Objective To assess the safety and efficacy of rituximab in a randomized, double-blind, placebo-phase, trial of adult and pediatric myositis. Methods Adults with refractory polymyositis and adults and children with refractory dermatomyositis were enrolled. Entry criteria included muscle weakness and ≥2 additional abnormal core set measures (CSM) for adults. JDM patients required ≥ 3 abnormal CSM with or without muscle weakness. Patients were randomized to either ‘rituximab early’ or ‘rituximab late’ and glucocorticoid and immunosuppressive therapy were allowed at entry. The primary endpoint compared the time to achieve the preliminary International Myositis Assessment and Clinical Studies Group definition of improvement (DOI) between the 2 groups. The secondary endpoints were time to achieve ≥20% improvement in muscle strength, and the proportion of early and late rituximab patients achieving DOI at week 8. Results Among 200 randomized patients (76 PM/76 DM/48 JDM), 195 showed no difference in the time to DOI between the rituximab late (n=102) and rituximab early (n=93) groups (p=0.74, log rank) with a median time to DOI of 20.2 weeks and 20.0 weeks respectively. The secondary endpoints also did not significantly differ between the two treatment groups. However, 161 (83%) of randomized patients met the DOI and individual CSM improved in both groups throughout the 44-week trial. Conclusion Although there were no significant differences in the two treatment arms for the primary and secondary endpoints, 83% of refractory adult and juvenile myositis patients met the DOI. The role of B cell depleting therapies in myositis warrants further study with consideration for a different trial design.
Objective To compare the cumulative survival and event free survival in patients with Jo-1 versus non-Jo-1 anti-tRNA synthetase autoantibodies (anti-synAb). Methods Anti-synAb positive patients initially evaluated from 1985 to 2009 were included regardless of the connective tissue disease (CTD) diagnosis. Clinical data were extracted from a prospectively collected database and chart review. Survival between Jo-1 and non-Jo-1 was compared by log rank and Cox proportional hazards methods. Results 202 patients possessed anti-synAb: 122 Jo-1 and 80 non-Jo-1 (35 PL-12; 25 PL-7; 9 EJ; 6 KS; 5 OJ). The diagnoses at first visit for Jo-1 and non-Jo-1 patients were myositis in 83% and 40.0%, overlap or undifferentiated CTD in 17% and 47.5%, and systemic sclerosis in 0% and 12.5%, respectively (p<0.001). The median delay in diagnosis was 0.4 years in Jo-1 patients versus 1.0 year in non-Jo-1 patients (p<0.001). The most common causes of death in the overall cohort were pulmonary fibrosis in 49% and pulmonary hypertension in 11%. The 5- and 10-year unadjusted cumulative survival was 90% and 70% for Jo-1 patients, and 75% and 47% for non-Jo-1 patients ( p<0.005). The hazard ratio (HR) of non-Jo-1 patients compared with Jo-1 patients was 1.9 (p=0.01) for cumulative and 1.9 (p=0.008) for event free survival from diagnosis. Age at first diagnosis and diagnosis delay but not gender, ethnicity and CTD diagnosis influenced survival. Conclusions Non-Jo-1 anti-synAb positive patients have decreased survival compared with Jo-1 patients. The difference in survival may be partly attributable to a delay in diagnosis in the non-Jo-1 patients.
Objectives: There is a known association between myositis and cancer. The risk is greater in dermatomyositis (DM) than polymyositis (PM), although reliable methods to predict cancer risk in specific patients with myositis are not presently available. This study was undertaken to determine whether risk of developing cancer in myositis can be predicted by antibody profiling. Methods: A cross-sectional study of UK Caucasian adults with PM (n = 109), DM (n = 103) and connective tissue disease overlap (myositis/CTD-overlap, n = 70). Patients were tested for a comprehensive range of myositis-specific/associated autoantibodies. Sensitivity and specificity analyses were performed for the optimal identification of cancer risk. Results: Sixteen patients had cancer-associated myositis (CAM) (15 DM, 1 myositis/CTD-overlap). CAM patients were older at disease onset, and patients without myositis-specific/associated autoantibodies on ''routine'' laboratory testing (negative for anti-Jo-1, anti-PM-Scl, anti-U1-RNP, anti-U3-RNP, anti-Ku antibodies) had a significantly increased risk of CAM. Possession of the antibody against 155 kDa and 140 kDa protein specificities (anti-155/140 antibody) represented a significant risk factor for CAM, and was found exclusively in DM. A positive anti-155/140 antibody result proved highly specific, moderately sensitive, with high negative predictive value for CAM. A ''negative routine myositis antibody panel'' result was highly sensitive, with high negative predictive value for CAM. The combination of these two approaches was 94% sensitive, detecting 15 of 16 CAM, with 100% sensitivity and negative predictive value in DM. Conclusions: These results may help clinicians predict which patients with myositis are at greater risk of developing cancer, thus identifying those requiring aggressive diagnostic evaluation and intensive cancer surveillance at myositis onset and follow-up.
Objective. To determine the long-term outcome and associated clinical, serologic, and pathologic features in a cohort of patients with connective tissue disease (CTD) and the anti-signal recognition particle (anti-SRP) autoantibody.Methods. Sera and clinical data were collected prospectively from consecutive adult patients with polymyositis (PM; n ؍ Conclusion. The anti-SRP autoantibody is not specific for PM. Severe muscle weakness and atrophy were prominent features in PM patients with anti-SRP.
Objective Epidemiology studies suggest that Systemic Sclerosis is more common, occurs at a younger age and is more severe in African-Americans than Caucasians. However, the scleroderma autoantibody profile is very different between these two ethnic subgroups. This study examines the demographic and disease features, frequency and severity of internal organ system involvement and survival in African-American and Caucasian SSc patients with particular attention to their serum autoantibody profiles. Methods Demographic, clinical, autoantibody, natural history of organ involvement and survival were studied in consecutive African-American and Caucasian patients seen between 1972 and 2007 as part of the Pittsburgh Scleroderma Database. The Medsger Disease Severity Scale was used to determine severe disease. Results African-American patients were more likely to have anti topoisomerase, anti U1RNP and U3 RNP auto-antibodies. Comparing African-American and Caucasians with these antibodies, African-American patients with anti topoisomerase antibody had more frequent and more severe pulmonary fibrosis than Caucasians and an associated decreased survival. Pulmonary fibrosis was also more severe in the U1 RNP patients but was not associated with a difference in survival between African Americans and Caucasians. Anti U3 RNP was associated with more severe gastrointestinal involvement in African-American’s compared to Caucasians. Conclusions African Americans with systemic sclerosis have more severe disease complications than Caucasians both because of the type of autoantibody they have and because they have more severe interstitial lung disease even within the antibody subset. Early aggressive intervention in all African Americans with interstitial lung disease should be a priority.
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