Efficacy, Safety of Abatacept SC/IV and Anti-TNF mAbs Found Comparable

SAN DIEGO, CA—A cross-trial comparison of two routes of administration of abatacept and the anti-tumor necrosis factor (TNF) monoclonal antibodies, adalimumab and infliximab, provides “insight into the efficacy and safety of these biologic agents,” according to a presentation at the 2013 ACR/ARHP Annual Meeting.

Noting “a paucity of clinical trial data exists comparing the efficacy and safety of biologic therapies for rheumatoid arthritis,” Michael H. Schiff, MD, a clinical professor of medicine in the Rheumatology Division at the University of Colorado School of Medicine, Denver, CO, and colleagues, evaluated remission rates and safety for patients treated with subcutaneous (SC) or intravenous (IV) abatacept compared with adalimumab and infliximab from two side-by-side trials, AMPLE and ATTEST.

In the head-to-head AMPLE study, patients were randomized to SC abatacept 125mg/week (n=318) or SC adalimumab 40mg/biweekly (n=328) (plus background methotrexate). In the ATTEST study, patients were randomized 3:3:2 to IV abatacept ~10mg/kg every 4 weeks (n=156), infliximab 3mg/kg every 8 weeks (n=165), or placebo (plus background methotrexate). In both trials, patients had active rheumatoid arthritis, inadequate response to methotrexate, and were biologic-naïve.

“Remission according to DAS28 (CRP) and SDAI was evaluated post hoc over 12 months of treatment for all randomized and treated patients with data available at the visit of interest,” they reported. “Safety was evaluated for all patients who received ≥1 dose of study drug.”

In the AMPLE study, baseline DAS28 (CRP) scores (mean±SD) were 5.5±1.1 and, in ATTEST, 6.4±0.9.

Duration of rheumatoid arthritis was 1.9±1.4 years for SC abatacept and 1.7±1.4 years for adalimumab in AMPLE and 7.9±8.5 years for IV abatacept and 7.3±6.2 years for infliximab in ATTEST. Remission rates were similar for the treatment groups in each study over 12 months.

Over 12 months, 11 (3.5%) SC abatacept vs. 20 (6.1%) adalimumab-treated patients, and 5 (3.2%) IV abatacept vs. 12 (7.3%) infliximab-treated patients discontinued due to adverse events (AEs). Serious adverse events (SAEs) occurred in 32 patients (10.1%) in the SC abatacept group vs. 30 (9.1%) in the adalimumab group, and in 15 (9.6%) in the IV abatacept vs. 30 (18.2%) in the infliximab groups.

Serious infections were reported in 7 patients (2.2%) treated with SC abatacept vs. 9 (2.7%) treated with adalimumab in AMPLE and 3 (1.9%) treated with IV abatacept vs. 14 (8.5%) treated with infliximab in ATTEST; 0/7 vs. 5/9 and 0/3 vs. 4/14 serious infections, respectively, led to discontinuation. Opportunistic infections occurred in 1 (0.3%) vs. 1 (0.3%) and 0 vs. 5 (3.0%) patients.

“Greater proportions of patients in the AMPLE trial achieved remission outcomes vs. ATTEST; however, patients in AMPLE had shorter disease duration and lower disease activity at baseline,” Dr. Schiff noted. “Over time, both routes of abatacept administration provided similar remission rates to the anti-TNF therapies, regardless of disease duration.”

They found safety outcomes to be mostly balanced. Increased SAEs and serious infections were observed for infliximab vs. abatacept, and increased discontinuations due to AEs and serious infections in both anti-TNF groups vs. abatacept.

“This analysis suggests that SC and IV abatacept provide similar efficacy benefits to monoclonal anti-TNF therapies with a more favorable safety profile, thus providing valuable comparative insight into the efficacy and safety of these biologic agents,” the investigators concluded, adding that “caution should be used when drawing conclusions from cross-trial comparisons, such as those presented here.”