Discontinuation of Infliximab Therapy in Patients with Crohn’s Disease

Sine Buhl; Casper Steenholdt; Jørn Brynskov; Katrine Risager Christensen; Maria Dorn-Rasmussen; Ole Østergaard Thomsen; Klaus Bendtzen; Tobias Wirenfeldt Klausen; Jens Frederik Dahlerup; Niels Thorsgaard; Jørgen Jahnsen; Akbar Molazahi; Natalia Pedersen; Jens Kjeldsen; Sven Almer; Eva Efsen Dahl; Ida Vind; Annett Gerhardt Cannon; Jan Marsal; Taina Sipponen; Jørgen Steen Agnholt; Hendrika Adriana Linda Kievit; Synnøve Louise Aure; Lars Martinsen; Svetlana Meisner; Jane Møller Hansen; Mark Andrew Ainsworth

doi:10.1056/EVIDoa2200061

Discontinuation of Infliximab Therapy in Patients with Crohn’s Disease

Sine Buhl, Casper Steenholdt, Jørn Brynskov, Katrine Risager Christensen, Maria Dorn-Rasmussen, Ole Østergaard Thomsen, Klaus Bendtzen, Tobias Wirenfeldt Klausen, Jens Frederik Dahlerup, Niels Thorsgaard, Jørgen Jahnsen, Akbar Molazahi, Natalia Pedersen, Jens Kjeldsen, Sven Almer, Eva Efsen Dahl, Ida Vind, Annett Gerhardt Cannon, Jan Marsal, Taina SipponenJørgen Steen Agnholt, Hendrika Adriana Linda Kievit, Synnøve Louise Aure, Lars Martinsen, Svetlana Meisner, Jane Møller Hansen, Mark Andrew Ainsworth

Abstract

BACKGROUND: Whether infliximab therapy can be successfully discontinued after patients with Crohn’s disease have attained sustained, clinical, biochemical, and endoscopic remission is unknown. METHODS: We conducted a multicenter, randomized, double-blind, placebo-controlled withdrawal study of infliximab in patients with Crohn’s disease who were in clinical, biochemical, and endoscopic remission after standard infliximab maintenance therapy for at least 1 year. Patients were randomly assigned 1:1 to continue infliximab therapy or to receive matching placebo for 48 weeks. The primary end point was time to relapse. RESULTS: This study randomly assigned 115 patients to either the infliximab-continuation group or to the infliximab-discontinuation group. No relapses were observed among the 59 patients continuing infliximab, whereas 23 of 56 patients discontinuing infliximab experienced relapse. Time to relapse was significantly shorter among patients who discontinued infliximab than among those who continued infliximab (hazard ratio, 0.080; 95% confidence interval [CI], 0.035 to 0.186; P<0.001). At the end of the trial at week 48, relapse-free survival was 100% in the infliximab-continuation group and 51% in the infliximab-discontinuation group. The key secondary end point, time to loss of remission, was significantly shorter among patients discontinuing infliximab therapy than those continuing infliximab (hazard ratio, 0.025; 95% CI, 0.003 to 0.187; P<0.001). No unexpected adverse events were reported. CONCLUSIONS: Discontinuation of infliximab for patients with Crohn’s disease receiving long-term infliximab therapy and in clinical, biochemical, and endoscopic remission leads to a considerable risk of relapse. (Funded by the Nordic Trial Alliance [NordForsk], the Medical Fund of the Danish Regions [Regionernes Medicin og Behandlingspulje], the Danish Colitis-Crohn Association, and the A.P. Moller Foundation; ClinicalTrials.gov number, NCT01817426; EudraCT number, 2012-002702-51.)

Original language	English
Journal	NEJM Evidence
Volume	1
Issue number	8
Pages (from-to)	EVIDoa2200061
DOIs	https://doi.org/10.1056/EVIDoa2200061
Publication status	Published - Aug 2022

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10.1056/EVIDoa2200061

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Buhl, S., Steenholdt, C., Brynskov, J., Christensen, K. R., Dorn-Rasmussen, M., Thomsen, O. Ø., Bendtzen, K., Klausen, T. W., Dahlerup, J. F., Thorsgaard, N., Jahnsen, J., Molazahi, A., Pedersen, N., Kjeldsen, J., Almer, S., Dahl, E. E., Vind, I., Cannon, A. G., Marsal, J., ... Ainsworth, M. A. (2022). Discontinuation of Infliximab Therapy in Patients with Crohn’s Disease. NEJM Evidence, 1(8), EVIDoa2200061. https://doi.org/10.1056/EVIDoa2200061

Buhl, S , Steenholdt, C , Brynskov, J , Christensen, KR, Dorn-Rasmussen, M, Thomsen, OØ, Bendtzen, K, Klausen, TW, Dahlerup, JF, Thorsgaard, N, Jahnsen, J, Molazahi, A, Pedersen, N, Kjeldsen, J, Almer, S, Dahl, EE , Vind, I, Cannon, AG, Marsal, J, Sipponen, T, Agnholt, JS, Kievit, HAL, Aure, SL, Martinsen, L, Meisner, S, Hansen, JM & Ainsworth, MA 2022, 'Discontinuation of Infliximab Therapy in Patients with Crohn’s Disease', NEJM Evidence, vol. 1, no. 8, pp. EVIDoa2200061. https://doi.org/10.1056/EVIDoa2200061

@article{69ab89f13f83448c82277d76d08a0624,

title = "Discontinuation of Infliximab Therapy in Patients with Crohn{\textquoteright}s Disease",

abstract = "BACKGROUND: Whether infliximab therapy can be successfully discontinued after patients with Crohn{\textquoteright}s disease have attained sustained, clinical, biochemical, and endoscopic remission is unknown. METHODS: We conducted a multicenter, randomized, double-blind, placebo-controlled withdrawal study of infliximab in patients with Crohn{\textquoteright}s disease who were in clinical, biochemical, and endoscopic remission after standard infliximab maintenance therapy for at least 1 year. Patients were randomly assigned 1:1 to continue infliximab therapy or to receive matching placebo for 48 weeks. The primary end point was time to relapse. RESULTS: This study randomly assigned 115 patients to either the infliximab-continuation group or to the infliximab-discontinuation group. No relapses were observed among the 59 patients continuing infliximab, whereas 23 of 56 patients discontinuing infliximab experienced relapse. Time to relapse was significantly shorter among patients who discontinued infliximab than among those who continued infliximab (hazard ratio, 0.080; 95% confidence interval [CI], 0.035 to 0.186; P<0.001). At the end of the trial at week 48, relapse-free survival was 100% in the infliximab-continuation group and 51% in the infliximab-discontinuation group. The key secondary end point, time to loss of remission, was significantly shorter among patients discontinuing infliximab therapy than those continuing infliximab (hazard ratio, 0.025; 95% CI, 0.003 to 0.187; P<0.001). No unexpected adverse events were reported. CONCLUSIONS: Discontinuation of infliximab for patients with Crohn{\textquoteright}s disease receiving long-term infliximab therapy and in clinical, biochemical, and endoscopic remission leads to a considerable risk of relapse. (Funded by the Nordic Trial Alliance [NordForsk], the Medical Fund of the Danish Regions [Regionernes Medicin og Behandlingspulje], the Danish Colitis-Crohn Association, and the A.P. Moller Foundation; ClinicalTrials.gov number, NCT01817426; EudraCT number, 2012-002702-51.)",

author = "Sine Buhl and Casper Steenholdt and J{\o}rn Brynskov and Christensen, {Katrine Risager} and Maria Dorn-Rasmussen and Thomsen, {Ole {\O}stergaard} and Klaus Bendtzen and Klausen, {Tobias Wirenfeldt} and Dahlerup, {Jens Frederik} and Niels Thorsgaard and J{\o}rgen Jahnsen and Akbar Molazahi and Natalia Pedersen and Jens Kjeldsen and Sven Almer and Dahl, {Eva Efsen} and Ida Vind and Cannon, {Annett Gerhardt} and Jan Marsal and Taina Sipponen and Agnholt, {J{\o}rgen Steen} and Kievit, {Hendrika Adriana Linda} and Aure, {Synn{\o}ve Louise} and Lars Martinsen and Svetlana Meisner and Hansen, {Jane M{\o}ller} and Ainsworth, {Mark Andrew}",

note = "doi: 10.1056/EVIDoa2200061",

year = "2022",

month = aug,

doi = "10.1056/EVIDoa2200061",

language = "English",

volume = "1",

pages = "EVIDoa2200061",

journal = "NEJM Evidence",

issn = "2766-5526",

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TY - JOUR

T1 - Discontinuation of Infliximab Therapy in Patients with Crohn’s Disease

AU - Buhl, Sine

AU - Steenholdt, Casper

AU - Brynskov, Jørn

AU - Christensen, Katrine Risager

AU - Dorn-Rasmussen, Maria

AU - Thomsen, Ole Østergaard

AU - Bendtzen, Klaus

AU - Klausen, Tobias Wirenfeldt

AU - Dahlerup, Jens Frederik

AU - Thorsgaard, Niels

AU - Jahnsen, Jørgen

AU - Molazahi, Akbar

AU - Pedersen, Natalia

AU - Kjeldsen, Jens

AU - Almer, Sven

AU - Dahl, Eva Efsen

AU - Vind, Ida

AU - Cannon, Annett Gerhardt

AU - Marsal, Jan

AU - Sipponen, Taina

AU - Agnholt, Jørgen Steen

AU - Kievit, Hendrika Adriana Linda

AU - Aure, Synnøve Louise

AU - Martinsen, Lars

AU - Meisner, Svetlana

AU - Hansen, Jane Møller

AU - Ainsworth, Mark Andrew

N1 - doi: 10.1056/EVIDoa2200061

PY - 2022/8

Y1 - 2022/8

N2 - BACKGROUND: Whether infliximab therapy can be successfully discontinued after patients with Crohn’s disease have attained sustained, clinical, biochemical, and endoscopic remission is unknown. METHODS: We conducted a multicenter, randomized, double-blind, placebo-controlled withdrawal study of infliximab in patients with Crohn’s disease who were in clinical, biochemical, and endoscopic remission after standard infliximab maintenance therapy for at least 1 year. Patients were randomly assigned 1:1 to continue infliximab therapy or to receive matching placebo for 48 weeks. The primary end point was time to relapse. RESULTS: This study randomly assigned 115 patients to either the infliximab-continuation group or to the infliximab-discontinuation group. No relapses were observed among the 59 patients continuing infliximab, whereas 23 of 56 patients discontinuing infliximab experienced relapse. Time to relapse was significantly shorter among patients who discontinued infliximab than among those who continued infliximab (hazard ratio, 0.080; 95% confidence interval [CI], 0.035 to 0.186; P<0.001). At the end of the trial at week 48, relapse-free survival was 100% in the infliximab-continuation group and 51% in the infliximab-discontinuation group. The key secondary end point, time to loss of remission, was significantly shorter among patients discontinuing infliximab therapy than those continuing infliximab (hazard ratio, 0.025; 95% CI, 0.003 to 0.187; P<0.001). No unexpected adverse events were reported. CONCLUSIONS: Discontinuation of infliximab for patients with Crohn’s disease receiving long-term infliximab therapy and in clinical, biochemical, and endoscopic remission leads to a considerable risk of relapse. (Funded by the Nordic Trial Alliance [NordForsk], the Medical Fund of the Danish Regions [Regionernes Medicin og Behandlingspulje], the Danish Colitis-Crohn Association, and the A.P. Moller Foundation; ClinicalTrials.gov number, NCT01817426; EudraCT number, 2012-002702-51.)

AB - BACKGROUND: Whether infliximab therapy can be successfully discontinued after patients with Crohn’s disease have attained sustained, clinical, biochemical, and endoscopic remission is unknown. METHODS: We conducted a multicenter, randomized, double-blind, placebo-controlled withdrawal study of infliximab in patients with Crohn’s disease who were in clinical, biochemical, and endoscopic remission after standard infliximab maintenance therapy for at least 1 year. Patients were randomly assigned 1:1 to continue infliximab therapy or to receive matching placebo for 48 weeks. The primary end point was time to relapse. RESULTS: This study randomly assigned 115 patients to either the infliximab-continuation group or to the infliximab-discontinuation group. No relapses were observed among the 59 patients continuing infliximab, whereas 23 of 56 patients discontinuing infliximab experienced relapse. Time to relapse was significantly shorter among patients who discontinued infliximab than among those who continued infliximab (hazard ratio, 0.080; 95% confidence interval [CI], 0.035 to 0.186; P<0.001). At the end of the trial at week 48, relapse-free survival was 100% in the infliximab-continuation group and 51% in the infliximab-discontinuation group. The key secondary end point, time to loss of remission, was significantly shorter among patients discontinuing infliximab therapy than those continuing infliximab (hazard ratio, 0.025; 95% CI, 0.003 to 0.187; P<0.001). No unexpected adverse events were reported. CONCLUSIONS: Discontinuation of infliximab for patients with Crohn’s disease receiving long-term infliximab therapy and in clinical, biochemical, and endoscopic remission leads to a considerable risk of relapse. (Funded by the Nordic Trial Alliance [NordForsk], the Medical Fund of the Danish Regions [Regionernes Medicin og Behandlingspulje], the Danish Colitis-Crohn Association, and the A.P. Moller Foundation; ClinicalTrials.gov number, NCT01817426; EudraCT number, 2012-002702-51.)

U2 - 10.1056/EVIDoa2200061

DO - 10.1056/EVIDoa2200061

M3 - Journal article

C2 - 38319804

SN - 2766-5526

VL - 1

SP - EVIDoa2200061

JO - NEJM Evidence

JF - NEJM Evidence

IS - 8

ER -

Discontinuation of Infliximab Therapy in Patients with Crohn’s Disease

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