P0947 A switch to infliximab may be more effective than ustekinumab following adalimumab pharmacodynamic failure in pediatric patients with Crohn’s disease

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Abstract Background Loss of response (LOR) to first biologic agent is not uncommon. One of the most challenging mechanisms of LOR is pharmacodynamic LOR (inflammatory activity in the presence of adequate trough concentrations, TC). We aimed to explore the outcomes of pediatric patients with Crohn’s disease following adalimumab pharmacodynamic failure. Methods We conducted a retrospective longitudinal cohort study in 6 Israeli pediatric centers. Data of patients who experienced adalimumab LOR (as first biologic agent) with adequate TC (>7.5 mcg/ml) and switched to either infliximab or ustekinumab were retrieved. Results The cohort included 67 patients (66% males, mean age at diagnosis 12.2±2.8, B2 or B3 phenotype 16%, perianal disease 24%), with median duration on adalimumab of 17 (IQR 8-24) months and follow-up of 13 months (IQR 7-29) on the subsequent therapy. Median adalimumab TC before switching was 11.4 (IQR 8.5-16 mcg/ml). For the overall cohort, corticosteroid-free clinical remission and response were achieved in 43% and 67%, respectively. Of 36 follow-up colonoscopies, 25% achieved endoscopic remission. Most patients (84%) received intensified regimen after switching. Nine patients (13%) underwent surgical resection during follow-up. The two treatment groups (infliximab (n=32) and ustekinumab (n=35)) were comparable for all basic, demographic and disease severity parameters at the time of switching. The median follow-up period of both groups was similar, 12 (6-24) months. The infliximab group demonstrated better outcomes over ustekinumab at the end of follow-up in terms of clinical response (97% vs. 57%; p<0.001), corticosteroid-free clinical remission (56% vs. 31%; p=0.04), endoscopic response (83% vs. 28%; p=0.002), fecal calprotectin<250 (60% vs. 27%; p=0.03), drug sustainability (91% vs. 31%; p<0.001) and surgical rate (3% vs. 23%; p=0.02, 1 infliximab, 8 ustekinumab). Month 3 PCDAI was significantly lower [8.7 (IQR 0-17.5) vs. 21 (IQR 9-35); p<0.01), CRP remission was higher (60% vs. 23%; p=0.01) and median albumin concentration was higher [4.3 (IQR 39-4.5) vs. 3.8 (IQR 3.4-4); p=0.005] in the infliximab group. Conclusion Pediatric patients with Crohn’s disease following adalimumab pharmacodynamic failure with TL>7.5mcg/mL demonstrated moderate response to subsequent therapy. A switch in-class to infliximab may be more effective than a switch out of class to ustekinumab.