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.

Figure 1

Kaplan-Meier curves for probability of meeting the definition of improvement (DOI) according to myositis autoantibody (autoAb) subset. Patients were classified into 4 subsets: those with antisynthetase autoantibodies (including anti–Jo-1), those with anti–Mi-2, those with other autoantibodies, and those with no detectable autoantibodies.

Figure 2

Kaplan-Meier curves for probability of meeting the definition of improvement (DOI) according to myositis clinical subgroups. Patients were classified as having either adult myositis (polymyositis or dermatomyositis) or juvenile

Figure 3

Kaplan-Meier curves for probability of meeting the definition of improvement (DOI) according to degree of myositis disease damage. Patients were classified as having low damage (score of ≤23 a 100-mm visual analog scale [VAS]) or high damage (score of >23 on a 100-mm VAS).