Abstract

Ustekinumab versus adalimumab for induction and maintenance therapy in biologic-naive patients with moderately to severely active Crohn's disease: a multicentre, randomised, double-blind, parallel-group, phase 3b trial

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

 

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

 
     

Author information

Collaborators

SEAVUE Study Group: 

Anita AfzaliLilia AitovaXavier Aldeguer I ManteMatthieu AllezIstván AltorjayFederico Argüelles AriasAlessandro ArmuzziMonika AugustynMauro BafuttoJesus BarrioJakob BegunClint BehrendGeert BezemerGuillaume BonnaudMarija BrankovicIk Jang ByungXavier Calvet CalvoKaren ChachuJulio Maria Fonseca ChebliJae Hee CheonHalina Cichoz-LachLarry ClarkFraser CummingsKunal DalalSilvio DaneseNanne De BoerMaria De Lourdes FerrariEtienne DésiletsPredrag DugalicGeorge DuvallOlga FedorishinaRafal FilipCristina FloresRonald FogelJames FonMichael FrankelKeith FriedenbergWalter FriesVassileva GalinaPiotr GietkaRishi GoelPeter HasselblattHans HerfarthLászló HerszényiPieter HindryckxFrank HoentjenCarmen Horjus Talabur HorjeSatish IduruPeter IrvingRobert IsfortVipul JairathMichael JonesDilara KalimullinaJeffry KatzManreet KaurSunil K KhuranaJoo Sung KimYoungho KimDariusz KleczkowskiSlavko KnezevicAaron KnollLouis Y KormanIskren KotzevAndrey KulyapinKang Moon LeeDesiree LeemreisJaroslaw LeszczyszynJimmy LimdiJack LissauerEdward LoftusEwa Malecka-PanasJohn MarshallEmese MihályLukas MilanGiovanni MonteleoneAleksandar NagorniDanuta OwczarekNichole PalekarRemo PanaccioneYoung Soo ParkSang Hyoung ParkRogério ParraÁrpád PataiKamal PatelBhaktasharan PatelAnatoly PershkoElina PetrovaGuillaume Pineton de ChambrunCharles RandallSabino Riestra MenendezTimothy RitterMontserrat RiveroXavier RoblinRodolfo RoccaJacek RomatowskiGrazyna RydzewskaSimone SaibeniBruce SalzbergHarry SarlesJohn SaundersEdoardo Vincenzo SavarinoZuzana SerclovaOksana ShchukinaJonathan SiegelNajm SoofiMiles SparrowDavid StokesberryDaniel SuiterPetar SvorcanAlexander TkachevNikolay TsonevKristóf TündeJan UlbrychTomas VanasekMárta VargaSeverine VermeireRaquel Vicente LidonMichael L WeissEmma WesleyNathaniel WinsteadKatarzyna WojcikJoanna WypychCyrla ZaltmanZadorova 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.

 

 

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