Predictors of clinical improvement in rituximab-treated refractory adult and juvenile dermatomyositis and adult polymyositis.

Abstract

OBJECTIVE:

To identify the clinical and laboratory predictors of clinical improvement in a cohort of myositis patients treated with rituximab.

METHODS:

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.

RESULTS:

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.

CONCLUSION:

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.

• Authors: Rohit Aggarwal, Andriy Bandos, Ann M Reed, Dana P Ascherman, Richard J Barohn, Brian M Feldman, Frederick W Miller, Lisa G Rider, Michael O Harris-Love, Marc C Levesque, RIM Study Group, Chester V Oddis
• Journal: Arthritis & rheumatology (Hoboken, N.J.) (Arthritis Rheumatol) Vol. 66 Issue 3 Pg. 740-9 (Mar 2014) ISSN: 2326-5205 [Electronic] United States
• PMID: 24574235 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 by the American College of Rheumatology.

Chemical References

• Antibodies, Monoclonal, Murine-Derived
• Autoantibodies
• Immunologic Factors
• Rituximab

Topics

• Antibodies, Monoclonal, Murine-Derived (therapeutic use)
• Autoantibodies
• Dermatomyositis (drug therapy, immunology)
• Female
• Humans
• Immunologic Factors (therapeutic use)
• Male
• Polymyositis (drug therapy, immunology)
• Rituximab
• Severity of Illness Index
• Treatment Outcome