DOP86 Subcutaneous infliximab (CT-P13 SC) as maintenance therapy for Crohn’s disease: A phase 3, randomised, placebo-controlled study (LIBERTY-CD).
Colombel, J.F.(1)*;Hanauer, S.B.(2);Sandborn, W.(3);Sands, B.E.(4);Schreiber, S.(5);Danese, S.(6);Kierkus, J.(7);Kulynych, R.(8);Klopocka, M.(9);Lahat, A.(10);Gonciarz, M.(11);Osipenko, M.(12);Borzan, V.(13);Kowalski, M.(14);Saenko, D.(15);Sardinov, R.(16);Kim, S.(17);Bae, Y.(17);Lee, S.(17);Yang, S.(17);Lee, J.(17);Lee, S.J.(18);Lee, S.G.(18);Park, G.(18);
(1)Icahn School of Medicine at Mount Sinai, Gastroenterology, New York, United States;(2)Northwestern University/ Feinberg School of Medicine, Gastroenterology and Hepatology, Chicago- IL, United States;(3)University of California San Diego, Gastroenterology, La Jolla, United States;(4)Icahn School of Medicine at Mount Sinai, Dr. Henry D. Janowitz Division of Gastroenterology, New York, United States;(5)University Hospital Schleswig Holstein, Medicine I, Kiel, Germany;(6)IRCCS San Raffaele Hospital, Gastroenterology, Milan, Italy;(7)The Children Memorial Health Institute, Gastroenterology- Hepatology- Feeding Disorders and Pediatrics, Warsaw, Poland;(8)Zaporizhzhia regional clinical hospital, Gastroenterology and Endoscopy, Zaporizhzhia, Ukraine;(9)Nicolaus Copernicus University- Collegium Medicum in Bydgoszcz, Gastroenterology and Nutrition Disorders, Bydgoszcz, Poland;(10)Chaim Sheba Medical Center, Gastroenterology, Ramat Gan, Israel;(11)Military Institute of Medicine - National Research Institute, Gastroenterology and Internal Diseases, Warsaw, Poland;(12)Novosibirsk Medical University, Novosibirsk Medical University, Novosibirsk, Russian Federation;(13)Clinical Hospital Center Osijek- Faculty of medicine Osijek, Gastroenterology, Osijek, Croatia;(14)Centrum Diagnostyczno – Lecznicze Barska, Gastroenterology, Wloclawek, Poland;(15)LLC "Clinica UZI 4D", LLC "Clinica UZI 4D", Pyatigorsk- Stavropol Region, Russian Federation;(16)BioTechService LLC- St. Petersburg Medical and Social Institute, Therapy, Saint-Petersburg, Russian Federation;(17)Celltrion- Inc., Medical Science Division, Incheon, Korea- Republic Of;(18)Celltrion- Inc., Data Science Institute, Incheon, Korea- Republic Of; CT-P13 SC 3.8
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