Early combined immunosuppression for the management of Crohn's disease (REACT): A cluster randomised controlled trial

Reena Khanna; Brian Bressler; Barrett G. Levesque; Guangyong Zou; Larry W. Stitt; Gordon R. Greenberg; Remo Panaccione; Alain Bitton; Pierre Paré; Séverine Vermeire; Geert D'Haens; Donald Macintosh; William J. Sandborn; Allan Donner; Margaret K. Vandervoort; Joan C. Morris; Brian G. Feagan

doi:10.1016/S0140-6736(15)00068-9

Early combined immunosuppression for the management of Crohn's disease (REACT): A cluster randomised controlled trial

Reena Khanna, Brian Bressler, Barrett G. Levesque, Guangyong Zou, Larry W. Stitt, Gordon R. Greenberg, Remo Panaccione, Alain Bitton, Pierre Paré, Séverine Vermeire, Geert D'Haens, Donald Macintosh, William J. Sandborn, Allan Donner, Margaret K. Vandervoort, Joan C. Morris, Brian G. Feagan

Medicine

Research output: Contribution to journal › Article › peer-review

392 Citations (Scopus)

Abstract

Summary Background Conventional management of Crohn's disease features incremental use of therapies. However, early combined immunosuppression (ECI), with a TNF antagonist and antimetabolite might be a more effective strategy. We compared the efficacy of ECI with that of conventional management for treatment of Crohn's disease. Methods In this open-label cluster randomised controlled trial (Randomised Evaluation of an Algorithm for Crohn's Treatment, REACT), we included community gastroenterology practices from Belgium and Canada that were willing to be assigned to either of the study groups, participate in all aspects of the study, and provide data on up to 60 patients with Crohn's disease. These practices were randomly assigned (1:1) to either ECI or conventional management. The computer-generated randomisation was minimised by country and practice size. Up to 60 consecutive adult patients were assessed within practices. Patients who were aged 18 years or older; documented to have Crohn's disease; able to speak or understand English, French, or Dutch; able to access a telephone; and able to provide written informed consent were followed up for 2 years. The primary outcome was the proportion of patients in corticosteroid-free remission (Harvey-Bradshaw Index score ≤4) at 12 months at the practice level. This trial is registered with ClinicalTrials.gov, number NCT01030809. Findings This study took place between March 15, 2010, and Oct 1, 2013. Of the 60 practices screened, 41 were randomly assigned to either ECI (n=22) or conventional management (n=19). Two practices (one in each group) discontinued because of insufficient resources. 921 (85%) of the 1084 patients at ECI practices and 806 (90%) of 898 patients at conventional management practices completed 12 months follow-up and were included in an intention-to-treat analysis. The 12 month practice-level remission rates were similar at ECI and conventional management practices (66 [SD 14] and 61 [16 adjusted difference 25%, 95% CI -52% to 102%, p=05169). The 24 month patient-level composite rate of major adverse outcomes defined as occurrence of surgery, hospital admission, or serious disease-related complications was lower at ECI practices than at conventional management practices (277% and 351%, absolute difference [AD] 73%, hazard ratio [HR]: 073, 95% CI 062 to 086, p=00003). There were no differences in serious drug-related adverse events. Interpretation Although ECI was not more effective than conventional management for controlling Crohn's disease symptoms, the risk of major adverse outcomes was lower. The latter finding should be considered hypothesis-generating for future trials. ECI was not associated with an increased risk of serious drug-related adverse events or mortality. Funding AbbVie Pharmaceuticals.

Original language	English
Pages (from-to)	1825-1834
Number of pages	10
Journal	The Lancet
Volume	386
Issue number	10006
DOIs	https://doi.org/10.1016/S0140-6736(15)00068-9
Publication status	Published - Nov 7 2015

Bibliographical note

Funding Information:
RK has received personal and consulting fees for participation in AbbVie, Janssen, and Takeda Canada Inc Advisory Boards outside the submitted work. BB and PP have received personal fees from AbbVie and Janssen Inc outside the submitted work. BGL has received personal fees from AbbVie, Prometheus Labs Inc, Nestlé Health Sciences, Santarus, Takeda, Warner Chilcott, and UCB Pharma, outside the submitted work. LWS, AD, and MKV have received grants from AbbVie, during the conduct of the study. GRG has received personal fees from AbbVie, grants and personal fees from Janssen, grants from Millennium, and personal fees from Prometheus Lab Inc outside the submitted work. RP has received grants, personal fees, and non-financial support from AbbVie, outside the submitted work. SV has recieved grants and personal fees from AbbVie, MSD, Centocor, UCB Pharma, and personal fees from Takeda, Pfizer, Ferring, and Shire during the conduct of the study; also grants and personal fees from MSD, Abbvie, Centocor, Pfizer, Takeda, Ferring, UCB, and personal fees from Shire outside the submitted work. GDH has received grants and personal fees from AbbVie, during the conduct of the study; personal fees from AbbVie, Ablynx, ActoGeniX, AM Pharma, Boehringer Ingelheim GmbH, Centocor, ChemoCentryx, Cosmo Technologies, Elan Pharmaceuticals, Engene, Dr Falk Pharma, Ferring, Galapagos, Giuliani SpA, Given Imaging, GlaxoSmithKline, Jansen Biologics, Merck Sharp and Dohme Corp, Millennium Pharmceuticals Inc (now Takeda), Mitsubishi Tanabe Pharma, Neovacs, Novonordisk, Otsuka, PDL Biopharma, Pfizer, Receptos, Salix, Sandoz, Setpoint, Shire Pharmaceuticals, Schering-Plough, Sigma, Takeda, Tillotts Pharma, UCB Pharma, Versant, Vifor Pharma, Norgine, Tramedico; and grants from Abbott Laboratories/Abbvie, Janssen Biologics, Given Imaging, MSD, Dr Falk Pharma, Photopill, and Takeda, outside the submitted work. WJS has received personal fees from Robarts Clinical Trials; consulting fees from Abbott, ActoGeniX NV, AGI Therapeutics Inc, Alba Therapeutics Corp, Albireo, Alfa Wasserman, Amgen, AM-Pharma BV, Anaphore, Astellas, Athersys Inc, Atlantic Healthcare Ltd, Aptalis, BioBalance Corp, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Celek Pharmaceuticals, Cellerix SL, Cerimon Pharmaceuticals, ChemoCentryx, CoMentis, Cosmo Technologies, Coronado Biosciences, Cytokine Pharmasciences, Eagle Pharmaceuticals, EnGene Inc, Eli Lilly, Enteromedics, Exagen Diagnostics Inc, Ferring Pharmaceuticals, Flexio Therapeutics Inc, Funxional Therapeutics Ltd, Genzyme Corp, Gilead Sciences, Given Imaging, GSK, Human Genome Sciences, Ironwood Pharmaceuticals, KaloBios Pharmaceuticals, Lexicon Pharmaceuticals, Lycera Corp, Meda Pharmaceuticals, Merck Research Laboratories, Merck Serono, Millennium Pharmaceuticals, Nisshin Kyorin Pharmaceuticals, Novo Nordisk, NPS Pharmaceuticals, Optimer Pharmaceuticals, Orexigen Therapeutics Inc, PDL Biopharma, Pfizer, Procter and Gamble, Prometheus Laboratories, ProtAb Ltd, Purgenesis Technologies Inc, Relypsa Inc, Roche, Salient Pharmaceuticals, Salix Pharmaceuticals, Santarus, Schering-Plough, Shire Pharmaceuticals, Sigmoid Pharma Ltd, Sirtris Pharmaceuticals, SLA Pharma UK Ltd, Targacept, Teva Pharmaceuticals, Therakos, Tillotts Pharma, TxCell SA, UCB Pharma, Viamet Pharmaceuticals, Vascular Biogenics Ltd, Warner Chilcott UK Ltd and Wyeth; research grants from Abbott, Bristol Myers Squibb, Genentech, GSK, Janssen, Millennium Pharmaceuticals, Novartis, Pfizer, Procter and Gamble, Shire Pharmaceuticals and UCB Pharma; payments for lectures/speakers bureaux from Abbott, Bristol-Myers Squibb and Janssen; and holds stock or stock options in Enteromedics. JCM reports grants and non-financial support from AbbVie Corporation during the conduct of the study; and grants and non-financial support from AbbVie Corporation and grants from Janssen Inc outside the submitted work. BGF reports grants from AbbVie during the conduct of the study; grants and personal fees from AbbVie/Abbott, Amgen, Astra Zeneca, Bristol-Myers Squibb, Genentech/Roche, Janssen, Pfizer, Tillotts Pharma, and UCB, outside the submitted work personal fees from Actogenix and Albireo; personal fees from Avaxia Biologics, Axcan, Baxter Healthcare Corp, Boehringer-Ingelheim, Calypso Biotech, Celgene, Elan/Biogen, EnGene, Ferring, GiCare, Gilead, Given Imaging, GlaxoSmithKline, Ironwood, Kyowa Kakko Kirin Co Ltd, Lexicon, Lilly, Merck, Millennium, Nektar, Novo Nordisk, Prometheus Therapeutics, Receptos, Salix, Santarus, Shire, Sigmoid, Synergy, Takeda, Teva, Vertex, Warner-Chilcott, Wyeth, Zealand, and Zyngenia, outside the submitted work; and grants from Sanofi. The other authors declare no competing interests.

Publisher Copyright:
© 2015 Elsevier Ltd.

ASJC Scopus Subject Areas

General Medicine

PubMed: MeSH publication types

Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

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10.1016/S0140-6736(15)00068-9

Cite this

Khanna, R., Bressler, B., Levesque, B. G., Zou, G., Stitt, L. W., Greenberg, G. R., Panaccione, R., Bitton, A., Paré, P., Vermeire, S., D'Haens, G., Macintosh, D., Sandborn, W. J., Donner, A., Vandervoort, M. K., Morris, J. C., & Feagan, B. G. (2015). Early combined immunosuppression for the management of Crohn's disease (REACT): A cluster randomised controlled trial. The Lancet, 386(10006), 1825-1834. https://doi.org/10.1016/S0140-6736(15)00068-9

Khanna, R, Bressler, B, Levesque, BG, Zou, G, Stitt, LW, Greenberg, GR, Panaccione, R, Bitton, A, Paré, P, Vermeire, S, D'Haens, G, Macintosh, D, Sandborn, WJ, Donner, A, Vandervoort, MK, Morris, JC & Feagan, BG 2015, 'Early combined immunosuppression for the management of Crohn's disease (REACT): A cluster randomised controlled trial', The Lancet, vol. 386, no. 10006, pp. 1825-1834. https://doi.org/10.1016/S0140-6736(15)00068-9

@article{b33a65f9f0184393bf9a9dc5118a8226,

title = "Early combined immunosuppression for the management of Crohn's disease (REACT): A cluster randomised controlled trial",

abstract = "Summary Background Conventional management of Crohn's disease features incremental use of therapies. However, early combined immunosuppression (ECI), with a TNF antagonist and antimetabolite might be a more effective strategy. We compared the efficacy of ECI with that of conventional management for treatment of Crohn's disease. Methods In this open-label cluster randomised controlled trial (Randomised Evaluation of an Algorithm for Crohn's Treatment, REACT), we included community gastroenterology practices from Belgium and Canada that were willing to be assigned to either of the study groups, participate in all aspects of the study, and provide data on up to 60 patients with Crohn's disease. These practices were randomly assigned (1:1) to either ECI or conventional management. The computer-generated randomisation was minimised by country and practice size. Up to 60 consecutive adult patients were assessed within practices. Patients who were aged 18 years or older; documented to have Crohn's disease; able to speak or understand English, French, or Dutch; able to access a telephone; and able to provide written informed consent were followed up for 2 years. The primary outcome was the proportion of patients in corticosteroid-free remission (Harvey-Bradshaw Index score ≤4) at 12 months at the practice level. This trial is registered with ClinicalTrials.gov, number NCT01030809. Findings This study took place between March 15, 2010, and Oct 1, 2013. Of the 60 practices screened, 41 were randomly assigned to either ECI (n=22) or conventional management (n=19). Two practices (one in each group) discontinued because of insufficient resources. 921 (85%) of the 1084 patients at ECI practices and 806 (90%) of 898 patients at conventional management practices completed 12 months follow-up and were included in an intention-to-treat analysis. The 12 month practice-level remission rates were similar at ECI and conventional management practices (66 [SD 14] and 61 [16 adjusted difference 25%, 95% CI -52% to 102%, p=05169). The 24 month patient-level composite rate of major adverse outcomes defined as occurrence of surgery, hospital admission, or serious disease-related complications was lower at ECI practices than at conventional management practices (277% and 351%, absolute difference [AD] 73%, hazard ratio [HR]: 073, 95% CI 062 to 086, p=00003). There were no differences in serious drug-related adverse events. Interpretation Although ECI was not more effective than conventional management for controlling Crohn's disease symptoms, the risk of major adverse outcomes was lower. The latter finding should be considered hypothesis-generating for future trials. ECI was not associated with an increased risk of serious drug-related adverse events or mortality. Funding AbbVie Pharmaceuticals.",

author = "Reena Khanna and Brian Bressler and Levesque, {Barrett G.} and Guangyong Zou and Stitt, {Larry W.} and Greenberg, {Gordon R.} and Remo Panaccione and Alain Bitton and Pierre Par{\'e} and S{\'e}verine Vermeire and Geert D'Haens and Donald Macintosh and Sandborn, {William J.} and Allan Donner and Vandervoort, {Margaret K.} and Morris, {Joan C.} and Feagan, {Brian G.}",

note = "Funding Information: RK has received personal and consulting fees for participation in AbbVie, Janssen, and Takeda Canada Inc Advisory Boards outside the submitted work. BB and PP have received personal fees from AbbVie and Janssen Inc outside the submitted work. BGL has received personal fees from AbbVie, Prometheus Labs Inc, Nestl{\'e} Health Sciences, Santarus, Takeda, Warner Chilcott, and UCB Pharma, outside the submitted work. LWS, AD, and MKV have received grants from AbbVie, during the conduct of the study. GRG has received personal fees from AbbVie, grants and personal fees from Janssen, grants from Millennium, and personal fees from Prometheus Lab Inc outside the submitted work. RP has received grants, personal fees, and non-financial support from AbbVie, outside the submitted work. SV has recieved grants and personal fees from AbbVie, MSD, Centocor, UCB Pharma, and personal fees from Takeda, Pfizer, Ferring, and Shire during the conduct of the study; also grants and personal fees from MSD, Abbvie, Centocor, Pfizer, Takeda, Ferring, UCB, and personal fees from Shire outside the submitted work. GDH has received grants and personal fees from AbbVie, during the conduct of the study; personal fees from AbbVie, Ablynx, ActoGeniX, AM Pharma, Boehringer Ingelheim GmbH, Centocor, ChemoCentryx, Cosmo Technologies, Elan Pharmaceuticals, Engene, Dr Falk Pharma, Ferring, Galapagos, Giuliani SpA, Given Imaging, GlaxoSmithKline, Jansen Biologics, Merck Sharp and Dohme Corp, Millennium Pharmceuticals Inc (now Takeda), Mitsubishi Tanabe Pharma, Neovacs, Novonordisk, Otsuka, PDL Biopharma, Pfizer, Receptos, Salix, Sandoz, Setpoint, Shire Pharmaceuticals, Schering-Plough, Sigma, Takeda, Tillotts Pharma, UCB Pharma, Versant, Vifor Pharma, Norgine, Tramedico; and grants from Abbott Laboratories/Abbvie, Janssen Biologics, Given Imaging, MSD, Dr Falk Pharma, Photopill, and Takeda, outside the submitted work. WJS has received personal fees from Robarts Clinical Trials; consulting fees from Abbott, ActoGeniX NV, AGI Therapeutics Inc, Alba Therapeutics Corp, Albireo, Alfa Wasserman, Amgen, AM-Pharma BV, Anaphore, Astellas, Athersys Inc, Atlantic Healthcare Ltd, Aptalis, BioBalance Corp, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Celek Pharmaceuticals, Cellerix SL, Cerimon Pharmaceuticals, ChemoCentryx, CoMentis, Cosmo Technologies, Coronado Biosciences, Cytokine Pharmasciences, Eagle Pharmaceuticals, EnGene Inc, Eli Lilly, Enteromedics, Exagen Diagnostics Inc, Ferring Pharmaceuticals, Flexio Therapeutics Inc, Funxional Therapeutics Ltd, Genzyme Corp, Gilead Sciences, Given Imaging, GSK, Human Genome Sciences, Ironwood Pharmaceuticals, KaloBios Pharmaceuticals, Lexicon Pharmaceuticals, Lycera Corp, Meda Pharmaceuticals, Merck Research Laboratories, Merck Serono, Millennium Pharmaceuticals, Nisshin Kyorin Pharmaceuticals, Novo Nordisk, NPS Pharmaceuticals, Optimer Pharmaceuticals, Orexigen Therapeutics Inc, PDL Biopharma, Pfizer, Procter and Gamble, Prometheus Laboratories, ProtAb Ltd, Purgenesis Technologies Inc, Relypsa Inc, Roche, Salient Pharmaceuticals, Salix Pharmaceuticals, Santarus, Schering-Plough, Shire Pharmaceuticals, Sigmoid Pharma Ltd, Sirtris Pharmaceuticals, SLA Pharma UK Ltd, Targacept, Teva Pharmaceuticals, Therakos, Tillotts Pharma, TxCell SA, UCB Pharma, Viamet Pharmaceuticals, Vascular Biogenics Ltd, Warner Chilcott UK Ltd and Wyeth; research grants from Abbott, Bristol Myers Squibb, Genentech, GSK, Janssen, Millennium Pharmaceuticals, Novartis, Pfizer, Procter and Gamble, Shire Pharmaceuticals and UCB Pharma; payments for lectures/speakers bureaux from Abbott, Bristol-Myers Squibb and Janssen; and holds stock or stock options in Enteromedics. JCM reports grants and non-financial support from AbbVie Corporation during the conduct of the study; and grants and non-financial support from AbbVie Corporation and grants from Janssen Inc outside the submitted work. BGF reports grants from AbbVie during the conduct of the study; grants and personal fees from AbbVie/Abbott, Amgen, Astra Zeneca, Bristol-Myers Squibb, Genentech/Roche, Janssen, Pfizer, Tillotts Pharma, and UCB, outside the submitted work personal fees from Actogenix and Albireo; personal fees from Avaxia Biologics, Axcan, Baxter Healthcare Corp, Boehringer-Ingelheim, Calypso Biotech, Celgene, Elan/Biogen, EnGene, Ferring, GiCare, Gilead, Given Imaging, GlaxoSmithKline, Ironwood, Kyowa Kakko Kirin Co Ltd, Lexicon, Lilly, Merck, Millennium, Nektar, Novo Nordisk, Prometheus Therapeutics, Receptos, Salix, Santarus, Shire, Sigmoid, Synergy, Takeda, Teva, Vertex, Warner-Chilcott, Wyeth, Zealand, and Zyngenia, outside the submitted work; and grants from Sanofi. The other authors declare no competing interests. Publisher Copyright: {\textcopyright} 2015 Elsevier Ltd.",

year = "2015",

month = nov,

day = "7",

doi = "10.1016/S0140-6736(15)00068-9",

language = "English",

volume = "386",

pages = "1825--1834",

journal = "The Lancet",

issn = "0140-6736",

publisher = "Elsevier Limited",

number = "10006",

}

TY - JOUR

T1 - Early combined immunosuppression for the management of Crohn's disease (REACT)

T2 - A cluster randomised controlled trial

AU - Khanna, Reena

AU - Bressler, Brian

AU - Levesque, Barrett G.

AU - Zou, Guangyong

AU - Stitt, Larry W.

AU - Greenberg, Gordon R.

AU - Panaccione, Remo

AU - Bitton, Alain

AU - Paré, Pierre

AU - Vermeire, Séverine

AU - D'Haens, Geert

AU - Macintosh, Donald

AU - Sandborn, William J.

AU - Donner, Allan

AU - Vandervoort, Margaret K.

AU - Morris, Joan C.

AU - Feagan, Brian G.

N1 - Funding Information: RK has received personal and consulting fees for participation in AbbVie, Janssen, and Takeda Canada Inc Advisory Boards outside the submitted work. BB and PP have received personal fees from AbbVie and Janssen Inc outside the submitted work. BGL has received personal fees from AbbVie, Prometheus Labs Inc, Nestlé Health Sciences, Santarus, Takeda, Warner Chilcott, and UCB Pharma, outside the submitted work. LWS, AD, and MKV have received grants from AbbVie, during the conduct of the study. GRG has received personal fees from AbbVie, grants and personal fees from Janssen, grants from Millennium, and personal fees from Prometheus Lab Inc outside the submitted work. RP has received grants, personal fees, and non-financial support from AbbVie, outside the submitted work. SV has recieved grants and personal fees from AbbVie, MSD, Centocor, UCB Pharma, and personal fees from Takeda, Pfizer, Ferring, and Shire during the conduct of the study; also grants and personal fees from MSD, Abbvie, Centocor, Pfizer, Takeda, Ferring, UCB, and personal fees from Shire outside the submitted work. GDH has received grants and personal fees from AbbVie, during the conduct of the study; personal fees from AbbVie, Ablynx, ActoGeniX, AM Pharma, Boehringer Ingelheim GmbH, Centocor, ChemoCentryx, Cosmo Technologies, Elan Pharmaceuticals, Engene, Dr Falk Pharma, Ferring, Galapagos, Giuliani SpA, Given Imaging, GlaxoSmithKline, Jansen Biologics, Merck Sharp and Dohme Corp, Millennium Pharmceuticals Inc (now Takeda), Mitsubishi Tanabe Pharma, Neovacs, Novonordisk, Otsuka, PDL Biopharma, Pfizer, Receptos, Salix, Sandoz, Setpoint, Shire Pharmaceuticals, Schering-Plough, Sigma, Takeda, Tillotts Pharma, UCB Pharma, Versant, Vifor Pharma, Norgine, Tramedico; and grants from Abbott Laboratories/Abbvie, Janssen Biologics, Given Imaging, MSD, Dr Falk Pharma, Photopill, and Takeda, outside the submitted work. WJS has received personal fees from Robarts Clinical Trials; consulting fees from Abbott, ActoGeniX NV, AGI Therapeutics Inc, Alba Therapeutics Corp, Albireo, Alfa Wasserman, Amgen, AM-Pharma BV, Anaphore, Astellas, Athersys Inc, Atlantic Healthcare Ltd, Aptalis, BioBalance Corp, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Celek Pharmaceuticals, Cellerix SL, Cerimon Pharmaceuticals, ChemoCentryx, CoMentis, Cosmo Technologies, Coronado Biosciences, Cytokine Pharmasciences, Eagle Pharmaceuticals, EnGene Inc, Eli Lilly, Enteromedics, Exagen Diagnostics Inc, Ferring Pharmaceuticals, Flexio Therapeutics Inc, Funxional Therapeutics Ltd, Genzyme Corp, Gilead Sciences, Given Imaging, GSK, Human Genome Sciences, Ironwood Pharmaceuticals, KaloBios Pharmaceuticals, Lexicon Pharmaceuticals, Lycera Corp, Meda Pharmaceuticals, Merck Research Laboratories, Merck Serono, Millennium Pharmaceuticals, Nisshin Kyorin Pharmaceuticals, Novo Nordisk, NPS Pharmaceuticals, Optimer Pharmaceuticals, Orexigen Therapeutics Inc, PDL Biopharma, Pfizer, Procter and Gamble, Prometheus Laboratories, ProtAb Ltd, Purgenesis Technologies Inc, Relypsa Inc, Roche, Salient Pharmaceuticals, Salix Pharmaceuticals, Santarus, Schering-Plough, Shire Pharmaceuticals, Sigmoid Pharma Ltd, Sirtris Pharmaceuticals, SLA Pharma UK Ltd, Targacept, Teva Pharmaceuticals, Therakos, Tillotts Pharma, TxCell SA, UCB Pharma, Viamet Pharmaceuticals, Vascular Biogenics Ltd, Warner Chilcott UK Ltd and Wyeth; research grants from Abbott, Bristol Myers Squibb, Genentech, GSK, Janssen, Millennium Pharmaceuticals, Novartis, Pfizer, Procter and Gamble, Shire Pharmaceuticals and UCB Pharma; payments for lectures/speakers bureaux from Abbott, Bristol-Myers Squibb and Janssen; and holds stock or stock options in Enteromedics. JCM reports grants and non-financial support from AbbVie Corporation during the conduct of the study; and grants and non-financial support from AbbVie Corporation and grants from Janssen Inc outside the submitted work. BGF reports grants from AbbVie during the conduct of the study; grants and personal fees from AbbVie/Abbott, Amgen, Astra Zeneca, Bristol-Myers Squibb, Genentech/Roche, Janssen, Pfizer, Tillotts Pharma, and UCB, outside the submitted work personal fees from Actogenix and Albireo; personal fees from Avaxia Biologics, Axcan, Baxter Healthcare Corp, Boehringer-Ingelheim, Calypso Biotech, Celgene, Elan/Biogen, EnGene, Ferring, GiCare, Gilead, Given Imaging, GlaxoSmithKline, Ironwood, Kyowa Kakko Kirin Co Ltd, Lexicon, Lilly, Merck, Millennium, Nektar, Novo Nordisk, Prometheus Therapeutics, Receptos, Salix, Santarus, Shire, Sigmoid, Synergy, Takeda, Teva, Vertex, Warner-Chilcott, Wyeth, Zealand, and Zyngenia, outside the submitted work; and grants from Sanofi. The other authors declare no competing interests. Publisher Copyright: © 2015 Elsevier Ltd.

PY - 2015/11/7

Y1 - 2015/11/7

N2 - Summary Background Conventional management of Crohn's disease features incremental use of therapies. However, early combined immunosuppression (ECI), with a TNF antagonist and antimetabolite might be a more effective strategy. We compared the efficacy of ECI with that of conventional management for treatment of Crohn's disease. Methods In this open-label cluster randomised controlled trial (Randomised Evaluation of an Algorithm for Crohn's Treatment, REACT), we included community gastroenterology practices from Belgium and Canada that were willing to be assigned to either of the study groups, participate in all aspects of the study, and provide data on up to 60 patients with Crohn's disease. These practices were randomly assigned (1:1) to either ECI or conventional management. The computer-generated randomisation was minimised by country and practice size. Up to 60 consecutive adult patients were assessed within practices. Patients who were aged 18 years or older; documented to have Crohn's disease; able to speak or understand English, French, or Dutch; able to access a telephone; and able to provide written informed consent were followed up for 2 years. The primary outcome was the proportion of patients in corticosteroid-free remission (Harvey-Bradshaw Index score ≤4) at 12 months at the practice level. This trial is registered with ClinicalTrials.gov, number NCT01030809. Findings This study took place between March 15, 2010, and Oct 1, 2013. Of the 60 practices screened, 41 were randomly assigned to either ECI (n=22) or conventional management (n=19). Two practices (one in each group) discontinued because of insufficient resources. 921 (85%) of the 1084 patients at ECI practices and 806 (90%) of 898 patients at conventional management practices completed 12 months follow-up and were included in an intention-to-treat analysis. The 12 month practice-level remission rates were similar at ECI and conventional management practices (66 [SD 14] and 61 [16 adjusted difference 25%, 95% CI -52% to 102%, p=05169). The 24 month patient-level composite rate of major adverse outcomes defined as occurrence of surgery, hospital admission, or serious disease-related complications was lower at ECI practices than at conventional management practices (277% and 351%, absolute difference [AD] 73%, hazard ratio [HR]: 073, 95% CI 062 to 086, p=00003). There were no differences in serious drug-related adverse events. Interpretation Although ECI was not more effective than conventional management for controlling Crohn's disease symptoms, the risk of major adverse outcomes was lower. The latter finding should be considered hypothesis-generating for future trials. ECI was not associated with an increased risk of serious drug-related adverse events or mortality. Funding AbbVie Pharmaceuticals.

AB - Summary Background Conventional management of Crohn's disease features incremental use of therapies. However, early combined immunosuppression (ECI), with a TNF antagonist and antimetabolite might be a more effective strategy. We compared the efficacy of ECI with that of conventional management for treatment of Crohn's disease. Methods In this open-label cluster randomised controlled trial (Randomised Evaluation of an Algorithm for Crohn's Treatment, REACT), we included community gastroenterology practices from Belgium and Canada that were willing to be assigned to either of the study groups, participate in all aspects of the study, and provide data on up to 60 patients with Crohn's disease. These practices were randomly assigned (1:1) to either ECI or conventional management. The computer-generated randomisation was minimised by country and practice size. Up to 60 consecutive adult patients were assessed within practices. Patients who were aged 18 years or older; documented to have Crohn's disease; able to speak or understand English, French, or Dutch; able to access a telephone; and able to provide written informed consent were followed up for 2 years. The primary outcome was the proportion of patients in corticosteroid-free remission (Harvey-Bradshaw Index score ≤4) at 12 months at the practice level. This trial is registered with ClinicalTrials.gov, number NCT01030809. Findings This study took place between March 15, 2010, and Oct 1, 2013. Of the 60 practices screened, 41 were randomly assigned to either ECI (n=22) or conventional management (n=19). Two practices (one in each group) discontinued because of insufficient resources. 921 (85%) of the 1084 patients at ECI practices and 806 (90%) of 898 patients at conventional management practices completed 12 months follow-up and were included in an intention-to-treat analysis. The 12 month practice-level remission rates were similar at ECI and conventional management practices (66 [SD 14] and 61 [16 adjusted difference 25%, 95% CI -52% to 102%, p=05169). The 24 month patient-level composite rate of major adverse outcomes defined as occurrence of surgery, hospital admission, or serious disease-related complications was lower at ECI practices than at conventional management practices (277% and 351%, absolute difference [AD] 73%, hazard ratio [HR]: 073, 95% CI 062 to 086, p=00003). There were no differences in serious drug-related adverse events. Interpretation Although ECI was not more effective than conventional management for controlling Crohn's disease symptoms, the risk of major adverse outcomes was lower. The latter finding should be considered hypothesis-generating for future trials. ECI was not associated with an increased risk of serious drug-related adverse events or mortality. Funding AbbVie Pharmaceuticals.

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UR - http://www.scopus.com/inward/citedby.url?scp=84947036399&partnerID=8YFLogxK

U2 - 10.1016/S0140-6736(15)00068-9

DO - 10.1016/S0140-6736(15)00068-9

M3 - Article

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AN - SCOPUS:84947036399

SN - 0140-6736

VL - 386

SP - 1825

EP - 1834

JO - The Lancet

JF - The Lancet

IS - 10006

ER -

Early combined immunosuppression for the management of Crohn's disease (REACT): A cluster randomised controlled trial

Abstract

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PubMed: MeSH publication types

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