Effect of tight control management on Crohn's disease (CALM): a multicentre, randomised, controlled phase 3 trial

J.-F. Colombel, R. Panaccione, P. Bossuyt, M. Lukas, F. Baert, T. Vaňásek, A. Danalioglu, G. Novacek, A. Armuzzi, X. Hébuterne, S. Travis, S. Danese, W. Reinisch, W.J. Sandborn, P. Rutgeerts, D. Hommes, S. Schreiber, E. Neimark, B. Huang, Q. ZhouP. Mendez, J. Petersson, K. Wallace, A.M. Robinson, R.B. Thakkar, G. D'Haens

Research output: Contribution to journalArticle

Abstract

Background Biomarkers of intestinal inflammation, such as faecal calprotectin and C-reactive protein, have been recommended for monitoring patients with Crohn's disease, but whether their use in treatment decisions improves outcomes is unknown. We aimed to compare endoscopic and clinical outcomes in patients with moderate to severe Crohn's disease who were managed with a tight control algorithm, using clinical symptoms and biomarkers, versus patients managed with a clinical management algorithm. Methods CALM was an open-label, randomised, controlled phase 3 study, done in 22 countries at 74 hospitals and outpatient centres, which evaluated adult patients (aged 18–75 years) with active endoscopic Crohn's disease (Crohn's Disease Endoscopic Index of Severity [CDEIS] >6; sum of CDEIS subscores of >6 in one or more segments with ulcers), a Crohn's Disease Activity Index (CDAI) of 150–450 depending on dose of prednisone at baseline, and no previous use of immunomodulators or biologics. Patients were randomly assigned at a 1:1 ratio to tight control or clinical management groups, stratified by smoking status (yes or no), weight (2 years) after 8 weeks of prednisone induction therapy, or earlier if they had active disease. In both groups, treatment was escalated in a stepwise manner, from no treatment, to adalimumab induction followed by adalimumab every other week, adalimumab every week, and lastly to both weekly adalimumab and daily azathioprine. This escalation was based on meeting treatment failure criteria, which differed between groups (tight control group before and after random assignment: faecal calprotectin ≥250 μg/g, C-reactive protein ≥5mg/L, CDAI ≥150, or prednisone use in the previous week; clinical management group before random assignment: CDAI decrease of 200; clinical management group after random assignment: CDAI decrease of
Original languageEnglish
Pages (from-to)2779-2789
Number of pages11
JournalThe Lancet
Volume390
Issue number10114
DOIs
Publication statusPublished - Dec 23 2018

Fingerprint

Crohn Disease
Prednisone
Leukocyte L1 Antigen Complex
C-Reactive Protein
Biomarkers
Azathioprine
Immunologic Factors
Physiologic Monitoring
Therapeutics
Biological Products
Treatment Failure
Ulcer
Outpatients
Smoking
Inflammation
Weights and Measures
Control Groups
Adalimumab

Keywords

  • adalimumab
  • azathioprine
  • biological marker
  • C reactive protein
  • calgranulin
  • prednisone
  • antirheumatic agent
  • glucocorticoid, adult
  • aged
  • Article
  • attributable risk
  • body weight
  • clinical outcome
  • comparative study
  • controlled study
  • corticosteroid therapy
  • Crohn disease
  • Crohn Disease Activity Index
  • disease duration
  • disease severity
  • drug dose reduction
  • drug efficacy
  • drug safety
  • female
  • human
  • ileocolonoscopy
  • immunomodulation
  • intention to treat analysis
  • laboratory test
  • major clinical study
  • male
  • Mantel Haenszel test
  • multicenter study
  • open study
  • outcome assessment
  • outpatient
  • patient monitoring
  • patient safety
  • phase 3 clinical trial
  • priority journal
  • randomized controlled trial
  • remission
  • screening test
  • smoking
  • thorax radiography
  • treatment duration
  • treatment failure
  • adolescent
  • clinical trial
  • combination drug therapy
  • disease management
  • immunology
  • middle aged
  • severity of illness index
  • treatment outcome
  • young adult, Adalimumab
  • Adolescent
  • Adult
  • Aged
  • Antirheumatic Agents
  • Azathioprine
  • C-Reactive Protein
  • Crohn Disease
  • Disease Management
  • Drug Therapy, Combination
  • Female
  • Glucocorticoids
  • Humans
  • Male
  • Middle Aged
  • Prednisone
  • Remission Induction
  • Severity of Illness Index
  • Treatment Outcome
  • Young Adult

Cite this

Colombel, J-F., Panaccione, R., Bossuyt, P., Lukas, M., Baert, F., Vaňásek, T., ... D'Haens, G. (2018). Effect of tight control management on Crohn's disease (CALM): a multicentre, randomised, controlled phase 3 trial. The Lancet, 390(10114), 2779-2789. https://doi.org/10.1016/S0140-6736(17)32641-7

Effect of tight control management on Crohn's disease (CALM): a multicentre, randomised, controlled phase 3 trial. / Colombel, J.-F.; Panaccione, R.; Bossuyt, P.; Lukas, M.; Baert, F.; Vaňásek, T.; Danalioglu, A.; Novacek, G.; Armuzzi, A.; Hébuterne, X.; Travis, S.; Danese, S.; Reinisch, W.; Sandborn, W.J.; Rutgeerts, P.; Hommes, D.; Schreiber, S.; Neimark, E.; Huang, B.; Zhou, Q.; Mendez, P.; Petersson, J.; Wallace, K.; Robinson, A.M.; Thakkar, R.B.; D'Haens, G.

In: The Lancet, Vol. 390, No. 10114, 23.12.2018, p. 2779-2789.

Research output: Contribution to journalArticle

Colombel, J-F, Panaccione, R, Bossuyt, P, Lukas, M, Baert, F, Vaňásek, T, Danalioglu, A, Novacek, G, Armuzzi, A, Hébuterne, X, Travis, S, Danese, S, Reinisch, W, Sandborn, WJ, Rutgeerts, P, Hommes, D, Schreiber, S, Neimark, E, Huang, B, Zhou, Q, Mendez, P, Petersson, J, Wallace, K, Robinson, AM, Thakkar, RB & D'Haens, G 2018, 'Effect of tight control management on Crohn's disease (CALM): a multicentre, randomised, controlled phase 3 trial', The Lancet, vol. 390, no. 10114, pp. 2779-2789. https://doi.org/10.1016/S0140-6736(17)32641-7
Colombel J-F, Panaccione R, Bossuyt P, Lukas M, Baert F, Vaňásek T et al. Effect of tight control management on Crohn's disease (CALM): a multicentre, randomised, controlled phase 3 trial. The Lancet. 2018 Dec 23;390(10114):2779-2789. https://doi.org/10.1016/S0140-6736(17)32641-7
Colombel, J.-F. ; Panaccione, R. ; Bossuyt, P. ; Lukas, M. ; Baert, F. ; Vaňásek, T. ; Danalioglu, A. ; Novacek, G. ; Armuzzi, A. ; Hébuterne, X. ; Travis, S. ; Danese, S. ; Reinisch, W. ; Sandborn, W.J. ; Rutgeerts, P. ; Hommes, D. ; Schreiber, S. ; Neimark, E. ; Huang, B. ; Zhou, Q. ; Mendez, P. ; Petersson, J. ; Wallace, K. ; Robinson, A.M. ; Thakkar, R.B. ; D'Haens, G. / Effect of tight control management on Crohn's disease (CALM): a multicentre, randomised, controlled phase 3 trial. In: The Lancet. 2018 ; Vol. 390, No. 10114. pp. 2779-2789.
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AU - Colombel, J.-F.

AU - Panaccione, R.

AU - Bossuyt, P.

AU - Lukas, M.

AU - Baert, F.

AU - Vaňásek, T.

AU - Danalioglu, A.

AU - Novacek, G.

AU - Armuzzi, A.

AU - Hébuterne, X.

AU - Travis, S.

AU - Danese, S.

AU - Reinisch, W.

AU - Sandborn, W.J.

AU - Rutgeerts, P.

AU - Hommes, D.

AU - Schreiber, S.

AU - Neimark, E.

AU - Huang, B.

AU - Zhou, Q.

AU - Mendez, P.

AU - Petersson, J.

AU - Wallace, K.

AU - Robinson, A.M.

AU - Thakkar, R.B.

AU - D'Haens, G.

N1 - cited By 57

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Y1 - 2018/12/23

N2 - Background Biomarkers of intestinal inflammation, such as faecal calprotectin and C-reactive protein, have been recommended for monitoring patients with Crohn's disease, but whether their use in treatment decisions improves outcomes is unknown. We aimed to compare endoscopic and clinical outcomes in patients with moderate to severe Crohn's disease who were managed with a tight control algorithm, using clinical symptoms and biomarkers, versus patients managed with a clinical management algorithm. Methods CALM was an open-label, randomised, controlled phase 3 study, done in 22 countries at 74 hospitals and outpatient centres, which evaluated adult patients (aged 18–75 years) with active endoscopic Crohn's disease (Crohn's Disease Endoscopic Index of Severity [CDEIS] >6; sum of CDEIS subscores of >6 in one or more segments with ulcers), a Crohn's Disease Activity Index (CDAI) of 150–450 depending on dose of prednisone at baseline, and no previous use of immunomodulators or biologics. Patients were randomly assigned at a 1:1 ratio to tight control or clinical management groups, stratified by smoking status (yes or no), weight (2 years) after 8 weeks of prednisone induction therapy, or earlier if they had active disease. In both groups, treatment was escalated in a stepwise manner, from no treatment, to adalimumab induction followed by adalimumab every other week, adalimumab every week, and lastly to both weekly adalimumab and daily azathioprine. This escalation was based on meeting treatment failure criteria, which differed between groups (tight control group before and after random assignment: faecal calprotectin ≥250 μg/g, C-reactive protein ≥5mg/L, CDAI ≥150, or prednisone use in the previous week; clinical management group before random assignment: CDAI decrease of 200; clinical management group after random assignment: CDAI decrease of

AB - Background Biomarkers of intestinal inflammation, such as faecal calprotectin and C-reactive protein, have been recommended for monitoring patients with Crohn's disease, but whether their use in treatment decisions improves outcomes is unknown. We aimed to compare endoscopic and clinical outcomes in patients with moderate to severe Crohn's disease who were managed with a tight control algorithm, using clinical symptoms and biomarkers, versus patients managed with a clinical management algorithm. Methods CALM was an open-label, randomised, controlled phase 3 study, done in 22 countries at 74 hospitals and outpatient centres, which evaluated adult patients (aged 18–75 years) with active endoscopic Crohn's disease (Crohn's Disease Endoscopic Index of Severity [CDEIS] >6; sum of CDEIS subscores of >6 in one or more segments with ulcers), a Crohn's Disease Activity Index (CDAI) of 150–450 depending on dose of prednisone at baseline, and no previous use of immunomodulators or biologics. Patients were randomly assigned at a 1:1 ratio to tight control or clinical management groups, stratified by smoking status (yes or no), weight (2 years) after 8 weeks of prednisone induction therapy, or earlier if they had active disease. In both groups, treatment was escalated in a stepwise manner, from no treatment, to adalimumab induction followed by adalimumab every other week, adalimumab every week, and lastly to both weekly adalimumab and daily azathioprine. This escalation was based on meeting treatment failure criteria, which differed between groups (tight control group before and after random assignment: faecal calprotectin ≥250 μg/g, C-reactive protein ≥5mg/L, CDAI ≥150, or prednisone use in the previous week; clinical management group before random assignment: CDAI decrease of 200; clinical management group after random assignment: CDAI decrease of

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KW - Article

KW - attributable risk

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KW - clinical outcome

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