Background Certolizumab pegol (CZP) administered every 4 weeks (Q4W) for RA was shown to have an acceptable safety profile when given as monotherapy in FAST4WARD (NCT00548834) or with MTX in the 014 study (NCT00544154).1,2
Objectives To evaluate the long-term safety of 400mg CZP Q4W for RA over 5 years.
Methods Patients (pts) in FAST4WARD were randomized to CZP 400mg Q4W monotherapy or placebo (PBO) for 24 weeks (Wks). Study 014 was similar, but CZP was taken concomitantly with MTX. Those who completed or withdrew on/after Wk12 in either study were eligible to enter an open-label extension (OLE) of CZP 400mg Q4W as per original protocol (NCT00160693). Pts from FAST4WARD were permitted to take DMARDs in OLE. The primary OLE objective was to monitor safety. Pt retention rates are reported up to Wk280 (5.4yrs) (last time point all sites open), and safety results up to Wk364 (final data cut-point). Safety population consisted of all pts who entered the OLE.
Results From the CZP and PBO groups of the feeder studies, 210 and 192 pts, respectively, entered the OLE. At Wk280, 105 (50%) pts originally randomized to CZP and 89 (46%) pts originally randomized to PBO were still enrolled. Rates of adverse events (AEs), AEs leading to withdrawal, AEs leading to death, serious AEs and serious infections were similar between CZP$→ $CZP and PBO→CZP and in the range previously reported for anti-TNFs (Table). AEs of TB, candida and herpes viral infections occurred at 0 vs. 0.38, 1.41 vs. 0.63 and 5.84 vs. 5.25 events per 100 pt-yrs in the CZP$→ $CZP vs. PBO→CZP groups, respectively. Safety data was also available for the subset of pts from FAST4WARD who stayed on CZP monotherapy in the OLE (Table). At entry into OLE, DAS28-3(CRP) was 4.38 vs. 5.13 and HAQ-DI was 1.09 vs. 1.43 in the CZP vs PBO groups. On receiving CZP, prior PBO pts improved, but never attained the same level of disease activity and physical functioning as the CZP→CZP group at Wk280, the mean DAS28-3(CRP) was 2.98 and 3.12, and mean HAQ-DI was 0.83 and 1.09 in the CZP→CZP and PBO→CZP groups, respectively.
Conclusions Use of CZP 400mg Q4W combination or monotherapy has been confirmed to have an acceptable long-term safety profile in line with what would be expected from an anti-TNF. In this population, delayed CZP treatment resulted in higher disease activity and poorer function through 280 Wks.
Fleischmann R et al. Ann Rheum Dis. 2009;68:805-811.
Choy E et al. Accepted for publication in Rheumatology Nov 2011
Disclosure of Interest R. Fleischmann Grant/Research support from: UCB Pharma, Consultant for: UCB Pharma, R. van Vollenhoven Grant/Research support from: UCB Pharma, Consultant for: UCB Pharma, J. Vencovsky Consultant for: UCB Pharma, Speakers Bureau: UCB Pharma, R. Alten Grant/Research support from: UCB Pharma, Consultant for: UCB Pharma, Speakers Bureau: UCB Pharma, O. Davies Employee of: UCB Pharma, C. Stach Employee of: UCB Pharma, M. de Longueville Employee of: UCB, B. van Lunen Employee of: UCB Pharma, E. Choy Grant/Research support from: UCB Pharma, Consultant for: UCB Pharma, Speakers Bureau: UCB Pharma