ClinicalTrials.gov identifier: NCT00106184.
Predictors of Clinical Improvement in Rituximab-Treated Refractory Adult and Juvenile Dermatomyositis and Adult Polymyositis†
Article first published online: 25 FEB 2014
Copyright © 2014 by the American College of Rheumatology
Arthritis & Rheumatology
Volume 66, Issue 3, pages 740–749, March 2014
How to Cite
Aggarwal, R., Bandos, A., Reed, A. M., Ascherman, D. P., Barohn, R. J., Feldman, B. M., Miller, F. W., Rider, L. G., Harris-Love, M. O., Levesque, M. C., the RIM Study Group and Oddis, C. V. (2014), Predictors of Clinical Improvement in Rituximab-Treated Refractory Adult and Juvenile Dermatomyositis and Adult Polymyositis. Arthritis & Rheumatology, 66: 740–749. doi: 10.1002/art.38270
Dr. Oddis has received consulting fees from Questcor (less than $10,000) and has served as an expert witness concerning appropriateness of rituximab therapy in a patient with myositis.
- Issue published online: 25 FEB 2014
- Article first published online: 25 FEB 2014
- Accepted manuscript online: 18 NOV 2013 11:19AM EST
- Manuscript Accepted: 5 NOV 2013
- Manuscript Received: 25 JUN 2013
- NIH (National Institute of Arthritis and Musculoskeletal and Skin Diseases contract). Grant Number: N01-AR-4-2273)
- Intramural Program of the NIH (National Institute of Environmental Health Sciences)
- General Clinical Research Center/Clinical and Translational Science Award. Grant Number: M01-RR-023940/UL1-RR-033179
- University of Kansas Medical Center
- Genentech Inc.
To identify the clinical and laboratory predictors of clinical improvement in a cohort of myositis patients treated with rituximab.
We analyzed data for 195 patients with myositis (75 with adult polymyositis [PM], 72 with adult dermatomyositis [DM], and 48 with juvenile DM) in the Rituximab in Myositis trial. Clinical improvement was defined as 20% improvement in at least 3 of the following 6 core set measures of disease activity: physician's and patient's/parent's global assessment of disease activity, manual muscle testing, physical function, muscle enzymes, and extramuscular disease activity. We analyzed the association of the following baseline variables with improvement: myositis clinical subgroup, demographics, myositis damage, clinical and laboratory parameters, core set measures, rituximab treatment, and myositis autoantibodies (antisynthetase, anti–Mi-2, anti–signal recognition particle, anti–transcription intermediary factor 1γ [TIF-1γ], anti-MJ, other autoantibodies, and no autoantibodies). All measures were univariately assessed for association with improvement using time-to-event analyses. A multivariable time-dependent proportional hazards model was used to evaluate the association of individual predictive factors with improvement.
In the final multivariable model, the presence of an antisynthetase, primarily anti–Jo-1 (hazard ratio [HR] 3.08, P < 0.01), anti–Mi-2 (HR 2.5, P < 0.01), or other autoantibody (HR 1.4, P = 0.14) predicted a shorter time to improvement compared to the absence of autoantibodies. A lower physician's global assessment of damage (HR 2.32, P = 0.02) and juvenile DM (versus adult myositis) (HR 2.45, P = 0.01) also predicted improvement. Unlike autoantibody status, the predictive effect of physician's global assessment of damage and juvenile DM diminished by week 20. Rituximab treatment did not affect these associations.
Our findings indicate that the presence of antisynthetase and anti–Mi-2 autoantibodies, juvenile DM subset, and lower disease damage strongly predict clinical improvement in patients with refractory myositis.