P473 Corticosteroid-free clinical remission rates with guselkumab maintenance therapy in patients with moderately to severely active Crohn’s disease: Week 48 analyses from the phase 2 GALAXI 1 study
D'Haens, G.(1)*;Afzali, A.(2);Filip, R.(3);Rolim, A.(4);Terry, N.A.(5);Salese, L.(5);Sahoo, A.(5);Frustaci, M.E.(6);Yang, Z.(6);Andrews, J.M.(7);Danese, S.(8);Hisamatsu, T.(9);
(1)Amsterdam University Medical Centers, Department of Gastroenterology, Amsterdam, The Netherlands;(2)University of Cincinnati College of Medicine and Division of Digestive Diseases, Department of Internal Medicine, Cincinnati- OH, United States;(3)University of Rzeszow, Department of Gastroenterology with IBD Unit, Rzeszow, Poland;(4)Pesquisare Saúde, Coloproctology, Santo André- São Paulo, Brazil;(5)Janssen Research and Development LLC, Immunology, Spring House- PA, United States;(6)Janssen Research and Development LLC, Statistics and Decision Sciences, Spring House- PA, United States;(7)Royal Adelaide Hospital and University of Adelaide, Department of Gastroenterology and Hepatology, Adelaide, Australia;(8)IRCCS Ospedale San Raffaele and Università Vita-Salute San Raffaele, Gastroenterology and Endoscopy, Milano, Italy;(9)Kyorin University, Department of Gastroenterology and Hepatology, Tokyo, Japan; on behalf of the GALAXI 1 investigators
Background
Corticosteroids are often used in Crohn’s disease (CD) to control inflammation. However, they are associated with adverse events; thus, achieving and maintaining remission without corticosteroids is a major treatment goal. GALAXI 1, a phase 2b, double-blind, placebo (PBO)-controlled study, evaluated efficacy and safety of guselkumab (GUS), a selective interleukin-23p19 subunit antagonist, in patients (pts) with moderately to severely active CD. Primary efficacy and safety data were presented previously. Here, we report corticosteroid-free clinical remission rates through Week (Wk) 48.
Methods
Pts with moderately to severely active CD were randomised in a treat-through design to GUS 200, 600, 1200mg; ustekinumab (UST) ~6mg/kg; or PBO intravenous (IV) induction followed by maintenance dosing (GUS 200mg IV-->GUS 100mg subcutaneous [SC] every 8 weeks [q8w], GUS 600mg IV-->GUS 200mg SC q4w, GUS 1200mg IV-->GUS 200mg SC q4w, UST ~6mg/kg IV-->UST 90mg SC q8w, PBO nonresponders-->UST ~6mg/kg IV-->UST 90mg SC q8w, PBO responders-->PBO SC q4w). Corticosteroid tapering was mandatory from Wk12 if medically feasible. Efficacy endpoints included corticosteroid-free CD Activity Index (CDAI) clinical remission (<150) and pt-reported outcome (PRO)-2 remission at Wk48 in the primary efficacy population. Pts randomised to PBO were not included in Wk48 efficacy analyses. GALAXI 1 was not powered to evaluate efficacy differences between treatment groups at Wk48; UST was a reference arm. Analyses were prespecified but not multiplicity controlled.
Results
At Wk48, 55.7-71.4% of pts in the GUS dose groups achieved corticosteroid-free CDAI clinical remission (Table 1). Similar rates were observed when the corticosteroid-free duration was ≥30 or ≥90 days before Wk48. Among pooled pts in CDAI clinical remission at Wk48 in the GUS groups, 115/120 (95.8%) were corticosteroid free. At Wk48, 49.2-68.3% of pts in the GUS dose groups achieved corticosteroid-free PRO-2 remission (Table 1). Among pooled pts in PRO-2 remission at Wk48 in the GUS groups, 105/110 (95.5%) were corticosteroid free. Outcomes in the reference UST group are shown in Table 1. Among pts in the GUS dose groups, 30.2-39.3% were using corticosteroids at Wk0 (median prednisone equivalent dose 20.0mg/d in each group); at Wk48, 60.0-78.9% of these pts met corticosteroid-free criteria (Table 2).
Conclusion
High rates of corticosteroid-free CDAI clinical and PRO-2 remission were achieved at Wk48 in the GUS dose groups. Among pts in clinical remission, most were corticosteroid free. Nearly all pts maintained corticosteroid-free CDAI clinical remission for ≥90 days. GUS IV induction followed by SC maintenance therapy also effectively reduced corticosteroid use at Wk48.