Canadian Association of Gastroenterology Clinical Practice Guideline for the Management of Luminal Crohn's Disease

Abstract

Background & aims: Crohn's disease (CD) is a lifelong illness with substantial morbidity, although new therapies and treatment paradigms have been developed. We provide guidance for treatment of ambulatory patients with mild to severe active luminal CD.

Methods: We performed a systematic review to identify published studies of the management of CD. The quality of evidence and strength of recommendations were rated according to the Grading of Recommendation Assessment, Development and Evaluation (GRADE) approach. Statements were developed through an iterative online platform and then finalized and voted on by a group of specialists.

Results: The consensus includes 41 statements focused on 6 main drug classes: antibiotics, 5-aminosalicylate, corticosteroids, immunosuppressants, biologic therapies, and other therapies. The group suggested against the use of antibiotics or 5-aminosalicylate as induction or maintenance therapies. Corticosteroid therapies (including budesonide) can be used as induction, but not maintenance therapies. Among immunosuppressants, thiopurines should not be used for induction, but can be used for maintenance therapy for selected low-risk patients. Parenteral methotrexate was proposed for induction and maintenance therapy in patients with corticosteroid-dependent CD. Biologic agents, including tumor necrosis factor antagonists, vedolizumab, and ustekinumab, were recommended for patients failed by conventional induction therapies and as maintenance therapy. The consensus group was unable to clearly define the role of concomitant immunosuppressant therapies in initiation of treatment with a biologic agent.

Conclusions: Optimal management of CD requires careful patient assessment, acknowledgement of patient preferences, evidence-based use of existing therapies, and thorough assessment to define treatment success.

Keywords: 5-ASA; Guidance; Mucosal Healing; TNF.

Figure 1.

Consensus guided algorithm for management of mild to moderate active CD. *If patient has multiple risk factors for poor prognosis, consider moderate to severe algorithm. ^†Sulfasalazine may be used in mild colonic disease (refer to text). ^§May consider thiopurine maintenance therapy. CD, Crohn’s disease.

Figure 2.

Consensus guided algorithm for management of moderate to severe active CD. *Initiation of biologic therapy may be an alternative pathway to thiopurines. Despite the fact that certolizumab is FDA approved and used in the United States, it is not licensed for the treatment of CD in Canada or Europe and therefore was not included in this CPG. AZA, azathioprine; IM, intramuscular; MTX, methotrexate; SC, subcutaneous; TNF, tumor necrosis factor.

Figure 3.

Forest plot of randomized controlled trials of anti-TNF therapies versus placebo in inducing remission in active luminal CD. Reprinted by permission from Springer Nature, American Journal of Gastroenterology. Efficacy of biological therapies in inflammatory bowel disease: systematic review and meta-analysis. Ford AC, Sandborn WJ, Khan KJ, et al. ©2011. Reference. Anti-TNFα, anti-tumor necrosis factor-α; CD, Crohn’s disease; CI, confidence interval; M-H, Mantel-Haenszel.

Figure 4.

Forest plot of randomized controlled trials of anti-TNF therapies vs placebo in preventing relapse in quiescent CD. Reprinted by permission from Springer Nature, American Journal of Gastroenterology. Efficacy of biological therapies in inflammatory bowel disease: systematic review and meta-analysis. Ford AC, Sandborn WJ, Khan KJ, et al. ©2011. Reference. Anti-TNFα, anti-tumor necrosis factor-α; CD, Crohn’s disease; CI, confidence interval; M-H, Mantel-Haenszel.

Figure 5.

Forest plot of randomized controlled trials of vedolizumab in inducing remission in active luminal CD, stratified on basis of prior anti-TNF exposure. Chandar AK, Singh S, Murad MH, et al. Efficacy and safety of natalizumab and vedolizumab for the management of Crohn’s disease: a systematic review and meta-analysis. Inflamm Bowel Dis 2015;21:1695–708, by permission of Oxford University Press. Reference. Anti-TNF, anti-tumor necrosis factor; CD, Crohn’s disease; CI, confidence interval; M-H, Mantel-Haenszel; VEDO, vedolizumab.

Figure 6.

Forest plot of randomized controlled trials of ustekinumab in inducing remission in active luminal CD. Meta-analysis conducted for the consensus. Note the placebo groups in the UNITI trials have been split to avoid double-counting. CD, Crohn’s disease; CI, confidence interval; M-H, Mantel-Haenszel.