AN OPEN-LABEL STUDY OF THE SAFETY OF RITUXIMAB (RTX) IN COMBINATION WITH OTHER BIOLOGIC DISEASE-MODIFYING ANTIRHEUMATIC DRUGS (DMARDS) IN PATIENTS WITH ACTIVE RHEUMATOID ARTHRITIS (RA)

Background: RTX plus methotrexate (MTX) is effective and well-tolerated in RA patients (pts). Pts with an inadequate response (IR) to RTX may receive other biologics while B-cell depleted. In some cases, pts with IR to a single biologic may consider combination of two biologics with non-biologic DMARDs. Objectives: The primary objective of the SUNDIAL (stage II) study is to characterize the safety of RTX in combination with biologic DMARDs in pts with RA. Methods: SUNDIAL (stage II) is an open-label study of RA pts with IR to ≥1 biologics. Pts aged 18-80 yrs who received a biologic for ≥12 weeks (wks) at a stable dose for ≥4 wks prior to baseline received RTX (500 mg IV x2) plus their current biologic and non-biologic DMARD therapy at a stable dose. Biologics included Etanercept (ETN) at 50 mg/wk, Adalimumab (ADA) at 40 mg every other wk, Infliximab (INF) at 3–5 mg/kg every 8 wks (with MTX), or Abatacept (ABA) at 500–1000 mg every 4 wks. The primary endpoint was the proportion of pts developing a serious adverse event (SAE) within 24 wks after one course of RTX. Serious infection events (SIEs) were any infections reported as SAEs or treated with an IV antibiotic. Results: Of 176 pts, mean (SD) age was 53.6 (11.7) yrs with 79% Caucasian and 88% female. Mean (SD) RA disease duration was 10.6 (9.0) yrs and pts had previously used a mean of 1.5 biologics. Mean (SD) baseline DAS28 was 6.2 (1.1) and 39% used baseline oral steroids. Pts received RTX + 18 different biologic/DMARD combinations; 110 (63%) received biologics only and 66 (38%) received biologics with non-biologic DMARDs (eg MTX, LEF, HCQ, SSZ). 16 (9.1%) pts withdrew before/at Wk 24, of which 4 withdrew due to an AE, including 2 SAEs of angioedema and cellulitis and two non-serious AEs of herpes zoster and injection reaction to ADA. Overall, 17 SAEs occurred in 14 (8.0%) pts, for an SAE rate (95% CI) over 78.2 pt-yrs of 21.7 events/100 pt-yr (13.5, 35.0) (Table). One pt treated with RTX+ADA died from dehydration associated with vomiting and diarrhea at wk 8. Of the 17 SAEs, 3 were SIEs in 3 (1.7%) pts and included cellulitis (which led to withdrawal as noted) in a pt treated with RTX+ABA+MTX+HCQ, pneumonia with RTX+ABA, and bronchitis with RTX+ADA. The SIE rate (95%CI) was 3.8 events/100 pt-yr (1.2, 11.9). Infusion reactions occurred in 48 (27%) and 22 (13%) pts after the 1st and 2nd infusions; none were serious or led to withdrawal. 42.6% of pts achieved EULAR moderate/good response at 24 wks. Table 1. Safety summary No. (%) Pts# EventsEvent Rate/100 Pt-yrsREFLEX (24-wk) (N=176)(95%CI)No. (%) Pts (Total Pt-yrs=78.2)(N=308) SAEs14 (8.0)1721.7 (13.5, 35.0)23 (7.5) Infections82 (46.6)129165.0 (138.8, 196.1)127 (41.2) Serious Infections3 (1.7)33.8 (1.2, 11.9)6 (1.9) Conclusions: The overall safety of a single course of RTX in combination with a biologic DMARD did not reveal any new or unexpected safety concerns. The safety profile was consistent with that previously reported for RTX + non-biologic DMARDs (eg MTX) or RTX + ETN or ADA. Efficacy results were difficult to interpret due to lack of control group and differences in baseline characteristics compared with previous studies. References: 1. Loveless J et al A&R 2009. 2. Cohen S et al. A&R 2006. 3. Greenwald M et al A&R 2009. Disclosure of Interest: W. Rigby Consultant for: Genentech, Roche, Biogen Idec, Speakers Bureau: Genentech, Roche, Biogen Idec, P. Mease Grant/Research support from: Genentech, Roche, Biogen Idec, Consultant for: Genentech, Roche, Biogen Idec, Speakers Bureau: Genentech, Roche, Biogen Idec, E. Olech Grant/Research support from: Genentech, Roche, Biogen Idec, Consultant for: Genentech, Roche, Biogen Idec, Speakers Bureau: Genentech, Biogen Idec, M. Ashby Shareholder of: Roche, Employee of: Genentech, S. Tole Shareholder of: Roche, Employee of: GenentechCitation: Annals of the Rheumatic Diseases, volume 70, supplement 3, year 2011, page 623Session: Rheumatoid arthritis – other biologic treatment (Poster Presentations )