A switch to infliximab may be more effective than ustekinumab following adalimumab pharmacodynamic failure in paediatric patients with Crohn's disease

Background: Loss of response (LOR) to anti-TNFα in patients with Crohn's disease (CD) is not uncommon. A particular challenge is pharmacodynamic LOR (inflammatory activity persisting despite adequate trough concentrations, TC). Aims: To explore the outcomes of paediatric patients with CD following adalimumab pharmacodynamic failure. Methods: We conducted a multi-centre retrospective cohort study. Data of patients who experienced adalimumab LOR with TC (≥7.5 µgr/ml) and switched to either infliximab or ustekinumab were retrieved. Results: The cohort included 70 patients (57 % male), with median duration on adalimumab of 13 months (IQR 8–24.5) and 12 months (IQR 6–29) of follow-up on subsequent therapy. Median adalimumab TC before switching was 11.1 (IQR 8.5–15.1 µgr/ml). At switching, the 2 group (infliximab=33, ustekinumab=37), were comparable for all disease variables. The infliximab group demonstrated superior outcomes in drug sustainability (88 % vs. 30 %; p = 0.001), corticosteroid-free clinical remission (58 % vs. 32 %; p = 0.03), lower surgical rate (3 % vs. 27 %; p = 0.006), higher C-reactive protein normalization (76 % vs. 24 %; p < 0.001), and albumin levels (4.1 ± 0.3 vs. 3.8 ± 0.4; p = 0.001) Conclusions: For paediatric patients with CD following adalimumab pharmacodynamic failure, a switch in-class to infliximab may be more effective than a switch to ustekinumab.