Open Access

Stefan Schreiber, Scott D. Lee, C. Janneke van der Woude, Ignacio Marín-Jiménez, Douglas C. Wolf, Elisabeth Schnoy, Bruce Salzberg, Christopher Busse, Maciej Nazar, Tony Ma, Stephan Borghorst, Christopher Gasink, Thomas Baker, Bridget Godwin, Omoniyi J. Adedokun, Brian G. Feagan, Scott Lee, Douglas Wolf, Bruce Salzberg, Elisabeth Schnoy, Stefan Schreiber, Jochen Klaus, Herbert Deppe, Anita Afzali, Thomas Krause, Yoram Bouhnik, Torsten Kucharzik, Oksana Shchukina, Renate Schmelz, Milan Lukas, Stephane Nancey, Byong Duk Ye, George DuVall, Stefanie Howaldt, Caprioli Flavio, Hyo-Jong Kim, Kamal Patel, Yoram Bouhnik, Pierre Blanc, Irina Blumenstein, Manreet Kaur, Jimmy Limdi, Annette Krummenerl, Peter Hasselblatt, Pilar Lopez Serrano, Ulf Helwig, Alessandro Armuzzi, Ana Echarri, Udayakumar Navaneethan, Britta Siegmund, Xavier Calvet Calvo, Parambir Dulai, Laurent Peyrin Biroulet, Wolfgang Reindl, Jeroen Jansen, Ignacio Marin Jimenez, Cristina Rodriquez Gutierrez, Raquel Vincente Lidon, Jessica Allegretti, Helga Török, Ji-Hye Park, Desirée Leemreis, Olga Fedorishina, Dawn Beaulieu, Sarah Glover, Charles Randall, Rodolfo Rocca, Mikael Lördal, William Holderman, Heba Iskandar, Laura Loy, Simone Saibeni, Maria Dolores Martin Arranz, Montserrat Rivero Tirado, Bincy Abraham, Robert Hirten, Tomas Vanasek, Guillaume Boughen, Pierre Desreumaux, Wolfgang Mohl, Taeoh Kim, Andrea van der Meulen, Pavel Makarchuk, Francis Farraye, Alexandra Kent

• Background The POWER study (NCT03782376) evaluated efficacy and safety of a single ustekinumab intravenous (IV) reinduction dose versus placebo under continued ustekinumab subcutaneous (SC) treatment in adult patients with moderately to severely active Crohn’s disease who demonstrated a secondary loss of response to ustekinumab every 8 weeks (q8w) maintenance therapy. Methods Patients were randomly assigned 1:1 at Week 0 to ustekinumab IV reinduction (ustekinumab ∼6 mg/kg and SC placebo) or continuous maintenance (IV placebo and SC ustekinumab 90 mg q8w). Clinical and biomarker assessments occurred at Weeks 0, 8, 16, and 24 with optional ileocolonoscopy at Weeks 0 and16. The primary endpoint was clinical response (≥100-point decrease from baseline Crohn’s Disease Activity Index [CDAI] score or CDAI <150) at Week 16. Safety events were analyzed through Week 36 and serum samples were collected for pharmacokinetic analyses and anti-ustekinumab antibody detection. Results Overall, 215Background The POWER study (NCT03782376) evaluated efficacy and safety of a single ustekinumab intravenous (IV) reinduction dose versus placebo under continued ustekinumab subcutaneous (SC) treatment in adult patients with moderately to severely active Crohn’s disease who demonstrated a secondary loss of response to ustekinumab every 8 weeks (q8w) maintenance therapy. Methods Patients were randomly assigned 1:1 at Week 0 to ustekinumab IV reinduction (ustekinumab ∼6 mg/kg and SC placebo) or continuous maintenance (IV placebo and SC ustekinumab 90 mg q8w). Clinical and biomarker assessments occurred at Weeks 0, 8, 16, and 24 with optional ileocolonoscopy at Weeks 0 and16. The primary endpoint was clinical response (≥100-point decrease from baseline Crohn’s Disease Activity Index [CDAI] score or CDAI <150) at Week 16. Safety events were analyzed through Week 36 and serum samples were collected for pharmacokinetic analyses and anti-ustekinumab antibody detection. Results Overall, 215 patients were randomized: 108 to the IV reinduction group and 107 to the SC group. In the IV reinduction group, 49.1% achieved clinical response at Week 16 versus 37.4% in the SC group (adjusted treatment difference 11.5% [95% CI: −1.5%, 24.5%; P = .089]). Proportions of patients with endoscopic remission and improvement, normalization of inflammatory biomarkers, and improvement in IBDQ score were greater in the IV reinduction group vs the SC group. No new safety signals were identified. Conclusions Although the primary endpoint of clinical response was not met at Week 16, ustekinumab IV reinduction showed numerical improvements in objective endpoints including inflammatory biomarkers and endoscopic outcomes compared with SC maintenance therapy. Safety and immunogenicity results were consistent with the established profile of ustekinumab.…