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Predictors and Outcomes of Ustekinumab Dose Intensification in Ulcerative Colitis: A Multicenter Cohort Study.

ABSTRACT: Ustekinumab has been shown to be effective for the treatment of ulcerative colitis (UC); however, >40% of patients have suboptimal clinical response after induction and maintenance dosing every 8 weeks.¹^,² The best management approach for these patients is unclear. Many undergo empiric dose intensification to every 4 weeks or every 6 weeks, a nonstandardized decision because of limited data supporting therapeutic drug monitoring of ustekinumab.³ In Crohn's disease, approximately 50% of patients undergo ustekinumab dose intensification, which seems to be effective based on prior work from our group and others.^4-8 However, similar data in UC are lacking. In this real-world multicenter cohort study, we sought to identify predictors and outcomes of ustekinumab dose intensification in UC.

SUBMITTER: Dalal RS

PROVIDER: S-EPMC8464615 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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Predictors and Outcomes of Ustekinumab Dose Intensification in Ulcerative Colitis: A Multicenter Cohort Study.

Dalal Rahul S RS Esckilsen Scott S Barnes Edward L EL Pruce Jordan C JC Marcus Jenna J Allegretti Jessica R JR

Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association 20210326 10

Ustekinumab has been shown to be effective for the treatment of ulcerative colitis (UC); however, >40% of patients have suboptimal clinical response after induction and maintenance dosing every 8 weeks.1,2 The best management approach for these patients is unclear. Many undergo empiric dose intensification to every 4 weeks or every 6 weeks, a nonstandardized decision because of limited data supporting therapeutic drug monitoring of ustekinumab.3 In Cro ...[more]

PMID: 33775893

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Project description:IntroductionUlcerative colitis (UC) is an idiopathic, chronic inflammatory disease of the large intestine. Ustekinumab is a monoclonal antibody against the p40 subunit of interleukin-12 and interleukin-23 and has proven efficacy in inducing and maintaining remission in adult patients with moderate-to-severe UC. In the Symptom Improvement of ulceRative colitis after an Induction dose of Ustekinumab study, we will document the initial treatment response (daily patient-reported outcomes for 8 weeks from first infusion) and treatment patterns of patients wih UC receiving an induction dose of ustekinumab in the real-world setting in Japan. We will also investigate the relationship between the treatment response at week 8 and early indicators of response and determine patient factors that may define the appropriate dosing interval for maintenance therapy.Methods and analysisFor this single-arm, prospective observational study at 24 centres in Japan with a follow-up period of 16/20 weeks, we aim to recruit 140 patients with moderate-to-severe UC between July 2021 and July 2022. All surveys will be conducted in Japanese and patient-reported outcomes relating to rectal bleeding, stool frequency, abdominal pain, nocturnal diarrhoea, tenesmus and perception of UC symptoms will be recorded using a smartphone application, where the patients can enter their initial response to ustekinumab induction therapy on a daily basis. Dosing intervals and the reasons for selecting this interval, and concomitant medications taken during treatment with ustekinumab will be collected by a physician questionnaire at the end of the study. On completion of primary end point (8-week patient-reported outcomes) data collection, results will be reported sequentially.Ethics and disseminationThe study has been approved by the ethics committee of each facility involved and the Institutional Review Board of the non-profit organisation MINS.Trial registration numberUMIN000043753, NCT04963725.

Project description:BackgroundTofacitinib is an oral Janus kinase inhibitor for the treatment of ulcerative colitis (UC).ObjectivesTo investigate potential predictors of efficacy in RIVETING.DesignThis post hoc analysis included patients with UC in stable remission (⩾6 months) on tofacitinib 10 mg twice daily (BID) maintenance therapy (⩾2 years of treatment), who received tofacitinib 5/10 mg BID in RIVETING.MethodsAchievement of modified Mayo (mMayo) remission, remission (based on total Mayo score), partial Mayo score (PMS) remission, and modified PMS (mPMS) remission at month (M)6 was analyzed by baseline characteristics, duration of PMS remission at RIVETING entry, biomarkers, and patient-reported outcomes (PROs) to identify factors associated with achieving/maintaining efficacy outcomes, including following dose reduction.ResultsSeventy patients received tofacitinib 5 mg BID. At M6, PMS remission was maintained in 66.7%, 60.0%, 82.4%, 75.0%, and 90.0% of patients with baseline PMS remission durations of 6 to ⩽12, >12 to ⩽24, >24 to ⩽36, >36 to ⩽48, and >48 months, respectively. Patients in mMayo remission at M6 had smaller increases in PMS at M1 compared with those not in mMayo remission at M6, while numerically higher proportions of patients with a stool frequency subscore/rectal bleeding subscore/mPMS of 0 at M1/M3 achieved most efficacy endpoints at M6 compared with patients with respective subscores >0. Maintenance of mMayo remission was independent of the number of tumor necrosis factor inhibitors failed and/or prior corticosteroid use. In multivariable models (which included tofacitinib 10 mg BID data), endoscopic subscores (1 vs 0) at RIVETING baseline were significantly associated with lower odds of mMayo remission at M6 (odds ratio, 0.33; 95% confidence interval, 0.11-0.94; p = 0.0379).ConclusionPrior duration of remission/baseline endoscopic subscore may help guide tofacitinib dose reduction, while PROs may be useful early indicators of efficacy. Close monitoring of patients following dose reduction could identify those unlikely to achieve/maintain efficacy. Trial registration: ClinicalTrials.gov: NCT03281304.

Dataset Information

Predictors and Outcomes of Ustekinumab Dose Intensification in Ulcerative Colitis: A Multicenter Cohort Study.

Publications

Predictors and Outcomes of Ustekinumab Dose Intensification in Ulcerative Colitis: A Multicenter Cohort Study.

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