Byong Duk Ye1, Marina Pesegova2, Olga Alexeeva3, Marina Osipenko4, Adi Lahat5, Andriy Dorofeyev6, Sigal Fishman7, Olena Levchenko8, Jae Hee Cheon9, Maria Lia Scribano10, Radu-Bogdan Mateescu11, Kang-Moon Lee12, Chang Soo Eun13, Sang Joon Lee14, Sung Young Lee14, HoUng Kim14, Stefan Schreiber15, Heather Fowler16, Raymond Cheung16, Young-Ho Kim17. 1. University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea. 2. Krasnoyarsk Regional Clinical Hospital, Krasnoyarsk, Russia. 3. Nizhny Novgorod Regional Clinical Hospital N A Semashko, Nizhny Novgorod, Russia. 4. Novosibirsk State Medical University, Novosibirsk, Russia. 5. Department of Gastroenterology, Sheba Medical Center, Tel Hashomer, Israel; Sackler Faculty of Medicine, Tel Aviv University, Ramat-Gan, Israel. 6. Medical Center LLC Ukrainian German Antiulcer Gastroenterology Center BIK Kyiv, Kyiv, Ukraine. 7. Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Sackler Faculty of Medicine, Tel Aviv University, Ramat-Gan, Israel. 8. Munipial Institution Odesa Regional Clinical Hospital, Odesa, Ukraine. 9. Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea. 10. Gastroenterology Unit, Azienda Ospedaliera San Camillo Forlanini, Rome, Italy. 11. Gastroenterology Department, Colentina Clinical Hospital, Bucharest, Romania; Carol Davila University of Medicine and Pharmacy, Bucharest, Romania. 12. St Vincent's Hospital, College of Medicine, The Catholic University of Korea, Suwon, South Korea. 13. Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, South Korea. 14. Celltrion, Incheon, South Korea. 15. University-Hospital Schleswig-Holstein, Christian-Albrechts-University, Dep Medicine I, Kiel, Germany. 16. Pfizer, New York, NY, USA. 17. Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea. Electronic address: bowelkim@gmail.com.
Abstract
BACKGROUND: The infliximab biosimilar CT-P13 was approved for use in Crohn's disease after clinical comparison with originator infliximab in ankylosing spondylitis and rheumatoid arthritis; however, concerns about such indication extrapolation have been expressed. This study investigated whether CT-P13 is non-inferior to infliximab in patients with Crohn's disease who were naive to biological therapy. METHODS: In this randomised, multicentre, double-blind, phase 3 non-inferiority study, we enrolled patients with active Crohn's disease who had not responded to, or were intolerant to, non-biological treatments. Patients were randomly assigned (1:1:1:1) to receive CT-P13 then CT-P13, CT-P13 then infliximab, infliximab then infliximab, or infliximab then CT-P13, with switching occurring at week 30. Patients received 5 mg/kg CT-P13 or infliximab at weeks 0, 2, 6, and then every 8 weeks up to week 54. The primary endpoint was the proportion of patients with a decrease of 70 points or more in Crohn's Disease Activity Index (CDAI) from baseline to week 6. A non-inferiority margin of -20% was set (CT-P13 was non-inferior to infliximab if the lower limit of the two-sided 95% CI for the treatment difference was greater than -20). This trial is registered with ClinicalTrials.gov, number NCT02096861, and is completed. FINDINGS:Between Aug 20, 2014, and Feb 15, 2017, 308 patients were assessed for eligibility, and 220 patients were enrolled: 111 were randomly assigned to initiate CT-P13 (56 to the CT-P13-CT-P13 group and 55 to the CT-P13-infliximab group) and 109 to initiate infliximab (54 to the infliximab-infliximab group and 55 to the infliximab-CT-P13 group). CDAI-70 response rates at week 6 were similar for CT-P13 (77 [69·4%, 95% CI 59·9 to 77·8] of 111) and infliximab (81 [74·3%, 95% CI 65·1 to 82·2] of 109; difference -4·9% [95% CI -16·9 to 7·3]), thereby establishing non-inferiority. Over the total study period, 147 (67%) patients experienced at least one treatment-emergent adverse event (36 [64%] in the CT-P13-CT-P13 group, 34 [62%] in the CT-P13-infliximab group, 37 [69%] in the infliximab-infliximab group, and 40 [73%] in the infliximab-CT-P13 group). INTERPRETATION: This study showed non-inferiority of CT-P13 to infliximab in patients with active Crohn's disease. Biosimilar CT-P13 could be a new option for the treatment of active Crohn's disease. FUNDING: Celltrion, Pfizer.
RCT Entities:
BACKGROUND: The infliximab biosimilar CT-P13 was approved for use in Crohn's disease after clinical comparison with originator infliximab in ankylosing spondylitis and rheumatoid arthritis; however, concerns about such indication extrapolation have been expressed. This study investigated whether CT-P13 is non-inferior to infliximab in patients with Crohn's disease who were naive to biological therapy. METHODS: In this randomised, multicentre, double-blind, phase 3 non-inferiority study, we enrolled patients with active Crohn's disease who had not responded to, or were intolerant to, non-biological treatments. Patients were randomly assigned (1:1:1:1) to receive CT-P13 then CT-P13, CT-P13 then infliximab, infliximab then infliximab, or infliximab then CT-P13, with switching occurring at week 30. Patients received 5 mg/kg CT-P13 or infliximab at weeks 0, 2, 6, and then every 8 weeks up to week 54. The primary endpoint was the proportion of patients with a decrease of 70 points or more in Crohn's Disease Activity Index (CDAI) from baseline to week 6. A non-inferiority margin of -20% was set (CT-P13 was non-inferior to infliximab if the lower limit of the two-sided 95% CI for the treatment difference was greater than -20). This trial is registered with ClinicalTrials.gov, number NCT02096861, and is completed. FINDINGS: Between Aug 20, 2014, and Feb 15, 2017, 308 patients were assessed for eligibility, and 220 patients were enrolled: 111 were randomly assigned to initiate CT-P13 (56 to the CT-P13-CT-P13 group and 55 to the CT-P13-infliximab group) and 109 to initiate infliximab (54 to the infliximab-infliximab group and 55 to the infliximab-CT-P13 group). CDAI-70 response rates at week 6 were similar for CT-P13 (77 [69·4%, 95% CI 59·9 to 77·8] of 111) and infliximab (81 [74·3%, 95% CI 65·1 to 82·2] of 109; difference -4·9% [95% CI -16·9 to 7·3]), thereby establishing non-inferiority. Over the total study period, 147 (67%) patients experienced at least one treatment-emergent adverse event (36 [64%] in the CT-P13-CT-P13 group, 34 [62%] in the CT-P13-infliximab group, 37 [69%] in the infliximab-infliximab group, and 40 [73%] in the infliximab-CT-P13 group). INTERPRETATION: This study showed non-inferiority of CT-P13 to infliximab in patients with active Crohn's disease. Biosimilar CT-P13 could be a new option for the treatment of active Crohn's disease. FUNDING: Celltrion, Pfizer.
Authors: Nerea Martín-Gutiérrez; José Germán Sánchez-Hernández; Noemí Rebollo; Alejandra F Pordomingo; Fernando Muñoz; María José Otero Journal: Eur J Hosp Pharm Date: 2020-10-28
Authors: Emily C L Wong; Elisa Buffone; So Jeong Lee; Parambir S Dulai; John K Marshall; Walter Reinisch; Neeraj Narula Journal: J Crohns Colitis Date: 2021-07-05 Impact factor: 9.071