Rituximab effectively reduced skin sclerosis and appeared to have a beneficial effect on interstitial lung disease (ILD) for patients with systemic sclerosis (SSc) in a randomized, clinical trial.
At 24 weeks’ follow-up, there was significant improvement in total skin thickness scores among patients who received four once-weekly rituximab infusions, compared with patients who received placebo infusions. Among patients who received rituximab, there were also small but significant improvements in percentage of forced vital capacity (FVC). Among patients who received placebo, FVC worsened, reported Ayumi Yoshizaki, MD, of the University of Tokyo, Tokyo, Japan, and colleagues.
“Systemic sclerosis is considered to have high unmet medical needs because of its poor prognosis and the lack of satisfactory and effective treatments,” he said at the American College of Rheumatology (ACR) 2021 Annual Meeting, which was held online.
“Several clinical studies have suggested that B-cell depletion therapy with rituximab anti-CD20 antibody is effective in treating skin and lung fibrosis of SSc. However, no randomized, placebo-controlled trial has been able to confirm the efficacy of rituximab in SSc,” Yoshizaki said.
A rheumatologist who is currently conducting an investigator-initiated trial in which patients with SSC are undergoing treatment with rituximab followed by belimumab (Benlysta) said in an interview with Medscape Medical News that he found the data to be “super interesting.”
“There are a lot of reasons to think that B cells might be important in systemic sclerosis, and actually that’s why our group had previously done an investigator-initiated trial with belimumab years ago,” said Robert Spiera, MD, director of the Scleroderma, Vasculitis, and Myositis Center at the Hospital for Special Surgery in New York City.
Randomized Trial
Yoshizaki and colleagues conducted the randomized, placebo-controlled DESIRES trial in four hospitals in Japan to evaluate the safety and efficacy of rituximab for the treatment of SSc.
In the investigator-initiated trial, patients aged 20–79 years who fulfilled ACR and European Alliance of Associations for Rheumatology classification criteria for systemic sclerosis and who had a Modified Rodnan Skin Score (mRSS) of ≥10 and a life expectancy of ≥6 months were randomly assigned to receive infusions with either rituximab 375 mg/m2 or placebo once weekly for 4 weeks. Patients and clinicians were masked to treatment allocation.
The trial included 56 patients (51 women, five men). Of all patients enrolled, 27 of 28 who were allocated to receive rituximab and 22 of 28 who were allocated to receive placebo underwent at least one infusion and completed 24 weeks of follow-up.
The absolute change in mRSS at 24 weeks after the start of therapy, the primary endpoint, was -6.30 in the rituximab group, compared with +2.14 in the placebo group, a difference of -8.44 (P < .0001).
In a subgroup analysis, rituximab was superior to placebo regardless of disease duration, disease type (diffuse cutaneous or limited cutaneous SSc), prior receipt of systemic corticosteroids or immunosuppressants, or having C-reactive protein levels <0.3 mg/dL or ≥0.3 mg/dL.
However, there was no significant benefit with rituximab for patients with baseline mRSS of ≥20 or for those without ILD at baseline.
There was also evidence that rituximab reduced lung fibrosis. For patients assigned to the active drug, the absolute change in FVC at 24 weeks was +0.09% of the predicted value, compared with -3.56% for patients who received placebo (P = .044).
The researchers also observed radiographic evidence of lung improvement. The absolute change in the percentage of lung field occupied with interstitial shadows was -0.32% in the rituximab arm, vs +2.39% in the placebo arm (P = .034). There was no significant between-group difference in the absolute change in diffusing capacity of lung for carbon monoxide, however.
Adverse events that occurred more frequently with rituximab included oral mucositis, diarrhea, and decreased neutrophil and white blood cell counts.
Convincing Results
“What I thought the Japanese study did was to give a much more convincing proof of concept than has been out there,” Spiera told Medscape Medical News.
“There have been some preliminary experiences that have been encouraging with rituximab in scleroderma, most of which has been open label,” he said.
He also referred to a retrospective study by EUSTAR, the European Scleroderma Trials and Research group, which indicated that patients who had previously received rituximab seemed to have had better outcomes than patients who had been treated with other therapies.
Spiera added that although he was glad to see the data from a randomized, placebo-controlled trial in this population, he was uncomfortable with the idea of leaving patients untreated for 6 months.
“From the standpoint of somebody wanting to know what strategies might be promising, this is great for us, but I would not have designed the trial that way,” he said.
The study results were previously published in The Lancet Rheumatology.
The study was supported by grants from the Japan Agency for Medical Research and Development and the Zenyaku Kogyo Company. Yoshizaki disclosed no relevant financial relationships. Spiera has received grant/research support from and has consulted for Roche/Genentech, maker of rituximab, and has received compensation from other companies.
American College of Rheumatology (ACR) 2021 Annual Meeting: Abstract 0496. Presented November 6, 2021.
Neil Osterweil, an award-winning medical journalist, is a long-standing and frequent contributor to Medscape.
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