Malignancy and mortality in paediatric‐onset inflammatory bowel disease: a 3‐year prospective, multinational study from the paediatric <scp>IBD</scp> Porto group of <scp>ESPGHAN</scp>

Background: Recent studies report increased risks of both cancer and mortality in paediatric onset inflammatory bowel disease (pIBD) but the reproducibility of this is unknown. Aim: To estimate the risk of cancer and mortality in the Danish and Finnish pIBD population in a 23-year period compared to the general population. Methods: The pIBD population was defined as individuals registered in the national patient registries with a diagnosis of Crohn's disease (CD), ulcerative colitis (UC) or IBD-unclassified before their 18th birthday from 1992 to 2014. This cohort was cross referenced with the national cancer and mortality registries identifying all pIBD patients who subsequently developed cancer and/ or died and followed up to the end of 2014. Risk estimates are presented as standardised incidence ratios calculated based on incidence figures from the populations. Results: Six thousand six hundred and eight-nine patients with pIBD were identified (median age at follow-up 22.3 years; median follow-up: 9.6 years [interquartile range:4.8-16.0]). Seventy-two subsequently developed cancer and 65 died. The standardised incidence ratio of cancer in general was 2.6 (95% CI: 1.8-3.7) and 2.5 (95% CI: 1.8-3.4) in CD and UC, respectively. The standardised mortality ratios were 2.2 (95% CI: 1.4-3.4) and 3.7 (95% CI: 2.7-5.0) in CD and UC, respectively. The leading causes for mortality were cancer, suicide and infections. Conclusions:We found an increased risk of cancer and mortality in pIBD. This underlines the importance of cancer surveillance programs and assessment of mental health in the standard of care in adolescent pIBD patients. S U PP O RTI N G I N FO R M ATI O NAdditional supporting information will be found online in the Supporting Information section at the end of the article.How to cite this article: Malham M, Jakobsen C, Paerregaard A, Virta LJ, Kolho K-L, Wewer V. The incidence of cancer and mortality in paediatric onset inflammatory bowel disease in Denmark and Finland during a 23-year period: a populationbased study. Aliment Pharmacol Ther. 2019;50:33-39. https://

Section: Discussionsupporting

confidence: 89%

“…In pIBD knowledge is sparse regarding the risk and causes of mortality. Joosse et al published a 3‐year prospective study in 2018 from multiple centres in Europe . They reported 26 deaths with the main causes of mortality being cancer and infections.…”

Section: Introductionmentioning

confidence: 99%

The incidence of cancer and mortality in paediatric onset inflammatory bowel disease in Denmark and Finland during a 23‐year period: a population‐based study

Malham

Jakobsen

Pærregaard

et al. 2019

“…12 This number was comparable with other studies reporting around 1/3 patients undergoing a surgical procedure during childhood. 17,18 In contrast to the increasing incidence of disease, the rates of paediatric surgery have not been reported to change over time. 19,20 The impact of increasing use of anti-TNF therapy on surgical procedure rates during childhood is important to guide use of these medications and understand prognoses for patients and families.…”

Section: Introductionmentioning

confidence: 99%

Increased prevalence of anti‐TNF therapy in paediatric inflammatory bowel disease is associated with a decline in surgical resections during childhood

Ashton

Borca

Mossotto

et al. 2019

Summary Background Anti‐tumour necrosis factor‐α (anti‐TNF) therapy use has risen in paediatric‐onset inflammatory bowel disease (PIBD). Whether this has translated into preventing/delaying childhood surgery is uncertain. The Wessex PIBD cohort was analysed for trends in anti‐TNF‐therapy and surgery. Aim To assess patients diagnosed with PIBD within Wessex from 1997 to 2017. The prevalence of anti‐TNF‐therapy and yearly surgery rates (resection and perianal) during childhood (<18 years) were analysed (Pearson's correlation, multivariate regression, Fisher's exact). Results Eight‐hundred‐and‐twenty‐five children were included (498 Crohn's disease, 272 ulcerative colitis, 55 IBD‐unclassified), mean age at diagnosis 13.6 years (1.6‐17.6), 39.6% female. The prevalence of anti‐TNF‐treated patients increased from 5.1% to 27.1% (2007‐2017), P = 0.0001. Surgical resection‐rate fell (7.1%‐1.5%, P = 0.001), driven by a decrease in Crohn's disease resections (8.9%‐2.3%, P = 0.001). Perianal surgery and ulcerative colitis resection‐rates were unchanged. Time from diagnosis to resection increased (1.6‐2.8 years, P = 0.028) but mean age at resection was unchanged. Patients undergoing resections during childhood were diagnosed at a younger age in the most recent 5 years (2007‐2011 = 13.1 years, 2013‐2017 = 11.9 years, P = 0.014). Resection‐rate in anti‐TNF‐therapy treated (16.1%) or untreated (12.2%) was no different (P = 0.25). Patients started on anti‐TNF‐therapy <3 years post‐diagnosis (11.6%) vs later (28.6%) had a reduction in resections, P = 0.047. Anti‐TNF‐therapy prevalence was the only significant predictor of resection‐rate using multivariate regression (P = 0.011). Conclusions The prevalence of anti‐TNF‐therapy increased significantly, alongside a decrease in surgical resection‐rate. Patients diagnosed at younger ages still underwent surgery during childhood. Anti‐TNF‐therapy may reduce the need for surgical intervention in childhood, thereby influencing the natural history of PIBD.

“…Alternatively, trough levels can also be increased by escalating the dose of infliximab or by shortening the interval between infusions of infliximab—a strategy known as “optimised infliximab monotherapy.” The latter may have the advantage of increased safety, as high trough levels were not associated with an increased risk of complications . Conversely, combination treatment has a well‐documented increased risk of infection and malignancy . Elevated cost could be a potential shortcoming of optimised infliximab monotherapy due to higher drug consumption because of less favourable pharmacokinetics than the combination treatment.…”

Section: Introductionmentioning

confidence: 99%

Optimised infliximab monotherapy is as effective as optimised combination therapy, but is associated with higher drug consumption in inflammatory bowel disease

Drobne

Kurent

Golob

et al. 2019

Background: Combination treatment with azathioprine for 6-12 months is the preferred strategy for starting infliximab due to improved pharmacokinetics. However, optimised infliximab monotherapy with proactive dose escalations in case of low trough levels is a potentially safer but under-studied alternative.Aim: To compare the clinical success and infliximab consumption of combination vs optimised monotherapy strategies.Methods: We studied the clinical success and infliximab consumption with both strategies in 149 patients (94 Crohn's disease; 55 ulcerative colitis) starting infliximab and undergoing intensive drug monitoring assisted treatment optimisation.Results: The drug retention rates were similar for optimised monotherapy and combination treatment after induction (96% vs 97%, P = 0.73), after the first year (90% vs 83%, P = 0.23) and at the end of follow-up (74% vs 75%, P = 0.968). Similarly, no significant differences were observed for steroid use at year 1 (5% vs 14%, P = 0.08) or mucosal healing at the end of follow-up (64% vs 67%, P = 0.8). Higher infliximab consumption (7.6 mg/kg q8 weeks [interquartile range (IQR): 5.9-10.3] vs 6.4 mg/kg q8 weeks [IQR: 5.2-8.0], P = 0.019) combined with lower trough levels (1.7 µg/mL [IQR: 0.3-6.6] vs 5.0 µg/mL [2.5-8.7], P = 0.012) resulted in almost 3-fold higher drug-to-trough ratio (3.9 vs 1.5) in monotherapy compared to combination strategy at year 1. At the end of follow-up, when azathioprine had been discontinued for a median of 14 [IQR: 3-33] months, these differences disappeared. Conclusions:In this study, optimised infliximab monotherapy was as clinically effective as combination therapy, but was associated with significantly higher infliximab consumption. The infliximab-sparing effect disappeared after azathioprine withdrawal.