PMID- 18055472 OWN - NLM STAT- MEDLINE DCOM- 20080811 LR - 20220409 IS - 1468-2060 (Electronic) IS - 0003-4967 (Print) IS - 0003-4967 (Linking) VI - 67 IP - 8 DP - 2008 Aug TI - Efficacy and safety of abatacept or infliximab vs placebo in ATTEST: a phase III, multi-centre, randomised, double-blind, placebo-controlled study in patients with rheumatoid arthritis and an inadequate response to methotrexate. PG - 1096-103 AB - OBJECTIVES: This double-blind trial evaluated the efficacy and safety of abatacept or infliximab vs placebo. The primary objective of this study was to evaluate the mean change from baseline in Disease Activity Score (based on erythrocyte sedimentation rates; DAS28 (ESR)) for the abatacept vs placebo groups at day 197. METHODS: Patients with rheumatoid arthritis (RA) and an inadequate response to methotrexate (MTX) were randomised 3:3:2 to abatacept ( approximately 10 mg/kg every 4 weeks, n = 156), infliximab (3 mg/kg every 8 weeks, n = 165), or placebo (every 4 weeks, n = 110) and background MTX. Safety and efficacy were assessed throughout the study. RESULTS: Similar patient demographics and clinical characteristics were present at baseline between groups, with mean scores of approximately 1.7 for HAQ-DI and 6.8 for DAS28 (ESR). At 6 months, mean changes in DAS28 (ESR) were significantly greater for abatacept vs placebo (-2.53 vs -1.48, p<0.001) and infliximab vs placebo (-2.25 vs -1.48, p<0.001). For abatacept vs infliximab treatment at day 365, reductions in the DAS28 (ESR) were -2.88 vs -2.25. At day 365, the following response rates were observed for abatacept and infliximab, respectively: American College of Rheumatology (ACR) 20, 72.4 and 55.8%; ACR 50, 45.5 and 36.4%; ACR 70, 26.3 and 20.6%; low disease activity score (LDAS), 35.3 and 22.4%; DAS28-defined remission, 18.7 and 12.2%; good European League Against Rheumatism (EULAR) responses, 32.0 and 18.5%; and Health Assessment Questionnaire Disability Index (HAQ-DI), 57.7 and 52.7%. Mean changes in physical component summary (PCS) were 9.5 and 7.6, and mental component summary (MCS) were 6.0 and 4.0, for abatacept and infliximab, respectively. Over 1 year, adverse events (AEs) (89.1 vs 93.3%), serious AEs (SAEs) (9.6 vs 18.2%), serious infections (1.9 vs 8.5%) and discontinuations due to AEs (3.2 vs 7.3%) and SAEs (2.6 vs 3.6%) were lower with abatacept than infliximab. CONCLUSIONS: In this study, abatacept and infliximab (3 mg/kg every 8 weeks) demonstrated similar efficacy. Overall, abatacept had a relatively more acceptable safety and tolerability profile, with fewer SAEs, serious infections, acute infusional events and discontinuations due to AEs than the infliximab group. TRIAL REGISTRATION NUMBER: NCT00095147. FAU - Schiff, M AU - Schiff M AD - Denver Arthritis Clinic, 200 Spruce Street #100, Denver, CO 80230, USA. Lmschiff@aol.com FAU - Keiserman, M AU - Keiserman M FAU - Codding, C AU - Codding C FAU - Songcharoen, S AU - Songcharoen S FAU - Berman, A AU - Berman A FAU - Nayiager, S AU - Nayiager S FAU - Saldate, C AU - Saldate C FAU - Li, T AU - Li T FAU - Aranda, R AU - Aranda R FAU - Becker, J-C AU - Becker JC FAU - Lin, C AU - Lin C FAU - Cornet, P L N AU - Cornet PL FAU - Dougados, M AU - Dougados M LA - eng SI - ClinicalTrials.gov/NCT00095147 PT - Clinical Trial, Phase III PT - Comparative Study PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20071129 PL - England TA - Ann Rheum Dis JT - Annals of the rheumatic diseases JID - 0372355 RN - 0 (Antibodies, Monoclonal) RN - 0 (Antirheumatic Agents) RN - 0 (Immunoconjugates) RN - 0 (Immunosuppressive Agents) RN - 0 (Placebos) RN - 7D0YB67S97 (Abatacept) RN - B72HH48FLU (Infliximab) RN - YL5FZ2Y5U1 (Methotrexate) SB - IM CIN - Nat Clin Pract Rheumatol. 2009 Mar;5(3):126-7. PMID: 19252515 MH - Abatacept MH - Adult MH - Analysis of Variance MH - Antibodies, Monoclonal/adverse effects/*therapeutic use MH - Antirheumatic Agents/therapeutic use MH - Arthritis, Rheumatoid/*drug therapy/immunology/psychology MH - Blood Sedimentation MH - Double-Blind Method MH - Drug Administration Schedule MH - Female MH - Humans MH - Immunoconjugates/adverse effects/*therapeutic use MH - Immunosuppressive Agents/adverse effects/*therapeutic use MH - Infliximab MH - Male MH - Methotrexate/therapeutic use MH - Middle Aged MH - Placebos MH - Quality of Life MH - Safety MH - Treatment Failure MH - Treatment Outcome PMC - PMC2564802 COIS- Competing interests: RA is an employee of Bristol-Myers Squibb and owns stocks. JCB is an employee of Bristol-Myers Squibb, with stock options and restricted shares. PLNC is an employee of Bristol-Myers Squibb and owns shares. MD has received research grants, consulting fees and been on the speakers' bureau for Bristol-Myers Squibb, Abbott and Wyeth, and has also received research grants and consulting fees from Centocor and Schering Plough. MK has received research grants and consulting fees from, and is an Advisory Board Member for, Bristol-Myers Squibb. TL is an employee of Bristol-Myers Squibb and owns stocks and shares. CL is an employee of Bristol-Myers Squibb and owns stocks and shares. MS has received research grants and consulting fees from Amgen, Bristol-Myers Squibb, Centocor and Wyeth. EDAT- 2007/12/07 09:00 MHDA- 2008/08/12 09:00 PMCR- 2007/11/29 CRDT- 2007/12/07 09:00 PHST- 2007/12/07 09:00 [pubmed] PHST- 2008/08/12 09:00 [medline] PHST- 2007/12/07 09:00 [entrez] PHST- 2007/11/29 00:00 [pmc-release] AID - ard.2007.080002 [pii] AID - ar80002 [pii] AID - 10.1136/ard.2007.080002 [doi] PST - ppublish SO - Ann Rheum Dis. 2008 Aug;67(8):1096-103. doi: 10.1136/ard.2007.080002. Epub 2007 Nov 29.