Lancet. 2022 Jun 11;399(10342):2200-2211.doi: 10.1016/S0140-6736(22)00688-2.

Bruce E Sands ¹, Peter M Irving ², Timothy Hoops ³, James L Izanec ⁴, Long-Long Gao ⁴, Christopher Gasink ⁴, Andrew Greenspan ⁴, Matthieu Allez ⁵, Silvio Danese ⁶, Stephen B Hanauer ⁷, Vipul Jairath ⁸, Tanja Kuehbacher ⁹, James D Lewis ¹⁰, Edward V Loftus Jr ¹¹, Emese Mihaly ¹², Remo Panaccione ¹³, Ellen Scherl ¹⁴, Oksana B Shchukina ¹⁵, William J Sandborn ¹⁶, SEAVUE Study Group

Author information

Collaborators

SEAVUE Study Group: 

Anita Afzali, Lilia Aitova, Xavier Aldeguer I Mante, Matthieu Allez, István Altorjay, Federico Argüelles Arias, Alessandro Armuzzi, Monika Augustyn, Mauro Bafutto, Jesus Barrio, Jakob Begun, Clint Behrend, Geert Bezemer, Guillaume Bonnaud, Marija Brankovic, Ik Jang Byung, Xavier Calvet Calvo, Karen Chachu, Julio Maria Fonseca Chebli, Jae Hee Cheon, Halina Cichoz-Lach, Larry Clark, Fraser Cummings, Kunal Dalal, Silvio Danese, Nanne De Boer, Maria De Lourdes Ferrari, Etienne Désilets, Predrag Dugalic, George Duvall, Olga Fedorishina, Rafal Filip, Cristina Flores, Ronald Fogel, James Fon, Michael Frankel, Keith Friedenberg, Walter Fries, Vassileva Galina, Piotr Gietka, Rishi Goel, Peter Hasselblatt, Hans Herfarth, László Herszényi, Pieter Hindryckx, Frank Hoentjen, Carmen Horjus Talabur Horje, Satish Iduru, Peter Irving, Robert Isfort, Vipul Jairath, Michael Jones, Dilara Kalimullina, Jeffry Katz, Manreet Kaur, Sunil K Khurana, Joo Sung Kim, Youngho Kim, Dariusz Kleczkowski, Slavko Knezevic, Aaron Knoll, Louis Y Korman, Iskren Kotzev, Andrey Kulyapin, Kang Moon Lee, Desiree Leemreis, Jaroslaw Leszczyszyn, Jimmy Limdi, Jack Lissauer, Edward Loftus, Ewa Malecka-Panas, John Marshall, Emese Mihály, Lukas Milan, Giovanni Monteleone, Aleksandar Nagorni, Danuta Owczarek, Nichole Palekar, Remo Panaccione, Young Soo Park, Sang Hyoung Park, Rogério Parra, Árpád Patai, Kamal Patel, Bhaktasharan Patel, Anatoly Pershko, Elina Petrova, Guillaume Pineton de Chambrun, Charles Randall, Sabino Riestra Menendez, Timothy Ritter, Montserrat Rivero, Xavier Roblin, Rodolfo Rocca, Jacek Romatowski, Grazyna Rydzewska, Simone Saibeni, Bruce Salzberg, Harry Sarles, John Saunders, Edoardo Vincenzo Savarino, Zuzana Serclova, Oksana Shchukina, Jonathan Siegel, Najm Soofi, Miles Sparrow, David Stokesberry, Daniel Suiter, Petar Svorcan, Alexander Tkachev, Nikolay Tsonev, Kristóf Tünde, Jan Ulbrych, Tomas Vanasek, Márta Varga, Severine Vermeire, Raquel Vicente Lidon, Michael L Weiss, Emma Wesley, Nathaniel Winstead, Katarzyna Wojcik, Joanna Wypych, Cyrla Zaltman, Zadorova Zdena

Affiliations

¹Dr Henry D Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Electronic address: bruce.sands@mssm.edu.

²Department of Gastroenterology, Guy's and St Thomas' NHS Foundation Trust, London, UK; School of Immunology and Microbial Sciences, King's College London, London, UK.

³Immunology Global Medical Affairs, Janssen Pharmaceutical Companies of Johnson & Johnson, Horsham, PA, USA.

⁴Janssen Scientific Affairs, Horsham, PA, USA.

⁵Gastroenterology Department, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris (AP-HP), INSERM U1160, Université de Paris, Paris, France.

⁶Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and Università Vita-Salute San Raffaele, Milan, Italy.

⁷Northwestern University Feinberg School of Medicine, Chicago, IL, USA.

⁸Division of Gastroenterology, Department of Medicine, University Hospital, London, ON, Canada; Division of Epidemiology and Biostatistics, Western University, London, ON, Canada.

⁹Department of Internal Medicine, Gastroenterology, Diabetology, Hemato-Oncology, and Palliative Medicine, Medius Clinic Nuertingen, Nürtingen, Germany.

¹⁰Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.

¹¹Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science, Rochester, MN, USA.

¹²Department of Internal Medicine and Hematology, Semmelweis University, Budapest, Hungary.

¹³Inflammatory Bowel Disease Unit, Division of Gastroenterology and Hepatology, University of Calgary, Calgary, AB, Canada.

¹⁴Weill Department of Medicine, New York Presbyterian Hospital Weill Cornell Medicine, New York, NY, USA.

¹⁵Division The City Center for IBD Diagnosis and Treatment, Saint Petersburg State Budgetary Health Institution, City Clinical Hospital 31, Saint Petersburg, Russia.

¹⁶Division of Gastroenterology, University of California San Diego, La Jolla, CA, USA.

Abstract

Background: Active-comparator trials are important to inform patient and physician choice. We aimed to evaluate the efficacy and safety of monotherapy with either ustekinumab or adalimumab in biologic-naive patients with moderately to severely active Crohn's disease.

Methods: We conducted a randomised, double-blind, parallel-group, active-comparator, phase 3b trial (SEAVUE) at 121 hospitals or private practices in 18 countries. We included biologic-naive patients aged 18 years or older with moderately to severely active Crohn's disease and a Crohn's Disease Activity Index (CDAI) score of 220-450, who had not responded to or were intolerant to conventional therapy (or were corticosteroid dependent) and had at least one ulcer of any size at baseline endoscopic evaluation. Eligible patients were randomly assigned (1:1; via an interactive web response system) to receive ustekinumab (approximately 6 mg/kg intravenously on day 0, then 90 mg subcutaneously once every 8 weeks) or adalimumab (160 mg on day 0, 80 mg at 2 weeks, then 40 mg once every 2 weeks, subcutaneously) through week 56. Study treatments were administered as monotherapy and without dose modifications. Patients, investigators, and study site personnel were masked to treatment group assignment. The primary endpoint was the proportion of patients who were in clinical remission (CDAI score <150) at week 52 in the intention-to-treat population (ie, all patients who were randomly assigned to a treatment group). This trial is registered with ClinicalTrials.gov, NCT03464136, and EudraCT, 2017-004209-41.

Findings: Between June 28, 2018, and Dec 12, 2019, 633 patients were assessed for eligibility and 386 were enrolled and randomly assigned to receive ustekinumab (n=191) or adalimumab (n=195). 29 (15%) of 191 patients in the ustekinumab group and 46 (24%) of 195 in the adalimumab group discontinued study treatment before week 52. There was no significant difference between the ustekinumab and adalimumab groups in the occurrence of the primary endpoint; at week 52, 124 (65%) of 191 patients in the ustekinumab group versus 119 (61%) of 195 in the adalimumab group were in clinical remission (between-group difference 4%, 95% CI -6 to 14; p=0·42). Safety for both groups was consistent with previous reports. Serious infections were reported in four (2%) of 191 patients in the ustekinumab group and five (3%) of 195 in the adalimumab group. No deaths occurred through week 52 of the study.

Interpretation: Both ustekinumab and adalimumab monotherapies were highly effective in this population of biologic-naive patients, with no difference in the primary outcome between the drugs.

Funding: Janssen Scientific Affairs.