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. 2023 Feb 1;76(2):174-182.
doi: 10.1097/MPG.0000000000003656. Epub 2022 Nov 18.

Development of Inflammatory Bowel Disease in Children With Juvenile Idiopathic Arthritis Treated With Biologics

Ilse J Broekaert  1 , Ariane Klein  1   2 , Daniel Windschall  3   4 , Betina Rogalski  5 , Frank Weller-Heinemann  6 , Prasad Oommen  7 , Michael Küster  8 , Ivan Foeldvari  9 , Kirsten Minden  10 , Anton Hospach  11 , Markus Hufnagel  1 , Thomas Berger  12 , Til Geikowski  13 , Jürgen Quietzsch  14 , Gerd Horneff  1   2
Affiliations

Development of Inflammatory Bowel Disease in Children With Juvenile Idiopathic Arthritis Treated With Biologics

Ilse J Broekaert et al. J Pediatr Gastroenterol Nutr. .

Abstract

Objective: The aim of our study was to describe the distinct features of inflammatory bowel disease (IBD) in juvenile idiopathic arthritis (JIA) patients and to identify risk factors for its development.

Methods: Data from the German biologics in pediatric rheumatology registry (Biologika in der Kinderrheumatologie) collected between 2001 and 2021 were analyzed retrospectively.

Results: In 5009 JIA patients, 28 developed confirmed IBD before the age of 18 years: 23 (82.1%) with Crohn disease (CD), 4 (14.3%) with ulcerative colitis (UC), and 1 (3.6%) with IBD-unclassified (IBD-U). The incident rate of IBD during 20 years of observation was 0.56% (0.46% for CD, 0.08% for UC, and 0.02% for IBD-U), of whom 20.3% were HLA-B27 positive, 25% had enthesitis-related arthritis, and 14.3% psoriatic arthritis. Within 90 days before IBD diagnosis, 82.1% (n = 23) received treatment with etanercept (ETA), 39.3% (n = 11) non-steroidal anti-inflammatory drugs, 17.9% (n = 5) systemic corticosteroids, 8 (28.6%) methotrexate (MTX), 14.3% (n = 4) sulfasalazine, 10.7% (n = 3) leflunomide, and 3.6% (n = 1) adalimumab and infliximab, respectively. The incidence of IBD was lower in patients treated with MTX, but higher in patients treated with ETA except if ETA was combined with MTX. Also in patients on leflunomide or sulfasalazine, the IBD incidence was higher.

Conclusions: In our JIA cohort, an increased IBD incidence is observed compared to the general population, and the ratio of CD to UC is markedly higher hinting at a distinct phenotype of IBD. Pretreatment with MTX seems to be protective. Treatment with ETA does not prevent IBD development and JIA patients treated with leflunomide and sulfasalazine may be at an increased risk for IBD development.

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Conflict of interest statement

I.F. received honorary fees from Novartis, Hexal, Pfizer, and Lilly. A.H. received speaker fees for advisory boards of Sobi and Novartis. G.H. received honorary fees from Abbvie, Chugai, Novartis, Pfizer, MSD, Roche, Sanofi, and Sobi. M.H. has been invited to an advisory board meeting by Novartis. A.K. received honorary fees from Novartis. K.M. received honoraria from Pfizer, Novartis, and medac. P.O. received honorary fees from Novartis. D.W. received honorary fees from Novartis, Pfizer, Abbvie, MEDAC, Roche, and Sobi. The remaining authors report no conflicts of interest.

References

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    1. Berntson L, Fasth A, Andersson-Gare B, et al. Construct validity of ILAR and EULAR criteria in juvenile idiopathic arthritis: a population based incidence study from the Nordic countries. International League of Associations for Rheumatology. European League Against Rheumatism. J Rheumatol. 2001;28:2737–43.
    1. Minden K, Niewerth M, Listing J, Zink A. Health care provision in pediatric rheumatology in Germany--national rheumatologic database. J Rheumatol. 2002;29:622–8.
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