作者
Bruce E. Sands,Peter M. Irving,Timothy Hoops,James Izanec,Lei Gao,Christopher Gasink,Andrew Greenspan,Matthieu Allez,Silvio Danese,Stephen B. Hanauer,Vipul Jairath,Tanja Kuehbacher,James D. Lewis,Edward V. Loftus,Emese Mihály,Remo Panaccione,Ellen Scherl,О. Б. Щукина,William J. Sandborn,Anita Afzali,Lilia Aitova,Xavier Aldeguer i Mante,Matthieu Allez,István Altorjay,Federico Argüelles Arias,Alessandro Armuzzi,Monika Augustyn,Mauro Boiocchi,Jesús Barrio,Jakob Begun,Clint Behrend,Geert Bezemer,G Bonnaud,Marija Branković,Ik Jang Byung,Xavier Calvet,Karen A. Chachu,Júlio Maria Fonseca Chebli,Jae Hee Cheon,Halina Cichoż‐Lach,Larry Clark,Fraser Cummings,Kunal Dalal,Silvio Danese,Nanne de Boer,Maria de Lourdes Abreu Ferrari,Étienne Désilets,Predrag Dugalić,George Duvall,Olga Fedorishina,Rafał Filip,Cristina Flores,Ronald Fogel,James Fon,Michael Frankel,Keith Friedenberg,Walter Fries,Vassileva Galina,Piotr Gietka,Rishi Goel,Peter Hasselblatt,Hans H. Herfarth,László Herszényi,Pieter Hindryckx,Frank Hoentjen,Carmen Horjus Talabur Horje,Satish Iduru,Peter M. Irving,Robert J. Isfort,Vipul Jairath,Michael P. Jones,Dilara Kalimullina,Jeffry Katz,Manreet Kaur,Sunil K Khurana,Sang Woo Kim,Young‐Ho Kim,D Kleczkowski,S Knežević,Aaron Knoll,Louis Y Korman,Iskren Kotzev,Andrey Kulyapin,Kang Moon Lee,Desirée Leemreis,Jarosław Leszczyszyn,Jimmy K. Limdi,Jack J. Lissauer,Edward V. Loftus,Ewa Małecka‐Panas,John K. Marshall,Emese Mihály,Milan Lukáš,Giovanni Monteleone,Aleksandar Nagorni,Danuta Owczarek,Nichole Palekar,Remo Panaccione,Young Soo Park,Sang Hyoung Park,Rogério Serafim Parra,Árpád V. Patai,Kamal Patel,Bhaktasharan Patel,Anatoly Pershko,Elina Petrova,Guillaume Pineton de Chambrun,Charles Randall,S. Riestra Menéndez,Timothy E. Ritter,Montserrat Rivero,Xavier Roblin,Rodolfo Rocca,J Romatowski,Grażyna Rydzewska,Simone Saibeni,Bruce Salzberg,H Sarles,John B. Saunders,Edoardo Savarino,Zuzana Šerclová,О. Б. Щукина,Jonathan H. Siegel,Najm Soofi,Miles Sparrow,David Stokesberry,Daniel Suiter,Petar Svorcan,А. В. Ткачев,Nikolay Tsonev,Tünde Kristóf,Jan Ulbrych,Tomáš Vaňásek,Márta Varga,Séverine Vermeire,Raquel Vicente Lidon,Michael L Weiss,Emma Wesley,Nathaniel S. Winstead,Katarzyna Wójcik,Joanna Wypych,Cyrla Zaltman,Zdena Zadorova
摘要
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.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.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.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.Janssen Scientific Affairs.