Effectiveness and Safety of Ustekinumab Intensification at 90 mg Every 4 Weeks in Crohn’s Disease: A Multicentre Study

Abstract

Introduction The approved maintenance regimens for ustekinumab in Crohn’s disease (CD) are 90 mg every 8 or 12 weeks. Some patients will partially respond to ustekinumab or will experience a secondary loss of response. It remains poorly known if these patients may benefit from shortening the interval between injections Methods All patients with active CD, as defined by Harvey-Bradshaw score ≥ 4 and one objective sign of inflammation (CRP > 5 mg/L and/or fecal calprotectin > 250 µg/g and/or radiologic and/or endoscopic evidence of disease activity) who required ustekinumab dose escalation to 90mg every 4 weeks for loss of response or incomplete response to ustekinumab 90mg every 8 weeks were included in this retrospective multicenter cohort study. Results One hundred patients, with a median age of 35 years (Interquartile Range (IQR), 28 – 49) and median disease duration of 12 (7 – 20) years were included. Dose intensification was performed after a median of 5.0 (2.8 - 9.0) months of ustekinumab treatment and was associated with corticosteroids and immunosuppressants in respectively 29% and 27% of cases. Short-term clinical response and clinical remission were observed in respectively 61% and 31% after a median of 2.4 (1.3 - 3.0) months. After a median follow-up of 8.2 (5.6-12.4) months, 61% of patients were still treated with ustekinumab, and 26% in steroid-free clinical remission. Among the 39 patients with colonoscopy during follow-up, 14 achieved endoscopic remission (no ulcers). At the end of follow-up, 27% of patients were hospitalized, and 19% underwent intestinal resection surgery. Adverse events were reported in 12% of patients, including five serious adverse events. Conclusion In this multicenter study, two-thirds of patients recaptured response following treatment intensification with ustekinumab 90 mg every 4 weeks.

A nationwide real-world study on dynamic ustekinumab dosing and concomitant medication use among Crohn’s disease patients in Finland

“…Importantly 87.2% of patients who underwent a dose intensification persisted on ustekinumab therapy at the end of the follow-up. This is in line with the findings from previous dose-intensified patient cohorts where 61-79% of patients continued ustekinumab treatment at last follow-up [11,24,25].…”

“…Our data on dosing patterns support the findings of other real-world registry studies of ustekinumab maintenance treatment where the majority or all the patients commenced their ustekinumab maintenance therapy with q8w dosing [6,10,12,13,22]. Interestingly, data on recapturing or improvement of ustekinumab response in CD patients with q4w dosing is emerging [11,[22][23][24][25]. In the present study, a sixth of patients received shorter dosing than q8wat the end of follow-up.…”

“…However, some recent studies report clinical outcomes derived from specific real-world cohorts consisting of only dose optimized patients [11,[23][24][25]. Where reported, 22-52% of patients needed dose intensification, which appeared successful in around half of the patients [10,11,[22][23][24][25].In the present study, one-third of patients on ustekinumab maintenance therapy required dose intensification. Among patients initiating maintenance therapy with q12w dosing, two-thirds shortened the interval.…”

“…While the analysis of dosing patterns in IM-UNITI trial suggested regaining clinical response in 55% of patients following dose intensification from q12w to q8w [3,21], data on dose optimization in real-world situations remains scarce [10,22]. However, some recent studies report clinical outcomes derived from specific real-world cohorts consisting of only dose optimized patients [11,[23][24][25]. Where reported, 22-52% of patients needed dose intensification, which appeared successful in around half of the patients [10,11,[22][23][24][25].In the present study, one-third of patients on ustekinumab maintenance therapy required dose intensification.…”

How to Optimize Treatment With Ustekinumab in Inflammatory Bowel Disease: Lessons Learned From Clinical Trials and Real-World Data

“…Unlike with anti-TNF agents the optimal management of loss of response to UST is not fully established. Shortening the interval of administration and also re-induction with iv UST have been described in patients after an initial inadequate response or secondary loss of response with good results (96)(97)(98)(99)(100)(101). However, data about the efficacy of both strategies in patients failing q8w dosing are still scarce.…”