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Patients with Crohn’s Disease Are More Likely to Remain on Biologics than Immunomodulators: A Meta-Analysis of Treatment Durability

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Abstract

Background and Aim

The comparative effectiveness of treatments for moderate-to-severe Crohn’s disease can be influenced by the likelihood of remaining on medication. We aimed to clarify this treatment durability by assessing subject discontinuations from clinical trials in the context of treatment efficacy.

Methods

We conducted a literature search for double-blind RCT of Crohn’s disease therapies recommended in international guidelines or with recent positive phase III trial results. Durability was defined through study discontinuation due to adverse events or disease exacerbation represented by number needed to discontinue (NND). Efficacy was defined as clinical remission represented by number needed to treat (NNT). The primary endpoint was NND/NNT, with a higher value representing more durable and effective treatment.

Results

Treatment with azathioprine/6-mercaptopurine (AZA/6MP) was associated with more discontinuations than with clinical remission (NND/NNT = 0.92) in maintenance trials. For induction, methotrexate was associated with similar rates of discontinuations and remission (NND/NNT = 1.4). In one maintenance trial, the remission rate for methotrexate was greater than the study discontinuation rate (NND/NNT = 23.3). In contrast, anti-TNF trials revealed greater durability among induction (no excess discontinuation) and maintenance (NND/NNT = 37.9) trials. Trials of anti-trafficking agents had fewer discontinuations in the drug treatment arms than placebo resulting in most favorable NND/NNT ratios.

Conclusions

For patients with Crohn’s disease, biologic therapies had higher durability than immunomodulators for induction and maintenance therapy. We also report the results of a novel NND/NNT ratio that should be validated in a prospective head-to-head placebo-controlled trial.

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Conflict of interest

Eric Shah and Kelly Chong have no conflicts of interest. Corey Siegel has served as a consultant and on the advisory board for Abbvie, Given Imaging, Jannsen, Prometheus, and Takeda, has delivered CME talks for Abbvie and Jannsen, and has received grant support from Abbvie, Janssen, Salix, UCB, and Warner Chilcott. Gil Melmed has served as a consultant and on the advisory board for Abbvie, Celgene, Given Imaging, Jannsen, and Luitpold and has conducted research on behalf of Pfizer.

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Authors and Affiliations

  1. Division of Gastroenterology, Department of Medicine, Cedars-Sinai Medical Center, 8730 Alden Dr. #203B, Los Angeles, CA, 90048, USA

    Eric D. Shah & Gil Y. Melmed

  2. Section of Gastroenterology, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA

    Corey A. Siegel

  3. Department of Veterans Affairs, Los Angeles, CA, USA

    Kelly Chong

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  1. Eric D. Shah
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  2. Corey A. Siegel
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  4. Gil Y. Melmed
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Correspondence to Gil Y. Melmed.

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Shah, E.D., Siegel, C.A., Chong, K. et al. Patients with Crohn’s Disease Are More Likely to Remain on Biologics than Immunomodulators: A Meta-Analysis of Treatment Durability. Dig Dis Sci 60, 2408–2418 (2015). https://doi.org/10.1007/s10620-015-3618-8

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