P493 QUASAR Induction Study 1 Cumulative Response to Guselkumab in Patients With Moderately to Severely Active Ulcerative Colitis
Peyrin-Biroulet, L.(1)*;Rubin, D.(2);Lichtenstein, G.(3);Shipitofsky, N.(4);Huang, K.H.(4);Germinaro, M.(4);Wilson, R.(5);Zhang, H.(5);DuVall, G.A.(6);Cao, Q.(7);Allegretti, J.(8);Feagan, B.(9);Hisamatsu, T.(10);Panés, J.(11);Dignass, A.(12);Bressler, B.(13);Sands, B.(14);
(1)Nancy University Hospital, Gastroenterology, Nancy, France;(2)University of Chicago Medicine, Inflammatory Bowel Disease Center, Chicago, United States;(3)Raymond and Ruth Perelman School of Medicine of the University of Pennsylvania, Department of Medicine- Division of Gastroenterology, Philadelphia, United States;(4)Janssen Research & Development- LLC, Immunology, Spring House, United States;(5)Janssen Research & Development- LLC, Biostatistics, Spring House, United States;(6)Tyler Research Institute- LLC, Gastroenterology, Tyler, United States;(7)Zhejiang University School of Medicine, School of Medicine, Hangzhou, China;(8)Brigham and Women’s Hospital Crohn’s and Colitis Center, Gastroenterology- Hepatology and Endoscopy, Boston, United States;(9)Alimentiv Inc, Gastroenterology, London, Canada;(10)Kyorin University, Gastroenterology and Hepatology, Tokyo, Japan;(11)Hospital Clínic de Barcelona- IDIBAPS- CIBERehd, Gastroenterology, Barcelona, Spain;(12)Agaplesion Markus Hospital, Department of Medicine, Frankfurt, Germany;(13)University of British Columbia, Division of Gastroenterology, Vancouver, Canada;(14)Icahn School of Medicine at Mount Sinai, Dr. Henry D. Janowitz Division of Gastroenterology, New York, United States; QUASAR Investigators
Background
Guselkumab (GUS), an IL-23p19 antagonist, had greater efficacy than placebo (PBO) in achieving clinical response and clinical remission at Week (Wk) 12 in the randomized, controlled Phase 2b QUASAR Induction Study 1 (NCT04033445) in patients with moderately to severely active ulcerative colitis (UC).1 Patients who were not in clinical response at Wk 12 received GUS treatment through Wk 24. Here, we report GUS cumulative efficacy and safety results for Induction Study 1.
Methods
Eligible patients had moderately to severely active UC (modified Mayo score of 5 to 9 with a Mayo endoscopy subscore ≥2) at baseline. Patients were randomized 1:1:1 to IV GUS 200mg, 400mg, or PBO at Wks 0, 4, and 8. Patients who were not in clinical response to IV induction at Wk 12 received GUS treatment (PBO IV→GUS 200mg IV; GUS 200mg IV→GUS 200mg SC; GUS 400mg IV→GUS 200mg SC) at Wks 12, 16, and 20 and were evaluated at Wk 24 (Figure 1). Matching IV or SC PBO was administered to maintain the blind.
Results
Three hundred thirteen patients were randomized and treated at baseline. Demographic and disease characteristics at baseline were similar among the treatment groups, and approximately 50% had a prior inadequate response or intolerance to advanced UC therapy. At Wk 12, clinical response was achieved by 61.4% (62/101) and 60.7% (65/107) of patients randomized to GUS 200mg and GUS 400mg IV vs 27.6% (29/105) of patients randomized to PBO IV (both p<0.001). Of the patients in the GUS groups who were not in clinical response at Wk 12, 54.3% (19/35) in the GUS 200mg IV→200mg SC group and 50.0% (19/38) in the GUS 400mg IV→200mg SC group achieved clinical response at Wk 24. Clinical response at Wk 12 or 24 was achieved by 80.2% of patients who were randomized to GUS 200mg IV and 78.5% of patients who were randomized to GUS 400mg IV. For patients who received PBO IV→GUS 200mg IV, clinical response at Wk 24 (65.2%) was similar to Wk 12 clinical response following GUS 200mg IV induction (61.4%). The most frequent adverse events among all GUS-treated pts (n=274) were anemia (7.7%), headache (5.1%), worsening UC (4.4%), COVID-19 (3.6%), arthralgia (2.9%) and abdominal pain (2.6%) which are consistent with Wk 12 results.
Conclusion
Overall, approximately 80% of patients randomized to receive GUS achieved clinical response at Wk 12 or 24. Continued treatment with SC GUS allowed 50-54.3% of IV GUS Wk 12 clinical nonresponders to achieve clinical response at Wk 24. No new safety concerns for GUS were identified.