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Tofacitinib Appears Well Tolerated and Effective for the Treatment of Patients with Refractory Crohn’s Disease

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An Editorial to this article was published on 14 March 2022

Abstract

Background

Active Crohn’s disease increases the risk of strictures, fistulas, and abscesses. Less than 30% of patients with Crohn’s disease achieve endoscopic remission on any therapy. Tofacitinib may be a therapeutic option for patients with refractory Crohn’s disease.

Aims

We aimed to evaluate the safety and effectiveness of off-label tofacitinib for refractory Crohn’s disease.

Methods

We retrospectively assessed adverse events and clinical/endoscopic response after therapy.

Results

Forty-four patients were included in the safety analysis and 35 were included in the clinical and/or endoscopic assessments. The mean age was 41.8 years and the mean disease duration was 17.4 years. All patients had prior biologic exposure. Adverse events were reported in 52.3% of patients; 13.6% had ≥ 1 serious adverse event after a median 54.6 weeks of treatment. Seventy percent achieved clinical response after a mean 29.4 (SD 15.1) weeks, and 33.3% achieved clinical remission after a mean 33.4 (SD 17.6) weeks of therapy. Endoscopic improvement occurred in 25.0%, endoscopic remission in 12.5%, and endoscopic healing in 4.2% of patients after a mean 52.0 (SD 15.0) weeks of therapy. The mean Simple Endoscopic Score in Crohn’s disease significantly improved from 23.1 ± 3.7 to 18.0 ± 13.7 after treatment (P = .02).

Conclusions

In the short term, tofacitinib appears well tolerated. The most common adverse event was minor infection. One serious infection and one colorectal cancer occurred. While half of patients reported adverse events, this likely reflects the severe refractory disease in this population and no new safety events were observed. Tofacitinib achieved clinical and endoscopic improvement in some patients with refractory Crohn’s disease. Further research is needed to understand the long-term safety and efficacy of tofacitinib in Crohn’s disease.

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Funding

This study did not receive specific funding.

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Authors and Affiliations

  1. Division of Gastroenterology, University of Washington, 1959 NE Pacific Street, Seattle, WA, 98195, USA

    Scott David Lee, Anand Singla, Jason Harper, Mitra Barahimi, Jeffrey Jacobs, Kendra J. Kamp & Kindra Dawn Clark-Snustad

Authors
  1. Scott David Lee
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  2. Anand Singla
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  3. Jason Harper
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  4. Mitra Barahimi
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  5. Jeffrey Jacobs
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  6. Kendra J. Kamp
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  7. Kindra Dawn Clark-Snustad
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by SL, KC-S, AS, and KK. The first draft of the manuscript was written by SL and KC-S and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Scott David Lee.

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Conflict of interest

Scott Lee receives grant and research support from the following: AbbVie Pharmaceuticals, Janssen Pharmaceuticals, Inc., Takeda Pharmaceuticals, Inc., Bristol Myers Squibb Pharmaceuticals, Inc., Pfizer Pharmaceuticals, Inc., Atlantic Pharmaceuticals, Ltd., Gilead Sciences, Inc., Tetherex Pharmaceuticals, Arena Pharmaceuticals, Shield Therapeutics PLC and is a consultant for UCB Pharma, Cornerstones, Janssen Pharmaceuticals, Inc., Takeda Pharmaceuticals, Inc., and Eli Lilly Company. Kindra Clark-Snustad has been a consultant for Pfizer Pharmaceuticals, Inc., Takeda Pharmaceuticals, Inc., AbbVie Pharmaceuticals, and Bristol Myers Squibb Pharmaceuticals, Inc. Kendra J. Kamp is supported, in part, by the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases Program, at the University of Washington (Grant Nr. T32DK007742). For the remaining authors no conflicts of interest were declared.

Ethical approval

Declarations: All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study was approved by the University of Washington Human Subjects Division.

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An editorial commenting on this article is available at https://doi.org/10.1007/s10620-022-07448-1.

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Lee, S.D., Singla, A., Harper, J. et al. Tofacitinib Appears Well Tolerated and Effective for the Treatment of Patients with Refractory Crohn’s Disease. Dig Dis Sci 67, 4043–4048 (2022). https://doi.org/10.1007/s10620-022-07444-5

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  • DOI: https://doi.org/10.1007/s10620-022-07444-5

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