Comparison of Certolizumab Pegol Versus Adalimumab: 2 Year Efficacy and Safety Results from a Superiority, Investigator-Blind, Head-to-Head Study

Roy Fleischmann¹, Gerd-Rüdiger Burmester², Bernard Combe³, Jeffrey R. Curtis⁴, Stephen Hall⁵, Boulos Haraoui⁶, Ronald van Vollenhoven⁷, Christopher Cioffi⁸, Cécile Ecoffet⁹, Lucian Ionescu⁹, Leon Gervitz¹⁰, Luke Peterson⁸ and Josef Smolen¹¹, ¹University of Texas Southwestern Medical Center at Dallas Metroplex Clinical Research Center, Dallas, TX, ²Charité – University Medicine Berlin, Berlin, Germany, ³Montpellier University Hospital, Montpellier, France, ⁴Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, AL, ⁵Cabrini Medical Centre, Monash University, Melbourne, Australia, ⁶Department of Medicine, Centre Hospitalier de l'Université de Montréal, Montréal, QC, Canada, ⁷Amsterdam Rheumatology and Immunology Center (ARC), Amsterdam, Netherlands, ⁸UCB Pharma, Raleigh, NC, ⁹UCB Pharma, Brussels, Belgium, ¹⁰RA Patient Value Mission, UCB Pharma, Brussels, Belgium, ¹¹Medical University of Vienna and Hietzing Hospital, Vienna, Austria

Meeting: 2016 ACR/ARHP Annual Meeting

Date of first publication: September 28, 2016

Keywords: Adalimumab, anti-TNF therapy, certolizumab pegol and rheumatoid arthritis (RA), Early Rheumatoid Arthritis

Session Information

Date: Tuesday, November 15, 2016

Title: Plenary Session III: Discovery 2016

Session Type: ACR Plenary Session

Session Time: 11:00AM-12:30PM

Background/Purpose: Head-to-head comparisons of biological (b)DMARDs in the treatment of RA should provide rigorous evidence on the comparative efficacy of different treatments. Although there are several head-to-head trials comparing TNF inhibitors (TNFi) with bDMARDs that have different mechanisms of action,^1-3 there have been no reports of prospective head-to-head trials comparing the efficacy and safety of bDMARDS within the same class, including TNFi.

Methods: EXXELERATE (NCT01500278) was a 104-wk randomized, investigator-blind, parallel-group, head-to-head superiority study comparing the early (Wk 12)- and later (Wk 104)-term efficacy and safety of certolizumab pegol (CZP)+MTX and adalimumab (ADA)+MTX (Figure). Patients (Pts) were randomized 1:1 to CZP+MTX or ADA+MTX. At Wk 12, pts were classified as responders (achieving either DAS28[ESR] ≤3.2 or DAS28[ESR] reduction from baseline [BL] of ≥1.2 at Wk 12) or non-responders (NR). NRs to one were switched to the respective other TNFi (Figure). Primary endpoints were the percentage of pts achieving ACR20 at Wk 12 and low disease activity (LDA; DAS28[ESR] ≤3.2) at Wk 104 (Wk 12 NRs were considered LDA NRs). Secondary endpoints included the proportion of pts achieving ACR20 at Wk 6, DAS28(ESR) LDA at Wks 6, 12, 52, and the proportion of Wk 12 responding pts achieving LDA at Wk 104. Exploratory endpoints included the proportion of Wk 12 responding pts achieving ACR20/50/70, and DAS28(ESR) and CDAI defined LDA and remission (REM), at each study visit.

Results: At BL, 915 pts were randomized to either CZP+MTX (n=457) or ADA+MTX (n=458). At Wk 12 there were 359 CZP+MTX (78.6%) and 369 ADA+MTX (80.6%) responder pts. No statistically significant difference was observed between ACR20 response at Wk 12 (69.2% and 71.4%; odds ratio (OR): 0.90 [95% CI: 0.67, 1.20]), and DAS28(ESR) LDA at Wk 104 (35.5% and 33.5%; OR: 1.09 [95% CI: 0.82, 1.45]) for CZP+MTX and ADA+MTX, respectively. No differences between treatment arms were evident in secondary and exploratory efficacy endpoints (Table). A similar proportion of CZP+MTX and ADA+MTX pts reported treatment emergent adverse events (TEAEs; 75.4% and 73.8%), serious TEAEs (13.0% and 11.1%), and serious infections and infestations (3.3% and 3.1%), by treatment at AE onset (event rate per 100 pt years 257.5 vs 260.0).

Conclusion: EXXELERATE, the first direct head-to-head comparison of two TNFis, reinforces the early and later term efficacy of both CZP and ADA in combination with MTX without demonstrating clinical evidence of differences between both agents. CZP+MTX and ADA+MTX demonstrated comparable safety over 2 years. References: 1. Porter D. Lancet 2016;S0140-6736(16)00380–9; 2. Gabay C. Lancet 2013;381(9877):1541–1550; 3. Weinblatt M. Arthritis Rheum 2013;65(1):28–38

Disclosure: R. Fleischmann, Genentech, Roche, Abbott, Amgen, UCB Pharma, Pfizer, Bristol-Myers Squibb, Eli Lilly, Sanofi-Aventis, MSD, Novartis, AstraZeneca, Janssen, 2,Roche, Abbott, Amgen, UCB Pharma, Pfizer, Bristol-Myers Squibb, Eli Lilly, Sanofi-Aventis, Novartis, AstraZeneca, Janssen, 5; G. R. Burmester, AbbVie, MSD, Pfizer, Roche UCB Pharma, 5; B. Combe, Merck, Pfizer, Roche-Chugai, 2,Merck, Pfizer, Roche-Chugai, UCB Pharma, Bristol-Myers Squibb, Celgene, Eli Lilly, Novartis, 5,Merck, Pfizer, Roche-Chugai, UCB Pharma, Bristol-Myers Squibb, Celgene, Eli Lilly, Novartis, 8; J. R. Curtis, Roche, Genentech, UCB Pharma, Janssen, CORRONA, Amgen, Pfizer, Bristol-Myers Squibb, Crescendo, AbbVie, 2,Roche, Genentech, UCB Pharma, Janssen, CORRONA, Amgen, Pfizer, Bristol-Myers Squibb, Crescendo, AbbVie, 5; S. Hall, None; B. Haraoui, Abbott, Amgen, Bristol-Myers Squibb, Janssen, Pfizer, Roche, UCB Pharma, 2,Abbott, Amgen, Bristol-Myers Squibb, Janssen, Pfizer, Roche, UCB Pharma, 5,Abbott, Amgen, Bristol-Myers Squibb, Janssen, Pfizer, Roche, UCB Pharma, 8; R. van Vollenhoven, AbbVie, Bristol-Myers Squibb, GlaxoSmithKline, Pfizer, Roche, UCB Pharma, 2,AbbVie, Biotest, Bristol-Myers Squibb, GlaxoSmithKline, Janssen, Eli Lilly, Merck, Pfizer, Roche, UCB Pharma, Vertex, 5; C. Cioffi, UCB Pharma, 3; C. Ecoffet, UCB Pharma, 3; L. Ionescu, UCB Pharma, 3; L. Gervitz, UCB Pharma, 3; L. Peterson, UCB Pharma, 3; J. Smolen, UCB Pharma, 2,UCB Pharma, 5,UCB Pharma, 9.

To cite this abstract in AMA style:

Fleischmann R, Burmester GR, Combe B, Curtis JR, Hall S, Haraoui B, van Vollenhoven R, Cioffi C, Ecoffet C, Ionescu L, Gervitz L, Peterson L, Smolen J. Comparison of Certolizumab Pegol Versus Adalimumab: 2 Year Efficacy and Safety Results from a Superiority, Investigator-Blind, Head-to-Head Study [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/comparison-of-certolizumab-pegol-versus-adalimumab-2-year-efficacy-and-safety-results-from-a-superiority-investigator-blind-head-to-head-study/. Accessed .

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