs. Change in GC toxicity is measured by the Glucocorticoid Toxicity Index (GTI) following an assessment of GC toxicity at entry into the cohort using the GT-SNAPSHOT (range: 0-1592). Quality-of-life is assessed longitudinally using the Short Form-36 and EQ-5D We report the baseline characteristics of first 90 individuals, stratified by those who had ≤ 6 months vs >6 months of prior GC exposure. RESULTS: Of the initial 90 enrolled in LONG-TOX (mean age 59.2 years, 62 % female, most common rheumatic disease PMR and/or GCA [41 %]), the median (IQR) prior cumulative GC use duration was 71 days (23, 605). The overall median (IQR) baseline GT-SNAPSHOT score was 165 (122, 251). Those with >6 months of prior GC exposure had numerically higher median GT-SNAPSHOT scores (205 vs. 160, p = 0.08) and significantly lower SF-36 Energy/Fatigue (35 vs. 50, p = 0.01) and General Health (30 vs. 60, p < 0.001) scores than those with ≤ 6 months of exposure. CONCLUSIONS: In this prospective cohort of individuals with autoimmune diseases, those with >6 months of GC exposure had higher baseline GC-related toxicity and lower quality-of-life than those with ≤ 6 months of exposure. This novel cohort captures important patient- and clinician-reported outcomes that will lead to a better understanding of the impact of GCs and their toxicities.
OBJECTIVE: Although musculoskeletal symptoms are common in patients with inflammatory bowel disease (IBD), spondyloarthritis (SpA) remains underdiagnosed. This systematic review aimed at identifying and comparing self-ad...OBJECTIVE: Although musculoskeletal symptoms are common in patients with inflammatory bowel disease (IBD), spondyloarthritis (SpA) remains underdiagnosed. This systematic review aimed at identifying and comparing self-administered screening questionnaires for SpA in IBD patients. METHODS: We conducted a systematic review according to PRISMA guidelines using PubMed, Cochrane, and ACR/EULAR congress databases, with the last search on April 21, 2024. Studies focusing on self-administered screening questionnaires for SpA in IBD patients were included. We extracted questionnaire characteristics and their psychometric data. The content validity of each questionnaire was assessed using the COSMIN method. RESULTS: A total of 1491 articles were screened. Eight were included and six screening questionnaires were identified. Two questionnaires assessed axial, one peripheral and three both axial and peripheral symptoms of SpA. The IBIS-Q questionnaire showed the highest sensitivity (92.7 %), while the Queiro's axial questionnaire had the highest specificity (89.8 %). The DETAIL questionnaire gave the highest post-test probability to have a SpA with a positive likelihood ratio of at least 14, using a threshold of three affirmative responses. None of these questionnaires met all criteria of the COSMIN methodology to evaluate their quality. The content validity of the questionnaires was judged to be sufficient or inconsistent by reviewers with moderate qualities of evidence at best. CONCLUSIONS: Six self-administered questionnaires have been developed to screen for SpA in IBD patients. Limited methodological transparency hinders direct comparison. Although none of the available questionnaires fully meets validation standards, the DETAIL questionnaire appears to offer the greatest clinical potential, despite only moderate-quality evidence.
AIMS: To identify the factors associated with frailty in Chinese participants with rheumatoid arthritis (RA), guided by the health ecology theory, and to provide a culturally adapted and psychometrically validated Chines...AIMS: To identify the factors associated with frailty in Chinese participants with rheumatoid arthritis (RA), guided by the health ecology theory, and to provide a culturally adapted and psychometrically validated Chinese version of the Comprehensive Rheumatologic Assessment of Frailty (CRAF) to support context-specific assessments in clinical practice. METHODS: This cross-sectional study involved the translation and cultural adaptation of the CRAF using a modified Brislin method. Psychometric properties were evaluated, and factors associated with frailty were identified through multivariate ordered logistic regression, guided by the health ecology theory. RESULTS: A total of 1288 RA participants were recruited. The Cronbach's alpha for the Chinese CRAF was 0.75, and the intraclass correlation coefficient was 0.92. The Item-content validity index (CVI) ranged from 0.80 to 1.00, with an average CVI of 0.92. A significant positive correlation between the CRAF and the FRAIL Scale was found (P < 0.001), with the CRAF demonstrating better discriminatory power than the FRAIL scale (P = 0.041). Factors significantly associated with frailty included disease duration, pain intensity, limitations in physical function, the use of methotrexate, non-steroidal anti-inflammatory drugs, glucocorticoids, and biologic disease-modifying antirheumatic drugs, as well as comorbidities such as hypertension, diabetes, cardiovascular disease, stroke/transient ischemic attack, pulmonary disease, diminished grip strength, smoking, depression, and lack of social participation. CONCLUSION: The Chinese version of the CRAF is a reliable and valid tool for assessing frailty in RA participants. Targeted interventions addressing the identified risk factors may help prevent or delay frailty progression, ultimately improving prognosis and quality of life.
OBJECTIVE: To identify associated and protective factors of rapid spinal radiographic progression in axial spondyloarthritis (axSpA) using artificial intelligence (AI). METHODS: We conducted a hospital-based retrospectiv...OBJECTIVE: To identify associated and protective factors of rapid spinal radiographic progression in axial spondyloarthritis (axSpA) using artificial intelligence (AI). METHODS: We conducted a hospital-based retrospective cohort study involving 242 axSpA patients taken ≥2 lateral spine radiographs between 2002 and 2024. Spinal damage was assessed with modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) by a deep learning model. Each pair of consecutive radiographs defined an observational interval (total 379 intervals); annual mSASSS progression rate was calculated for each interval. Demographics, clinical features, baseline mSASSS, activity indices, cumulative dosage of prescriptions, and laboratory recordings were collected. Time-dependent generalized estimating equations (GEE) were applied to identify associated or protective factors of rapid spinal radiographic progression (ΔmSASSS/year >1), accounting for within-patient correlation. RESULTS: For recorded intervals, mean mSASSS progression was 0.5/year; 26.7% of intervals showed progression >1/year. For enrolled patients, mean mSASSS progression was 0.6/year; 27.3% of intervals showed progression >1/year. Conditional multivariable GEE analysis revealed age at baseline mSASSS, especially ≥40 years, was independently associated with rapid mSASSS progression [adjusted odds ratio (aOR), 1.03; 95% confidence interval (CI), 1.003-1.06]. Higher cumulative dosage of non-steroidal anti-inflammatory drugs (NSAIDs) during the intervals was negatively associated with rapid mSASSS progression (aOR, 0.38; 95% CI, 0.19-0.75). Cumulative dosage of tumor necrosis factor inhibitors and secukinumab during the intervals was independent of rapid mSASSS progression. CONCLUSIONS: Using AI-assisted mSASSS scoring, this retrospective cohort study identified older age at assessment as an associated factor and full-dose NSAIDs use as protective factor for rapid spinal radiographic progression.
OBJECTIVES: Diffuse idiopathic skeletal hyperostosis (DISH) is a systemic condition characterized by ligamentous ossification along the spine. While its prevalence has been well described in the general population, data...OBJECTIVES: Diffuse idiopathic skeletal hyperostosis (DISH) is a systemic condition characterized by ligamentous ossification along the spine. While its prevalence has been well described in the general population, data on its occurrence in oncology patients remain limited. This study aimed to assess the prevalence and distribution of DISH and early-phase DISH in newly diagnosed cancer patients undergoing initial staging with Computed Tomography (CT). MATERIALS AND METHODS: In this retrospective cross-sectional study, 1053 adult oncology patients who underwent thoraco-abdominopelvic CT for initial staging were evaluated. DISH and early-phase DISH were diagnosed using established radiologic criteria. Vertebral body densities were measured, and associated extraspinal enthesopathies and ligamentous ossifications were documented. RESULTS: DISH was present in 30.3 % of patients, including 13.8 % with established DISH and 16.5 % with early-phase DISH. Prevalence was higher in older patients and males (p < 0.01). Notably, renal (43.2 %), gastric (37.5 %), and colorectal (33.7 %) cancers demonstrated significantly higher DISH rates, whereas esophageal cancer showed a lower prevalence (13.4 %). DISH was associated with decreased vertebral bone density and frequent extraspinal enthesopathies. No significant correlations were found with BMI, diabetes, or hypertension. CONCLUSION: DISH is common among oncology patients and often coexists with extraspinal enthesopathies and reduced bone density. These findings suggest possible shared pathogenic mechanisms and underscore the importance of further studies exploring the relationship between DISH and malignancy.
OBJECTIVE: Osteoarthritis (OA) of the first metatarsophalangeal (MTP) joint is accompanied by pain and stiffness and associated with reduced health-related quality of life. Although prevalence of radiographic 1st MTP joi...OBJECTIVE: Osteoarthritis (OA) of the first metatarsophalangeal (MTP) joint is accompanied by pain and stiffness and associated with reduced health-related quality of life. Although prevalence of radiographic 1st MTP joint OA is high, the incidence of clinical 1st MTP joint OA is unknown. Therefore, we aimed to determine the incidence and management of general practice (GP) consultations for symptomatic 1st MTP joint OA. METHODS: A retrospective cohort study was conducted using electronic health records of GPs. An algorithm was defined to identify 1st MTP joint OA patients based on free text and codified data between 2013 and 2022. First MTP joint OA incidence rate, comorbidities and management strategies were assessed. RESULTS: The overall 1st MTP joint OA incidence was 0.74/1000 person-years in patients ≥35 years. The most initiated management by GPs was explanation/reassurance (360/672 (53.6 %)), followed by referral to podiatry (171/672 (25.4 %)) and orthopedic surgeon consultation (162/672 (24.1 %)). Of the 823 patients consulting their GP with foot/toe problems in the year before diagnosis, 491 (47.1 %) were referred to radiology, and 271 (26 %) for orthopedic surgeon consultation. CONCLUSION: The incidence of 1st MTP joint OA has been estimated for the first time in general practice. Most patients are diagnosed after referral to radiology or orthopedic surgeon consultation. From diagnosis, half of 1st MTP joint OA patients are referred, mostly for orthopedic surgeon consultation and podiatry. As evidence for these diagnostic and management strategies is lacking, research into their effectiveness for 1st MTP joint OA in general practice is needed.
OBJECTIVES: Juvenile-onset mixed connective tissue disease (jMCTD) accounts for 7-23 % of MCTD cases but remains poorly described. We aimed to characterize clinical features, treatments, and outcomes of patients with jMC...OBJECTIVES: Juvenile-onset mixed connective tissue disease (jMCTD) accounts for 7-23 % of MCTD cases but remains poorly described. We aimed to characterize clinical features, treatments, and outcomes of patients with jMCTD, and compare them to adult-onset MCTD (aMCTD) patients. METHODS: We conducted a multicenter, retrospective, case-control study within the French MCTD cohort. Each jMCTD patient was compared to 3 matched aMCTD patients. RESULTS: Forty-seven jMCTD patients (93.6 % girls; median age at onset 14 [11-16] years) were included. Forty-four (93.6 %) jMCTD patients fulfilled either Sharp or Kasukawa diagnostic criteria. None of them met other diagnostic criteria without fulfilling Sharp or Kasukawa criteria. At diagnosis, jMCTD patients' main manifestations were Raynaud's phenomenon, arthralgia, and myalgia. jMCTD patients had less frequently puffy fingers than aMCTD (p < 0.0001). Cumulatively, jMCTD patients mainly received glucocorticoids (80.9 %), hydroxychloroquine (95.7 %) and immunosuppressants (93.6 %). They received a higher initial dose of glucocorticoids (30 [20-60] mg/day vs. 15 [10-35] mg/day, p = 0.02), and significantly more frequently methotrexate (Methotrexate) and rituximab (p = 0.01) over time compared to aMCTD. After a median follow-up of 9.8 [6.6-16.2] years, 29 (61.7 %) jMCTD patients were in remission (vs. 62 (44.0 %) aMCTD; p < 0.05), 36 % had progressed to another CTD (vs. 30.5 % aMCTD; p = 0.5), mainly systemic lupus erythematosus, 11 (23.4 %) had developed interstitial lung disease, 2 (4.3 %) pulmonary arterial hypertension, and 1 (2.1 %) died. CONCLUSIONS: jMCTD share the same clinical characteristics as aMCTD patients, but less frequently have puffy fingers. Outcomes appear more favorable in jMCTD than aMCTD, with higher remission rates, albeit at the cost of more intensive treatment.
OBJECTIVE: To explore the development of fatigue over the past 17 years and its relationship to physician- and patient-reported outcomes and social factors in inflammatory rheumatic diseases. METHODOLOGY: Data from ≈9300...OBJECTIVE: To explore the development of fatigue over the past 17 years and its relationship to physician- and patient-reported outcomes and social factors in inflammatory rheumatic diseases. METHODOLOGY: Data from ≈9300 patients per year from the German National Database (2007-2023) were included, considering arthritides, spondyloarthritides, connective tissue diseases and vasculitides. Fatigue was assessed on a numeric rating scale (0-10) with >2 defined as present and >6 as severe. Presence and severity were compared by diagnosis, gender and year. Fatigue clusters were identified based on trajectory patterns over three consecutive visits. RESULTS: Fatigue affected 55 % (adult onset Still disease) to 67 % (systemic sclerosis) of patients, with severe fatigue in up to 26 % (systemic sclerosis). Substantial proportions of women (47-61 %) and men (35-52 %) experienced moderate-to-severe fatigue. Despite marked improvements in inflammation-responsive outcomes (CRP -40 %, tender joints -50 %, physician disease activity -42 %) and employment (52 %→70 %), mean fatigue remained stable. Trajectory analysis identified 35 % with persistent low, 23 % persistent high, 24 % worsening, and 19 % improving fatigue. Tender joints and morning stiffness effectively discriminated between persistent high versus low fatigue clusters. Emotional well-being, physical functioning, coping, and sleep quality showed stronger associations with fatigue trajectories than inflammatory markers. Differences across fatigue clusters substantially exceeded those between diagnostic groups. CONCLUSION: Fatigue affected a large proportion of both women and men across diagnoses. Fatigue trajectories reflect complex interplay of clinical and psychosocial factors. Management should incorporate multidimensional interventions addressing emotional well-being, physical function and social support beyond traditional inflammatory control.
OBJECTIVE: To investigate the characteristics of axial spondyloarthritis (axSpA) and understand rheumatologists' and patients' experiences of axSpA management in a large real-world population using data from a cross-sect...OBJECTIVE: To investigate the characteristics of axial spondyloarthritis (axSpA) and understand rheumatologists' and patients' experiences of axSpA management in a large real-world population using data from a cross-sectional survey. METHODS: Rheumatologists recruited from France, Germany, Italy, Spain, and the UK completed surveys for their next eight consulting adult patients with axSpA. The same patients were asked to voluntarily complete a survey, allowing rheumatologist- and patient-reported responses to be matched and compared. Surveys covered clinical status, symptoms and treatment decisions, preferences, and satisfaction. RESULTS: Between June 2023 and June 2024, 268 rheumatologists provided data on 2165 patients, 538 of whom completed the survey. At the time of the survey, patients continued to experience symptoms of axSpA (morning stiffness [35 %], inflammatory back, hip, or buttock pain [25 %], and fatigue [25 %]), despite 77 % having received disease-modifying advanced therapy. There was moderate agreement between patients and their rheumatologists on disease severity (86 % weighted agreement at the time of the survey, κ=0.515) and on their satisfaction with current treatment. The most common treatment target for rheumatologists was to achieve low disease activity (76 %), while the most common target for patients was to alleviate pain (61 %). Rheumatologists highlighted lack of efficacy, pain control, and flare control, and residual fatigue as reasons for treatment dissatisfaction. CONCLUSION: Patients and their rheumatologists were moderately aligned on their perception of disease severity and treatment satisfaction but differed in their expectations regarding treatment target. The study highlights the need for ongoing involvement of patients in discussions and decisions about axSpA management.
OBJECTIVE: To clarify the real-world effectiveness of nintedanib continuation beyond 12 months on pulmonary function in progressive pulmonary fibrosis (PPF) associated with systemic autoimmune rheumatic disease-related i...OBJECTIVE: To clarify the real-world effectiveness of nintedanib continuation beyond 12 months on pulmonary function in progressive pulmonary fibrosis (PPF) associated with systemic autoimmune rheumatic disease-related interstitial lung disease (SARD-ILD). METHODS: We conducted a review of all consecutive SARD-ILD patients from the KEIO-SARD-ILD cohort who received nintedanib for PPF between 2015 and 2025. The primary outcome was the 12-month change in percent predicted forced vital capacity (%FVC) between patients who continued nintedanib for 12 months and those who discontinued treatment earlier. Secondary outcomes included 12-month changes in Krebs von den Lungen-6 (KL-6) levels and mortality between the two groups. RESULTS: Among the 65 patients, systemic sclerosis was the most common underlying condition (n = 16), followed by idiopathic inflammatory myopathies (n = 15), and rheumatoid arthritis (n = 13). The overall 12-month retention rate of nintedanib was 69.2 %. Both the continuation and discontinuation groups exhibited a comparable decline in %FVC in 12 months prior to nintedanib initiation (-3.6 % vs. -3.8 %, p = 0.58), but after 12 months of treatment, the continuation group demonstrated a significantly greater improvement in %FVC (1.8 % vs. -3.5 %, p = 0.01) and KL-6 (-175 vs 71 U/mL, p = 0.04) compared to the discontinuation group. The ILD-related survival rates were better in the continuation group compared to the discontinuation group (p = 0.02). CONCLUSIONS: Continuation of nintedanib beyond 12 months, compared with discontinuation within 12 months, is associated with significant improvements in pulmonary function, biomarkers, and survival in patients with SARD-ILD-related PPF, suggesting that long-term nintedanib therapy plays a critical role in stabilizing disease progression.
Day JA, de Araújo DB, Essouma M
… +15 more, Conticini E, Rider LG, Gibson D, Elias AM, Magalhães CS, Appenzeller S, Schiffenbauer A, van der Koi AJ, Moghadam-Kia S, Paula VT, Guimarães JB, Marrani E, Doria AS, Shinjo SK, IMACS WBMRI in Myopathies Working Group
Semin Arthritis Rheum
· 2025 Dec · PMID 41330175
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Magnetic resonance imaging (MRI) has emerged as a key non-invasive tool for the evaluation of idiopathic inflammatory myopathies (IIM); however, heterogeneity in techniques, protocols, and grading systemics impedes stand...Magnetic resonance imaging (MRI) has emerged as a key non-invasive tool for the evaluation of idiopathic inflammatory myopathies (IIM); however, heterogeneity in techniques, protocols, and grading systemics impedes standardization. This scoping review systematically examined the MRI techniques, protocols, and grading systems reported in the adult IIM literature. A systematic search of PubMed, EMBASE, and Cochrane databases was conducted from 2000 to 2024 using keywords related to IIM and MRI. Studies involving adults with IIM who underwent MRI were screened and reviewed for inclusion. Forty-nine studies were included in the analysis, 13 of which evaluated whole-body MRI and 36 evaluated dedicated body-part MRI, collectively reporting data from 2810 IIM patients. A wide range of imaging protocols was observed with variations in scanner type, field strength, sequence combinations, and anatomical coverage. Semi-quantitative visual grading was the most commonly used assessment method (31/49, 63.2 %), with binary scoring in 23/31 and software-assisted or automated techniques in 8/31. Six studies used descriptive analysis alone. Inter-rater agreement was reported in 15 studies, with variable reliability observed for both muscle edema (intraclass correlation coefficient [ICC] range: 0.78-1.00; kappa range: 0.30-1.00) and replacement of skeletal muscle by fat (ICC range: 0.77-0.97; kappa range: 0.54-0.93). Several studies have reported that WB-MRI patterns correlate with clinical measures of disease activity and can discriminate between myopathic diseases and IIM subtypes. In summary, despite the clinical utility of MRI for IIM, significant methodological variability remains. Future research should focus on standardizing protocols and grading systems to enhance the consistency and reliability of MRI assessments for IIM.
OBJECTIVES: Janus kinase (JAK) inhibitors have been subject to multiple safety warnings recently. Patient treatment decisions should be evidence-based using the most up-to-date data on the efficacy and safety of JAK inhi...OBJECTIVES: Janus kinase (JAK) inhibitors have been subject to multiple safety warnings recently. Patient treatment decisions should be evidence-based using the most up-to-date data on the efficacy and safety of JAK inhibitors. METHODS: In a systematic review and cumulative meta-analysis (CMA), Medline, Embase and the Cochrane Library were searched from inception to June 11, 2024. Eligible studies included randomised controlled trials (RCTs) of adult patients with rheumatoid arthritis (RA), treated with a JAK inhibitor, placebo or active treatment (conventional synthetic disease-modifying anti-rheumatic drugs [csDMARDs] or biologic DMARDs [bDMARDs]) and at least one of the protocol defined outcomes. Literature screening was conducted by two reviewers independently. Data extraction and risk-of-bias (ROB) assessment were done by one reviewer in a standardised manner and checked for accuracy by a second reviewer. The following outcomes were assessed: disease activity score erythrocyte sedimentation rate (DAS28-ESR) and DAS28 C-reactive protein (DAS28-CRP) [co-primary outcomes]; American College of Rheumatology (ACR) response (20/50/70), and Health Assessment Questionnaire-Disability Index (HAQ-DI) [secondary outcomes]; adverse events (AEs), treatment-related AEs (TRAEs) serious adverse events (SAEs), major adverse cardiac events (MACE), venous thromboembolism (VTE), serious infections and malignancies [safety outcomes]. Pooled effect-estimates were computed using a random-effects model and heterogeneity was assessed (I² statistic). PROSPERO registration (CRD42023460537). RESULTS: Of 5971 citations screened, 46 reports (of 31 unique trials) were included. Overall, ROB was considered 'low' across the trials. A statistically significant improvement in DAS was found for JAK inhibitors vs. placebo: (DAS28-CRP: mean difference [MD] -1.06, 95 % CI -1.17 to -0.95; DAS28-ESR:1.03, 95 % CI -1.21 to -0.85); versus csDMARDs (DAS28-CRP:0.79, 95 % CI -1.05 to -0.53; DAS28-ESR:0.54, 95 % CI -0.73 to -0.36); and versus bDMARDs (DAS28-CRP:0.35, 95 % CI -0.48 to -0.23; DAS28-ESR:0.33, 95 % CI -0.65 to -0.01). Similar efficacy improvements in secondary outcomes (HAQ-DI, ACR response) were also observed in patients treated with JAK inhibitors compared to placebo or active treatment. In patients treated with JAK inhibitors, a statistically significant increased risk of AEs, TRAEs and serious infections (versus placebo), serious infections (versus csDMARDs) and SAEs and MACE (versus bDMARDs) was found. CONCLUSION: JAK inhibitors are more effective than placebo and active treatment in improving symptoms of RA including DAS, ACR response, and HAQ-DI. This improvement in symptoms was clearly shown in the CMA over time as each new trial was published, in some instances from the second published trial. Safety outcomes were inconsistent over time in the CMA, probably owing to small sample sizes in some trials, difficulty in studying uncommon outcomes and short follow-up. Safety warnings for JAK inhibitors could not have been pre-empted sooner as the trials were not adequately powered to determine this. JAK inhibitors offer advantages to patients with RA and physicians should consider them an effective, fast-acting oral treatment compared to csDMARDs or bDMARDs, whilst acknowledging the limitations of their use in certain high-risk patient populations and the respective safety warnings.
Ohnishi T, Zhao M, Shi M
… +12 more, Volochayev R, Jackson SH, Jansen A, Bayat N, Farhadi PN, Sarkar K, Flegel WA, Parks CG, Weinberg CR, Miller FW, Schiffenbauer A, Rider LG
Semin Arthritis Rheum
· 2025 Dec · PMID 41289616
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OBJECTIVE: Systemic autoimmune rheumatic diseases (SARDs) are influenced by genetic and environmental factors. We examined pregnancy complications, early life events (birth season, birth order, feeding), and exposures to...OBJECTIVE: Systemic autoimmune rheumatic diseases (SARDs) are influenced by genetic and environmental factors. We examined pregnancy complications, early life events (birth season, birth order, feeding), and exposures to tobacco smoking in relation to SARD diagnosis. METHODS: In a case-control study, probands with SARDs were compared to same-sex close-in-age unaffected siblings (US), and demographically-matched unrelated controls (UC); 329 children (probands=124, US=115, UC=90) and 184 adults (probands=76, US=63, UC=45) were included. Conditional and unconditional logistic regression were used to examine proband-US and proband-UC comparisons. We examined associations between SARDs and exposures to smoking while adjusting for HLA-DRB1*03:01 in White probands and UC. RESULTS: No specific pregnancy complication was associated with SARDs; however, the total number of pregnancy complications was greater in juvenile probands. A higher proportion of juvenile-onset probands than UC were exposed to tobacco smoking, both in utero and after birth (prenatal, 20 % vs 4 %, OR=4.04, 95 %CI=1.20-17.7; household smoking before age 3, 14 % vs 3 %, OR=4.83, 95 %CI=1.31-26.1). Among adult-onset probands and US, household smoking exposure before age 10 was associated with SARDs (60 % vs 42 %, OR=10.06, 95 %CI=1.23-82.0). Among White subjects, HLA-DRB1*03:01 was associated with SARDs (juvenile-onset OR=2.03, 95 %CI=1.04-4.10; adult-onset OR=7.67, 95 %CI=2.72-26.4). After adjusting for HLA-DRB1*03:01, household smoking exposure was associated with juvenile- and adult-onset SARDs (OR=5.49, 95 %CI=1.22-39.7, and OR=4.01, 95 %CI=1.11-17.2). CONCLUSION: Early life exposure to tobacco smoking is associated with SARDs; the effect remained after adjusting for the genetic risk of HLA. These findings support a role for early environmental exposures in autoimmune diseases.
BACKGROUND: Seropositive arthralgia (SA), defined as joint pain without clinical synovitis in individuals positive for rheumatoid factor (RF) and/or anti-citrullinated protein antibodies (ACPA), is considered a preclinic...BACKGROUND: Seropositive arthralgia (SA), defined as joint pain without clinical synovitis in individuals positive for rheumatoid factor (RF) and/or anti-citrullinated protein antibodies (ACPA), is considered a preclinical stage of rheumatoid arthritis (RA). Early identification of individuals at risk is key for timely intervention. OBJECTIVES: To estimate the prevalence of SA in a large early arthritis cohort, compare its baseline features with RA, and identify predictors of progression to RA at one year. METHODS: This prospective study was conducted within Reuma-Check, a structured diagnostic program for early rheumatologic assessment in Argentina. Patients with SA and RA were identified based on standardized clinical, serological, and imaging assessments. SA patients were followed for 12 months. Logistic regression was used to identify independent predictors of RA development. RESULTS: Among 1730 patients, 208 (12%) were classified as SA and 225 (13%) as RA. Compared to RA, SA patients had fewer tender and swollen joints, lower inflammatory markers, and less Power Doppler positivity on ultrasound. At one year, 21% of SA patients progressed to RA, 14% developed other immune-mediated conditions, and 65% remained stable. In multivariate analysis, ACPA positivity was the only independent predictor of RA progression (OR: 7.7, 95% CI: 1.2-60). CONCLUSIONS: In the Reuma-Check cohort, among individuals with seropositive arthralgia, ACPA positivity is the most robust predictor of progression to rheumatoid arthritis at 1 year.
OBJECTIVE: To characterize the clinical and radiographic osteoarticular features of patients with Gitelman Syndrome (GS) in a prospective Chinese cohort. METHODS: Patients with clinically and genetically diagnosed GS wer...OBJECTIVE: To characterize the clinical and radiographic osteoarticular features of patients with Gitelman Syndrome (GS) in a prospective Chinese cohort. METHODS: Patients with clinically and genetically diagnosed GS were prospectively and systematically screened for osteoarticular involvement. Clinical manifestations, laboratory parameters, and radiographic findings were recorded. Patients were categorized as: chondrocalcinosis, or calcium pyrophosphate deposition (CPPD), non-chondrocalcinosis osteoarticular abnormalities, and non-radiographic GS. Group differences were analyzed. RESULTS: A total of 110 patients with GS were enrolled (mean age 39.90±13.70 years, 52.73% females), and 46 (41.82%) reported arthralgia. Radiographically, 46 patients (41.82%) were classified as CPPD, 15 (13.64%) showed non-chondrocalcinosis abnormalities, and 49 (44.54%) had no detectable osteoarticular involvement. CPPD patients were significantly older and had lower serum magnesium and estimated glomerular filtration rate (eGFR) compared with non-radiographic patients. Arthralgia occurred in 78.26% of CPPD cases. Knees were the most frequently involved joints in patients with CPPD, followed by cervical spine, Archilles tendon, hips, hands, shoulders, and wrists. Remarkably, non-chondrocalcinosis findings included dense bone islands and condensing osteitis of the sacroiliac joint. CONCLUSION: CPPD presents in 41.82% of patients with GS. Low serum magnesium and decreased eGFR are risk factors for CPPD. In addition to chondrocalcinosis, GS may be associated with other osteoarticular manifestations, including dense bone islands and condensing osteitis.
OBJECTIVES: Peripheral neuropathy affects quality of life in patients with anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis. Early recognition and treatment initiation are essential to prevent irreve...OBJECTIVES: Peripheral neuropathy affects quality of life in patients with anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis. Early recognition and treatment initiation are essential to prevent irreversible nerve damage. The aim of this study was to identify baseline factors associated with peripheral neuropathy in ANCA-associated vasculitis. METHODS: A total of 111 consecutive patients with newly diagnosed, treatment-naïve, active ANCA-associated vasculitis were enrolled. Baseline characteristics were compared among the three groups: patients without peripheral neuropathy, with sensory neuropathy, and with sensorimotor neuropathy. Analysis was further stratified by disease subtypes (eosinophilic granulomatosis with polyangiitis, EGPA; granulomatosis with polyangiitis, GPA; microscopic polyangiitis, MPA). RESULTS: Patients with EGPA (84.6 %) were most prone to having peripheral neuropathy compared with GPA (20.0 %) and MPA (28.9 %) (P < 0.001). Among patients with EGPA, baseline eosinophil counts showed a stepwise increase with peripheral neuropathy severity: 2340/μL in patients without peripheral neuropathy, 4276/μL with sensory neuropathy, and 11,859/μL with sensorimotor neuropathy (P = 0.004). The most useful cutoff values of baseline eosinophil counts to predict peripheral neuropathy and sensorimotor neuropathy were 2468/μL (sensitivity 90 % and specificity 75 %) and 6724/μL (sensitivity 80 % and specificity 71 %), respectively. In patients with GPA and MPA, the neutrophil-to-lymphocyte ratio tended to rise with increasing peripheral neuropathy severity, although the difference was not statistically significant. CONCLUSION: Baseline eosinophil counts may be useful predictors for both the presence and motor involvement of peripheral neuropathy in patients with EGPA, highlighting their clinical utility and early risk stratification. In GPA and MPA, neutrophil-driven inflammation may contribute to peripheral neuropathy development.