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

Abstract

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

Methods: In this 24-week, multicentre, randomised, double-blind, placebo-controlled study, 220 patients previously failing > or =1 disease-modifying antirheumatic drug (DMARD) were randomised 1:1 to receive subcutaneous certolizumab pegol 400 mg (n = 111) or placebo (n = 109) every 4 weeks. The primary endpoint was 20% improvement according to the American College of Rheumatology criteria (ACR20) at week 24. Secondary endpoints included ACR50/70 response, ACR component scores, 28-joint Disease Activity Score Erythrocyte Sedimentation Rate 3 (DAS28(ESR)3), patient-reported outcomes (including physical function, health-related quality of life (HRQoL), pain and fatigue) and safety.

Results: At week 24, the ACR20 response rates were 45.5% for certolizumab pegol 400 mg every 4 weeks 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 > or =1 DMARD compared with placebo, and demonstrated an acceptable safety profile.

Trial registration number: NCT00548834.

Figure 1

Patient disposition. Modified intent to treat (mITT) population: all randomised patients who had taken at least one dose of study medication.

Figure 2

Efficacy of certolizumab pegol: American College of Rheumatology (ACR) response rates (modified intent to treat (mITT) population). A. Treatment with certolizumab pegol 400 mg was statistically significant vs placebo at week 24 for ACR20 and ACR50 (p<0.001) and ACR70 (p⩽0.05). B. ACR20, ACR50 and ACR70 responses with certolizumab pegol 400 mg were statistically significant vs placebo over time (p⩽0.05 at all time points, with the exceptions of ACR70 at weeks 1, 2, 4 and 16).

Figure 3

Least squares mean change from baseline in American College of Rheumatology (ACR) core component scores (modified intent to treat (mITT) population). Least squares mean change from baseline in (A) tender joint count, (B) swollen joint count, (C) Health Assessment Questionnaire Disability Index (HAQ-DI) and (D) patient’s assessment of arthritis pain (100-mm visual analogue scale (VAS)) were all statistically significantly superior for certolizumab pegol 400 mg vs placebo from week 1 following administration of study drug and at all time points throughout the 24-week study period (p⩽0.01).