Issue 03

Clinical Question

Should adalimumab (ADA) be prescribed as monotherapy or combination therapy (i.e., with an immunomodulator) when treating Crohn’s disease (CD) or ulcerative colitis (UC)?

Editor’s Bottom Line

The body of evidence points toward ADA monotherapy being equally effective as ADA + immunomodulator combination therapy.

Editorial Note

The increased rate of mucosal healing in the ADA + immunomodulator combination therapy group should encourage clinicians to carefully consider subgroups that require combination therapy and to encourage further clinical studies.

References

Matsumoto T, Motoya S, Watanabe K, et al; DIAMOND study group. Adalimumab monotherapy and a combination with azathioprine for Crohn’s disease: a prospective, randomized trial. J Crohns Colitis. 2016 Nov;10(11):1259–66. https://www.ncbi.nlm.nih.gov/pubmed/27566367

Colombel JF, Jharap B, Sandborn WJ, et al. Effects of concomitant immunomodulators on the pharmacokinetics, efficacy and safety of adalimumab in patients with Crohn’s disease or ulcerative colitis who had failed conventional therapy. Aliment Pharmacol Ther. 2017 Jan;45(1):50–62. https://www.ncbi.nlm.nih.gov/pubmed/27883215

Synopsis

Matsumoto et al.
In this 52 week study, patients with moderate–severe CD and naïve to anti-TNFs and thiopurines were randomized to receive standard induction and remission therapy with either ADA monotherapy or ADA + azathioprine (AZA) combination therapy. Patients were started at 25–50 mg/d AZA which could be increased to a maximum of 100 mg/d between weeks 0–4. The primary end point was clinical remission at week 26, while secondary endpoints included mucosal healing at weeks 26 and 52. Of the 176 patients recruited, clinical remission rates at week 26 were not significantly different between the ADA and ADA+AZA groups (71.8% vs. 68.1%, P=0.63), although the ADA+AZA group had a higher rate of endoscopic improvement (84.2% vs. 63.8%, P=0.019). Withdrawal due to side effects were higher in the ADA+AZA group (16.5% vs.1.2%).

Colombel et al.
This was a retrospective post hoc analysis of six randomized, double-blind, placebo controlled trials (Classic-I, GAIN, Charm, Extend, Ultra 1 and Ultra 2) investigating ADA in CD or UC for induction, remission, and mucosal healing. The current analysis compared ADA mono vs. combination therapy (n=518) for ITT efficacy outcomes (defined as clinical remission) and adverse events. ADA mono and ADA plus immunomodulator therapy had a similar percentage of patients achieving clinical remission and mucosal healing, as well as adverse events.

Details

Matsumoto et al.
Study Design: Prospective, randomized open label trial
Funding: None
Allocation: n/a
Setting: Multiple centres, Japan
Level of Evidence: 2b (Oxford Levels of Evidence)

Colombel et al.
Study Design: Meta-analysis
Funding: AbbVie Inc. funded the original studies and the current summary
Allocation: n/a
Setting: Multiple
Level of Evidence: 1a (Oxford Levels of Evidence)

The summary and conclusion in this issue of E-mentoring in IBD pertains to the manuscript(s) being reviewed, and should be considered in the context of what is already known surrounding the topic and incorporated into practice as deemed appropriate by the individual learner.