Safety and Tolerability of Rituximab in the Treatment of Systemic Sclerosis.

Rituximab (RTX) has been used for the treatment of systemic sclerosis (SSс) for a long time and has shown good efficacy for skin fibrosis and interstitial lung disease (ILD). However, data on tolerability and long-term adverse events (AEs) during RTX therapy in SSc are insufficient. The objective of this study was to assess the tolerability and safety of RTX in patients with SSс in a long-term prospective follow-up. Our open-label prospective study included 151 SSс patients who received at least one RTX infusion. The mean age of the patients was 47.9 ± 13.4 years; the majority of them were women (83%). The mean disease duration was 6.4 ± 5.8 years. The mean follow-up period after the first RTX infusion was 5.6 ± 2.6 years (845.6 patient-years (PY)). All patients received RTX in addition to ongoing therapy with prednisone and/or immunosuppressants. AEs were assessed and recorded by a doctor in the hospital immediately after RTX infusion and then by patient's reported outcome during the observation period. All causes of death were considered, regardless of treatment. A total of 85 AEs (56%) were registered, the overall incidence of AEs was 10/100 PY (95% confidence interval (CI) 8-12). The highest frequency of all AEs was observed in the first 2-6 months after the first course of RTX, however, these were mainly mild and moderate AEs (71%). The most frequent AEs were infections, they were observed in 40% of cases, with no serious opportunistic infections reported. The overall incidence of all infections was 7.1/100 PY (95% CI 5.5-9), serious infections-1.5/100 PY (95% CI 0.9-2.6). Infusion reactions occurred in 8% of patients. Other AEs were noted in 3% (0.6/100 PY, 95% CI 0.3-1.4). The overall incidence of serious AEs was 18%-3.2/100 PY (95% CI 2.2-4.6). There was a significant decrease of the immunoglobulin G (Ig G) during follow-up; however, its average values remained within normal limits. There were 17 deaths (11%) (2/100 PY, 95% CI 1.3-3.2). In most cases, patients died from the progression of the major organ failure, which arose before RTX treatment. In our study, the safety profile of RTX in SSс was assessed as favorable. It was similar to the AE profile in other autoimmune diseases treated with RTX. With an increase in the cumulative dose of RTX, no increase in AEs was observed. The mortality is comparable to the other severe autoimmune diseases in observational studies. Monitoring of IgG may be useful for patients with SSс on RTX therapy for early detection of the risk of developing infectious complications. RTX could be considered as a relatively safe drug for the complex therapy of SSс when standard therapy is ineffective or impossible.