Ab0423 safety and Tolerability of Rituximab in the Treatment of Systemic Sclerosis: Long-Term Follow-Up

Abstract

Background:Rituximab (RTX) has been used for the treatment of systemic sclerosis (SSc) for a long time, but data on tolerance and long-term adverse events (AE) are insufficient.Objectives:To assess the tolerability and safety of RTX in the patients (pts) with SSc in long-term prospective follow-up.Methods:Data on the safety and tolerability of RTX were evaluated in 149 SSc pts who received at least one RTX infusion in a long-term open-label prospective observational study. The mean age was 48±13,5 years (17-74), women - 122 (82%), diffuse cutaneous subset of the disease had 52%, limited-37% and overlap-11%. The mean disease duration was 6,4±5,8 years (0,5-30). The observation period was 12 years. All pts received prednisolone at a dose of 11,7±4,8mg/day, and 73 patients (49%) received immunosuppressants at inclusion. The indications for the appointment of RTX were ineffectiveness or impossibility of standard therapy and a severe course of the disease with high activity and unfavorable prognosis factors. AE were assessed and recorded by a physician at a hospital immediately after the infusion of RTX, then by patient reported outcome during the observation period. Severe AE were defined as those that required hospitalization for more than 24 hours, exacerbation of the disease requiring therapy, malignancies, life-threatening situations. All causes of death were considered, regardless of treatment.Results:The mean follow-up period after the first infusion of RTX was 5,6±2,6 years [834,4 patient-years (PY)]. Pts received a mean of 3,4 courses of RTX (1–10). The cumulative mean dose of RTX was 3,2±2,4 gr (0,5-11). AE were reported in 77 patients (52%), the overall frequency of AE was 9,3/100 PY (95% Confidence Interval (CI) 8-11). The highest frequency of all AE was observed in the first 2-6 months after the first infusion of RTX, however these were mainly mild AE (71%). There was a decrease of AE in the follow-up period (3,4/100 PY, 95% CI 2,4-4,9 – at the period from 3 to 10 course of RTX). The overall incidence of serious AE was 2,22/100 PY (95% CI 1,4–3,5). The specter of serious AE included: pneumonia in 7 pts, infusion reactions in 5, as well as in one case: cerebral ischemia, acute pancreatitis, allergic pneumonitis, lymphoma of pharynx, purulent arthritis, lower limb vein thrombosis, pulmonary embolism of small arteries. The most frequent AE were infections (n=53), with no serious opportunistic infections reported. The overall incidence of all infections was 6,4/100 PY (95% CI 4,9-8,3), serious infections – 1,32/100 PY (95% CI 0,7-2,4). The level of immunoglobulin G during follow-up period decreased from 12,9±4,9 to 10,1±3,4g/l (p=0,0001), but remained within normal limits. Infusion reactions occurred in 15 pts (1,8/100 PY, 95% CI 1-3). Other AE were observed in 9 pts (6%) (1,1/100 PY, 95% CI 0,53-2,12). Sixteen deaths were recorded – 10,7% or 1,91/100 PY, 95% CI 1,2-3,1. In most cases, pts died from the progression of the major organ failure. The causes of death were: progression of the interstitial lung disease (ILD) in 4 pts, heart failure associated with SSc cardiomyopathy (2), renal crisis (4), pulmonary arterial hypertension and ILD (2), pneumonia (2), sepsis after tooth extraction (1), acute pulmonary embolism (1).Conclusion:In our study, we considered the overall safety profile of RTX in SSc as favorable. It was similar to the AE profile in other autoimmune diseases treated with RTX. With an increase of the cumulative dose of RTX, there was no increase in AE. RTX could be considered as a relatively safe drug for the complex therapy of SSc when standard therapy is ineffective or impossible.Disclosure of Interests:None declared