AB1410 EARLY SYMPTOMATIC IMPROVEMENT WITH GUSELKUMAB INDUCTION TREATMENT IN MODERATELY TO SEVERELY ACTIVE ULCERATIVE COLITIS: RESULTS FROM THE PHASE 3 QUASAR INDUCTION STUDY

Background:

The Phase 3 QUASAR Induction Study (NCT04033445) was a randomized, double-blind, placebo-controlled, parallel-group, multicenter study of guselkumab (GUS), an interleukin-23 p19 subunit antagonist, in patients with moderately to severely active ulcerative colitis (UC).

Objectives:

To evaluate the early onset of symptom improvement.

Methods:

Patients were randomized in a 3:2 ratio to receive intravenous (IV) GUS 200mg or placebo (PBO) at Weeks 0, 4, and 8. The primary analysis population included treated patients with a baseline modified Mayo score of 5 to 9, and an endoscopy subscore ≥2 (centrally read). Through Week 12, patients recorded stool production and episodes of rectal bleeding in a diary. Symptomatic remission at Weeks 2, 4, and 12 were major secondary endpoints. All other analyses were not multiplicity controlled (nominal p-values).

Results:

The primary analysis population included 701 randomized and treated patients (baseline mean UC duration, 7.5 years; Mayo endoscopy subscore=3 [severe disease], 67.9%; and mean modified Mayo score, 6.9). At baseline, 49.1% had prior inadequate response/intolerance to advanced therapies (ADT-IR) for UC; nearly half of these (47.4%) had ≥2 ADT-IR classes. At baseline, for the GUS and PBO groups, the mean absolute number of stools per day were 7.10 and 6.96; stool frequency subscores of 0 or 1 were observed in 10.0% and 9.6%; and mean rectal bleeding subscores were 1.7 and 1.8, respectively. As early as Week 1 and increasing through Week 12, greater symptomatic improvement was seen in patients treated with GUS compared with PBO (Figure 1). At Weeks 2, 4, 8, and 12, symptomatic remission was achieved by GUS- vs PBO-treated patients in 12.1% vs 9.3%, 22.6% vs 12.9%, 39.7% vs 20.7%, and 49.9% vs 20.7% (all p<0.001, except Week 2, p=0.210), respectively. For GUS vs PBO, percentages of patients with stool frequency subscore of 0 or 1 at Weeks 2, 4, 8, and 12 were 26.1% vs 18.2%, 41.3% vs 25.4%, 53.4% vs 29.6%, and 60.1% vs 31.8% (all p<0.001, except Week 2, p<0.05), respectively; percentages of patients with rectal bleeding subscores of 0 at Weeks 2, 4, 8, and 12 were 24.2% vs 19.3%, 36.8% vs 22.9%, 55.8% vs 33.2%, and 64.6% vs 28.6% (all p<0.001, except Week 2, p=0.110), respectively. Treatment differences for GUS vs PBO were evident across Week 12 symptomatic outcomes (Table 1).

Conclusion:

GUS 200mg IV induction was effective in improving symptoms as early as 1 week after the first dose in patients with moderately to severely active UC. Symptomatic improvements increased through Week 12. REFERENCES: NIL.

Acknowledgements:

NIL.

Disclosure of Interests:

Kuan-Hsiang G. Huang Owns Johnson & Johnson stock/stock options, Employee of Johnson & Johnson, Gary R. Lichtenstein Stock options for Virgo, Consultant for Abbvie, Allergan, Celgene, Eli Lilly, Endo Pharmaceuticals, Ferring, Gilead, Janssen/Janssen Orthobiotech, MedEd Consultants, Merck, Morphic Therapeutics, Pfizer Pharmaceuticals, Prometheus Laboratories, Inc, Romark, Sandoz, Salix Pharmaceuticals/Valeant, Shire Pharmaceuticals, Takeda, UCB, Virgo, Research/grant support from Celgene, Janssen/Janssen Orthobiotech (Funding to University of PA [IBD Fellow Education]), Takeda (Funding to University of PA [IBD Fellow Education]), UCB, Axel Dignass Payment from lectures from AbbVie, Biogen, CED Service GmbH, Celltrion, Falk Foundation, Ferring, Galapagos, Gilead, High5MD, Janssen, Materia Prima, MedToday, MSD, Pfizer, Streamed-Up, Takeda, Tillotts, and Vifor Pharma, Service on speakers bureaus from AbbVie, Biogen, CED Service GmbH, Celltrion, Falk Foundation, Ferring, Galapagos, Gilead, High5MD, Janssen, Materia Prima, MedToday, MSD, Pfizer, Streamed-Up, Takeda, Tillotts, and Vifor Pharma, Consultancy fees from AbbVie, Amgen, Arena Pharmaceuticals, Biogen, Boehringer Ingelheim, Bristol Myers Squibb/Celgene, Celltrion, Dr Falk Foundation, Ferring Pharmaceuticals, Fresenius Kabi, Galapagos, Janssen, Lilly, MSD, Pfizer, Pharmacosmos, Roche/Genentech, Sandoz/Hexal, Takeda, Tillotts, and Vifor Pharma, Fees for participation in clinical trials, review activities such as data monitoring boards, statistical analysis and end point committees from Abivax, AbbVie, Arena Pharmaceuticals, Bristol Myers Squibb/Celgene, Dr Falk Foundation, Galapagos, Gilead, Janssen, and Pfizer; payment for manuscript preparation from Falk Foundation, Takeda, Thieme, and UniMed Verlag, David T. Rubin Co-founder of Cornerstones Health, Inc., Consultant to AbbVie, Altrubio, Allergan, Inc., Arena Pharmaceuticals, Aslan Pharmaceuticals, Athos Therapeutics, Bellatrix Pharmaceuticals, Boehringer Ingelheim, Ltd., Bristol Myers Squibb, Celgene Corp/Syneos, Connect BioPharma, GalenPharma/Atlantica, Genentech/Roche, InDex Pharmaceuticals, Ironwood Pharmaceuticals, Iterative Scopes, Janssen Pharmaceuticals, Eli Lilly, Materia Prima, Pfizer, Prometheus Biosciences, Reistone, Takeda, Techlab, Inc., Research funding from Takeda, Shadi Yarandi Owns Johnson & Johnson stock/stock options, Employee of Johnson & Johnson, Matthew Germinaro Owns Johnson & Johnson stock/stock options, Employee of Johnson & Johnson, Ye Miao Owns Johnson & Johnson stock/stock options, Employee of Johnson & Johnson, Hongyan Zhang Owns Johnson & Johnson stock/stock options, Employee of Johnson & Johnson, Dennis McGonagle Research grants from AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, and UCB, Jaroslaw Kierkuś Clinical investigator and consultant for Janssen, Ursula Seidler Advisor/speaker for Janssen, Abbvie, Galapagos, and Lilly, Research grants from Janssen, Abbvie, Eli Lilly, Abivax, Gilead, and BMS, Atsuo Maemoto Clinical investigator and consultant for Janssen, Jessica R. Allegretti Speaker for BMS, Abbvie, and Janssen, Consultant for Janssen, Pfizer, Abbvie, Finch Therapeutics, Seres Therapeutics, Ferring, Merck, Bristol Myers Squibb, and Adiso, Research support from Pfizer and Merck, Brian Bressler Advisor/speaker for Abbvie, BMS, Ferring, Janssen, Merck, Novartis, Organon, Pfizer, Sandoz, and Takeda, Stock options for Qu Biologic, Advisor for Alimentiv, Allergan, AMT, Bausch Health, BMS, Celgene, Celltrion Healthcare, Eupraxia, Fresenius Kabi, Genentech, Gilead, Iterative Scopes, Jamp Pharma, Merck Amgen, Microbiome Insights, Mylan, Pendopharm, Protagonist, and Viatris, Research support from Abbvie, Amgen, BI, BMS, Genentech, GSK, Janssen, Merck, and Qu Biologic, Laurent Peyrin-Biroulet Stock options from CTMA, Grants from AbbVie, MSD, and Takeda.