Beyond the Gut: A Systematic Review and Meta-analysis of Advanced Therapies for Inflammatory Bowel Disease-associated Extraintestinal Manifestations

Ágnes Eszter Tímár; Andrea Párniczky; Kinga Anna Budai; Márk Viktor Hernádfői; Emese Kasznár; Péter Varga; Péter Hegyi; Szilárd Váncsa; Réka Tóth; Dániel Sándor Veres; Miklós Garami; Katalin Eszter Müller

doi:10.1093/ecco-jcc/jjae002

Beyond the Gut: A Systematic Review and Meta-analysis of Advanced Therapies for Inflammatory Bowel Disease-associated Extraintestinal Manifestations

J Crohns Colitis. 2024 Jan 8:jjae002. doi: 10.1093/ecco-jcc/jjae002. Online ahead of print.

Authors

Ágnes Eszter Tímár^{1

2}, Andrea Párniczky^{1

2}, Kinga Anna Budai^{2

3}, Márk Viktor Hernádfői^{2

4}, Emese Kasznár², Péter Varga^{2

5}, Péter Hegyi^{2

6

7}, Szilárd Váncsa^{2

6

7}, Réka Tóth², Dániel Sándor Veres^{2

8}, Miklós Garami^{2

9}, Katalin Eszter Müller^{1

2

10}

Affiliations

¹ Heim Pál National Pediatric Institute, Budapest, Hungary.
² Centre for Translational Medicine, Semmelweis University, Budapest, Hungary.
³ University Pharmacy Department of Pharmacy Administration, Semmelweis University, Budapest, Hungary.
⁴ Bethesda Children's Hospital, Budapest, Hungary.
⁵ Department of Obstetrics and Gynecology, Semmelweis University, Budapest, Hungary.
⁶ Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary.
⁷ Institute of Pancreatic Diseases, Semmelweis University, Budapest, Hungary.
⁸ Department of Biophysics and Radiation Biology, Semmelweis University, Budapest, Hungary.
⁹ Pediatric Center, Semmelweis University, Budapest, Hungary.
¹⁰ Department of Family Care Methodology, Faculty of Health Sciences, Semmelweis University, Budapest, Hungary.

PMID: 38189533
DOI: 10.1093/ecco-jcc/jjae002

Abstract

Background and aims: Extraintestinal manifestations are frequent in patients with inflammatory bowel disease and have a negative impact on quality of life. Currently, however, there is no evidence available to determine which drug should be recommended for these patients beyond anti-TNF treatment. We aimed to analyse the frequency of new extraintestinal manifestations and the behaviour of pre-existing extraintestinal manifestations during advanced therapy.

Methods: We conducted a systematic search on November 15th, 2022, and enrolled randomised controlled trials, cohorts and case series reporting the occurrence and behaviour of extraintestinal manifestations in patients with inflammatory bowel disease receiving advanced therapy (non-TNF inhibitor biologicals and JAK inhibitors). Proportions of new, recurring, worsening, and improving extraintestinal manifestations were calculated with 95% confidence intervals (CIs). The risk of bias was assessed with QUIPS tool.

Results: Altogether, 61 studies comprising 13,806 patients reported eligible data on extraintestinal manifestations. The overall proportion of new extraintestinal manifestations was 8% (95%CI, 6% to 12%) during advanced therapy. There was no significant difference between the frequency of new extraintestinal manifestations during vedolizumab and ustekinumab therapy (11%, 95%CI, 8% to 15% versus 6%, 95%CI, 3% to 11%, p=0.166). The improvement of pre-existing manifestations was comparable between vedolizumab and ustekinumab-treated patients, except for joint involvement (42%, 95%CI, 32% to53% versus 54%, 95%CI, 42% to65%, p=0.029).

Conclusion: The proportion of new extraintestinal manifestations was low during advanced therapy. Furthermore, the improvement of pre-existing manifestations was comparable between advanced therapies, except for pre-existing joint manifestations.

Keywords: biological products; extraintestinal manifestations; inflammatory bowel diseases.