Session Type: Abstract Session
Session Time: 10:00AM-10:50AM
Background/Purpose: To assess the efficacy and tolerability of tocilizumab (anti-IL-6R, TCZ), in a multi-center, randomized, double blind, placebo-controlled trial in refractory adult dermatomyositis (DM) and polymyositis (PM) patients.
Methods: Adult patients with refractory DM and PM were enrolled in a phase IIb double blind; placebo-controlled, clinical trial randomized 1:1 for active drug:placebo for 6 months, with a targeted enrollment of 40 subjects. Inclusion criteria included: (a) probable or definite PM or DM (modified Bohan and Peter criteria), (b) either a classic DM rash, a myositis associated autoAb or a PM diagnosis vetted by adjudication, (c) refractory myositis defined by glucocorticoid (GC) failure, or GC/at least one other immunosuppressive failure and (d) active disease defined by at least 3 of 6 abnormal myositis core set measures (CSM) including an MMT< 136/150 or if MMT >136 then the 3 abnormal CSM plus a cutaneous VAS ≥ 3/10 cm. Subjects were randomized to receive either 6 doses of TCZ (8 mg/kg IV) or placebo every 4 weeks for 24 weeks. The primary endpoint compared the Total Improvement Score (TIS; 2016 ACR/EULAR Criteria) between both arms at weeks 4-24, using a GEE model including treatment, diagnosis and time. Secondary outcomes included time to meeting minimal improvement, changes in CSM, steroid-sparing effect, proportion of patients meeting minimal, moderate and major improvement, and safety/tolerability outcomes between both treatment arms.
Results: 36 subjects (23DM, 13PM) were randomized (18 in each arm) and analyzed using intention to treat. All but 4 (2 TCZ/2 placebo) completed 24 weeks of treatment. There was no significant difference (p=0.86) in the TIS (primary outcome) over 24 weeks between TCZ and placebo in the entire cohort or by subgroup (DM alone). There was no significant difference in the mean TIS score over 4-24 weeks between the two arms [mean (SD) all visits: TIS 26.4 (16.75) vs. 29.3 (16.76)] (Figure 1). However, the mean TIS improved significantly (p=0.02) from baseline to the last study visit in both arms. The proportion of patients meeting no, minimal, moderate and major improvement at last study visit, were similar (p=0.22) in both arms [TCZ: 8 (44.4%), 3 (16.7%), 4 (22.2%), and 3 (16.7%); placebo: 5 (27.7%), 5 (27.7%), 6 (33.3%) and 2 (11.1%), (Figure 2)]. The secondary endpoints of time to minimal improvement, CSM change, and steroid-sparing effect were not significantly different between treatment arms. The adverse/serious adverse events (AE/SAE) were not significantly different between both arms [TCZ: 14 events (44.4 % of pts) vs. 9 events (33.3% of pts)]. TCZ was well tolerated and only 4 patients stopped treatment early due to disease worsening (n=3) or SAE (n=1).
Conclusion: TCZ treatment did not meet the primary or secondary efficacy outcomes in refractory DM and PM in this 24-week phase IIb study. TCZ was safe and well tolerated.
To cite this abstract in AMA style:Aggarwal R, Rockette H, Venturupalli S, Marder G, Dimachkie M, Gazeley D, Ernste F, Crofford L, Moghadam-Kia S, Koontz D, Zhu L, Oddis C. Tocilizumab in Myositis: Results of a Phase IIb Double-Blind Randomized Controlled Trial [abstract]. Arthritis Rheumatol. 2020; 72 (suppl 10). https://acrabstracts.org/abstract/tocilizumab-in-myositis-results-of-a-phase-iib-double-blind-randomized-controlled-trial/. Accessed October 26, 2021.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/tocilizumab-in-myositis-results-of-a-phase-iib-double-blind-randomized-controlled-trial/