Rahul S. Dalal, MD, Cheikh Njie, MD, Gupta Sanchit, MD, MS, Jessica R. Allegretti, MD, MPH; Brigham & Women's Hospital, Boston, MA
Introduction: Ustekinumab (UST) is an IL-12/23 antagonist approved for the treatment of Crohn’s disease (CD), however many pts lose response to the standard maintenance dose interval of every 8 wks. There is little data to support UST dose intensification, and identification of factors that may predict success or failure after intensification is needed. We sought to identify clinical predictors of failure after UST dose intensification for pts with CD. Methods: Retrospective cohort study of adult CD pts undergoing UST dose intensification at a tertiary referral center between 1/1/2016 and 1/31/2019. Electronic health records were reviewed to obtain pt demographics, CD history, and laboratory data. Two outcomes were chosen to assess failure of UST within 12 mo after dose intensification: failure to achieve corticosteroid-free remission (defined as Harvey Bradshaw Index < 5 with no use of systemic corticosteroids) and change to a new biologic (defined as discontinuation of UST with initiation of new biologic therapy). Student’s t-test and Pearson’s chi-squared test were used to compare characteristics of pts by status of remission. Multivariable logistic regression (MVLR) was used to identify predictors of failure to achieve remission. Cox regression was performed to identify predictors of time to new biologic and a related Kaplan-Meier (KM) curve was constructed. Results: We included 238 pts who were initiated on UST. Among these pts, 123 (51.7%) underwent dose interval intensification ranging from every 4 to 7 wks. Perianal disease was more common among pts who failed to achieve remission compared to pts who achieved remission within 12 mo after intensification (60.0% vs. 34.8%, p=0.01). Other characteristics compared by remission status are presented in table 1. MVLR demonstrated that perianal disease and opioid use at time of intensification were associated with failure to achieve remission (Fig 1). Cox regression demonstrated that perianal disease and corticosteroid use at time of intensification were associated with shorter time to a new biologic; KM analysis demonstrated a non-significant separation in rate curves of time to new biologic stratified by perianal disease (log-rank test p=0.05) (Fig 2). Discussion: Perianal disease, current opioid use, and current corticosteroid use are associated with UST failure after dose intensification in CD. Alternative therapeutic strategies should be considered for CD pts with these risk factors failing standard UST therapy.