652 Ustekinumab Intravenous Reinduction Therapy Is Effective at Recapturing Response in Patients With Crohn's Disease

Abstract

Listen

Translate article

INTRODUCTION: Ustekinumab is a monoclonal antibody used in the treatment of Crohn's Disease that acts as an antagonist to interleukin-12 and interleukin-23. It is administered as a single intravenous infusion followed by subcutaneous maintenance dosing. There is paucity of literature evaluating the efficacy of repeating an intravenous infusion to recapture response among patients experiencing secondary loss of response to ustekinumab. We report on a cohort of patients who received a second intravenous ustekinumab loading dose after secondary loss of response at a large, academic IBD center. METHODS: We performed a retrospective cohort study of patients, who lost response to ustekinumab after initial intravenous standard induction followed by subcutaneous maintenance therapy and received a second intravenous ustekinumab loading dose following the standard weight-based dosing recommendations. We analyzed clinical and demographic characteristics of this patient population, including phenotype, prior therapies, and the efficacy of ustekinumab after the second infusion, including the subsequent maintenance dose after the second infusion. Response was defined as resolution or improvement of clinical symptoms that led to a second intravenous infusion. RESULTS: Among 372 patients treated with ustekinumab between 2016 and 2019, 18 (5%) patients received a second intravenous loading dose after experiencing secondary loss of response to their initial standard intravenous regimen. These patients had all failed prior biologic therapy and were placed on ustekinumab as second line (22%), third line (27%), fourth line (33%), fifth line (6%), or sixth line therapy (11%). After the second intravenous re-induction clinical response was observed in 15 patients (83%), whereas 3 (17%) patients did not respond and ustekinumab was stopped. Clinical and demographic characteristics of patients receiving a second loading dose are shown in Table 1. Among the 15 patients remaining on ustekinumab, 5 (33%) continued every 8-week dosing, 6 (40%) utilized every 6-week dosing, and 4 (27%) required every 4-week dosing regimens. CONCLUSION: A second intravenous ustekinumab loading dose is an effective strategy to recapture the therapeutic efficacy of ustekinumab after secondary loss of response. In addition, our data suggests that escalation in dosing frequency of maintenance subcutaneous therapy after a second intravenous loading dose should be considered for an ongoing durable response to ustekinumab.