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NEW YORK (Reuters Health) – Rituximab seemed to be a safe and effective treatment for systemic sclerosis in a placebo-controlled validation trial in Japan.

“A number of studies have examined B-cell depletion therapy for systemic sclerosis, and many of them have suggested that (this) is effective in treating systemic sclerosis,” Dr. Ayumi Yoshizaki told Reuters Health by email. However, until now, no placebo-controlled trials have shown the efficacy of the drug.

“We recognize that further studies are needed before rituximab can be accepted as a standard therapy for systemic sclerosis worldwide,” Dr. Yoshizaki said, “since this trial was conducted only in Japanese patients.”

“Nevertheless,” he added, “we believe that the clinical trial we conducted will serve as a helpful model for many trials to be conducted in the future.”

As reported in The Lancet Rheumatology, Dr. Yoshizaki and colleagues conducted a randomized, reviews alesse placebo-controlled trial in 56 individuals at four hospitals in Japan.

Patients had a mean age of 49; about 96% were women; all fulfilled the 2013 American College of Rheumatology and European League Against Rheumatism classification criteria for systemic sclerosis, with a modified Rodnan Skin Score (mRSS) of 10 or greater; and had an expected survival of at least six months. They were randomly assigned (1:1) to receive intravenous rituximab(375 mg/m2) or placebo once weekly for four weeks.

The primary endpoint was the absolute change in mRSS 24 weeks after initiation of treatment, measured in all patients who received at least one dose and had one endpoint assessment.

Almost all (96%) patients in the rituximab group 79% of those in the placebo group received at least one dose of their allocated treatment and completed 24 weeks of follow-up.

The absolute change in mRSS at 24 weeks was lower in the rituximab group than in the placebo group (-6.30 vs 2.14).

Adverse events were similar in both groups and occurred in all patients in the rituximab group and 88% of those on placebo. The most common adverse event was upper respiratory infection, which occurred in 39% of those taking rituximab and 38% of those on placebo.

One serious adverse event leading to treatment discontinuation occurred in one patient in each group (decreased serum albumin in the rituximab group and biliary enzyme increase in the placebo group).

No deaths occurred during follow-up.

Dr. Yoshizaki noted, “It is true that rituximab is an effective drug for systemic sclerosis, but after many years of continuous administration, the levels of gamma globulin in the blood will decrease. This leads to an increased susceptibility to infections.”

“Especially in the midst of the COVID19 pandemic,’ he said, “long-term treatment with rituximab may not be welcomed by both physicians and patients.”

Dr. Dinesh Khanna of Michigan Medicine, University of Michigan in Ann Arbor, coauthor of a related editorial, commented in an email to Reuters Health. “These data are different than recently published large international trials where the researchers have seen marked heterogeneity in the mRSS (despite standardization of mRSS) and (this) has led to negative trials.

“An example includes the recently published phase 3 trial of tocilizumab in early systemic sclerosis where 210 patients were randomized to either weekly tocilizumab or placebo for 52 weeks (https://bit.ly/3iTqYt5),” he said. “The primary outcome measure was mRSS, which was statistically non-significant, but tocilizumab showed clinically meaningful effect on lung function, which led to the FDA approval of tocilizumab for SSc-related interstitial lung disease.”

“To provide confidence in the (current) trial, the researchers should plan a well-designed international trial with standardization of end points, and include clinically meaningful end points such as forced vital capacity, and composite end points such as ACR CRISS score before rituximab can be advocated for treatment of early SSc with progressive skin involvement,” Dr. Khanna concluded.

The study was funded in part by Zenyaku Kogyo. No competing interests were declared.

SOURCE: https://bit.ly/3cUUuv0 and https://bit.ly/3cUCq49 The Lancet Rheumatology, online May 26, 2021.

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