Background Certolizumab pegol (CZP) + methotrexate (MTX) is approved in Europe as a maintenance dose of 200mg CZP every 2 weeks (Q2W) for patients (pts) with active rheumatoid arthritis (RA); 400mg CZP Q4W has been assessed as an alternative and is approved in the USA.1,2
Objectives To compare the clinical efficacy of two maintenance dosing regimens of CZP (200mg Q2W + MTX or 400mg Q4W + MTX) in pts with active RA who achieved ACR20 after a 16 weeks (Wk) open-label run-in period of CZP 200mg Q2W + MTX.
Methods DOSEFLEX was an open-label run-in and double-blind (DB) placebo (PBO)-controlled randomized study in pts with active RA (NCT00580840). During run-in all pts received 400mg CZP at Wks 0, 2, and 4, and 200mg CZP Q2W to Wk16. ACR20 responders at Wk16 were randomized 1:1:1 at Wk18 to receive 200mg CZP Q2W, 400mg CZP Q4W, or PBO (all + MTX). Primary efficacy end-point was ACR20 response at Wk34. ACR responses and DAS28/SDAI/CDAI remission were assessed using NRI and DAS28(ESR) using LOCF.
Results 333 pts entered run-in; 53.5% had prior TNF inhibitor exposure. At Wk16, 61.3% pts achieved ACR20 response; 209 pts were randomized at Wk18 (CZP 200mg n=70; CZP 400mg n=70; PBO n=69). Mean baseline characteristics were similar among the 3 groups. At Wk34, ACR20/50/70 response rates were comparable between 200mg and 400mg groups (67.1/50.0/30.0% and 65.2/52.2/37.7%) and significantly higher than CZP→PBO (44.9/30.4/15.9%, p<0.05 for CZP 200mg ACR20/50 and CZP 400mg ACR20/50/70). DAS28 change from baseline to Wk34 was significantly greater in the CZP 200mg and 400mg groups (LS Mean -2.8 vs. -3.0) vs. CZP→PBO (-1.65 p<0.001 for both) (Fig). More pts in the CZP 200mg and 400mg groups compared to CZP→PBO had DAS28 (18.6% vs. 29.0% vs. 5.8%, p<0.05 for both), SDAI (17.1% vs. 29.0% vs. 13.0%, p<0.05 for CZP 400mg) and CDAI (21.4% vs. 27.5% vs. 15.9%) remission at Wk34. CZP was well tolerated (adverse event [AE] rates in DB phase: 62.9% vs. 60.9% vs. 62.3%; serious AE rates: 7.1% vs. 2.9% vs. 0% in CZP 200mg, 400mg and CZP→PBO groups). The most common serious AEs were infections and infestations (4.3% in CZP 200mg groups; 0 in the other groups). No cases of TB were reported.
Conclusions In RA pts with active disease and incomplete response to MTX, 200mg CZP Q2W and 400mg CZP Q4W showed comparable efficacy in maintaining clinical response to Wk34 following a 16 Wk run-in, whereas withdrawal of CZP led to worse outcomes.
Fleischmann et al. Ann Rheum Dis 2009;68:805–811.
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Disclosure of Interest D. Furst Grant/Research support from: UCB Pharma, Consultant for: UCB Pharma, Speakers Bureau: UCB Pharma, S. Shaikh: None Declared, M. Greenwald: None Declared, B. Bennett Shareholder of: UCB Pharma, F. Staelens Employee of: UCB Pharma, W. Koetse Employee of: UCB Pharma, P. Bertin: None Declared