A Randomized, Double-Blind, Placebo-Controlled Phase 3 Study Evaluating Treatment Strategies (Continuation Versus Withdrawal) for Maintaining Low Disease Activity after 1 Year of Certolizumab Pegol in DMARD-Naive Patients with Early and Progressive, Active RA

Michael Weinblatt¹, Clifton Bingham III², Gerd-Rüdiger Burmester³, Vivian P. Bykerk⁴, Daniel E. Furst⁵, Xavier Mariette⁶, Désirée van der Heijde⁷, Ronald van Vollenhoven⁸, Brenda VanLunen⁹, Cécile Ecoffet¹⁰, Christopher Cioffi⁹ and Paul Emery¹¹, ¹Brigham and Women's Hospital, Boston, MA, ²Johns Hopkins University, Baltimore, MD, ³Charité – University Medicine Berlin, Berlin, Germany, ⁴Divison of Rheumatology, Hospital for Special Surgery, New York, NY, ⁵David Geffen School of Medicine at UCLA, Los Angeles, CA, ⁶Université Paris-Sud, Paris, France, ⁷Leiden University Medical Center, Leiden, Netherlands, ⁸Amsterdam Rheumatology and Immunology Center (ARC), Amsterdam, Netherlands, ⁹UCB Pharma, Raleigh, NC, ¹⁰UCB Pharma, Brussels, Belgium, ¹¹University of Leeds, Leeds, United Kingdom

Meeting: 2016 ACR/ARHP Annual Meeting

Date of first publication: September 28, 2016

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

Session Information

Date: Sunday, November 13, 2016

Title: Rheumatoid Arthritis – Small Molecules, Biologics and Gene Therapy I: Treatment Strategies

Session Type: ACR Concurrent Abstract Session

Session Time: 2:30PM-4:00PM

Background/Purpose: There is interest in tapering or stopping biologic DMARD therapy in RA patients (pts) who have achieved sustained disease control.¹ We report the results from C-EARLY Period 2 (P2), in which pts continuing on certolizumab pegol (CZP; standard and reduced dose-frequency) were compared with pts stopping CZP.

Methods: Pts from C-EARLY Period 1 (P1; NCT01519791)² treated with dose-optimized MTX and CZP (200 mg Q2W) or placebo (PBO) who achieved sustained low disease activity (sLDA; DAS28[ESR] ≤3.2 at both Weeks [wks] 40 and 52) entered P2 (NCT01521923),¹ a randomized, double-blind dose withdrawal study. CZP-treated pts were randomized 2:3:2 to CZP standard dose (200 mg Q2W+MTX), reduced dose-frequency (200mg Q4W+MTX) or CZP stopped (PBO+MTX). The primary endpoint was the percentage of pts in maintained (Wks 52–104 without flares) LDA. The hierarchical testing scheme compared CZP standard dose vs CZP stopped; if p<0.05 was achieved, then CZP reduced dose-frequency vs CZP stopped was compared. Data presented use imputation: NRI for primary endpoint; LOCF for continuous variables; linear extrapolation for mTSS.

Results: The study was powered assuming 455 CZP-treated pts would achieve sLDA in P1 and enter P2; however, only 293 pts (64%) were eligible and entered P2. 49% CZP standard and 53% reduced dose-frequency pts in sLDA were able to maintain LDA to Wk 104 vs 39% CZP stopped pts (p=0.112 and p<0.05, respectively; the study did not achieve its primary endpoint). 44% CZP standard and 43% reduced dose-frequency pts were able to maintain remission (DAS28[ESR] <2.6) to Wk 104 vs 33% CZP stopped pts. Overall, a higher proportion of CZP-treated pts (standard and reduced dose-frequency) achieved LDA at Wk 104 vs CZP stopped pts (Figure A). At Wk 104, more pts continuing CZP (standard and reduced dose-frequency) had radiographic non-progression (change from baseline mTSS ≤0.5) vs CZP stopped and MTX alone pts (Figure B). The safety profiles of all 4 groups were similar, with no new safety signals for pts continuing CZP treatment up to 2 years.

Conclusion: The study did not achieve its primary endpoint of maintained LDA at all visits in CZP-treated pts (standard and reduced dose-frequency) vs those who stopped CZP; however, there was a numerical difference between these groups. One possible reason may have been that 36% fewer pts were eligible for P2 than planned, based on the entry criteria. A higher proportion of CZP-treated pts (standard and reduced dose-frequency) achieved LDA and radiographic stabilization compared with those who stopped CZP. Additionally, despite clinical improvement, more pts treated with MTX alone experienced radiographic progression than pts treated with CZP over 2 years. References: 1. Emery P. Ann Rheum Dis 2016;75(S2):143; 2. Emery P. Ann Rheum Dis 2016;doi:10.1136/annrheumdis-2015-209057

Disclosure: M. Weinblatt, Amgen, Bristol-Myers Squibb, Crescendo Bioscience, UCB Pharma, 2,AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Crescendo Bioscience, Eli Lilly, MedImmune, Merck, Novartis, Pfizer, Roche, UCB Pharma, 5; C. Bingham III, UCB Pharma, 5; G. R. Burmester, AbbVie, MSD, Pfizer, Roche, and UCB Pharma, 5; V. P. Bykerk, AbbVie, Bristol-Myers Squibb, Pfizer, Roche/Genentech, Regeneron, and UCB Pharma, 5; D. E. Furst, Abbott, Actelion, Amgen, Bristol-Myers Squibb, Gilead, GlaxoSmithKline, NIH, Novartis, Pfizer, Roche/Genentech, UCB Pharma, 2,Abbott, Actelion, Amgen, Bristol-Myers Squibb, Biogen, Janssen, Gilead, GlaxoSmithKline, NIH, Novartis, Pfizer, Roche/Genentech, UCB Pharma, 5,Abbott, Actelion, Amgen, Bristol-Myers Squibb, Biogen, Janssen, Gilead, NIH, Roche/Genentech, UCB Pharma, 9; X. Mariette, Pfizer, GlaxoSmithKline, and Roche, 2,Bristol-Myers Squibb, GlaxoSmithKline, Pfizer, Roche, UCB Pharma and Sanofi-Aventis, 5; D. van der Heijde, AbbVie, Amgen, AstraZeneca, Augurex, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Centocor, Chugai, Covagen, Daiichi, Eli-Lilly, Galapagos, GlaxoSmithKline, Janssen, Merck, Novo-Nordisk, Otsuka, Pfizer, Roche, Sanofi-Aventis, UCB Pharma, Vertex, 5,AbbVie, Amgen, AstraZeneca, Augurex, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Centocor, Chugai, Covagen, Daiichi, Eli-Lilly, Galapagos, GlaxoSmithKline, Janssen, Merck, Novo-Nordisk, Otsuka, Pfizer, Roche, Sanofi-Aventis, UCB Pharma, Vertex, 2,Director of Imaging at Rheumatology BV, 3; R. van Vollenhoven, AbbVie, Bristol-Myers Squibb, GlaxoSmithKline, Pfizer, Roche, and UCB Pharma, 2,AbbVie, Biotest, Bristol-Myers Squibb, GlaxoSmithKline, Janssen, Eli-Lilly, Merck, Pfizer, Roche, UCB Pharma, and Vertex, 5; B. VanLunen, UCB Pharma, 3; C. Ecoffet, UCB Pharma, 3; C. Cioffi, UCB Pharma, 3; P. Emery, Pfizer, MSD, AbbVie, UCB Pharma, Roche, Bristol-Myers Squibb, Schering-Plough, Novartis, and Samsung, 5.

To cite this abstract in AMA style:

Weinblatt M, Bingham C III, Burmester GR, Bykerk VP, Furst DE, Mariette X, van der Heijde D, van Vollenhoven R, VanLunen B, Ecoffet C, Cioffi C, Emery P. A Randomized, Double-Blind, Placebo-Controlled Phase 3 Study Evaluating Treatment Strategies (Continuation Versus Withdrawal) for Maintaining Low Disease Activity after 1 Year of Certolizumab Pegol in DMARD-Naive Patients with Early and Progressive, Active RA [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/a-randomized-double-blind-placebo-controlled-phase-3-study-evaluating-treatment-strategies-continuation-versus-withdrawal-for-maintaining-low-disease-activity-after-1-year-of-certolizumab-pegol-in/. Accessed .

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