Risk of Cancer in Pediatric-Onset Inflammatory Bowel Diseases: A Nation-Wide Study from the Epi-Iirn

Abstract

Background: Pediatric-onset IBD (PIBD) is characterized by a more extensive phenotype than adults and a higher utilization of immunosuppressive medications; both may be associated with malignancy. We aimed to assess the risk of cancer in a nationwide cohort of PIBD and to explore the risks associated with medical treatments. Methods: PIBD cases were included from the epi-IIRN cohort , covering 98% of the Israeli population from 2005, linked to the national cancer registry. We matched PIBD cases to non-IBD children for calculating the cumulative incidence of cancer. Finding: 3,944 PIBD cases were included (2,642 [67%] Crohn's disease, 1,302 [33%] ulcerative colitis) translating into 23,635 person-years of follow-up , individually matched to 13,005 non-IBD children. By 30 years of age, 14 IBD patients (0.35%, 5.9/10,000 patient-years) were diagnosed with cancer and one (0.03%) with haemophagocytic-lymphohistiocytosis (HLH), compared with 14 (0.11%, 1.9/10,000 patient-years) cases of cancer (OR 2.5 [95%CI 1.05-6.2]; p=0.04) and no HLH in the comparison-group. There were no cases of hepatosplenic T-cell lymphoma, adenocarcinoma or cholangiocarcinoma. Cancer risk was 15.6 cases/10,000 person-years in those treated with thiopurines alone (OR compared with those never exposed to either thiopurines or anti-tumor necrosis factor (TNF) 1.8 (95%CI 0.6-6.1); p=0.2), 11.1/10,000 in those treated with anti-TNF alone (OR 1.3 [95%CI 0.3-6.6]; p=0.5), and 23.1/10,000 treated with combination therapy of anti-TNF and thiopurines (OR 2.8 [95%CI 0.6-13.8]; p=0.2). Interpretation: PIBD confers an increased risk for malignancy compared with non-IBD children. The risk was not statistically associated with treatment, likely since the absolute risk was very low. Funding Statement: None to declare. Declaration of Interests: ID- Has received consultation fee, research grant or honorarium from Janssen, Pfizer, Abbvie, Takeda, Genentech/Roche, Neopharm, Ferring, Rafa Laboratories, Falk Pharma, Nestle, Given Imaging/Medtronic, Gilead, Celgene, Arena, Sublimity, Celltrion Altman Research; DT - Has received consultation fee, research grant, royalties, or honorarium from Janssen, Pfizer, Hospital for Sick Children, Ferring, Abbvie, Takeda, Biogen, Neopharm, Uniliver, Atlantic Health, Shire, Celgene, Lilly, Roche; all other authors have nothing to declare. Ethics Approval Statement: This study was approved by the local ethics committee.