Background/Purpose: Rituximab (RTX) is an approved treatment for rheumatoid arthritis (RA) in patients (pts) with an inadequate response to anti–TNF therapy (aTNF-IR). Long-term infection risk data of RTX use in real-world settings are limited. The objective of this study was to describe the frequency of significant infections in pts with RA initiating RTX in the US.

Methods: SUNSTONE was a prospective observational cohort study designed to evaluate the safety of RTX in TNF-IR RA pts in a real-world setting. Pts were evaluated and treated according to their physicians‘ standard practices and followed at visits every 6 months. Pts were followed for 5 years (regardless of RTX discontinuation or start of another biologic DMARD), until death, withdrawal of consent or loss to follow-up. Significant infections were defined as infections that meet FDA serious AE criteria or require IV antibiotics. For calculation of incidence rates (IRs), pts were censored at the time of first event, switch to another biologic DMARD, death, withdrawal of consent or loss to follow-up. IRs by year after RTX initiation and by RTX course are described. Course was defined as 2 × 1000-mg infusions separated by ≤21 days. Pts not treated according to this regimen were excluded from the course analysis. Among pts who switched to another biologic DMARD during follow-up, the IRs of significant infection before and after switch were also calculated. IR calculations after switch were censored at the time of first event, death, withdrawal of consent or loss to follow-up. IRs per 100 pt-yrs (PY) are reported.

Results: Overall, 938 pts (3778 PY) received RTX (82% F; median age, 58 y; median disease duration, 9 y; 72% RF+). Mean duration of follow-up was 4 y and mean number of RTX courses was 4; however, not all pts were treated following the labeled dose regimen. Four pts with insufficient information to calculate IRs were excluded. Significant infections were reported in 160 pts (17%), with an IR of 6.4 (95% CI, 5.5 to 7.4). IRs in 1-y increments following RTX initiation were 7.1 (95%CI: 5.5-9.2), 6.5 (95%CI: 4.8-8.7), 8.0 (95%CI: 5.9-10.9), 9.2 (95%CI: 6.6-12.7) and 7.0 (95%CI:4.7-10.3) in years 0-1, 1-2, 2-3, 3-4, and 4-5, respectively. See table for IR and 95%CI by course; exposure is less than 100PY from Course 7 onward resulting in wide 95%CIs around IR estimates. Among 338 pts who switched to another biologic DMARD, IRs before and after switch were 4.6 (95% CI, 3.1 to 6.7) and 4.5 (95% CI, 3.3 to 6.2), respectively.

Conclusion : Data from SUNSTONE with up to 5 years of follow-up showed that risk of significant infection among pts with refractory RA that were treated with RTX after an inadequate response to an aTNF agent did not increase over time and with multiple courses. In addition, switch from RTX to another biologic DMARD was not associated with an increased risk of significant infection.