Background/Purpose: Rituximab (RTX) is used for the treatment of rheumatoid arthritis (RA) in patients (pts) with an inadequate response to anti-TNF therapy (TNF-IR). Long-term safety data on real world RTX use in RA are limited. The objective of this study is to describe the frequency of targeted safety events in an observational cohort of RA pts initiating RTX in the US.

Methods: SUNSTONE is a prospective observational cohort study designed to evaluate the safety of RTX in RA pts in the real-world setting. Pts are evaluated and treated according to their physician’s standard practice and followed at standard of care visits every 6 mo. All pts were required to receive ≥1 RTX course but could subsequently receive other RA therapies including biologic DMARDs. Pts are assessed at baseline and at follow-up visits every ≤6 mo. Data collection focuses on targeted adverse events (AEs) (significant infections [infections that meet serious AE criteria or require IV antibiotics], cardiovascular [CV] thrombotic events, seizures, deaths, and pregnancies. Pts are followed for 5 y (regardless of time of RTX discontinuation or start of another biologic therapy), until death, withdrawal of consent or loss to follow-up. Interim analysis results (Apr 1, 2013) are presented (study completion expected 2014). Baseline demographic and disease characteristics, and safety events captured during follow-up are summarized. For calculating incidence rates (IR), patients were censored at the time of first event^1-3. Crude IR per 100 pt-yrs (PY) are reported.

Results: Overall, 994 pts (3800 PY) received RTX (82% female; median age 58 y; median disease duration 9 y; 72% RF+). Mean follow-up was 3.8 y; mean number of RTX courses was 4; 72% received ≥2 courses. Significant infections were reported in 195 pts (20%), with a corresponding IR of 5.8 (95% CI: 5.0–6.7) per 100 PY. Respiratory (n=75), skin/soft tissue (n=32) and genitourinary infections (n=24) were the most common infections observed. IR per 100 PY (95% CI) of other safety events were: myocardial infarction 0.6 (0.4–0.9), stroke 0.5 (0.3–0.8), pulmonary embolism 0.3 (0.1–0.5), deep vein thrombosis 0.4 (0.2–0.7) and seizures 0.1 (0.1–0.3). Eight pregnancies were reported.  No cases of progressive multifocal leukoencephalopathy or tuberculosis were reported. Overall, 62 deaths were reported (1.6/100 PY; 95% CI 1.3–2.1). CV disease (n = 14), malignancy (n = 12) and infection (n = 15) were the most common causes of death.

Conclusion: This interim analysis provides a preliminary summary of the frequency of targeted safety events from the SUNSTONE registry of RA pts who were TNF-IR and initiated RTX treatment. Although there are important limitations when comparing the results of the SUNSTONE registry with similarly designed observational studies, these results are consistent with registries of aTNF’s and provide real-world data for rituximab.^1-3

1. Askling et al. Ann Rheum Dis. 2007;66:1339-44.
2. Carmona et al. Ann Rheum Dis 2007;66:880-885.
3. Thyagarajan V, et al.  Semin Arthritis Rheum 2012;42(3):223-33.