| Abstract
| - Background. Certolizumab pegol (CZP), an inhibitor of TNF-alpha, has demonstrated rapid and sustained efficacy in RA patients in multiple clinical trials and is approved for the treatment of RA in many countries. Switching from one anti-TNF therapy to another has been investigated in many open-label uncontrolled studies, but in few controlled trials. Objectives. This double blind (DB) controlled study was to examine the effect of 12 weeks treatment with CZP or placebo on measures of disease activity in patients with RA on stable concomitant methotrexate (MTX) or other non-biologic therapy and who had discontinued a TNF-alpha inhibitor other than CZP. Methods. This randomized, multi-center, DB, parallel group 12-week study randomized (2:1 ratio) 37 subjects who were secondary non-responders (primary non-responders were excluded) or intolerant to TNF-alpha inhibitors to either CZP (27 subjects) or placebo (10 subjects) in addition to background MTX or other DMARDs. Subjects were required to washout from previous TNF inhibitors for at least 4 weeks. CZP was administered subcutaneously in approved doses. After the Week 12 visit, all subjects could participate in an open-label phase with CZP dosing for an additional 12 weeks (to be reported at a later date). (NCT01147341). Results. Of the 37 subjects who were randomized for safety, 35 (26 on CZP and 9 on placebo) were in the Efficacy Population (completed at least 4 weeks of dosing). Demographic/baseline characteristics of the 2 treatment groups were similar: average age 56 vs 59 years, mean disease duration 12 vs 14 years, mean MTX dose 16.4 vs 16.1 mg/week, #TNF failed 1.40 vs 1.33 and DAS 5.48 vs 5.44 (placebo vs active). Adverse events occurred in 16/27 (59.3%) CZP subjects and 4/10 (40%) placebo subjects. There were no serious adverse events, deaths, neoplasms, opportunistic or serious infections. Efficacy EndpointsPlacebo, n/N (%)CZP, n/N (%)p-value*CDAI Decrease ≥10 (primary)2/9 (22.2)22/26 (84.6)0.001ACR 20 (primary)0/9 (0)16/26 (61.5)0.001CDAI LDAS+Remission0/9 (0)6/26 (23.1)0.303EULAR good and moderate0/9 (0)17/26 (65.4)0.001CDAI ≥13.9 Decrease0/9 (0)17/26 (65.4)0.001 *Two-sided p-value from Fisher’s exact test. Conclusions. In this double-blind controlled 12-week study in incomplete secondary responders to TNF-alpha inhibitors, statistically significant efficacy with CZP compared to placebo was observed for both primary efficacy endpoints and most secondary endpoints. The ACR 20 response rate observed with CZP (61.5%) is higher than that reported in most previous studies of incomplete TNF responders. In addition, CZP demonstrated good safety and tolerability. This study supports the use of CZP in RA patients who are secondary non-responders to TNF inhibitors or intolerant to them. Disclosure of Interest. M. Schiff Grant/Research support from: UCB, R. Goldblum: None Declared, J. Tesser Consultant for: UCB. This is an investigator initiated study.
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