OBJECTIVES: To evaluate the risk of interstitial lung disease (ILD) and safety outcomes of disease-modifying antirheumatic drug (DMARD) classes in rheumatoid arthritis (RA), focusing on patients with RA-associated ILD (R...OBJECTIVES: To evaluate the risk of interstitial lung disease (ILD) and safety outcomes of disease-modifying antirheumatic drug (DMARD) classes in rheumatoid arthritis (RA), focusing on patients with RA-associated ILD (RA-ILD). METHODS: We conducted a nationwide cohort study using Korean National Health Insurance Service data (2011-2020). Adults with newly diagnosed RA prescribed at least one csDMARD were included and followed until 2022. Four treatment groups were evaluated: TNFi, non-TNFi biologics (abatacept, rituximab, tocilizumab), JAKi, and csDMARDs. RA-ILD was defined as ≥2 ILD claims plus chest computed tomography confirmation. Outcomes included ILD incidence, hospitalisation, infection, MACE, and all-cause mortality. Time-varying Cox models with inverse probability of treatment weighting were applied for first-event analyses. RESULTS: We analysed 26,120 patients with RA (209,852 treatment episodes), including 641 RA-ILD patients (1688 episodes). Adjusted ILD incidence was similar across DMARD classes. In RA and RA-ILD, non-TNFi biologics were associated with higher risks of hospitalisation (RA aHR 1.30, 95% CI 1.21-1.40; RA-ILD 1.35, 1.02-1.80), infection (RA 1.16, 1.05-1.28; RA-ILD 1.51, 1.06-2.15), and mortality (RA 4.09, 3.04-5.50; RA-ILD 4.31, 2.21-8.41) compared with csDMARDs. ILD-related admissions were similar, but pneumonia-related hospitalisations and recurrences were higher with non-TNFi biologics. TNFi and JAKi showed no significant associations with hospitalisation or infection. MACE risk did not differ across groups. CONCLUSIONS: DMARD class was not associated with ILD incidence or ILD-related hospitalisation. Non-TNFi biologics were consistently linked to increased pneumonia-related hospitalisation, recurrence, and mortality, highlighting the need for close infection monitoring in patients receiving these agents.
OBJECTIVE: This study aims to explore the relationship of obesity with clinical manifestations and disease burden including biologic/targeted DMARD (btDMARD), SpA-related surgery, work productivity loss, and patient-repo...OBJECTIVE: This study aims to explore the relationship of obesity with clinical manifestations and disease burden including biologic/targeted DMARD (btDMARD), SpA-related surgery, work productivity loss, and patient-reported health status. METHODS: An ancillary analysis of the Assessment of Spondyloarthritis International Society PerSpA (PERipheral involvement in SpA) cross-sectional study from 24 participating countries. The PerSpA study included the data of clinical characteristics, btDMARD use and history (number of btDMARD kinds ever-prescribed, number of discontinuation, and the reasons for discontinuation), SpA-related surgery, work productivity and activity impairment, and patient-reported health status (ASAS Health Index, Bath Ankylosing Spondylitis Functional Index, and global wellbeing). Patients were divided into three groups according to the current BMI (BMI) and comparisons between the obese patients, overweights, and normal weights were performed for the above-mentioned parameters. The study population was also divided into different three groups according to their 20-year-old BMI (BMI) and they were compared in itself. RESULTS: Among the 4449 patients, 34.6% were overweight, 21% obese, and 44.4% normal-weight. Obese/overweight patients had a higher btDMARD burden, btDMARD inefficacy, work impairment, and worse patient-reported health (p < 0.05 for all). The differences were preserved in comparisons adjusted for age, gender, and smoking. When the patients were compared according to their BMI, similar differences were also found. CONCLUSIONS: Obesity invites a biological therapy burden, work productivity loss, and worse patient-reported health status in patients with SpA.
OBJECTIVES: To examine (i) the association of adiposity with pain intensity and/or effusion-synovitis in people with knee osteoarthritis (OA), adjusting for body mass index (BMI), and (ii) whether indicators of systemic...OBJECTIVES: To examine (i) the association of adiposity with pain intensity and/or effusion-synovitis in people with knee osteoarthritis (OA), adjusting for body mass index (BMI), and (ii) whether indicators of systemic immune inflammation (i.e., the systemic immune-inflammation index (SII) and the systemic immune response index (SIRI)) moderate the above associations. METHODS: Individuals with knee OA were sampled from the Western Ontario Registry for Early Osteoarthritis Knee Study. Total body and visceral fat percentages were measured using bioimpedance analysis, and effusion-synovitis was graded using knee ultrasonography. Multiple regression models with interaction terms were used to examine the association between fat percentages and pain intensity (linear)/effusion-synovitis (logistic), and the interaction effect of fat and SII/SIRI on pain intensity/effusion-synovitis. The analyses were adjusted for confounders (age, sex, BMI, radiographic severity of the opposite knee, and anxio-depressive symptoms). RESULTS: Data from 225 participants (mean age: 61.1 (10.9), 68% female, mean BMI: 31.7 (7.7)) were analyzed. The associations for adjusted fat and pain intensity models were as follows: total body fat: β): - 0.03 (-0.54 to 0.46) and visceral fat: β (: -0.25 (-1.03 to 0.51)., The odds ratios for adjusted fat and effusion-synovitis models were total body fat: OR): 0.98 (0.92 to 1.05) and visceral fat: OR (): 1.01 (0.91 to 1.11)). Neither the main nor the interaction effects were significant. CONCLUSION: Our preliminary results do not support an association of adiposity and its interaction with generalized inflammation with pain/effusion-synovitis adjusted for BMI. Further studies are needed.
BACKGROUND: Knee osteoarthritis (KOA) is a leading cause of disability worldwide; however current therapies offer only symptomatic relief. Metformin, a widely used antidiabetic agent, has been demonstrated to have anti-i...BACKGROUND: Knee osteoarthritis (KOA) is a leading cause of disability worldwide; however current therapies offer only symptomatic relief. Metformin, a widely used antidiabetic agent, has been demonstrated to have anti-inflammatory and chondroprotective effects in preclinical models, suggesting its KOA modifying properties. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials evaluating the effects of metformin in patients with KOA. A comprehensive search of PubMed, Embase, and Cochrane Library was performed up to May 2025. Two reviewers independently screened studies and extracted data. Statistical analyses were conducted using a random-effects model to account for between-study heterogeneity. Subgroup analyses based on formulation, treatment duration, and nonsteroidal anti-inflammatory drugs (NSAIDs) co-administration were also performed. RESULTS: Five studies (n = 337) were included. Metformin significantly reduced pain scores (standardized mean difference [SMD] = -1.295; 95 % confidence interval [CI]: -2.063 to -0.526) and stiffness (SMD = -0.746; 95 % CI: -1.385 to -0.107), improved physical function (SMD = -2.042; 95 % CI: -3.372 to -0.712), and health-related quality of life (SMD = -1.505; 95 % CI: -2.896 to -0.115). Effects were consistent regardless of oral or topical metformin use, treatment duration, and NSAID use, although the benefits were greater when metformin was combined with NSAIDs. CONCLUSION: While metformin demonstrated consistent benefits in pain and functional outcomes, these findings should be interpreted as symptomatic and adjunctive effects rather than definitive disease modification. Future trials incorporating structural endpoints are needed to confirm disease-modifying potential.
OBJECTIVES: To investigate whether systemic autoimmune rheumatic diseases (SARDs) were disproportionately reported as adverse events following COVID-19 vaccination compared with other vaccines, using data from the Vaccin...OBJECTIVES: To investigate whether systemic autoimmune rheumatic diseases (SARDs) were disproportionately reported as adverse events following COVID-19 vaccination compared with other vaccines, using data from the Vaccine Adverse Event Reporting System (VAERS). METHODS: We conducted a retrospective disproportionality analysis of VAERS reports collected between December 2020 and December 2024. Reports were identified using a structured query based on MedDRA terms for specific SARDs, including polymyalgia rheumatica, giant cell arteritis, systemic lupus erythematosus, systemic sclerosis, Sjögren's syndrome, myositis, and other vasculitides. For each disease, the proportional reporting ratio (PRR), reporting odds ratio (ROR), and Bayesian information component (IC) were calculated, comparing COVID-19 vaccines (BNT162b2, mRNA-1273, Ad26.COV2.S) with all other vaccines in VAERS. Analyses were further stratified by sex to explore consistency. RESULTS: Among approximately 680,000 valid adverse event reports, encompassing both COVID-19 and non-COVID-19 vaccines, no significant disproportionality signal was identified for any SARD. Polymyalgia rheumatica, giant cell arteritis, systemic lupus erythematosus, systemic sclerosis, Sjögren's syndrome, and myositis showed no evidence of disproportionate reporting following COVID-19 vaccination. The category "other vasculitides" displayed a lower reporting frequency following COVID-19 vaccination compared with other vaccines. Stratified analyses yielded consistent findings across sex subgroups. CONCLUSION: In a large national pharmacovigilance dataset, COVID-19 vaccines were not associated with a disproportionate increase in reports of any SARD. These results support the favorable safety profile of COVID-19 vaccines with respect to autoimmune rheumatic events, while highlighting the value of ongoing post-marketing surveillance for rare immune-mediated reactions.
OBJECTIVES: To empirically compare the discriminant capacities of three outcome measurement instruments for assessment of physical functioning for psoriatic arthritis (PsA): HAQ-DI, SF36-PF and SF36-PCS. METHODS: We appl...OBJECTIVES: To empirically compare the discriminant capacities of three outcome measurement instruments for assessment of physical functioning for psoriatic arthritis (PsA): HAQ-DI, SF36-PF and SF36-PCS. METHODS: We applied a network meta-analysis technique in a sample of randomized trials (RCTs) for PsA. For randomized comparison, we calculated net effect size estimates for each outcome measurement instrument using standardized mean differences (SMDs); positive values indicated a beneficial effect of the intervention compared to the control groups. We analyzed the differences between outcome measurement instruments at the trial level by applying a multiple-treatment meta-analysis to compare the SMDs within and across randomized comparisons for each outcome measurement instrument. RESULTS: From 42 articles (31 RCTs), 57, 18, and 18 randomized comparisons enabled a direct comparison between HAQ-DI and SF36-PCS (difference in SMDs: 0.057, 95 % confidence interval, CI: 0.003 to 0.110), SF36-PF and SF36-PCS (difference in SMDs: 0.101, 95 % CI: 0.018 to 0.184); and HAQ-DI and SF36-PF (difference in SMDs:0.059, 95 % CI:0.142 to 0.024), respectively. The network meta-analysis technique confirmed that both HAQ-DI and SF36-PF were more responsive to change than SF36-PCS, with differences between SMDs of 0.057 (95 % CI: 0.003 to 0.110) and 0.109 (95 % CI: 0.032 to 0.185), respectively. No difference in discriminatory capacity between HAQ-DI and SF36-PF was noted. CONCLUSIONS: HAQ-DI and SF-36-PF were equally responsive to change and superior to SF36-PCS in PsA RCTs. We illustrated a new method for quantitative comparison of the performance of different outcome measurement instruments for a particular domain.
PURPOSE: To compare the characteristics, treatment patterns, and long-term outcomes of patients with concurrent calcium pyrophosphate deposition disease (CPPD) and rheumatoid arthritis (RA) to patients with RA without CP...PURPOSE: To compare the characteristics, treatment patterns, and long-term outcomes of patients with concurrent calcium pyrophosphate deposition disease (CPPD) and rheumatoid arthritis (RA) to patients with RA without CPPD. METHODS: We studied patients with RA from the Veteran's Affairs RA (VARA) registry and identified patients with CPPD using administrative codes. We compared characteristics of patients with concurrent CPPD and RA to those with RA alone at enrollment. We used parsimonious multivariable logistic regression to study the probability of achieving a low disease activity as well as receiving prednisone and new biologic or targeted synthetic disease modifying antirheumatic drugs (b/tsDMARDs) over follow-up, adjusting for pre-hypothesized confounders and stratifying by autoantibody status. RESULTS: Among 2771 U.S. veterans with RA, we identified 64 (2.3 %) patients with CPPD at enrollment. Patients with CPPD were older [68.5 (9.0) v. 64.2 (11.0), p < 0.001], had higher rates of comorbidities, including osteoarthritis (93.8 % v. 80.1 %, p = 0.007), spine disease, and diabetes, and were less likely to have ACPA (63.5 % v. 77.8 %, p = 0.01). While those with CPPD were numerically less likely to achieve low disease activity over time, this was not statistically significant. Among seronegative patients, CPPD patients exhibited more prednisone use (OR 2.44 [95 % CI 1.15-5.22]) and more frequent initiation of b/tsDMARDs (OR 2.79 [95 % CI 1.46-5.32]) as well as higher rates of joint replacement and death during follow-up. CONCLUSIONS: Seronegative RA patients with CPPD changed therapies more frequently, used more prednisone, and had worse long-term outcomes. These findings suggest some seronegative RA may represent CPPD and require alternative diagnostic and treatment approaches.
OBJECTIVES: To assess the proportion of axial spondylarthritis (axSpA) patients reporting PASS, explore variables associated with PASS and determine the relation with axSpA Disease Activity Score (ASDAS) to predict PASS...OBJECTIVES: To assess the proportion of axial spondylarthritis (axSpA) patients reporting PASS, explore variables associated with PASS and determine the relation with axSpA Disease Activity Score (ASDAS) to predict PASS in two Dutch standard-of-care cohorts. METHODS: Patients from the GLAS cohort were included in this cross-sectional analysis. External validation was performed in the SpA-Net cohort. Univariable and multivariable logistic regression were performed to identify determinants of PASS. The predictive accuracy and threshold of the ASDAS for predicting PASS were determined using AUC and highest Youden's index. RESULTS: Of 673 included GLAS patients, 63 % were male, mean age was 48 (±14) years, and mean ASDAS 2.3 (±0.9). In total, 77 % perceived their symptom state as acceptable. Of these patients, 44 % had an ASDAS ≥2.1. In multivariable regression, lower ASDAS, absence of tender entheses and older age were independently associated with reported PASS (R² = 0.39). The ASDAS showed good accuracy in predicting PASS, with AUC of 0.84 (95 % CI 0.80-0.85) and optimal cut-off value of 2.6 (sensitivity 78 %, specificity 77 %). Similar results were found in the 159 patients from SpA-Net. CONCLUSION: In daily clinical practice, 3 out of 4 axSpA patients report an acceptable symptom state, although almost half of them have high disease activity. In line, the ASDAS threshold for predicting PASS is 2.6. Our results show that the PASS question provides additional information to disease activity, which can contribute to better shared decision making.
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
Chin A, Rahulan LM, Lalwani D
… +13 more, Moore R, Day JA, Shinjo SK, Agunbiade T, Kumar A, Luk TH, Tang YK, Fornaro M, Anuja A, So H, Limaye VS, Agarwal V, Gupta L
INTRODUCTION AND AIMS: Cardiovascular disease (CVD) is a leading contributor of morbidity and mortality in patients with idiopathic inflammatory myopathies (IIM). The British Society for Rheumatology (BSR) 2022 guideline...INTRODUCTION AND AIMS: Cardiovascular disease (CVD) is a leading contributor of morbidity and mortality in patients with idiopathic inflammatory myopathies (IIM). The British Society for Rheumatology (BSR) 2022 guidelines recommend that IIM patients should undergo a regular cardiovascular risk assessment; however, many tools underestimate scores in IIM due to their sole focus on traditional risk factors. Cardiovascular Risk Score (QRISK) incorporates risk factors that are more relevant in IIM, such as corticosteroid use. The National Institute for Health and Care Excellence (NICE) guidelines recommend offering statin therapy for the primary prevention of CVD in patients with an estimated 10-year CVD risk of ≥10 %. This study aimed to undertake an audit of cardiovascular risk assessment in a multinational cohort of patients with IIM, based on BSR and NICE recommendations. METHODS: A multi-centre, international retrospective chart review was conducted in IIM cohorts from centres in India, Hong Kong, Brazil, Italy, Australia, and the United Kingdom, of patients who attended clinics between 2020 and 2023. Data were collected from medical records to evaluate CVD risk using both WHO cardiovascular risk charts and QRISK3 score. Based on their risk of cardiovascular events in the next 10 years, patients were defined as high-risk (>20 %), moderate-risk (10-20 %), or low-risk (<10 %). Adherence to the BSR and NICE guidelines was evaluated. RESULTS: A total of 336 patients were included. All centres, except one, did not routinely assess CVD risk. More than a third of patients were deemed moderate-high risk for CVD as per QRISK3, although only 34 % in this group were prescribed a statin as per NICE guidelines. Disease subtype immune-mediated necrotizing myopathy was strongly associated with moderate-high risk scores (OR = 4.64; 95 %CI = 1.88-11.45, p < 0.001), as was active steroid use [OR = 1.76 (95 % CI = 1.06-2.92), p = 0.03] and dyslipidaemia [OR = 1.22 (95 % CI = 1.03-1.45), p = 0.02]. There was a moderate level of agreement between WHO and QRISK3 scores. CONCLUSION: Over a third of patients with IIM are at moderate-high-risk of cardiovascular events in 10 years. Steroid use and dyslipidaemia were modifiable risk factors that were statistically significant predictors of risk. Despite this, there is a lack of adherence to current guidelines advising regular CVD risk assessment and use of statins for primary prevention in this moderate-high risk group.
OBJECTIVE: Ocular manifestations frequently occur in ANCA-associated vasculitides (AAV). Orbital inflammatory disease (OID) is a subset with limited management guidelines. This systematic review evaluated interventions f...OBJECTIVE: Ocular manifestations frequently occur in ANCA-associated vasculitides (AAV). Orbital inflammatory disease (OID) is a subset with limited management guidelines. This systematic review evaluated interventions for AAV-OID. METHODS: We searched Embase, MEDLINE, Web of Science, ClinicalTrials.gov, and Cochrane Central without language or date restrictions for clinical trials, case-control studies, observational studies, and case series (≥5 patients) of adults treated for AAV-OID. Included studies reported therapy type and clinical response after ≥1 month. The primary outcome was clinical response, defined as any improvement in signs or symptoms, up to and including remission. Secondary outcomes included remission, relapse, sustained remission (>6 months), and serious adverse events. Two reviewers independently screened records and appraised studies using the Newcastle-Ottawa Scale (NOS). A qualitative synthesis and meta-analysis of proportions were performed using a random effects model. RESULTS: Of 1001 studies screened, 18 met inclusion criteria (277 patients; 14 retrospective cohorts, 4 case series). Most (17/18) had NOS scores ≥5. Thirteen studies included rituximab (RTX), 10 cyclophosphamide, 7 RTX + another immunosuppressant (IS), 11 conventional IS, and 7 surgical therapies. Most studies involved refractory/relapsing cases. In 4 RTX monotherapy series, 95% (95 %CI 89-100%, p < 0.001) had a clinical response and 84% (95%CI 72-95%, p < 0.001) achieved remission at 6 months. CONCLUSION: Our results suggest high remission rates of OID with RTX but highlight the need for high-quality prospective studies examining treatments for AAV-OID.
OBJECTIVES: to investigate the impact of cutaneous, vascular, and musculoskeletal (MSK) involvements on hand function-related patient-reported outcomes (PROs) by assessing clinical, radiographic, and ultrasonographic (US...OBJECTIVES: to investigate the impact of cutaneous, vascular, and musculoskeletal (MSK) involvements on hand function-related patient-reported outcomes (PROs) by assessing clinical, radiographic, and ultrasonographic (US) features in a real-world cohort of Systemic Sclerosis (SSc) patients. METHODS: patients were enrolled in a multicentre cross-sectional study. PROs included Cochin Hand Function Scale (CHFS). Medical history and clinical examination, hands and wrists' ultrasonography and radiography were collected. Analogue data were obtained from an external validation cohort. Separate and pooled cohorts' analyses were conducted. RESULTS: 140 consecutive patients were enrolled from 3 centres. In both univariate and multivariate analyses, CHFS scores showed a significant correlation with modified Rodnan Skin Score (mRSS) (p<0.001) and with US-detected tenosynovitis (p<0.01). A trend was observed for the presence of US-detected tenosynovitis with a sclerosing pattern and for the presence of calcinosis, with statistically significant correlations in univariate analysis (p=0.01 and 0.02, respectively) but not in multivariate analysis (p=0.06 and 0.055, respectively). CONCLUSION: our findings support the multifactorial origin of hand function impairment in SSc patients, with mostly contributions from cutaneous and MSK involvement. Skin fibrosis and US-detected tenosynovitis were the most significant variables explaining hand disability as measured by CHFS. Ultrasonography may represent a valuable complementary tool, assessing MSK disease severity and activity. WHAT WAS ALREADY KNOWN: cutaneous, vascular and musculoskeletal involvement contribute to hand function impairment in SSc patients WHAT WAS LEARNED FROM THIS STUDY: ● Skin fibrosis and US-detected tenosynovitis are the most relevant features. ● Ultrasonography may provide complementary information in the routine care of SSc patients.
Manfredi A, Vacchi C, Cerri S
… +14 more, Ledda RE, D'Amico R, Luppi F, Pancaldi F, Cassone G, Rai A, Andrisani D, Gozzi F, Della Casa G, Dardani L, Atzeni F, Patsoura A, Cozzini F, Sebastiani M
BACKGROUND: Interstitial lung disease (ILD) is a severe pulmonary complication of Sjögren disease (SjD), but its prevalence, natural history and survival are not completely understood. Our study aimed to investigate prev...BACKGROUND: Interstitial lung disease (ILD) is a severe pulmonary complication of Sjögren disease (SjD), but its prevalence, natural history and survival are not completely understood. Our study aimed to investigate prevalence, incidence, and mortality of SjD-ILD in a cohort of unselected consecutive SjD patients. METHODS: all consecutive SjD patients referred to our centre were enrolled in the study. A careful assessment for respiratory symptoms was periodically performed for each patient, and high-resolution computed tomography (HRCT) was requested in case of new-onset dyspnoea, persistent dry cough, or detection of velcro crackles by mean of electronic auscultation (VECTOR). FINDINGS: At enrolment, ILD was detected in 61/257 patients with a prevalence of 23.7 %. During a mean follow-up of 42.6 ± 14.6 months, 3 new cases of ILD were recorded, with an incidence of 0.41 new cases per 100 patients/year. Multivariate analysis showed a direct association between ILD and male sex, age at SjD diagnosis, and erythro‑sedimentation rate >40 mm, and an inverse correlation with sicca syndrome. Nonspecific interstitial pneumonia was the most observed HRCT pattern, followed by usual interstitial pneumonia. During the follow-up, 21 patients (8.2 %) died, with a statistically significant difference between the overall survival of patients with (66.5 %±11.7) and without ILD (88.4 %±5.5) (p<0.001). A fibrotic pattern was associated to a worse survival rate, while no difference was observed according to the radiologic pattern. Anti-SSA antibody was a protective factor for death, while the age at diagnosis of SjD, and the extent of ILD at HRCT were directly associated to an increased mortality. INTERPRETATION: ILD can be identified in a high number of SjD patients, inducing a significant impairment in survival. The ILD extent, but not HRCT pattern of ILD, represents the main predictor of mortality. Therefore, careful monitoring, by a multidisciplinary team, should be ensured to all SjD-ILD patients.