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 α (TNFα) is a proinflammatory cytokine involved in the pathogenesis of rheumatoid arthritis (RA). Treatment with TNFα 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 TNFα 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 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 ⩾1 DMARD compared with placebo, and demonstrated an acceptable safety profile.Trial registration number:NCT00548834.

Evaluation of therapeutic targets in animal models of arthritis: How does it relate to rheumatoid arthritis?

“…Two new TNF inhibitors, golimumab (a fully human anti-TNF␣ monoclonal antibody) and certolizumab pegol (a PEGylated FabЈ fragment of a humanized anti-TNF monoclonal antibody), have more recently been shown to be effective in the treatment of RA (83)(84)(85)(86)(87)(88). Thus, TNF␣ has clearly been proven to be a good target for RA treatment and has fulfilled the expectations raised during the preclinical studies performed in animal models.…”

Rapid Improvement in the Signs and Symptoms of Rheumatoid Arthritis Following Certolizumab Pegol Treatment Predicts Better Longterm Outcomes: Post-hoc Analysis of a Randomized Controlled Trial

“…In this respect the tumor necrosis factor-α (TNF-α) inhibitors, which rapidly improve clinical signs and symptoms 5,6,7,8 and health-related quality of life (HRQOL) 7,9,10,11 , and inhibit structural damage 7,8,9,12 , have been an important addition to treatment options for patients with RA. Certolizumab pegol (CZP), a PEGylated anti-TNF used either as monotherapy or with methotrexate (MTX), resulted in significant improvement in the signs and symptoms of RA from Week 1 8,13,14 . CZP + MTX also rapidly inhibited the progression of structural damage (as early as Week 16) and were associated with rapid improvements in physical function/HRQOL and pain relief 8,14 .…”

Turkish Compliance and Adaptation of EULAR 2013 Recommendations for the Management of Rheumatoid Arthritis with Synthetic and Biological Disease-Modifying Antirheumatic Drugs: Expert Opinion of TLAR

“…[37][38][39] Studies have shown certolizumab pegol to be as effective as the other anti-TNF agents. Particularly in pregnancy, certolizumab passes through placenta in smaller amounts than other TNF inhibitors and its level in umbilical cord blood is low.…”