RA Treatment Strategies
L43. The Efficacy and Safety of Abatacept or Infliximab in RA Patients with an Inadequate response to MTX: Results from a 1-year Double-blind, Randomized, Placebo-controlled Trial
M Schiff, M Keiserman, C Codding, S Songcharoen, A Berman, S Nayiager, S Saldate, R Aranda, J-C Becker, C. Lin, PLN Cornet, M Dougados.
BACKGROUND: Few head-to-head studies have been conducted comparing biological therapies. This trial was designed to investigate the safety and efficacy effect of abatacept (ABA) or infliximab (IFX) vs placebo (PBO) in patients with RA.
METHODS: This was a three arm parallel group randomized placebo and active comparator study of abatacept (10 mg/kg every 4 weeks), Infliximab (3 mg/kg every 8 weeks), or placebo infusions in RA patients with an inadequate response to MTX but had not previously received TNF antagonists. Patients randomized to PBO were switched to ABA after Day 197, but were not included in the 365-day analysis. The primary outcome was the reduction in mean DAS28 for ABA vs placebo at day 197. Additional outcomes assessed included other efficacy and safety endpoints.
RESULTS: Patients had similar baseline characteristics (DAS28 6.8, swollen joints 20-21, tender joints 30-32, mean HAQ scores of 1.7-1.8). Mean MTX doses were similar (16.2-16.6 mg/wk) and steroids used in 70-76% of subjects. Completers were similar in the groups at 6 months 86-88%.
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Efficacy Analyses |
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Day 197 |
Day 365 |
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| ABA (n=156) | IFX (n=165) | PBO (n=110) | ABA (n=156) | IFX (n=165) | ||
| DAS28 (mean change from baseline) | -2.5† | -2.3† | -1.5 | -2.9 | -2.3 | |
| ACR 20 responders (%) | 66.7† | 59.4† | 41.8 | 72.4 | 55.8 | |
| ACR 50 responders (%) | 40.4† | 37.0† | 20.0 | 45.5 | 36.4 | |
| ACR 70 responders (%) | 20.5† | 24.2† | 9.1 | 26.3 | 20.6 | |
| HAQ change >0.3 units (%) | 61.5† | 58.8† | 40.9 | 57.7 | 52.7 | |
| †p<0.05 vs PBO | ||||||
The frequency of adverse events (AEs) was 82.7, 84.4 and 83.6%; and serious AEs (SAEs) was 5.1, 11.5 and 11.8% for ABA, IFX and PBO, respectively. The frequency of acute infusion related AEs was 5.1 % for ABA, 18.2% for IFX, and 10% for PBO. Infections reported as SAEs were more frequently reported with IFX than with ABA (8.5 vs 1.9%). Two cases of tuberculosis were reported, both in patients treated with IFX. Acute infusional AEs were more frequent with IFX than with ABA (24.8 vs 7.1%).
CONCLUSIONS: Efficacy measured by DAS28, ACR response rates, HAQ, and SF-36 was similar following treatment with either ABA or IFX (3 mg/kg every 8 weeks) at 6 months. Further improvement in efficacy was seen with ABA between 6-12 months. The safety and tolerability results through 1 year suggest that ABA has a more favorable benefit risk profile than IFX.
EDITORIAL COMMENT: This study demonstrates that comparison trials between biological therapies are possible to perform even when the timing of infusions, etc may differ between preparations. The results of this study however are confounded by a relatively high placebo effect at all levels of response commonly seen in studies of infused medication. The possibility of dose/frequency escalation of infliximab was not permitted in the study which may have contributed to lower responses over time compared to abatacept. Detailed information concerning time courses of response and assessment of integrated measurements of improvement over time may also be important in data presentation comparing biological therapies with different mechanisms of action and potentially different timing to maximal effect.
