Long-term safety and efficacy of certolizumab pegol in combination with methotrexate in the treatment of rheumatoid arthritis: 5-year results from the RAPID 1 trial and open-label extension

Abstract

ObjectivesTo examine the safety and efficacy of 5-year administration of certolizumab pegol (CZP)+methotrexate (MTX) in patients with active rheumatoid arthritis (RA).MethodsEligible patients from the Rheumatoid Arthritis Prevention of Structural Damage (RAPID)1 randomised controlled trial (RCT) were treated in open-label extension (OLE) with CZP 400 mg every other week (Q2W), reduced to 200 mg Q2W after ≥6 months, +MTX. Combined safety data from RCT and OLE are presented from initiation of CZP treatment to 12 wks post last visit in patients receiving ≥1 dose of CZP (Safety population, N=958). Efficacy data are presented to start of first site closure (wk 256 of CZP treatment: 52 wks in RCT+204 wks in OLE) for all patients randomised to receive CZP (intent-to-treat (ITT) population, N=783) and CZP patients who completed the 52 wk RCT and enrolled into OLE (wk 52 CZP completers, N=508). Disease Activity Score (DAS)28 (Erythrocyte Sedimentation Rate (ESR)), American College of Rheumatology Criteria (ACR) 20/50/70, Health Assessment Questionnaire – Disability Index (HAQ-DI), and patient retention (Kaplan–Meier analysis) were assessed.ResultsOverall event rate per 100 patient-years (ER) of adverse events (AEs) was 290.4, most frequently: urinary tract infections (ER=7.9), nasopharyngitis (ER=7.3) and upper respiratory tract infections (ER=7.3). ER of serious AEs was 20.3 (infections=5.9, malignancies=1.2). 21 patients (2.2%) experienced an AE resulting in death (incidence rate=0.6). At wk 256 of treatment, 55.3% of the CZP ITT population were estimated to remain on treatment (68.7% if solely withdrawals due to AE or lack of efficacy were considered). In wk 52 CZP completers and CZP ITT population, DAS28 (ESR) remission rates and improvements from baseline were sustained to wk 256.ConclusionsCZP+MTX treatment provided a favourable risk-benefit profile over 5 years in patients with active RA. No new safety signals were identified.

Certolizumab pegol plus methotrexate 5-year results from the rheumatoid arthritis prevention of structural damage (RAPID) 2 randomized controlled trial and long-term extension in rheumatoid arthritis patients

“…The long-term safety and efficacy of CZP reported here appears comparable to studies with other anti-TNFs [19-21, 24, 26], however, comparisons are limited due to differences in study design. These results not only confirm previously reported short-term data from the RAPID 2 RCT [2], they additionally support and expand the results from the RAPID 1 clinical trial and OLE [17]. Improvements reported in minimally clinically important difference (MCID) for health-assessment questionnaire-disability index (HAQ-DI), patient's assessment of arthritic pain, patient's global assessment of disease activity (PtGA), short form-36 physical component summary (SF-36 PCS) and fatigue in certolizumab pegol (CZP) intention-to-treat (a) and CZP completers (b).…”

“…However, it should be noted that patient retention in clinical trials is often better than in real-world clinical practice. Clinical (ACR20/50/70, DAS28(ESR)) and patient-reported (HAQ-DI, PtGA, pain, fatigue, SF-36 PCS) improvements in RA signs, symptoms, and physical function observed over the 24-week RAPID 2 RCT were maintained for up to approximately 4.5 years in both the CZP ITT and week-24 CZP completer populations, consistent with sustained improvements observed in the RAPID 1 study [17]. Efficacy was also maintained in the dose-reduction population, demonstrating that CZP 200 mg Q2W + MTX was just as efficacious as CZP 400 mg Q2W + MTX during the maintenance phase.…”

“…In the phase 3 multicenter RAPID 2 RCT and OLE, assessment of CZP as an additional medication to MTX in patients with active RA confirmed that long-term efficacy of CZP was sustained for almost 5 years, with no new safety signals observed compared to previous studies [17]. Efficacy was maintained following dose reduction from 400 mg to 200 mg Q2W, the approved dose of CZP, and early response to CZP at week 12 was again associated with improved long-term clinical outcomes.…”

“…Treatment of RA patients with CZP + MTX over 5 years in this study revealed no new safety signals compared with the RAPID 1 evaluation of CZP + MTX, [17] and no increases in AEs or SAEs over time were observed. Patient retention was high in the RAPID 2 OLE, which indicates an acceptable tolerability profile and sustained efficacy of CZP.…”

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.…”