Long-Term Safety of Rituximab in Rheumatoid Arthritis: Analysis From the SUNSTONE Registry

Abstract

Objective: To evaluate the long-term safety of rituximab in an observational cohort of patients with rheumatoid arthritis (RA) who had an inadequate response to ≥ 1 antitumor necrosis factor therapies in the United States (SUNSTONE Registry).

Methods: In this prospective, observational cohort study, patients received rituximab according to their physician's standard practice and were evaluated at standard-of-care follow-up visits at least every 6 months. The primary outcome was the incidence of protocol-defined significant infections. Secondary outcomes included serious adverse events potentially associated with rituximab, cardiovascular or thrombotic (CVT) events, seizures, deaths and pregnancies. Posthoc analyses assessed outcomes by concomitant medication use.

Results: Overall, 989 patients (safety-evaluable population) received ≥ 1 dose of rituximab, with a total follow-up of 3844 patient-years (PYs; mean duration, 3.9 years). In total, 341 significant infections occurred in 197 patients (19.9%). The incidence rates (95% CI) for significant infections, CVT events, and seizures were 8.87 (7.98, 9.86), 1.95 (1.56, 2.45), and 0.18 (0.09, 0.38) per 100 PYs, respectively. The incidence of significant infections did not increase with time or with cumulative rituximab exposure. During the study, 64 patients died (crude mortality [95% CI]: 1.66 per 100 PYs [1.30, 2.13]). The most common causes of death were infections (19 patients), malignancy (14), and cardiovascular events (13). Eight pregnancies were reported in 7 patients.

Conclusion: In patients with RA treated with rituximab for up to 5 years, the rates of significant infections were stable over time and higher in patients who received long-term systemic steroid treatment. This article is protected by copyright. All rights reserved.

Figure 1

Patient disposition.

Figure 2

Incidence rates of significant infection by number of rituximab courses (A), and over time (B). IR = incidence rate; PYs = patient‐years; 95% CI = 95% confidence interval.

Figure 3

Incidence rates of significant infection by demographics, disease characteristics, rheumatoid arthritis (RA) treatment, medications, and comorbidities. The large diamond and solid vertical line show the incidence rate of significant infections for the entire safety‐evaluable population (dashed lines show 95% confidence intervals [95% CIs]). BMI = body mass index; HAQ DI = Health Assessment Questionnaire disability index; csDMARD = conventional synthetic disease‐modifying antirheumatic drug; SLE = systemic lupus erythematosus; IR = incidence rate; PYs = patient‐years.

Figure 4

Incidence rates of cardiovascular or thrombotic (CVT) events by demographics, disease characteristics, rheumatoid arthritis (RA) treatment, medications, and comorbidities. The large diamond and solid vertical line show the incidence rate of CVT events for the entire safety‐evaluable population (dashed lines show 95% confidence intervals [95% CIs]). BMI = body mass index; HAQ DI = Health Assessment Questionnaire disability index; IR = incidence rate; PYs = patient‐years.