1957 - Safety of Rituximab in Combination with a TNF Inhibitor and Methotrexate in Patients with Active Rheumatoid Arthritis: Results From a Randomized Controlled Trial (TAME)

Tuesday, October 20, 2009: 5:45 PM
113 A (Pennsylvania Convention Center)
M. Greenwald, Desert Medical Advances, Palm Desert, CA, W. Shergy, Univ of Alabama, Huntsville, AL, J. L. Kaine, Sarasota Arthritis Center, Sarasota, FL, M. T. Sweetser, Biogen Idec, Cambridge, MA, K. Gilder, Biogen Idec, San Diego and M. D. Linnik, Biogen Idec, San Diego, CA
Presentation Number: 1957

Purpose: Rituximab (RTX) improves signs and symptoms and slows joint damage progression in patients (pts) with rheumatoid arthritis (RA).  This study explored the safety of RTX in combination with a TNF inhibitor (etanercept or adalimumab) and MTX in pts with active RA. 

Methods: Pts with active RA (swollen joint count ≥5 and tender joint count ≥5) receiving a stable dose of etanercept (50 mg qw) or adalimumab (40 mg q2w) and methotrexate (10-25 mg qw) for at least 12 weeks were eligible.  Pts were randomized 2:1 and treated with 500 mg RTX or placebo (PLA) on Days 1 and 15.  After Wk 24, eligible pts could enter open-label treatment with RTX.  The primary endpoint was the proportion of pts who experience ≥1 serious infection through Wk 24.   Secondary endpoints evaluated additional safety and efficacy parameters.

Results: Fifty-one pts received at least one dose of study treatment (33 RTX, 18 PLA).  The concomitant TNF inhibitors were balanced between treatment groups: etanercept (76% vs 78%) and adalimumab (24% vs 22%) for RTX and PLA, respectively.  Baseline characteristics were balanced between groups, including disease duration (10.5 yrs), duration on TNF inhibitor (2.2  yrs), HAQ (1.4) and CRP (0.92 mg/dL) with the exception of oral steroid use (36% RTX vs. 17% PLA).  Through Wk 24, there was 1 (3%) serious infection (pneumonia on Day 45) in the RTX group and 0 in PLA.  Any infection was reported in 18 (55%) RTX pts and 11 (61%) PLA pts with an average duration of 12.6 days (sd 9.6) and 14.5 days (sd 5.2), respectively.  Grade 3 infections were reported in 3 (9%) RTX pts (pneumonia on Day 45, influenza on Day 105 and postoperative infection on Day 116) and 0 PLA pts.  There were no grade 4 infections.  There were 2 (6%) pts with serious adverse events in RTX and 0 in PLA.  Through Wk 24, there was 1 serious infection in 15.55 pt-yrs of exposure in the RTX group (6.43 events per 100 pt-yrs, 95% CI: 0.91-45.65) and none in PLA.  Overall data, including the open label extension phase, revealed no further serious infections in 46.35 pt-yrs (2.16 events per 100 pt-yrs, 95% CI: 0.30-15.32) in pts receiving 1 or 2 courses of RTX.  At Wk 24, the percentage of pts with ACR20 and ACR50 responses was 30% vs 17% and 12% vs 6% for RTX and PLA, respectively.

Conclusions:   The preliminary safety profile of RTX in combination with a TNF inhibitor (etanercept or adalimumab) and MTX was consistent with the safety profile of RTX with MTX in other RA trials without a TNF inhibitor, with no new safety signals seen.  A larger open-label study evaluating the safety profile of RTX in combination with TNF inhibitors and non-biologic DMARDs is in progress. 

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Keywords: anti-TNF therapy, rheumatoid arthritis (RA) and rituximab

Disclosure: M. Greenwald, Genentech and Biogen Idec, 2 ; W. Shergy, Genentech , 8 ; J. L. Kaine, None; M. T. Sweetser, Biogen Idec, 3 ; K. Gilder, Biogen Idec, 3 ; M. D. Linnik, Biogen Idec, 1, Biogen Idec, 3 .