Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.

Safety of Rituximab in Combination with Other Biologic Disease-Modifying Antirheumatic Drugs in Rheumatoid Arthritis: 48-Week Data From SUNDIAL.

Rigby1,  William, Mease2,  Philip J., Olech3,  Ewa, Ashby4,  Mark, Tole4,  Swati

Dartmouth Medical School, Lebanon, NH
Swedish Medical Center, Seattle, WA
Oklahoma Medical Research Foundation, Oklahoma City, OK
Genentech, Inc., South San Francisco, CA


Combination biologic therapy may be used in selected patients (pts) with an inadequate response (IR) to a single biologic. In addition, pts with an IR to rituximab (RTX) may receive other biologics while B-cell depleted. The objective of SUNDIAL (stage II) was to characterize the safety of RTX (single and repeat dose) in combination with biologic DMARDs in pts with RA.


An open-label study of adult pts with active RA and an IR to >=1 biologic. Pts who received a biologic for >=12 wks at a stable dose for >=4 wks prior to baseline were treated with RTX (500 mg IV ×2) plus their current biologic (etanercept, adalimumab, infliximab, or abatacept) and non-biologic DMARD treatment at a stable dose. After 24 wks, pts with a DAS >=2.6 were offered retreatment with RTX. Primary endpoint: proportion of pts developing a serious adverse event (SAE) within 24 wks of receiving the first course of RTX. Secondary endpoints included additional safety endpoints and efficacy at 24 and 48 wks. Missing values due to pt discontinuation were handled as non-responders. Some imputation was done for missing ACR components if the pt continued on study.


The safety analysis population comprised 176 pts (mean age 53.6 yrs; 88% female, mean RA disease duration 10.6 yrs; mean baseline DAS28-ESR 6.21; baseline oral steroid use 39.2%; mean number of prior anti-TNFs 1.5). Pts received RTX with 18 different biologic/DMARD combinations: 110 (62.5%) biologics alone and 66 (37.5%) biologics with non-biologic DMARDs. The most common combinations were with adalimumab alone (n=46; 26.1%) and etanercept alone (n=37; 21.0%). Of the 176 pts, 160 (90.9%) completed 24 wks and 134 (76.1%) completed 48 wks. Between wks 24 and 40, 147 (83.5%) pts were retreated with RTX. Among the 147 retreated pts, rates of SAEs, infections, and serious infections were not increased compared with the overall study population at 24 or 48 wks (Table). No SAEs occurred during/within 24 h of any RTX infusion.

Table. Summary of safety data (Event rate/100 pt-yrs [95% CI])

 Safety population up to wk 24 (n=176) (Total pt-yrs=78.2)Safety population up to wk 48 (n=176) (Total pt-yrs=147.1)Retreated population up to wk 48 (n=147) (Total pt-yrs=134.5)
SAEs21.7 (13.5–35.0)22.4 (15.9–31.6)16.4 (10.8–24.8)
Infections165.0 (138.8–196.1)144.8 (126.6–165.6)145.7 (126.7–167.6)
Serious infectionsa3.8 (1.2–11.9)2.7 (1.0–7.2)2.2 (0.7–6.9)
aSAE or any infection treated with an IV antibiotic.

ACR responses increased from wk 24 to 48 (ACR20: 30.1 to 47.2%; ACR50: 10.2 to 21.6%; ACR70: 5.1 to 9.1%). At wk 48, 61.4% of pts achieved EULAR moderate/good response; 22.1 and 7.0% achieved DAS28 low disease activity and remission, respectively. Mean HAQ-DI score improved by -0.32 from baseline at wk 48.


The overall safety profile of RTX used in combination with a biologic DMARD at 48 wks was consistent with that previously reported for RTX + methotrexate1 and RTX + nonbiologic DMARDs.2 Despite patterns consistent with clinical benefit, conclusions regarding efficacy results cannot be drawn due to the lack of a control group and differences in baseline characteristics compared with previous studies.


1.Cohen,  et al. Arthritis Rheum 2006;54:2793–806.

2.Loveless,  et al. Arthritis Rheum 2009;60(Suppl 10):1660.

To cite this abstract, please use the following information:
Rigby, William, Mease, Philip J., Olech, Ewa, Ashby, Mark, Tole, Swati; Safety of Rituximab in Combination with Other Biologic Disease-Modifying Antirheumatic Drugs in Rheumatoid Arthritis: 48-Week Data From SUNDIAL. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :2196

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