Background/Purpose:

Rituximab (RTX) in idiopathic inflammatory myopathies (IIM) failed to show efficacy in the placebo-controlled Rituximab in Myositis (RIM) trial. However, post hoc analyses indicated that patients with specific auto-antibodies may benefit from RTX treatment. The aim of this study was to evaluate the efficacy and safety of RTX in IIM subjects in relation to their auto-antibody profile.

Methods:

Adult IIM subjects registered in the Swedish Quality Registry (SRQ) who received ≥1 dose of RTX were enrolled. Clinical data were extracted from SRQ or medical records including myositis autoantibodies status (anti-aminoacyl-tRNA synthetase (ARS), anti-MDA5, anti-Mi2, anti-NXP2, anti-SAE, anti-SRP, and anti-TIF1-gamma antibodies). Efficacy was based on measures endorsed by the International Myositis Assessment and Clinical Studies group taken at baseline, after first and last RTX cycle. Safety assessment included serious infections, infusion reactions and death during study period. Comparisons between groups based on anti-ARS status were done using the Student’s t-test or Mann-Whitney U test for continuous variables, and Chi square or Fisher exact test for categorical variables.

Results:

Sixty-five subjects were included and 68% had a follow-up visit within 6 to 10 months (Table 1). At baseline, efficacy measures were similar except for higher HAQ score in the anti-ARS negative subjects (1.69 vs 0.75, p=0.003) (Table 2). After one cycle, the anti-ARS positive group had significantly lower patient global assessment (33.8 vs 51.4, p=0.042) and extra-muscular activity (9.9 vs 21.3, p=0.009) on visual analog scales (0-100) compared to the anti-ARS negative group. A steroid-sparing effect was only seen in the anti-ARS positive group (median steroid dosage 20 to 10mg, p <0.001). After several cycles, anti-ARS positive (n=19) compared to anti-ARS negative subjects (n=10) showed a faster decrease in disease activity, moreover, they had lower HAQ (0.5 vs 1.75, p=0.003), patient global assessment (mean 30.1 vs 57.8, p=0.011) and steroid doses (4.37 vs. 10mg, p=0.04). In the anti-ARS positive group, 3 deaths, 2 infusion reactions and 3 severe infections were recorded compared to 1 death, 1 infusion reaction and 2 severe infections in the negative group.

Conclusion:

In this observational study, we confirmed the benefit of RTX in anti-ARS positive patients who showed a significant decrease in several disease activity measures including patient-reported measure (ex: HAQ), in addition to a significant steroid-sparing effect. The effect was less dramatic in the anti-ARS negative group. These findings support the role of B cell in IIM pathogenesis.