Ustekinumab Dose Intensification Can Be Effective in Crohnʼs Disease Patients Not Responding to Induction

Abstract

Introduction: Ustekinumab, an IL-12/23 inhibitor is used for the treatment of Crohn's Disease (CD). Patients receive an IV infusion followed by subcutaneous injections every 8 weeks. There is limited data about the efficacy of dose intensification. This study aimed to analyze the response of ustekinumab dose escalation based on clinical and laboratory parameters. Methods: This is a retrospective cohort study from a large metropolitan IBD center. We analyzed data of all CD patients who had ustekinumab induction between September 26, 2016 and October 1, 2017 and required dose intensification. Data collected included demographics, prior immunosuppressant use, concomitant immunosuppressants, regimen of dose intensification, and response to therapy based on clinical and lab evaluation. Results: Among 122 consecutive CD patients on ustekinumab with a median follow-up of 146 days, 21(17%) required dose intensification. 4 patients (19%) had inflammatory, 7(33%) stricturing and 10(48%) penetrating disease. 20 patients (95%) had failed previously at least one anti-TNF. Dose escalation utilized was: increase in injection frequency to every 6 weeks (q6w, n=5), every 4 weeks (q4w, n=11), or a combination of IV booster and frequency change to q6w or q4w (n=5). 7 patients required dose escalation due to primary non-response, 4 due to secondary loss of response, and 10 due to poor initial response. Median follow-up after dose intensification was 177 days. Overall, 11 patients (52%) had clinical response after dose escalation. In this group, 2 patients (18%) were primary non-responders to induction while 9(82%) had poor initial clinical response. None of 4 patients with secondary loss of response were able to regain response. 5 of 11 (45%) patients on q4w regimen, 4 of 5 (80%) on q6w, and 2 of 5 (40%) on combination regimen achieved clinical response. Among 6 (27%) patients who were on steroids at baseline, one was weaned off and one was on a lower dose at the follow-up evaluation. Lab data before and after dose intensification are shown on the table below. Side effects reported were dizziness, fatigue, nausea, abdominal pain, dehydration, diarrhea, arthritis, and a perianal abscess. Conclusion: This retrospective cohort study reveals that dose intensification can be beneficial in patients who do not achieve clinical response on the q8w dosing regimen of ustekinumab. Further studies are needed to evaluate efficacy and safety of dose escalation.617 Figure 1 No Caption available.