Rheumatology (Oxford). 2021 Sep 11;keab678. doi: 10.1093/rheumatology/keab678.Online ahead of print.

Joeri W van Straalen ¹, Roline M Krol ¹, Gabriella Giancane ^2 3, Violeta Panaviene ^4 5, Laura Marinela Ailioaie ⁶, Pavla Doležalová ⁷, Marco Cattalini ⁸, Gordana Susic ⁹, Flavio Sztajnbok ¹⁰, Despoina Maritsi ¹¹, Tamas Constantin ¹², Sujata Sawhney ¹³, Marite Rygg ^14 15, Sheila Knupp Oliveira ¹⁶, Ellen Berit Nordal ^17 18, Claudia Saad-Magalhaes ¹⁹, Nadina Rubio-Perez ²⁰, Marija Jelusic ²¹, Sytze de Roock ¹, Nico M Wulffraat ¹, Nicolino Ruperto ², Joost F Swart ¹, Paediatric Rheumatology International Trials Organisation (PRINTO)

Author information

• ¹Department of Pediatric Immunology and Rheumatology, Wilhelmina Children's Hospital, Utrecht, The Netherlands.
• ²Clinica Pediatrica e Reumatologia, IRCCS Istituto Giannina Gaslini, Genoa, Italy.
• ³Dipartimento di Neuroscienze, Riabilitazione, Oftalmologia, Genetica e Scienze Materno-Infantili (DiNOGMI), Università degli Studi di Genova, Genoa, Italy.
• ⁴Children's Hospital, Affiliate of Vilnius University Hospital Santaros Clinic, Vilnius, Lithuania.
• ⁵Clinic of Children's Diseases, Vilnius University, Vilnius, Lithuania.
• ⁶Alexandru Ioan Cuza University of Iasi, Iasi, Romania.
• ⁷Department of Pediatrics and Inherited Metabolic Disorders, 1st Faculty of Medicine and General University Hospital, Charles University in Prague, Prague, Czech Republic.
• ⁸Unita' di Immunologia e Reumatologia Pediatrica, Clinica Pediatrica dell'Universita' di Brescia, Spedali Civili, Brescia, Italy.
• ⁹Division of Pediatric Rheumatology, Institute of Rheumatology of Belgrade, Belgrade, Serbia.
• ¹⁰Hospital Universitario Pedro Ernesto, Nucleo de Estudos da Saúde do Adolescente, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil.
• ¹¹2nd Department of Pediatrics Athens Medical School, National and Kapodistrian University of Athens (NKUA), Athens, Greece.
• ¹²Unit of Pediatric Rheumatology-Immunology, Second Department of Pediatrics, Semmelweis University, Budapest, Hungary.
• ¹³Sir Ganga Ram Hospital Marg, Centre for Child Health, Sir Ganga Ram Hospital, New Delhi, India.
• ¹⁴Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, NTNU-Norwegian University of Science and Technology, Trondheim, Norway.
• ¹⁵Department of Pediatrics, St. Olavs University Hospital of Trondheim, Trondheim, Norway.
• ¹⁶Instituto de Puericultura e Pediatria Martagao Gesteira (IPPMG), Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
• ¹⁷Department of Pediatrics, University Hospital of North Norway, Tromso, Norway.
• ¹⁸Department of Clinical Medicine, UiT the Arctic University of Norway, Tromso, Norway.
• ¹⁹São Paulo State University (UNESP), Botucatu, Brasil.
• ²⁰Departamento de Pediatria, Facultad de Medicina, Hospital Universitario "Dr. J. E. González", Universidad Autónoma de Nuevo León, Monterrey, NL, Mexico.
• ²¹Department of Paediatrics, University of Zagreb School of Medicine, Zagreb, Croatia.

Abstract

Objectives: To describe risk factors for inflammatory bowel disease (IBD) development in a cohort of children with juvenile idiopathic arthritis (JIA).

Methods: JIA patients who developed IBD were identified from the international Pharmachild register. Characteristics were compared between IBD and non-IBD patients and predictors of IBD were determined using multivariable logistic regression analysis. Incidence rates of IBD events on different disease-modifying anti-rheumatic drugs (DMARDs) were calculated, differences between therapies were expressed as relative risks (RR).

Results: Out of 8,942 patients, 48 (0.05%) developed IBD. These were more often male (47.9% vs 32.0%) and HLA-B27 positive (38.2% vs 21.0%) and older at JIA onset (median 8.94 vs 5.33 years) than patients without IBD development. They also had more often a family history of autoimmune disease (42.6% vs 24.4%) and enthesitis-related arthritis (ERA) (39.6% vs 10.8%). The strongest predictors of IBD on multivariable analysis were ERA (OR: 3.68, 95% CI: 1.41-9.40) and a family history of autoimmune disease (OR: 2.27, 95% CI: 1.12-4.54). Compared with methotrexate monotherapy, the incidence of IBD on etanercept monotherapy (RR: 7.69, 95% CI: 1.99-29.74), etanercept with methotrexate (RR: 5.70, 95% CI: 1.42-22.77) and infliximab (RR: 7.61, 95% CI: 1.27-45.57) therapy was significantly higher. Incidence on adalimumab was not significantly different (RR: 1.45, 95% CI: 0.15-13.89).

Conclusion: IBD in JIA was associated with ERA and a family history of autoimmune disease. An increased IBD incidence was observed for etanercept therapy regardless of concomitant methotrexate use.