Efficacy and safety of biosimilar CT-P13 compared with originator infliximab in patients with active Crohn's disease: an international, randomised, double-blind, phase 3 non-inferiority study

Byong Duk Ye, Marina Pesegova, Olga Alexeeva, Marina Osipenko, Adi Lahat, Andriy Dorofeyev, Sigal Fishman, Olena Levchenko, Jae Hee Cheon, Maria Lia Scribano, Radu Bogdan Mateescu, Kang Moon Lee, Chang Soo Eun, Sang Joon Lee, Sung Young Lee, Ho Ung Kim, Stefan Schreiber, Heather Fowler, Raymond Cheung, Young Ho Kim

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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.

Original languageEnglish
Pages (from-to)1699-1707
Number of pages9
JournalThe Lancet
Volume393
Issue number10182
DOIs
Publication statusPublished - 2019 Apr 27

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Biosimilar Pharmaceuticals
Crohn Disease
Safety
CT-P13
Infliximab

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Ye, Byong Duk ; Pesegova, Marina ; Alexeeva, Olga ; Osipenko, Marina ; Lahat, Adi ; Dorofeyev, Andriy ; Fishman, Sigal ; Levchenko, Olena ; Cheon, Jae Hee ; Scribano, Maria Lia ; Mateescu, Radu Bogdan ; Lee, Kang Moon ; Eun, Chang Soo ; Lee, Sang Joon ; Lee, Sung Young ; Kim, Ho Ung ; Schreiber, Stefan ; Fowler, Heather ; Cheung, Raymond ; Kim, Young Ho. / Efficacy and safety of biosimilar CT-P13 compared with originator infliximab in patients with active Crohn's disease : an international, randomised, double-blind, phase 3 non-inferiority study. In: The Lancet. 2019 ; Vol. 393, No. 10182. pp. 1699-1707.
@article{ad94aeffdc524bd1bdc87ad888121ecb,
title = "Efficacy and safety of biosimilar CT-P13 compared with originator infliximab in patients with active Crohn's disease: an international, randomised, double-blind, phase 3 non-inferiority study",
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.",
author = "Ye, {Byong Duk} and Marina Pesegova and Olga Alexeeva and Marina Osipenko and Adi Lahat and Andriy Dorofeyev and Sigal Fishman and Olena Levchenko and Cheon, {Jae Hee} and Scribano, {Maria Lia} and Mateescu, {Radu Bogdan} and Lee, {Kang Moon} and Eun, {Chang Soo} and Lee, {Sang Joon} and Lee, {Sung Young} and Kim, {Ho Ung} and Stefan Schreiber and Heather Fowler and Raymond Cheung and Kim, {Young Ho}",
year = "2019",
month = "4",
day = "27",
doi = "10.1016/S0140-6736(18)32196-2",
language = "English",
volume = "393",
pages = "1699--1707",
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Ye, BD, Pesegova, M, Alexeeva, O, Osipenko, M, Lahat, A, Dorofeyev, A, Fishman, S, Levchenko, O, Cheon, JH, Scribano, ML, Mateescu, RB, Lee, KM, Eun, CS, Lee, SJ, Lee, SY, Kim, HU, Schreiber, S, Fowler, H, Cheung, R & Kim, YH 2019, 'Efficacy and safety of biosimilar CT-P13 compared with originator infliximab in patients with active Crohn's disease: an international, randomised, double-blind, phase 3 non-inferiority study', The Lancet, vol. 393, no. 10182, pp. 1699-1707. https://doi.org/10.1016/S0140-6736(18)32196-2

Efficacy and safety of biosimilar CT-P13 compared with originator infliximab in patients with active Crohn's disease : an international, randomised, double-blind, phase 3 non-inferiority study. / Ye, Byong Duk; Pesegova, Marina; Alexeeva, Olga; Osipenko, Marina; Lahat, Adi; Dorofeyev, Andriy; Fishman, Sigal; Levchenko, Olena; Cheon, Jae Hee; Scribano, Maria Lia; Mateescu, Radu Bogdan; Lee, Kang Moon; Eun, Chang Soo; Lee, Sang Joon; Lee, Sung Young; Kim, Ho Ung; Schreiber, Stefan; Fowler, Heather; Cheung, Raymond; Kim, Young Ho.

In: The Lancet, Vol. 393, No. 10182, 27.04.2019, p. 1699-1707.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Efficacy and safety of biosimilar CT-P13 compared with originator infliximab in patients with active Crohn's disease

T2 - an international, randomised, double-blind, phase 3 non-inferiority study

AU - Ye, Byong Duk

AU - Pesegova, Marina

AU - Alexeeva, Olga

AU - Osipenko, Marina

AU - Lahat, Adi

AU - Dorofeyev, Andriy

AU - Fishman, Sigal

AU - Levchenko, Olena

AU - Cheon, Jae Hee

AU - Scribano, Maria Lia

AU - Mateescu, Radu Bogdan

AU - Lee, Kang Moon

AU - Eun, Chang Soo

AU - Lee, Sang Joon

AU - Lee, Sung Young

AU - Kim, Ho Ung

AU - Schreiber, Stefan

AU - Fowler, Heather

AU - Cheung, Raymond

AU - Kim, Young Ho

PY - 2019/4/27

Y1 - 2019/4/27

N2 - 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.

AB - 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.

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U2 - 10.1016/S0140-6736(18)32196-2

DO - 10.1016/S0140-6736(18)32196-2

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AN - SCOPUS:85064589346

VL - 393

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JO - The Lancet

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