DOSEFLEX was a 34 week, phase 3b study, with a 16 week open label run-in phase, followed by randomization into a double-blind, placebo controlled phase that was designed to compare the clinical efficacy of two maintenance dosing regimens of certolizumab pegol (200 mg every two weeks versus placebo and 400 mg every four weeks versus placebo) in combination with weekly MTX.
The study enrolled 333 patients with active RA who had experienced an incomplete response to MTX. Patients entered a 16-week open-label study, with a run-in period where in addition to their baseline MTX medication they received 400 mg certolizumab pegol at weeks 0, 2 and 4, and 200 mg certolizumab pegol every two weeks to week 16. At week 18, the ACR20 responders were randomized 1:1:1 to receive either 200 mg certolizumab pegol every two weeks with MTX, 400 mg certolizumab pegol every four weeks with MTX, or placebo with MTX for a further period of 16 weeks. The primary efficacy endpoint was ACR20 response at week 34. ACR20 indicates a 20 percent improvement in tender joint count or swollen joint count, as well as a 20 percent improvement in three of five other criteria, including patient and physician assessment of disease activity, patient assessment of pain and physical function, and levels of acute phase reactant (either the C-reactive protein level or the erythrocyte sedimentation rate).
At week 34, ACR20/50/70 response rates for the 200 mg every two weeks and the 400 mg every four weeks dosing regimens were 67.1%/50.0%/30.0% and 65.2%/52.2%/37.7%, respectively, and were significantly higher than placebo (44.9%/30.4%/15.9%, p<0.05 for 200 mg ACR20/50 and 400 mg ACR20/50/70).
At week 34, the post-hoc analysis showed that ACR20 scores in patients with and without prior anti-TNF exposure were 74.4% compared with 55.6% in the 200 mg every two weeks group, and 61.5% compared with 70.0% in the 400 mg every four weeks group.