ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 563

Abatacept Plus Methotrexate Can Effectively and Safely Regain the Target of Remission Following Re-Treatment for Flares after Drug-Free Withdrawal in Patients with Early Rheumatoid Arthritis

Paul Emery1, G Burmester2, VP Bykerk3, B Combe4, Daniel E. Furst5, M Maldonado6 and T. W. J. Huizinga7, 1University of Leeds, Leeds, United Kingdom, 2Charité – University Medicine Berlin, Berlin, Germany, 3Hospital for Special Surgery, New York, NY, 4Service d’Immuno-Rheumatologie, Montpellier, France, 5Medicine, University of California, Los Angeles, David Geffen School of Medicine, Los Angeles, CA, 6Bristol-Myers Squibb, Princeton, NJ, 7Leiden University Medical Center, Leiden, Netherlands

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: ,

Session Information

Date: Sunday, November 8, 2015

Title: Rheumatoid Arthritis - Small Molecules, Biologics and Gene Therapy Poster I

Session Type: ACR Poster Session A

Session Time: 9:00AM-11:00AM

Background/Purpose: Assessing Very Early Rheumatoid arthritis Treatment (AVERT) was a Phase IIIb, randomized, active-controlled study to evaluate the efficacy and safety of abatacept (ABA) treatment in three phased periods: during treatment, following withdrawal of all therapies and during re-exposure. Here, we present data from the withdrawal and re-exposure periods.

Methods: MTX-naïve, anti-cyclic citrullinated peptide 2-positive patients (pts) with early RA (active synovitis in ≥2 joints for ≥8 wks, DAS28 [CRP] ≥3.2 and onset of symptoms within ≤2 yrs) were initially randomized to 12 months of weekly SC ABA 125 mg + MTX, ABA 125 mg monotherapy or MTX alone (treatment period). Pts with DAS28 (CRP) <3.2 at Month 12 then entered a 12-month withdrawal period with no treatment. All pts with protocol-defined flare after Month 15 could receive open-label ABA + MTX (re-exposure period) for 6 months.

Results: Most pts could not remain treatment-free after complete treatment withdrawal, due to worsening disease activity (172/225; 76.4%) during the 12-month withdrawal period. Of those who entered the withdrawal period, rates of pts maintaining DAS28 (CRP) <2.6 free of all drugs at 24 months were 14.0, 12.3 and 11.3% for ABA + MTX, ABA mono and MTX alone, respectively. Rates of pts ever achieving a major clinical response (MCR) at 24 months were 40.3, 25.9 and 15.5% for ABA + MTX, ABA mono and MTX alone, respectively. A total of 146 pts entered the re-exposure period and 140 completed. Their baseline demographics and disease characteristics were similar to those of pts at study entry (mean RA duration ~0.5 yrs). The mean (SD) DAS28 at re-exposure period entry was 5.47 (1.27) and, at the end of the re-exposure period, was 2.43 (0.95). A total of 62% (78/126) of evaluable pts were in DAS28 (CRP) remission on re-exposure period Day 169. The mean (SD) HAQ at re-exposure period entry was 1.45 (0.64) and, at the end of the re-exposure period, was 0.63 (0.57). Over 12 months of the withdrawal period, the numbers (%) of serious AEs were 2 (2.4), 0 (0) and 5 (6.7), respectively, and only 1 serious infection was reported in the MTX alone arm (pyelonephritis; 337.4 pt-yrs). In the re-exposure period, no pts discontinued due to AEs and no serious infections were reported (292.2 pt-yrs). The overall rates of infections were 8.9 and 16 (incidence rate/100 pt-yrs) in the withdrawal and re-exposure periods, respectively (overall rates were 110.7 and 72.8 in the first and second 6 months of the initial treatment period). Multivariate analysis to identify predictors of time to flare and achieving DAS28 (CRP) <2.6 in the re-exposure period will be presented.

Conclusion: Re-treatment with abatacept + MTX can effectively recapture prior remission following flare after complete withdrawal of therapy. The likelihood of ever achieving a MCR was more likely in pts in the abatacept + MTX arm (> abatacept > MTX). There were far fewer infection events in the combined withdrawal period and re-exposure period than in the initial treatment period and only 1 serious infection was reported in the combined withdrawal period and treatment period suggesting re-treatment is well tolerated.

Disclosure: P. Emery, Abbott/Abbvie, Bristol-Myers Squibb, Pfizer, UCB, MSD, Roche, Novartis, Samsung, Takeda, Lilly, 5; G. Burmester, Abbvie, Pfizer, UCB, Roche, 2,Abbvie, Bristol-Myers Squibb, Pfizer, Merck, MedImmune, UCB, Roche, 5,Abbvie, Bristol-Myers Squibb, Pfizer, Merck, UCB, Roche, 8; V. Bykerk, Genentech, Bristol-Myers Squibb, UCB, BIPI, 2,Biogen, Novartis, 3,Amgen, Abbvie, Bristol-Myers Squibb, UCB, Antares, Regeneron, Genentech, 5; B. Combe, Pfizer, Roche-Chugai, 2,Bristol-Myers Squibb, Merck, Pfizer, Roche-Chugai, UCB, 8; D. E. Furst, Gilead, 2,GlaxoSmithKline, 2,NIH, 2,Novartis Pharmaceutical Corporation, 2,Pfizer Inc, 2,Roche Pharmaceuticals, 2,Genentech and Biogen IDEC Inc., 2,UCB, 2,Abbvie, 5,Actelion Pharmaceuticals US, 5,Amgen, 5,Bristol-Myers Squibb, 5,Cytori, 5,Janssen Pharmaceutica Product, L.P., 5,Gilead, 5,GlaxoSmithKline, 5,NIH, 5,Novartis Pharmaceutical Corporation, 5,Pfizer Inc, 5,Roche Pharmaceuticals, 5,Genentech and Biogen IDEC Inc., 5,UCB, 5,Abbvie, 8,Actelion Pharmaceuticals US, 8,Bristol-Myers Squibb, 2,Amgen, 2,Actelion Pharmaceuticals US, 2,Abbvie, 2,UCB, 8; M. Maldonado, Bristol-Myers Squibb, 1,Bristol-Myers Squibb, 3; T. W. J. Huizinga, Merck, UCB, Bristol-Myers Squibb, Biotest AG, Pfizer, GlaxoSmithKline, Novartis, Roche, Sanofi-Aventis, Abbott, Crescendo Bioscience, Nycomed, Boehringer, Takea, Zydus, Eli Lilly, 5,Roche, Abbott, 9.

To cite this abstract in AMA style:

Emery P, Burmester G, Bykerk V, Combe B, Furst DE, Maldonado M, Huizinga TWJ. Abatacept Plus Methotrexate Can Effectively and Safely Regain the Target of Remission Following Re-Treatment for Flares after Drug-Free Withdrawal in Patients with Early Rheumatoid Arthritis [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/abatacept-plus-methotrexate-can-effectively-and-safely-regain-the-target-of-remission-following-re-treatment-for-flares-after-drug-free-withdrawal-in-patients-with-early-rheumatoid-arthritis/. Accessed .

« Back to 2015 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/abatacept-plus-methotrexate-can-effectively-and-safely-regain-the-target-of-remission-following-re-treatment-for-flares-after-drug-free-withdrawal-in-patients-with-early-rheumatoid-arthritis/