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Isotretinoin Exposure and Risk of Inflammatory Bowel Disease: A Systematic Review with Meta-Analysis and Trial Sequential Analysis

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A Letter to the Editor to this article was published on 27 June 2023

A Letter to the Editor to this article was published on 27 June 2023

Abstract

Background

Cases of inflammatory bowel disease (IBD) following isotretinoin use have been reported previously, but whether isotretinoin exposure is associated with IBD has been unclear.

Objective

The aim was to evaluate whether isotretinoin use is associated with IBD.

Methods

We performed a systematic review and searched MEDLINE, Embase, and CENTRAL databases from inception to January 27, 2023 for relevant case–control and cohort studies. Our outcome was the pooled odds ratio (OR) for IBD and its two subtypes (Crohn disease and ulcerative colitis) in relation to isotretinoin exposure. We conducted a random-effects model meta-analysis and a sensitivity analysis by excluding low-quality studies. A subgroup analysis was undertaken by including studies considering antibiotic use. A trial sequential analysis (TSA) was performed to test the robustness of the conclusiveness of our results.

Results

We included eight studies (four case–control and four cohort studies) with a total of 2,522,422 participants. The meta-analysis found no increased odds for IBD among patients receiving isotretinoin (OR 1.01; 95% confidence interval [CI] 0.80–1.27). Nor did the meta-analysis find increased odds for either Crohn disease (OR 0.87; 95% CI 0.65–1.15) or ulcerative colitis (OR 1.27; 95% CI 0.94–1.73) associated with isotretinoin exposure. The sensitivity and subgroup analyses produced similar results. In TSA, the Z-curve reached the futility boundaries when using relative risk reduction thresholds ranging from 5% to 15%.

Conclusion

This meta-analysis with TSA found no evidence of an association of isotretinoin use with IBD. Isotretinoin should not be withheld because of unnecessary concerns for the development of IBD.

PROSPERO registration no

CRD42022298886.

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Authors and Affiliations

  1. Department of Pharmacy, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan

    Chia-Ling Yu & Li-Huei Chiang

  2. Department of Medical Education, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan

    Po-Yi Chou

  3. Department of Psychiatry, Beitou Branch, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan

    Chih-Sung Liang

  4. Department of Applied Cosmetology, Lee-Ming Institute of Technology, New Taipei, Taiwan

    Tzu-Yu Wang

  5. Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan

    Yu-Kang Tu

  6. Department of Dermatology, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan

    Ching-Chi Chi

  7. School of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan

    Ching-Chi Chi

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  1. Chia-Ling Yu
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Correspondence to Ching-Chi Chi.

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Conflict of interest

Ms. Yu, Dr. Chou, Dr. Liang, Ms. Chiang, Dr. Wang, Prof. Tu, and Prof. Chi have no conflicts of interest directly relevant to the content of this article.

Author contributions

Ms. Yu and Prof. Chi have full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Prof. Chi. Acquisition, analysis, or interpretation of data: Ms. Yu, Dr. Chou, Dr. Liang, Prof. Tu, and Prof. Chi. Drafting of the manuscript: Ms. Yu, Dr. Chou, and Dr. Liang. Critical revision of the manuscript for important intellectual content: Ms. Chiang, Dr. Wang, Prof. Tu, and Prof. Chi. Statistical analysis: Ms. Yu, Dr. Liang, and Prof. Tu. Administrative, technical, or material support: Prof. Chi. Study supervision: Prof. Chi.

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Data availability statement

The data that support the findings of this study are available within the material of this article and the supplementary material.

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Yu, CL., Chou, PY., Liang, CS. et al. Isotretinoin Exposure and Risk of Inflammatory Bowel Disease: A Systematic Review with Meta-Analysis and Trial Sequential Analysis. Am J Clin Dermatol 24, 721–730 (2023). https://doi.org/10.1007/s40257-023-00765-9

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