SUBCUTANEOUS INFLIXIMAB (CT-P13 SC) DOSE ESCALATION AS AN OPTION FOR MANAGING THE LOSS OF RESPONSE IN INFLAMMATORY BOWEL DISEASE POST HOC ANALYSIS OF LIBERTY-UC AND LIBERTY-CD STUDY

Abstract

Abstract INTRODUCTION Dose escalation of IV infliximab is an option for inflammatory bowel disease (IBD) patients who lose response after induction therapy. However, as yet, there is limited data for CT-P13 subcutaneous (SC) infliximab (CT-P13 SC) dose escalation in IBD patients. AIMS & METHODS The aim of the post hoc analysis was to evaluate the efficacy, safety, and immunogenicity of treatment with CT-P13 SC dose escalation in patients who initially responded but then lost response according to the loss of response (LOR) criteria in LIBERTY-UC and LIBERTY-CD studies, which were conducted in parallel over 54 weeks. Patients with moderately to severely active UC and CD were treated with 3 doses of infliximab IV 5mg/kg as induction therapy. Clinical responders at Week 10 were randomized (2:1) to receive either CT-P13 SC 120 mg or placebo every 2 weeks as maintenance therapy. From Week 22, the patients who received CT-P13 SC 120 mg every 2 weeks and who met LOR criteria were permitted to escalate the dose to CT-P13 SC 240 mg (double injection [2 shots] of CT-P13 SC 120 mg) every 2 weeks. RESULTS A total of 294 and 231 patients were randomized to CT-P13 SC 120mg in UC and CD study, each. Among them, dose escalation from CT-P13 SC 120 mg to CT-P13 SC 240 mg prior to Week 54was more common in UC than CD [27.6% (81/294) vs 16.9% (39/231)]. Of dose-escalated patients, 74.1% (60/81) and 51.3% (20/39) received their first dose of CT-P13 SC 240 mg at Week 22 in the UC and CD studies, respectively. In both UC and CD studies, patients showed improvement in terms of clinical remission [In UC, 24.7% (20/81), In CD, 53.8% (21/39)] or endoscopic response [In CD, 28.2% (11/39)] after dose escalation. Compared to the first dose escalation visits, patients who escalated the dose had almost a half, statistically significant, reduction in modified Mayo score in UC and CDAI score in CD at Week 54. (Table 1). The incidence rate of treatment-emergent adverse events (TEAEs) in the maintenance period of both studies was comparable between patients with and without dose escalation. [In UC, 72.8% (67/92) vs 65.2% (133/204), In CD, 71.1% (32/45) vs 72.5% (140/193)]. Among these, TEAEs of infection were as follows [In UC, 27.2% (25/92) vs 28.4% (58/204), In CD, 35.6% (16/45) vs 30.1% (58/193)]. In both studies, rates of anti-drug antibody (ADA) positive conversion up to Week 54 showed no difference in patients with and without dose escalation as follows [In UC, ADA 55.7% (49/88) and 67.3% (134/199), respectively. In CD, ADA 68.2% (30/44) and 64.4% (121/188), respectively]. CONCLUSION Dose escalation of CT-P13 SC from 120 mg to 240 mg every 2 weeks may be effective in restoring efficacy. Safety profiles including immunogenicity results were generally comparable between patients with or without dose escalation. No new safety concerns were found after dose escalation.