Efficacy and safety of certolizumab pegol monotherapy every 4 weeks in patients with rheumatoid arthritis failing previous disease-modifying antirheumatic therapy: the FAST4WARD study

Roy Fleischmann ^1*, Jiri Vencovsky ², Ronald van Vollenhoven ³, David Borenstein ⁴, Jane Box ⁵, Geoffroy Coteur ⁶, Niti Goel ⁷, Hans-Peter Brezinschek ⁸, Alison Innes ⁸ and Vibeke Strand ⁹

¹ University of Texas Southwestern Medical Center, United States
² Institute of Rheumatology, Czech Republic
³ Karolinska Institute, Sweden
⁴ George Washington University Medical Center, United States
⁵ Carolina Bone and Joint, United States
⁶ UCB, Belgium
⁷ UCB, United States
⁸ UCB, United Kingdom
⁹ Stanford University, United States

^* To whom correspondence should be addressed. E-mail: rfleischmann{at}arthdocs.com.

Accepted 29 October 2008

Abstract

Background: Tumour necrosis factor alpha (TNF) is a proinflammatory cytokine involved in the pathogenesis of rheumatoid arthritis (RA). Treatment with TNF inhibitors reduces disease activity and improves outcomes for RA patients. This study evaluated the efficacy and safety of certolizumab pegol 400 mg, a novel, PEGylated, Fc-free TNF inhibitor, as monotherapy in patients with active RA.

Methods: In this 24-week, multicentre, randomised, double-blind, placebo-controlled study, 220 patients previously failing 1 DMARDs were randomised 1:1 to receive subcutaneous certolizumab pegol 400 mg (n = 111) or placebo (n = 109) every 4 weeks (q4w). The primary endpoint was ACR20 response at week 24. Secondary endpoints included ACR50/70 response, ACR component scores, (DAS28[ESR]-3), patient-reported outcomes (including physical function, HRQoL, pain and fatigue) and safety.

Results: At week 24, the ACR20 response rates were 45.5% for certolizumab pegol 400 mg q4w vs 9.3% for placebo (p<0.001). Differences for certolizumab pegol vs placebo in the ACR20 response were statistically significant as early as week 1 through to week 24 (p<0.001). Significant improvements in ACR50, ACR components, DAS28(ESR)-3 and all patient-reported outcomes were also observed early with certolizumab pegol and were sustained throughout the study. Most adverse events were mild or moderate and no deaths or cases of tuberculosis were reported.

Conclusions: Treatment with certolizumab pegol 400 mg monotherapy every 4 weeks effectively reduced the signs and symptoms of active RA in patients previously failing 1 DMARDs compared with placebo, and demonstrated an acceptable safety profile (ClinicalTrials.gov identifier: NCT00548834).