P2212 - Clinical Outcomes and Biomarker Normalization Response at Week 16 in Patients With Inadequate Response or Intolerance to Prior Biologics in the POWER Trial

Scott D. Lee, MD¹, Stefan Schreiber, MD², C. Janneke van der Woude, MD, PhD³, Ignacio Marín-Jiménez, MD⁴, Douglas C.. Wolf, MD⁵, Elisabeth Schnoy, MD, PhD⁶, Bruce Salzberg, MD⁷, Christopher Busse, ⁸, Maciej Nazar, ⁹, Wayne Langholff, ¹⁰, Christopher Gasink, ⁸, Thomas Baker, ¹⁰, Bridget Godwin, MD⁸, Brian G. Feagan, MD^11
1University of Washington, Seattle, WA; ²University Hospital Schleswig-Holstein, Kiel, Schleswig-Holstein, Germany; ³Erasmus University Medical Center, Rotterdam, Drenthe, Netherlands; ⁴Hospital Universitario Gregorio Marañón, IiSGM, Rotterdam, Zuid-Holland, Netherlands; ⁵Atlanta Gastroenterology Associates, Atlanta, GA; ⁶University Hospital of Augsburg, Augsburg, Bayern, Germany; ⁷Atlanta Gastroenterology Specialists PC, IBD Center of Atlanta, Atlanta, GA; ⁸Janssen Scientific Affairs, LLC, Horsham, PA; ⁹Janssen-Cilag Polska Sp. z o.o, Warsaw, Mazowieckie, Poland; ¹⁰Janssen Research & Development, LLC, Spring House, PA; ¹¹Western University, London, ON, Canada

Introduction: The POWER study evaluated efficacy and safety of a single intravenous (IV) re-induction ustekinumab (UST) dose vs placebo on a background of continued UST subcutaneous (SC) treatment in Crohn’s disease (CD) patients (pts) with secondary loss of response (LoR) to standard q8w UST maintenance therapy. This subgroup analysis reports primary and major secondary endpoints up to week (W)16 in pts with/without a history of inadequate response or intolerance to prior biologics.

Methods: Adults with moderately–severely active CD who initially responded to UST IV induction therapy per label and later experienced LoR were included. LoR was defined as CD Activity Index (CDAI) score of ≥220 and ≤450, plus either elevated C-reactive protein (CRP; >3mg/L), fecal calprotectin (fCal; >250mg/kg), or endoscopy performed ≤3 months before W0 with evidence of active CD. At W0 randomized pts received ~6mg/kg IV UST/SC placebo (IV arm) or IV placebo/SC UST 90mg (SC arm) followed by 90mg SC UST at W8/16. Clinical/biomarker assessments occurred at W0/8/16. Primary endpoint: W16 clinical response (CRes; decrease of ≥100 points from W0 or CDAI < 150). Secondary endpoints: CRes; clinical remission (CRem); normalization of CRP and/or fCal at W8/16.

Results: The full analysis set comprised 215 pts at W0 (SC, n=107; IV, n=108). At W16, 86.0% (SC) and 92.6% (IV) of pts completed treatment. Most pts (SC, 92.5%; IV, 88.9%) had a history of inadequate response/intolerance to prior biologics. At W16, while CRes did not statistically differentiate between arms, secondary outcomes indicated a difference in the IV vs SC arm. In this analysis, differences were seen in bionaïve pts and those with inadequate response/intolerance to < 3 biologics. A numerically greater proportion of pts achieved CRes in the IV vs SC arms in all groups except pts with ≥3 prior biologics, with a nominal difference in pts with 1 prior biologic (p=0.043; Table). A similar trend was observed for pts achieving W16 CRem, albeit the nominal threshold was not reached. A numerically greater proportion of pts in the IV vs SC arm achieved normalization of CRP and/or fCal at W16, except those with ≥3 prior biologics, and with a nominal difference in pts with 1 prior biologic (p< 0.001).

Discussion: POWER is the first trial to assess the efficacy and safety of UST IV re-induction in pts with secondary LoR. This analysis suggests that both naïve pts and those with prior inadequate response or intolerance to biologics may benefit from UST re-induction therapy.


Disclosures:


Scott D. Lee, MD¹, Stefan Schreiber, MD², C. Janneke van der Woude, MD, PhD³, Ignacio Marín-Jiménez, MD⁴, Douglas C.. Wolf, MD⁵, Elisabeth Schnoy, MD, PhD⁶, Bruce Salzberg, MD⁷, Christopher Busse, ⁸, Maciej Nazar, ⁹, Wayne Langholff, ¹⁰, Christopher Gasink, ⁸, Thomas Baker, ¹⁰, Bridget Godwin, MD⁸, Brian G. Feagan, MD¹¹. P2212 - Clinical Outcomes and Biomarker Normalization Response at Week 16 in Patients With Inadequate Response or Intolerance to Prior Biologics in the POWER Trial, ACG 2023 Annual Scientific Meeting Abstracts. Vancouver, BC, Canada: American College of Gastroenterology.