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OP02 Ustekinumab versus adalimumab for induction and maintenance therapy in Moderate-to-Severe Crohn’s Disease: The SEAVUE study

Irving, P.M.(1,2);Sands, B.E.(3);Hoops, T.(4);Izanec, J.L.(4);Gao, L.L.(4);Gasink, C.(4);Greenspan, A.(4);Allez, M.(5,6);Danese, S.(7);Hanauer, S.B.(8);Jairath, V.(9,10);Kuhbacher, T.(11);Lewis, J.D.(12);Loftus Jr., E.V.(13);Mihaly, E.(14);Panaccione, R.(15);Scherl, E.(16);Shchukina, O.(17);Sandborn, W.J.(18)

(1)Guy’s and Saint Thomas’ Hospitals NHS Trust, Gastroenterology, London, United Kingdom;(2)King’s College London, School of Immunology and Microbial Sciences, London, United Kingdom;(3)Icahn School of Medicine at Mt Sinai, Gastroenterology, New York, United States;(4)Janssen Research & Development- LLC, Immunology, Horsham, United States;(5)INSERM UMRS 1160- Université de Paris, Gastroenterology, Paris, France;(6)Hôpital Saint-Louis Hospital- Assistance Publique-Hôpitaux de Paris AP-HP, Gastroenterology, Paris, France;(7)Humanitas Clinical and Research Center- Humanitas University, Inflammatory Bowel Disease Center and Department of Biomedical Sciences, Milan, Italy;(8)Northwestern University Feinberg School of Medicine, Gastroenterology, Chicago, United States;(9)Division of Gastroenterology- University Hospital, Medicine, Ontario, Canada;(10)Western University- London, Division of Epidemiology and Biostatistics, Ontario, Canada;(11)Asklepios Westklinikum Hamburg and Christian Albrechts University, Gastroenterology, Hamburg, Germany;(12)Perelman School of Medicine at the University of Pennsylvania, Gastroenterology, Philadelphia, United States;(13)Mayo Clinic College of Medicine, Gastroenterology and Hepatology, Rochester, United States;(14)Semmelweis University Medical School, 2nd Department of Internal Medicine, Budapest, Hungary;(15)University of Calgary, Inflammatory Bowel Disease Unit- Division of Gastroenterology and Hepatology, Alberta, Canada;(16)New York Presbyterian Hospital Weill Cornell Medicine, Weill Department of Medicine, New York, United States;(17)City Clinical Hospital #31, Gastroenterology, St-Petersburg, Russian Federation;(18)University of California San Diego, Gastroenterology, La Jolla, United States

Background

Background

We studied the efficacy and safety of ustekinumab (UST) vs adalimumab (ADA) through 1 year in biologic-naïve patients (pts) with moderate-to-severe Crohn's disease.

Methods

Methods

SEAVUE was a multicenter, randomized, blinded, parallel-group, active-controlled study in adults with CD Activity Index (CDAI) scores ≥220/≤450. Biologic-naïve pts failing/intolerant to conventional therapy with any size ulcer on baseline (BL) ileocolonoscopy were eligible. Pts were randomized 1:1 to UST (⁓6mg/kg IV at BL then 90mg SC every 8 weeks [Ws]) or ADA (160/80mg SC at BL/W2, then 40mg SC every 2 Ws) per US-approved regimens (no dose modifications). Primary endpoint was clinical remission at W52 (CDAI <150). Major secondary endpoints were corticosteroid-free remission, clinical response (≥100-point CDAI decrease from BL), remission in pt-reported CDAI components (PRO-2 symptom remission: abdominal pain mean daily score ≤1 and stool frequency mean daily score ≤3), and endoscopic remission (SES-CD score ≤3/0 for pts with BL score=3) at W52 and clinical remission at W16.

Results

Results

386 pts were randomized to UST or ADA. BL demographics and disease characteristics were balanced between groups and indicative of pts with early, moderate-to-severe CD (median CD duration, 2.58 years; CDAI, 289.5; SES-CD, 8.0). At W52, 65% of UST-treated and 61% of ADA-treated pts achieved clinical remission (Δ=4.0%; 95% CI, -5.5%, 13.5%; p=0.417). Major secondary endpoints, including endoscopic remission, were similar between groups (Table 1), as were remission rates at assessment points through W52. Some other secondary endpoints showed numerical (not statistical) differences between UST and ADA (Table 1). Key safety events are summarized in Table 2. Among UST-treated and ADA-treated pts, 34.0% and 40.5% had infections, 2.6% and 7.2% had serious adverse events (AEs) of worsening CD, and 6.3% and 11.3% had AEs that led to discontinuation (DC) of study drug, respectively. One ADA-treated pt had active pulmonary TB. Injection-site reactions associated with active treatment occurred in 1.0% of UST-treated and 10.3% of ADA-treated pts. Overall, 15.2% of UST-treated and 23.6% of ADA-treated pts DC before W52. Reasons for DC were primarily lack of efficacy (UST, 2.1% vs ADA, 5.1%), AEs (UST, 5.7% vs ADA, 10.7%), and withdrawal of consent (UST, 5.8% vs ADA, 5.1%). Time to treatment DC was longer with UST vs ADA (post hoc analysis).

Conclusion

Conclusion

Both UST and ADA were highly effective in this population of biologic-naïve pts. Rates of clinical remission at W52 were not statistically significantly different between treatment groups. DC rates were numerically lower for UST. Safety results were consistent with prior experience for both treatments.

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