BACKGROUND: Many patients with Crohn's disease (CD) who lose response to the standard ustekinumab dose interval of every 8 weeks (q8w) undergo dose intensification to q4w or q6w. However, baseline factors that predict success or failure after dose intensification are unknown. We sought to identify predictors of failure of ustekinumab after dose intensification for patients with CD. METHODS: This was a retrospective cohort study of adult CD patients undergoing ustekinumab dose intensification at a tertiary referral center between January 1, 2016, and January 31, 2019. Electronic health records were reviewed to obtain patient demographics, CD history, and laboratory data. The primary outcome was failure to achieve corticosteroid-free remission (Harvey-Bradshaw Index <5) within 12 months after intensification. The secondary outcome assessed was time to new biologic therapy after dose intensification. We used multivariable logistic regression and Cox regression to identify predictors of these outcomes. RESULTS: We included 123 patients who underwent ustekinumab dose intensification to q4w (n = 64), q5w (n = 1), q6w (n = 55), or q7w (n = 3). Multivariable logistic regression demonstrated that perianal disease, Harvey-Bradshaw Index, and opioid use at time of intensification were associated with failure to achieve remission. Cox regression demonstrated that perianal disease and corticosteroid use at time of intensification were associated with shorter time to a new biologic. CONCLUSION: Perianal disease, Harvey-Bradshaw Index, current opioid use, and current corticosteroid use are associated with ustekinumab failure after dose intensification in CD. Larger, prospective studies are needed to corroborate these findings and guide therapeutic strategies for patients who lose response to standard ustekinumab dosing.
BACKGROUND: Many patients with Crohn's disease (CD) who lose response to the standard ustekinumab dose interval of every 8 weeks (q8w) undergo dose intensification to q4w or q6w. However, baseline factors that predict success or failure after dose intensification are unknown. We sought to identify predictors of failure of ustekinumab after dose intensification for patients with CD. METHODS: This was a retrospective cohort study of adult CD patients undergoing ustekinumab dose intensification at a tertiary referral center between January 1, 2016, and January 31, 2019. Electronic health records were reviewed to obtain patient demographics, CD history, and laboratory data. The primary outcome was failure to achieve corticosteroid-free remission (Harvey-Bradshaw Index <5) within 12 months after intensification. The secondary outcome assessed was time to new biologic therapy after dose intensification. We used multivariable logistic regression and Cox regression to identify predictors of these outcomes. RESULTS: We included 123 patients who underwent ustekinumab dose intensification to q4w (n = 64), q5w (n = 1), q6w (n = 55), or q7w (n = 3). Multivariable logistic regression demonstrated that perianal disease, Harvey-Bradshaw Index, and opioid use at time of intensification were associated with failure to achieve remission. Cox regression demonstrated that perianal disease and corticosteroid use at time of intensification were associated with shorter time to a new biologic. CONCLUSION: Perianal disease, Harvey-Bradshaw Index, current opioid use, and current corticosteroid use are associated with ustekinumab failure after dose intensification in CD. Larger, prospective studies are needed to corroborate these findings and guide therapeutic strategies for patients who lose response to standard ustekinumab dosing.
Authors: William J Sandborn; Christopher Gasink; Long-Long Gao; Marion A Blank; Jewel Johanns; Cynthia Guzzo; Bruce E Sands; Stephen B Hanauer; Stephan Targan; Paul Rutgeerts; Subrata Ghosh; Willem J S de Villiers; Remo Panaccione; Gordon Greenberg; Stefan Schreiber; Simon Lichtiger; Brian G Feagan Journal: N Engl J Med Date: 2012-10-18 Impact factor: 91.245
Authors: Sang Hyoung Park; Satimai Aniwan; W Scott Harmsen; William J Tremaine; Amy L Lightner; William A Faubion; Edward V Loftus Journal: Inflamm Bowel Dis Date: 2019-05-04 Impact factor: 5.325
Authors: Bruce E Sands; Frank H Anderson; Charles N Bernstein; William Y Chey; Brian G Feagan; Richard N Fedorak; Michael A Kamm; Joshua R Korzenik; Bret A Lashner; Jane E Onken; Daniel Rachmilewitz; Paul Rutgeerts; Gary Wild; Douglas C Wolf; Paul A Marsters; Suzanne B Travers; Marion A Blank; Sander J van Deventer Journal: N Engl J Med Date: 2004-02-26 Impact factor: 91.245
Authors: Jacob E Ollech; Inessa Normatov; Noam Peleg; Jingzhou Wang; Shivani A Patel; Victoria Rai; Yangtian Yi; Jorie Singer; Sushila R Dalal; Atsushi Sakuraba; Russell D Cohen; David T Rubin; Joel Pekow Journal: Clin Gastroenterol Hepatol Date: 2020-02-26 Impact factor: 11.382
Authors: Akbar K Waljee; Beth I Wallace; Shirley Cohen-Mekelburg; Yumu Liu; Boang Liu; Kay Sauder; Ryan W Stidham; Ji Zhu; Peter D R Higgins Journal: JAMA Netw Open Date: 2019-05-03