Background/Purpose: Systemic sclerosis (SSc) is a systemic autoimmune disease belonging to collagen diseases, characterized by fibrosis of various organs including the skin and lungs, and vascular damage. SSc is considered to have a high unmet medical need because of its poor prognosis in severe cases and the lack of satisfactory and effective treatments. Previous studies have shown that B cells play a major role in the development of SSc. In fact, several clinical studies have suggested that B cell depletion therapy with rituximab, anti-CD20 antibody, is effective. However, no randomized, placebo-controlled trial has been able to confirm the efficacy of rituximab in SSc, which implies that there has been no high-quality evidence to date.

Methods: In this study, a multicenter, double-blind, placebo-controlled, parallel-group comparison, investigator-initiated clinical trial was conducted to evaluate the safety and efficacy of rituximab for SSc. Patients were randomized 1:1 to rituximab (375 mg/m²) or placebo and received the study drug intravenously once a week for 4 weeks. The primary endpoint was the change in the modified Rodnan total skin thickness score, a semiquantitative measure of the degree of skin sclerosis, 24 weeks after the start of the intervention. The main secondary endpoint was the change in %forced vital capacity (%FVC) at 24 weeks. This trial had been registered with ClinicalTrials.gov (NCT04274257) and UMIN-CTR (UMIN000030139).

Results: A total of 56 patients participated in the study, 54 of whom received rituximab or placebo. Twenty-four weeks after the start of the intervention, the modified Rodnan total skin thickness score was significantly improved in the rituximab group compared to the placebo group (6.30 decrease in the rituximab group vs. 2.14 increase in the placebo group; difference 8.44 [95% confidence interval -11.00 to -5.88]; P < 0.0001). In addition, the %FVC of 48 patients with interstitial lung disease was significantly improved in the rituximab group than in the placebo group at 24 weeks (0.09% improvement in the rituximab group vs. 2.87% deterioration in the placebo group; difference 2.96% [95% confidence interval 0.08 to 5.84]; P = 0.04). The incidence of adverse events was comparable between the two groups, and there were no significantly increased adverse events in either group. There were no deaths during the trial.

Conclusion: This study was the first to validate the efficacy and safety of rituximab for skin sclerosis in SSc. Moreover, this clinical trial suggested the efficacy of rituximab for SSc-associated interstitial lung disease. Therefore, it is promising that rituximab becomes a new standard therapy for SSc.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/safety-and-efficacy-of-rituximab-for-systemic-sclerosis-a-double-blind-parallel-group-comparison-investigators-initiated-confirmatory-randomized-clinical-trial-desires-study/