DOP86 Subcutaneous infliximab (CT-P13 SC) as maintenance therapy for Crohn’s disease: A phase 3, randomised, placebo-controlled study (LIBERTY-CD).

Abstract

Background CT-P13 subcutaneous (SC) infliximab formulation showed comparable efficacy and safety with CT-P13 intravenous (IV) infliximab in inflammatory bowel disease (IBD)1 and rheumatoid arthritis2. This study aimed to demonstrate the superiority of CT-P13 SC over placebo as maintenance therapy after induction therapy of CT-P13 IV in patient with Crohn’s disease (CD). Methods Moderately to severely active CD patients with Crohn’s disease activity index (CDAI) score 220 to 450 and simplified endoscopic activity score for Crohn’s disease (SES-CD) of ≥6 points for ileal-colonic CD or ≥4 points including ulcer score from at least 1 segment for ileal CD or colonic CD were enrolled LIBERTY-CD study (NCT03945019) and treated with open-label CT-P13 IV 5 mg/kg at Weeks 0, 2 and 6 as induction therapy. At Week 10, patients who had a clinical response were randomised (2:1) to receive either CT-P13 SC 120 mg (CT-P13 SC) or placebo every 2 weeks up to Week 54. At Week 54, clinical remission and endoscopic response were assessed as co-primary endpoints. Clinical response, clinical remission (alternative definition), endoscopic remission, and corticosteroid-free remission were assessed at Week 54 as key secondary endpoint. Safety was evaluated up to Week 54. Results A total of 396 patients were enrolled and 343 patients (86.6%) were randomised (231 in CT-P13 SC arm and 112 in placebo arm) at Week 10. At Week 54, the clinical remission rate was greater in CT-P13 SC arm than placebo arm (62.3% and 32.1% respectively, with P <0.0001). The endoscopic response rate was also greater in CT-P13 arm than placebo arm (51.1% and 17.9% respectively, with P <0.0001). CT-P13 SC also had significantly greater efficacy on key secondary endpoints results compared to placebo arm (Table 1). Safety profiles were generally comparable between CT-P13 SC and placebo arms, but a single death was reported during the maintenance phase (Table 2). Conclusion CT-P13 SC was more effective than placebo in clinical remission, endoscopic response, clinical response, clinical remission (alternative definition), endoscopic remission, and corticosteroid-free remission at Week 54. No new safety concerns were found during treatment of CT-P13 SC. These results demonstrate that maintenance therapy with CT-P13 SC provides both a robust clinical benefit and the convenience of SC administration to moderately to severely active CD patients. [1] Schreiber et al., 2021. Gastroenterology 2021;160:2340–23 [2] Westhovens et al., 2020. Rheumatology 2020;00:1

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“…For the exploratory analyses, the only additional full publication identified was for VISIBLE 2, a multinational, randomised, double-blind, placebo-controlled trial that evaluated VDZ SC maintenance treatment in patients with moderate-to-severe CD [ 33 ]. In addition, data for LIBERTY-CD and LIBERTY-UC were identified from recently published congress abstracts; both are randomised, placebo-controlled trials of IFX SC in patients with CD or UC [ 34 , 35 ].…”

“…Eligible patients were required to have a previous inadequate response or intolerance to corticosteroids, immunomodulators, and/or TNFis; 61% of the 275 patients randomised to VDZ SC had prior TNFi exposure [ 33 ]. In LIBERTY-CD and LIBERTY-UC, patients received open-label IFX SC 5mg/kg at Weeks 0, 2, and 6; at Week 10, clinical responders were randomised (2:1) to receive IFX SC 120 mg or placebo Q2W until Week 54 [ 34 , 35 ]. In terms of baseline characteristics for the VDZ SC arm of the VISIBLE 2 study, mean (SD) age was 38.2 (13.9) years, body weight was 74.1 (19.0) kg, disease duration was 9.5 (8.3) years, and 43% of patients were female [ 33 ].…”

“…In terms of baseline characteristics for the VDZ SC arm of the VISIBLE 2 study, mean (SD) age was 38.2 (13.9) years, body weight was 74.1 (19.0) kg, disease duration was 9.5 (8.3) years, and 43% of patients were female [ 33 ]. Baseline characteristics for the patients in the LIBERTY studies were not reported in the published congress abstracts [ 34 , 35 ].…”

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“…The LIBERTY-CD trial, a phase 3 randomized control trial of 396 patients, compared infliximab subcutaneous maintenance therapy with placebo [17]. Patients were given i.v.…”

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“…However, a SC form of IFX has been developed and a recent phase III trial compared its efficacy to placebo in maintenance of moderate to severe CD. 137 The LIBERTY-CD trial included 343 patients with moderate to severe CD who underwent IFX IV induction and had clinical response and then were randomized to receive IFX SC 120 mg every two weeks or placebo. At week 54, the rate of clinical remission was greater in the IFX SC compared to placebo (62.3% vs 32.1% respectively, P < 0.0001) as well as endoscopic response rate (51.1% vs 17.9% respectively, P < 0.0001).…”