Certolizumab Pegol as Salvage Therapy in Patients with CD Intolerant to or Without Adequate Response to Two Prior Anti-TNF Agents

Abstract

Purpose: Certolizumab pegol (CP), an anti-TNF agent has been recently approved by the Food and Drug Administration (FDA) for treatment of Crohn's disease(CD). Other FDA approved anti-TNF agents for treatment of CD include infliximab (INF) and adalimumab (ADA). The aim of present study was to assess the efficacy of CP in pts with CD who initially responded but subsequently lost response or were intolerant to previous therapy with other ant-TNF agents specifically INF and ADA at our Institution. Methods: A retrospective review of an electronic database was performed at our Institution. We reviewed all outpt records from 04/07-06/09 in our IBD center in order to identify patients with IBD who were treated with CP. CP was administered subcutaneously in the dose of 400 mg at week 0, 2 and 4 and then after every 4 weeks. The efficacy of CP was evaluated by Harvey-Bradshaw Index (HBI) prior (HBI 1) and after (HBI 2) initiation therapy with CP. Clinical response was defined as reduction of HBI score ≥ 3 points from baseline whereas clinical remission was defined as HBI score ≤ 4 points. Results: There were 1312 consecutive IBD pts identified over this time interval. Among them, 16 pts (10 women) with CD were treated with CP who initially responded but subsequently lost response (n=6) or were intolerant (n=10) to previous therapy with other ant-TNF agents specifically INF and ADA with a mean (± SD) age 36.8 (± 12.9)yrs. The mean duration of CD was 14.7 (± 8.1)yrs. Two pts with clinically active CD (12.5%) experienced infusion reactions after initiation therapy with CP (1 pt was intolerant to INF, 1 pt was intolerant to INF and ADA) and their HBI 2 scores were not available. Therefore HBI 1 and HBI 2 scores were calculated in 14 pts. The mean HBI 1 score was 7.9 ± 5.0 whereas the mean HBI 2 score was 6.2 ± 5.6 (p=0.04). The mean duration of follow-up on therapy with CP was 5.9 (±3.8) months. Prior to initiation of therapy with CP 9 of 14 pts (64.3%) had clinically active CD (mean HBI 1 10.9 ± 3.3) whereas 5 of 14 pts were in clinical remission (mean HBI 2 2.4 ± 1.5). Among 9 pts who received therapy with CP who had active CD, upon evaluation of HBI 2 score benefit was seen in 44% overall. Clinical remission was achieved by 3 of 9 (33 %) patients; clinical response was achieved by 1 of 9 pts (11%) whereas 5 pts (55.6%) did not respond to treatment with CP. All 5 pts who began treatment with CP with CD in remission were capable of maintaining their state of remission (mean follow-up 5.2 ± 4.0 months). Conclusion: Our preliminary data suggest that the use of a third anti-TNF agent particularly CP is an effective salvage therapy in pts with CD who are intolerant to or lose their initial response to two previous anti-TNF agents (INF and ADA). Disclosure: Dr Gary Lichtenstein - Received research/grant support, support for lectures and for scientific advisory committee for Salix, Shire, Axcan, Ferring, P&G, Centocor, Abbott, UCB Inc, Bristol Meyers Squibb, Elan and Prometheus.