Certolizumab pegol in the treatment of rheumatoid arthritis: a comprehensive review of its clinical efficacy and safety

Abstract

Biological agents, including TNF inhibitors, have revolutionized the treatment of RA in recent years. Certolizumab pegol (CZP) is a novel pegylated anti-TNF approved for the treatment of adult patients with moderately to severely active RA. This article provides an overview of three published clinical trials of CZP in RA in patients with active disease who have shown an inadequate response to DMARDs, including MTX: RA prevention of structural damage (RAPID) 1 and 2, which evaluated the efficacy and safety of CZP added to MTX when dosed every 2 weeks, and efficacy and safety of CZP - 4 weekly dosage in rheumatoid arthritis (FAST4WARD), which evaluated CZP monotherapy when dosed every 4 weeks. In the trials, CZP plus MTX or as monotherapy significantly improved the signs and symptoms of RA and RA disease activity, and CZP plus MTX significantly inhibited the progression of radiographic joint damage as early as Week 16 of the treatment. In addition, CZP treatment significantly improved patient-reported outcome measures, providing significant reductions in pain and fatigue and improvements in physical function as early as Week 1 of treatment; improvements in health-related quality of life were evident at the first assessment at Week 12. CZP treatment improved productivity at work, significantly reducing the number of days of missed work as well as the number of days with reduced productivity, and also increased productivity within the home and improved participation in family, social and leisure activities. CZP was generally well tolerated when used either as monotherapy or added to MTX; most adverse events were mild or moderate. Taken together, the results of these trials suggest that CZP is an effective new option for the treatment of RA.

Fig. 1

Mean change in DAS-28 from baseline to study end in the RAPID 1 (Week 52), RAPID 2 (Week 24) and FAST4WARD (Week 24) trials [4–6]. RAPID 1 and 2 compared CZP plus MTX Q2 W vs placebo plus MTX Q2 W; FAST4WARD compared CZP monotherapy Q4 W vs placebo alone Q4 W. *P ≤ 0.001 vs placebo plus MTX.

Fig. 2

Effect of CZP on productivity at home and on social, family and leisure activities in the RAPID 1 (Week 52) and RAPID 2 (Week 24) trials [26]. Results are shown at baseline and study end. (A) Household work days missed due to arthritis per month. (B) Days with household work productivity reduced by ≥50% due to arthritis per month. (C) Days with outside help hired due to arthritis per month. (D) RA interference with household work productivity per month (0–10 scale, 0 = no interference, 10 = complete interference). (E) Days of lost family, social and leisure activities per month. The analysis population in RAPID 1 and 2 trials was the intention-to-treat population. *P ≤ 0.05 vs placebo plus MTX. Analyses were performed using a non-parametric bootstrap t-test and the last observation carried forward approach. Adapted from Kavanaugh et al. [26] with permission of John Wiley & Sons Inc.

Fig. 3

Effect of CZP on productivity in the workplace in the RAPID 1 (Week 52) and RAPID 2 (Week 24) trials [26]. Results are shown at baseline and study end. (A) Work days missed (absenteeism) due to arthritis per month. (B) Days with work productivity reduced by ≥50% (presenteeism) due to arthritis per month. (C) RA interference with work productivity per month (0–10 scale, 0 = no interference, 10 = complete interference). The analysis population in RAPID 1 and 2 trials was the intention-to-treat population (employed patients only). *P ≤ 0.05 vs placebo plus MTX. Analyses were performed using a non-parametric bootstrap t-test and the last observation carried forward approach. Adapted from Kavanaugh et al. [26] with permission of John Wiley & Sons Inc.