Long-Term Maintenance of Certolizumab Pegol Safety and Efficacy, in Combination with Methotrexate and as Monotherapy, in Rheumatoid Arthritis Patients

Roy Fleischmann, Ronald F van Vollenhoven, Jiri Vencovský, Rieke Alten, Owen Davies, Irina Mountian, Marc de Longueville, David Carter, Ernest Choy, Roy Fleischmann, Ronald F van Vollenhoven, Jiri Vencovský, Rieke Alten, Owen Davies, Irina Mountian, Marc de Longueville, David Carter, Ernest Choy

Abstract

Introduction: The safety and efficacy of certolizumab pegol (CZP) 400 mg every 4 weeks (Q4W) monotherapy (FAST4WARD/NCT00548834) and in combination with methotrexate (MTX) (014/NCT00544154) in active rheumatoid arthritis (RA) has been published previously. This report outlines final long-term outcomes from the open-label extension (OLE) study (015/NCT00160693), which enrolled patients from these randomized controlled trials (RCTs).

Methods: Patients who withdrew from or completed the 24-week 014/FAST4WARD RCTs were enrolled and received CZP 400 mg Q4W with/without MTX. Exposure-adjusted event rates (ER) per 100 patient-years (PYs) of adverse events (AEs) and serious AEs (SAEs) were reported for all patients receiving ≥1 dose of CZP in RCTs or OLE (N = 427) between first CZP dose and up to 24 weeks after last CZP dose or study withdrawal. Efficacy assessments included clinical (ACR20/50/70 response rates, TJC, SJC) and patient-reported outcomes (HAQ-DI, PtGADA, pain, fatigue) to week 304 (5.8 years) in the CZP intent-to-treat population. SDAI and CDAI outcomes were analyzed post hoc. Outcomes for CZP monotherapy and CZP+MTX combination-therapy were compared.

Results: Globally, ERs of AEs and SAEs were 408.1 and 25.2 per 100 PY, respectively. Eleven patients had AEs leading to death (ER 0.6). Improvements in clinical and patient-reported outcomes during the 24-week RCTs were maintained to week 304, and were similar between all subpopulations.

Conclusions: The longest exposure duration to date with CZP 400 mg Q4W treatment confirmed the safety profile observed in previous studies. Initial improvements in signs and symptoms of RA, including PROs, were maintained in both CZP monotherapy and CZP + MTX combination-therapy patients.

Trial registration: ClinicalTrials.gov identifier, NCT00160693.

Funding: UCB Pharma.

Keywords: Certolizumab pegol; Monotherapy; Open-label extension; Rheumatoid arthritis.

Figures

Fig. 1
Fig. 1
Study design. *CZP monotherapy analysis excludes 1 FAST4WARD patient who was receiving MTX at baseline—patients were excluded from the CZP monotherapy analysis from the date of concomitant MTX administration. †CZP+MTX group includes all patients from Study 014 and one patient from FAST4WARD study who received MTX at baseline
Fig. 2
Fig. 2
Clinical efficacy outcomes for CZP ITT patients (N = 235), and the CZP monotherapy (n = 110) and CZP+MTX (n = 125) sub-populations: a ACR20/50/70 (NRI/LOCF); b mean SDAI (absolute values, LOCF); c Mean CDAI (absolute values, LOCF); d mean tender joint count (TJC; absolute values, LOCF) and swollen joint count (SJC; absolute values, LOCF)
Fig. 3
Fig. 3
Clinical and patient-reported outcomes for CZP ITT patients (N = 235), and the CZP monotherapy (n = 110) and CZP + MTX (n = 125) sub-populations: a HAQ-DI (absolute values, LOCF); b pain (PAAP; absolute values, LOCF); c fatigue (absolute values, LOCF); d PtGADA (absolute values, LOCF)
Fig. 4
Fig. 4
Proportion of CZP ITT and CZP monotherapy patients achieving minimal clinically important difference (MCID) in HAQ-DI, pain (PAAP), fatigue, patient global assessment of disease activity (PtGADA), and SF-36 physical (PCS) and mental (MCS) components summary (% of patients, NRI/LOCF). Week 292 data presented where week 304 unavailable. Patients initially assigned to the CZP monotherapy group who achieved an MCID but also received MTX rescue medication prior to each visit were still included in the CZP ITT analysis, but excluded from the CZP monotherapy analysis

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Source: PubMed

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