Effectiveness of ustekinumab dose escalation in Crohn’s disease patients with insufficient response to standard‐dose subcutaneous maintenance therapy

Summary Background Ustekinumab is effective in Crohn's disease. However, a substantial proportion of patients will not respond or lose response to ustekinumab. The current evidence to support the effectiveness of dose‐optimisation for ustekinumab nonresponse is limited. Aim To assess the effectiveness of dose escalation of ustekinumab. Methods This was a multicentre retrospective cohort study. We included active Crohn's disease patients who received a standard‐dose intravenous induction and at least one subcutaneous ustekinumab 90 mg dose. All enrolled patients received dose escalation by either shortening the interval between the doses to every 4 or 6 weeks, intravenous reinduction or a combination of strategies. The primary outcome of the study was clinical response at week 16 after dose escalation. Results A total of 142 patients (22 centres/14 countries) were included. The patients were dose‐escalated after a median treatment duration of 30 weeks. At week 16 from escalation, 73/142 (51.4%) responded to treatment, including 55/142 (38.7%) in clinical remission. Corticosteroid‐free remission was achieved in 6/34 (17.6%) patients on corticosteroids at the time of escalation; 118/142 (83%) continued treatment beyond week 16. Follow‐up data beyond week 16 were available for 74/118 (62.7%) patients. On the last follow‐up, 51/98 (52%) patients with available data responded to treatment, including 41/98 (42%) in clinical remission. Conclusions Intensification of ustekinumab maintenance dosage was effective in over 50% of the patients. This strategy should be considered in patients who are nonresponsive to every 8 weeks ustekinumab maintenance dosing.