POS1031 LOW INCIDENCE OF GASTROINTESTINAL-RELATED AND OVERALL SERIOUS ADVERSE EVENTS AMONG GUSELKUMAB-TREATED PATIENTS: POOLED ANALYSES OF VOYAGE 1 & 2 AND DISCOVER 1 & 2 THROUGH 1-YEAR
Authors: Mease P. J. , Foley P. , Reich K. , Bagel J. , Lebwohl M. , Yang Y. W. , Shawi M. , Miller M. , Kollmeier A. , Hsia E. C. , Xu X. L. , Izutsu M. , Ramachandran P. , Sheng S. , You Y. , Helliwell P. , Boehncke W. H. 
Published: May 2021

Background:

Guselkumab (GUS), a human monoclonal antibody that specifically binds to the p19-subunit of interleukin (IL)-23, demonstrated efficacy in the Phase 3 VOYAGE 1&2 trials of patients (pts) with moderate to severe plaque psoriasis (PsO)1,2 and in the DISCOVER 1&2 trials of pts with active psoriatic arthritis (PsA).3,4 IL-17 inhibitors used to treat PsO and PsA have been associated with exacerbation or new onset of inflammatory bowel disease (IBD) (e.g., Crohn’s disease or ulcerative colitis).5

Objectives:

Evaluate the incidence of gastrointestinal (GI)-related and overall serious adverse events (SAEs) from pooled safety data through 1-year of GUS 100 mg treatment from the VOYAGE 1&2 and DISCOVER 1&2 trials.

Methods:

Using pooled safety data from the VOYAGE 1&2 PsO trials and DISCOVER 1&2 PsA trials, SAEs related to GI disorders were identified using the Medical Dictionary for Regulatory Activities (MedDRA) system-organ class “GI disorders”. Pts with a previous history of IBD were not excluded in these trials; medical history of IBD was collected at baseline in DISCOVER 1&2. Rates of overall SAEs and GI-related SAEs were calculated as the number of SAEs per 100 pt-years (PY) of follow-up (95% confidence intervals). Data are presented for the placebo (PBO)-controlled period (Weeks 0-16 for VOYAGE 1&2; Weeks 0-24 for DISCOVER 1&2) and through 1-year (defined as through Week 48 for VOYAGE 1&2; through Week 60 for DISCOVER 1, and through Week 52 for DISCOVER 2). Events of uveitis and opportunistic infections were also analyzed.

Results:

Through the PBO-controlled period, the overall rates of GI-related SAEs per 100 PY for pooled VOYAGE 1&2 were: PBO 0.78 (0.02, 4.34), GUS q8w 0; and for pooled DISCOVER 1&2: PBO 0.58 (0.01, 3.23), GUS q8w 0.58 (0.01, 3.21), GUS q4w 0. The GI-related SAEs included: gastrointestinal hemorrhage (PBO; n=1) for pooled VOYAGE 1&2; and inflammatory bowel disease (PBO; n=1) and mechanical ileus (GUS q8w; n=1) for pooled DISCOVER 1&2. Through 1-year, the overall rates of GI-related SAEs for pooled VOYAGE 1&2 were: Combined GUS group (GUS q8w and PBO→GUS groups) 0.51 (0.17, 1.20); and for pooled DISCOVER 1&2: GUS q8w 0.52 (0.06, 1.88), GUS q4w 0, Combined GUS group (GUS q8w, GUS q4w, and PBO→GUS groups) 0.21 (0.02, 0.74). The GI-related SAEs in the Combined GUS group for pooled VOYAGE 1&2 included: gastritis, hemorrhoids, inguinal hernia, pancreatitis, and umbilical hernia (0.10/100PY [0.00, 0.57]; n=1 for each); and in the Combined GUS group for pooled DISCOVER 1&2: mechanical ileus and pancreatitis chronic (0.10/100PY [0.00, 0.57]; n=1 for each). Overall, no cases of exacerbation or new onset of IBD were reported in GUS-treated pts, including 2 pts with a prior history of IBD in DISCOVER 1&2 (total PY of follow-up for the Combined GUS groups in VOYAGE and DISCOVER were 974 and 973, respectively). Through the PBO-controlled period, rates of overall SAEs for GUS-treated pts were comparable to PBO-pts and SAE rates remained low through 1-year of follow-up in the VOYAGE 1&2 and DISCOVER 1&2 trials. There were no reported cases of uveitis, opportunistic infections, or tuberculosis in GUS-treated pts through 1-year.

Conclusion:

Through 1-year of follow-up with GUS treatment in pooled VOYAGE 1&2 and DISCOVER 1&2, GI-related SAE rates were low. There were no reported cases of uveitis, opportunistic infections, or new onset/exacerbation of IBD in GUS-treated pts. No new safety concerns were identified through 1-year.

References:

[1]Blauvelt A., et al. J Am Acad Dermatol. 2017;76:405-17.

[2]Reich K., et al. J Am Acad Dermatol. 2017;76:418-31.

[3]Deodhar A., et al. Lancet. 2020;395:1115-25.

[4]Mease P.J., et al. Lancet. 2020; 395:1126-36.

[5]Hohenberger M., et al. J Dermatolog Treat. 2018;29:13-8.

Disclosure of Interests:

Philip J Mease Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Novartis, Pfizer, SUN, and UCB, Grant/research support from: AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, SUN, and UCB, Peter Foley Speakers bureau: AbbVie, Celgene, Janssen, Lilly, Merck, Novartis, Pfizer, Valeant, Galderma, GSK, Leo Pharma, and Roche, Consultant of: Janssen, Lilly, Novartis, Pfizer, Galderma, AbbVie, Amgen, AstraZeneca, Arcutis, Aslan, Boehringer Ingelheim, Celgene, Hexima, Merck, Sun Pharma, UCB Pharma, Valeant, BMS, Celtaxsys, CSL, Cutanea, Dermira, Genentech, GSK, Leo Pharma, Regeneron Pharmaceuticals Inc, Reistone, Roche, and Sanofi, Grant/research support from: AbbVie, Amgen, Celgene, Janssen, Leo Pharma, Lilly, Merck, Novartis, Pfizer, Sanofi, and Sun Pharma; travel grants from AbbVie, Janssen, Lilly, Merck, Novartis, Pfizer, Galderma, Leo Pharma, Roche, Sun Pharma, and Sanofi

, Kristian Reich Consultant of: AbbVie, Amgen, Gilead, Janssen, Lilly, Novartis, Pfizer, and UCB Pharma, Grant/research support from: AbbVie, Amgen, and UCB Pharma, Jerry Bagel Speakers bureau: AbbVie, Celgene Corporation, Eli Lilly, Janssen Biotech, and Novartis, Consultant of: AbbVie, Amgen, Celgene Corporation, Eli Lilly and Company, Janssen Biotech, Leo Pharma, Novartis, Sun Pharmaceutical Industries Ltd, and Valeant Pharmaceuticals, Grant/research support from: AbbVie, Amgen, Arcutis Biotherapeutics, Boehringer Ingelheim, Bristol Myers Squibb, Celgene Corporation, Corrona, LLC, Dermavant Sciences, LTD, Dermira/UCB, Eli Lilly and Company, Glenmark Pharmaceuticals Ltd, Janssen Biotech, Kadmon Corporation, Leo Pharma, Lycera Corp, Menlo Therapeutics, Novartis, Pfizer, Regeneron Pharmaceuticals, Sun Pharma, Taro Pharmaceutical Industries Ltd, and Valeant Pharmaceuticals, Mark Lebwohl Consultant of: Aditum Bio, Allergan, Almirall, Arcutis, Inc., Avotres Therapeutics, BirchBioMed Inc., BMD skincare, Boehringer-Ingelheim, Bristol-Myers Squibb, Cara Therapeutics, Castle Biosciences, Corrona, Dermavant Sciences, Evelo, Evommune, Facilitate International Dermatologic Education, Foundation for Research and Education in Dermatology, Inozyme Pharma, Kyowa Kirin, LEO Pharma, Meiji Seika Pharma, Menlo, Mitsubishi, Neuroderm, Pfizer, Promius/Dr. Reddy’s Laboratories, Serono, Theravance, and Verrica, Grant/research support from: Abbvie, Amgen, Arcutis, Boehringer Ingelheim, Dermavant, Eli Lilly, Evommune, Incyte, Janssen, Leo Pharmaceutucals, Ortho Dermatologics, Pfizer, and UCB, Ya-Wen Yang Shareholder of: Johnson & Johnson, Employee of: Janssen Global Services, LLC, May Shawi Shareholder of: Johnson & Johnson, Employee of: Janssen Global Services, LLC, Megan Miller Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Alexa Kollmeier Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Elizabeth C Hsia Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Xie L Xu Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Miwa Izutsu Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Paraneedharan Ramachandran Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Shihong Sheng Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Yin You Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Philip Helliwell Consultant of: Galapagos, Janssen, Novartis, Grant/research support from: Abbvie, Janssen, Pfizer, Wolf-Henning Boehncke Speakers bureau: AbbVie, Almirall, Celgene, Janssen, Leo, Lilly, Novartis, and UCB Pharma, Consultant of: AbbVie, Almirall, Celgene, Janssen, Leo, Lilly, Novartis, and UCB Pharma, Grant/research support from: Pfizer