Identifying risk factors of anti‐TNF induced skin lesions and other adverse events in paediatric patients with inflammatory bowel disease

Objectives While higher infliximab (IFX) trough concentrations (TCs) are associated with better outcomes in patients with inflammatory bowel disease (IBD), they could pose a risk for adverse events (AEs), including IFX‐induced skin lesions. Therefore, we studied correlations between IFX TCs and occurrence of AEs in paediatric IBD patients. Methods In this single‐centre study, all children with Crohn's disease (CD) and ulcerative colitis (UC) receiving IFX maintenance therapy who underwent proactive drug monitoring between March 2015 and August 2022 were included. IFX doses/intervals/TCs and patient characteristics were systematically registered, as well as AEs and skin lesions appearance. Results A total of 109 patients (72 CD and 37 UC) contributed 2913 IFX TCs. During a median follow‐up of 3.0 [1.5–4.5] years, we observed 684 AEs in 101 patients and 49 skin lesions in 35 patients. There was no significant difference (p = .467) in median TCs between patients with and without skin lesions. However, higher median IFX doses were associated with an increased hazard rate of skin lesions [HR 1.084 (1.024–1.148), p = .005], in addition to female sex [2.210 (1.187–5.310), p = .016] and diagnosis of CD [1.695 (1.241–1.877), p = .011]. Considering IFX therapeutic TC cut‐offs of 5.0 and 9.0 µg/mL, there was no significant difference in AE rate (p = .749 and p = .833, respectively). Also, no significant association between IFX doses and AE rate (p = .159). Conclusions Increasing the IFX dose to achieve therapeutic TCs may not increase the overall risk of AEs in paediatric IBD patients. However, concerns arise regarding the risk of skin lesions, especially in female CD patients. What is Known Higher infliximab (IFX) trough concentrations have been consistently associated with better therapeutic outcome. Therefore, therapeutic drug monitoring has been recommended to optimise outcome, however these dosing adaptations should not be at the expense of more adverse events, such as IFX‐induced skin lesions or infections. What is New Increasing IFX dose to achieve therapeutic IFX trough concentrations led to a higher risk of developing IFX‐induced skin lesions, especially in female patients with Crohn's disease as independent risk factors for developing skin lesions. Our findings support the hypothesis that shortening the dosing interval is preferable to higher dosing for increasing IFX exposure in patients, thereby maintaining a lower peak concentration and possibly reducing