P377 Impact of moderate-to-severe endoscopic disease criteria on endoscopic response, endoscopic remission, and deep remission in patients receiving ustekinumab or adalimumab in the SEAVUE study
Allez, M.(1);Lewis, J.D.(2);Hanauer, S.B.(3);Danese, S.(4);Irving, P.M.(5,6);Gasink, C.(7);Hoops, T.(8);Izanec, J.L.(7);Ma, T.(7);Loftus- Jr., E.V.(9);Scherl, E.J.(10);Panaccione, R.(11);Sandborn, W.J.(12);Sands, B.E.(13);
(1)Hôpital Saint-Louis- Assistance Publique-Hôpitaux de Paris AP-HP- INSERM U1160 and Université de Paris, Gastroenterology Department, Paris, France;(2)Perelman School of Medicine at the University of Pennsylvania, Division of Gastroenterology, Philadelphia, United States;(3)Northwestern University Feinberg School of Medicine, Department of Gastroenterology, Chicago, United States;(4)IRCCS Ospedale San Raffaele and Università Vita-Salute San Raffaele, Gastroenterology and Endoscopy, Milan, Italy;(5)Guy’s and Saint Thomas’ Hospitals NHS Trust, Department of Gastroenterology, London, United Kingdom;(6)King’s College London, School of Immunology and Microbial Sciences, London, United Kingdom;(7)Janssen Scientific Affairs- LLC, Immunology, Horsham, United States;(8)Janssen Pharmaceutical Companies of Johnson & Johnson, Immunology Global Medical Affairs, Horsham, United States;(9)Mayo Clinic College of Medicine, Division of Gastroenterology and Hepatology, Rochester, United States;(10)New York Presbyterian Hospital Weill Cornell Medicine, Weill Department of Medicine, New York, United States;(11)University of Calgary, Inflammatory Bowel Disease Unit- Division of Gastroenterology and Hepatology, Calgary, Canada;(12)University of California San Diego, Division of Gastroenterology, La Jolla, United States;(13)Icahn School of Medicine at Mount Sinai, Dr. Henry D. Janowitz Division of Gastroenterology, New York, United States;
Entry criteria and outcome measures of Crohn’s disease (CD) clinical trials have evolved. Patients are now required to have active inflammation on screening endoscopy, with some studies requiring moderate-severe SES-CD scores. Recent trials have endoscopic response as a co-primary endpoint and endoscopic remission (ER) and deep remission (DR) as major secondary endpoints. Pivotal CD maintenance studies typically examine only responders to induction. The SEAVUE study required ≥1 ulceration of any size (SES-CD≥3) at baseline and had a treat-through design. To examine the results in the context of these trial design characteristics, we evaluated endoscopic outcomes at wk52 in the subgroup of pts with moderate-severe baseline SES-CD scores in SEAVUE, as well as those who were in clinical response after induction.
Biologic-naïve pts failing or intolerant to conventional therapy with CDAI≥220/≤450 and SES-CD≥3 were eligible. Pts were randomized 1:1 to UST (~6mg/kg IV at wk0 then 90mg SC q8w) or ADA (SC 160mg at wk0, 80mg at wk2, then 40mg q2w). Endoscopic outcomes were evaluated in all pts and the subgroup with moderate-severe endoscopic disease (baseline SES-CD≥6 for ileocolonic or colonic disease or SES-CD≥4 for isolated ileal disease). Endoscopic response was a ≥50% reduction from baseline in SES-CD, SES-CD≤3, or SES-CD=0 for pts with baseline SES-CD=3. ER was SES-CD≤3 or 0 in pts with baseline SES-CD=3. DR was CDAI<150 and ER.
Endoscopic outcomes for the subgroup with moderate-severe endoscopic disease were similar to those of the full cohort of pts. In UST-treated pts, endoscopic response was achieved at wk52 in 41.9% in the full cohort and 43.1% in the moderate-severe subgroup (Table 1). In ADA-treated pts, endoscopic responses were 36.9% and 35.4%, respectively. For pts who were in clinical response after induction (Table 1), endoscopic response rates were 48.2% in the full cohort and 49.5% in the moderate-severe subgroup for UST and 44.8% and 43.1%, respectively, for ADA. ER and DR rates were generally similar between the full cohort and the moderate-severe subgroup (Table 2; eg, ERs were UST 28.5% and ADA 30.7% in full cohort; UST 27.1% and 27.8% ADA in subgroup). ER and DR rates were 3%-7% higher in induction responders compared with the full cohort. Of note, even among wk16 nonresponders, some pts attained endoscopic outcomes at wk52 (eg, endoscopic responses in wk16 nonresponders were UST 21.4% and ADA 13.3%).
In SEAVUE, both the UST and ADA treatment groups achieved high endoscopic response, ER, and DR rates at wk52. Results in pts with moderate-severe endoscopic disease were similar to those of the full cohort, but clinical responders after induction had higher rates than the full cohort.