• Rheumatological Autoimmune Disorders
• Inflammatory Disorders Clinical Trials

The presence of myositis-associated autoantibodies is the strongest predictor of improvement in patients with adult and juvenile myositis treated with B-cell depletion.

Rohit Aggarwal, MD, MS, University of Pittsburgh, Pittsburgh, Pennsylvania, USA, described findings from the Rituximab for the Treatment of Refractory Adult and Juvenile Dermatomyositis (DM) and Adult Polymyositis (PM) [RIM] study, in which baseline clinical, laboratory, and serologic predictors of response were examined in rituximab-treated patients with refractory myositis, defined as failure of steroids and at least 1 other immunosuppressive agent. The study included 200 patients (76 with adult PM, 76 with adult DM, and 48 with juvenile DM) who were randomized to early (Weeks 0 and 1) or late (Weeks 8 or 9) rituximab with follow-up to 44 weeks.

The definition of improvement [Rider LG et al. Arthritis Rheum 2004] for this study is defined as improvement in 3 of any 6 core set measures (CSM) by ≥20%, with no more than 2 CSM worsening by ≥25% (excluding manual muscle testing) at 2 consecutive visits. The primary endpoint was to compare the time to improvement between the rituximab early and rituximab late groups. As reported previously [Oddis CV et al. Arthritis Rheum 2012], 83% of patients improved during the course of trial, with no difference in response between the 2 treatment groups.

For the current study, a list of the candidates' baseline clinical and laboratory parameters was compiled as potential predictor variables. All baseline variables were univariately assessed for association with time to improvement. All univariate variables that predicted or trended toward an association with time to improvement were then entered into a multivariate model. A final multivariate time-dependent Cox model was then created.

The final multivariate model consisted of global damage (high vs low) at Week 8 (p<0.01), disease subset (adult vs juvenile) at Week 8 (p<0.01), and myositis autoantibodies: Jo-1/other anti-syn (p<0.01) and Mi-2 (p<0.01) compared with no autoantibodies group. However, both global damage and disease subset washed out as significant predictive variables by Week 20, leaving anti-Jo-1 and anti-Mi-2 as the only significant markers of good prognosis and predictor of treatment response throughout the study.

In summary, the presence of juvenile DM and low global damage predicted a more rapid response than did adult onset myositis and high global damage, respectively. Although low global damage and juvenile DM were associated with more rapid improvement, there was no evidence that either predicts better prognosis if patients fail to improve early, said Dr. Aggarwal. The strongest predictor of improvement was the presence of myositis autoantibodies anti-Jo-1 and anti-Mi-2, which remained significant throughout the study period. In the future, myositis autoantibodies may serve as a prognostic marker and further investigation is needed for evaluation of anti-Jo-1 levels as a biomarker for myositis disease activity.

• © 2012 MD Conference Express®