Rituximab is efficacious for the treatment of patients with systemic sclerosis, according to study findings published in The Lancet Rheumatology.

Researchers conducted an open-label 24-week extension of the randomized, placebo-controlled, double-blind DESIRES trial in Japan between November 28, 2017, and November 6, 2018. In the original DESIRES study, the researchers randomly assigned 56 patients with systemic sclerosis to the rituximab group (n=28) or the placebo group (n=28). Among the 43 patients who completed the extension study, 24 patients were in the rituximab group and 19 patients were in the placebo group.

During the original study, patients received either 4 doses of rituximab 375 mg/m2 or 4 doses of placebo once weekly for 4 weeks. During the open-label extension, all patients in either the original rituximab group or placebo group received rituximab 375 mg/m2 intravenously once weekly for 4 weeks.


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The researchers analyzed the efficacy of rituximab by calculating the modified Rodnan Skin Score (mRSS) at baseline, at week 24 in the original trial, and at week 48 in the open-label extension.

For patients who received rituximab in both the original and extension trials, mRSS improved at week 24 of the original trial by -5.81 (SD 3.16) and at week 48 of the open-label trial by -8.88 (SD 3.10). Patients in the original placebo group demonstrated worsening symptoms on the mRSS by 2.14 (SD 5.51); however, these patients improved compared with baseline during the open-label extension after they received rituximab at week 48 by -6.05 (SD 4.43).

Patients demonstrated similar trends for the percentage of predicted forced vital capacity to measure the efficacy of rituximab in the subset of patients with interstitial lung disease secondary to systemic sclerosis.  

Adverse events occurred with similar frequency during the open-label extension up to week 48 compared with the double-blind original trial. The most common adverse event was upper respiratory tract infection in both the rituximab group and the placebo group that transitioned to rituximab. Two serious adverse events, cholangitis and pneumococcal pneumonia, occurred in only 1 patient per group, but both recovered. No adverse events resulted in treatment discontinuation or patient death.

Study limitations include small sample size in the DESIRES trial, a lack of generalizability outside of Japan, and the exclusion of patients with systemic sclerosis with renal crisis and pulmonary hypertension.

The study authors conclude, “[T]he results…showed that the improvement in skin sclerosis with repeated rituximab administration was sustained for 48 weeks.” They added, “Treatment for systemic sclerosis with rituximab appears to be relatively safe, at least for [2] courses and up to 48 weeks.”

Reference

Ebata S, Yoshizaki A, Oba K, et al. Safety and efficacy of rituximab in systemic sclerosis (DESIRES): open-label extension of a double-blind, investigators-initiated, randomised, placebo-controlled trial.  The Lancet Rheumatology. 2022;4(8):e546-e555. doi:10.1016/S2665-9913(22)00131-X