Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement

The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.

An Open-Label, Prospective Study (SUNDIAL) of the Safety of Rituximab in Combination with Disease-Modifying Anti-Rheumatic Drugs in Patients with Active Rheumatoid Arthritis (SUNDIAL)

Loveless1,  James, Olech2,  E., Pritchard3,  Charles H., Chai4,  A., Kelman4,  Ariella, Klearman4,  Micki

Intermountain Orthopedics, Boise, ID,
OK Med Research Foundation, Oklahoma City, OK,
Willow Grove, PA,
Genentech, South San Francisco, CA


Rituximab (RTX) in combination with methotrexate (MTX) is an effective and well-tolerated therapy in patients with rheumatoid arthritis (RA). The primary objective is to characterize the safety of RTX when used in combination with DMARDs other than MTX alone in patients with RA.


SUNDIAL is an open-label study of patients with RA who have had an inadequate response to >=1 DMARD. Patients aged 18–80 years who received a DMARD regimen for >=12 weeks received RTX (1000 mg IV × 2) plus their current DMARD therapy. Combinations included MTX (7.5–25 mg/wk), leflunomide (10–20 mg/day), sulfasalazine (1000–3000 mg/day), azathioprine (50–200 mg/day), and/or hydroxychloroquine (200–400 mg/day). Other than MTX alone or in combination with LEF, all other DMARDs (or combinations thereof) were permitted. The primary endpoint was the proportion of patients developing a serious adverse event (SAE) within 24 weeks after receiving one course of RTX.


Of 401 patients, the mean (SD) age was 53.3 (11.3) years with 75% Caucasian and 75% female. The mean (SD) RA disease duration was 10.0 (9.3) years and 54% had previously used biologics. Mean (SD) baseline disease activity (DAS28) was 6.2 (1.1). A total of 27 (6.7%) withdrew before/at Week 24, with 3 (0.7%) due to AE. Patients received 15 different DMARD combinations; 54% were on a MTX-containing regimen; 59% were on 2 or more DMARDs. Overall, 26 SAEs in 24 (6.0%) patients were observed for an event rate (95% CI) of 14.39 events/100 pt-yr (9.9, 21.1) (Table). The most common SAEs included chest pain (n=3), pneumonia (n=2), and cellulitis (n=2). One patient died from malignant lung neoplasm considered unrelated to RTX treatment. Seven (1.7%) patients experienced 7 serious infections for a rate (95% CI) of 3.8 events/100 pt-yr (1.8, 8.1). Infusion reactions occurred in 59 (14.7%) patients after the 1st infusion and in 25 (6.2%) patients after the 2nd infusion. One serious infusion reaction (chest pain) occurred with the 1st infusion and none after the 2nd infusion. At Week 24, 15 (3.7%) patients were HACA+. HACA positivity was not related to choice of concomitant DMARD.

Table. Safety summary

 No. (%) Patients (N=401)No. of EventsEvent Rate/100 Patient-years (95% CI) (Total Patient Years=180.6)
Any SAE24 (6.0%)2614.39 (9.9–21.1)
Any Infection164 (40.9%)269148.9 (132.1–167.8)
Serious Infections*7 (1.7%)73.8 (1.8–8.1)
*SAE or any infection that was treated with an IV antibiotic


The overall safety of a single course of rituximab in combination with multiple non-biologic DMARDs did not reveal any new or unexpected safety concerns. Safety data was consistent with that previously reported for RTX + MTX (Cohen et al; A&R, 2006,54:2793–806, Emery et al; A&R, 2006, 54:1390–400). Further follow-up is ongoing.

To cite this abstract, please use the following information:
Loveless, James, Olech, E., Pritchard, Charles H., Chai, A., Kelman, Ariella, Klearman, Micki; An Open-Label, Prospective Study (SUNDIAL) of the Safety of Rituximab in Combination with Disease-Modifying Anti-Rheumatic Drugs in Patients with Active Rheumatoid Arthritis (SUNDIAL) [abstract]. Arthritis Rheum 2009;60 Suppl 10 :1660
DOI: 10.1002/art.26734

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