AB0528 COMPARABLE SAFETY PROFILE OF GUSELKUMAB IN PSORIATIC ARTHRITIS AND PSORIASIS: RESULTS FROM PHASE 3 TRIALS THROUGH 1 YEAR
Authors: A. B. Gottlieb, J. F. Merola, A. Armstrong, R. Langley, M. Lebwohl, C. E. M. Griffiths, M. Shawi, Y. W. Yang, E. C. Hsia, A. Kollmeier, X. L. Xu, M. Izutsu, P. Ramachandran, S. Sheng, Y. You, M. Miller, C. T. Ritchlin, I. McInnes, P. Rahman
Journal: Annals of the Rheumatic Diseases (2021)

Background: DISCOVER 1&amp;2 (PsA) and VOYAGE 1&amp;2 (PsO) are Phase 3 trials of guselkumab (GUS). Objectives: Compare safety results through up to 1yr of GUS in PsA and PsO pts. Methods: In DISCOVER, 1120 pts with active PsA despite standard therapy were treated. Most pts were biologic-naïve; ~30% in DISCOVER 1 had previous exposure to 1-2 TNFi. Concomitant MTX (57%), oral corticosteroids (17%), and NSAIDs (64%) were permitted. Pts were randomized to SC GUS 100mg at W0, W4, then Q8W; GUS 100mg Q4W; or PBO. At W24, PBO patients were switched to GUS 100mg Q4W. In VOYAGE, in which concomitant MTX use was prohibited, 1245 pts with moderate to severe PsO were treated and randomized to SC GUS 100 mg at W0, W4, W12, then Q8W; or PBO at W0, W4, W12, with crossover to GUS at W16, W20, then Q8W. AEs and laboratory parameters, analyzed by National Cancer Institute-Common Terminology Criteria for AEs [NCI-CTCAE] toxicity grades, were summarized through the PBO-controlled periods and 1yr. Results: Safety profiles were generally consistent across the GUS PsO and PsA clinical programs (Table 1). Time-adjusted incidence rates for numbers of AEs, serious AEs, serious infections, malignancy, MACE and AEs leading to d/c were generally similar between PsO and PsA. No cases of anaphylaxis or opportunistic infections were reported. Proportions of pts with decreased neutrophil counts and elevations in hepatic transaminases were slightly higher in PsA vs PsO. These abnormalities were mostly of NCI-CTCAE Grade 1 or 2 (&lt;LLN-1000/mm 3 for neutrophils; &lt;5.0 x ULN for AST/ ALT), generally transient, required no medical interventions, resolved spontaneously, and did not lead to interruption or d/c of treatment. Through 1yr, proportions of pts with ALT/AST elevations in PsA trials were slightly higher for GUS Q4W than Q8W and in pts with vs without baseline MTX use. Conclusion: The GUS safety profile was generally consistent in PsA and PsO GUS-treated pts through 1yr of the DISCOVER and VOYAGE trials. Table 1. Treatment-Emergent AEs During PBO-controlled Period and Through 1Yr: VOYAGE &amp; DISCOVER Trials Pooled VOYAGE 1&amp;2 Pooled DISCOVER 1&amp;2 Time Period W0-16 Through 1Yr W0-24 b Through 1Yr (N=) PBO (422) GUS Q8W (823) Combined GUS a (1221) PBO c (372) GUS Q8W (375) GUS Q4W (373) GUS Q8W (375) GUS Q4W (373) Combined GUS† (1100) Total pt-yrs of follow-up 128 255 974 173 173 172 384 385 973 Incidence/100 pt-yrs (95% CI) d AEs 317 (287,349) 330 (308,353) 259 (249, 270) 219 (198,243) 256 (232,281) 221 (200, 245) 218 (203,233) 177 (164,191) 191 (182, 199) SAEs 5 (2, 10) 6 (4, 10) 6 (5, 8) 9 (5, 15) 4 (2, 8) 5 (2, 10) 6 (4, 9) 4 (2, 7) 6 (4, 7) AEs leading to study agent d/c 3 (0.9, 8) 4 (2, 8) 2 (2, 4) 4 (2, 8) 3 (1, 7) 7 (4, 12) 2 (1, 4) 4 (2, 6) 3 (2, 5) Infections 86 (71, 104) 98 (86, 111) 98 (92, 104) 58 (48, 71) 58 (47, 71) 63 (51, 76) 58 (50, 66) 53 (46, 61) 55 (50, 60) Serious Infections 0. 8 (0, 4) 0.4 (0, 2) 1 (0.5, 2) 4 (2, 8) 0.6 (0, 3) 2 (0.4, 5) 2 (0.6, 3) 1 (0, 2) 2 (0.9, 3) All Malignancy 0 (0, 2) 0.4 (0, 2) 1 (0.4, 2) 0.6 (0, 3) 1 (0, 4) 0 (0, 2) 0.5 (0, 2) 0 (0, 0. 8) 0 (0, 1) MACE 0 (0, 2) 0.4 (0, 2) 0.4 (0, 1) 0.6 (0, 3) 0 (0, 2) 0.6 (0, 3) 0 (0, 0.8) 0.3 (0, 1.4) 0.1 (0, 0.6) % pts with ≥1 injection site rxn 3.1 4.5 5.0 0.3 1.3 1.1 1.6 2.4 1.7 a Placebo crossover pts were included in the combined GUS column after crossover to GUS b For all pts who d/c study treatment early with the last dose of PBO/GUS prior to W24 and who did not receive any PBO/GUS at or after Wk24, all data including the final safety follow-up visit collected through 1yr were included c For pts in PBO group who switched to GUS due to cross-over or inadvertently, only data prior to first administration of GUS were included. d CI based on an exact method assuming observed number of events follows a Poisson distribution Disclosure of Interests: Alice B Gottlieb Consultant of: Anaptyps Bio, Avotres Therapeutics, Beiersdorf, Boehringer Ingelheim, Bristol-Myers-Squibb, Eli Lilly, Janssen, LEO Pharma, Novartis, Sun Pharmaceuticals, UCB, and Xbiotech, Grant/research support from: Boehringer Ingelheim, Janssen, Novartis, Sun Pharmaceuticals, UCB, and Xbiotech, Joseph F. Merola Consultant of: AbbVie, Arena, Biogen, BMS, Dermavant, Eli Lilly, Janssen, Novartis, Pfizer, Sun Pharma, UCB, April Armstrong Consultant of: AbbVie, Janssen, Lilly, Leo, Novartis, UCB, Ortho Dermatologics, Dermira, KHK, Sanofi, Regeneron, Sun Pharma, BMS, Dermavant, and Modernizing Medicine, Richard Langley Speakers bureau: AbbVie, Amgen, Boehringer Ingelheim, Celgene, Eli Lilly, Janssen, LEO Pharma, Merck, Novartis, Pizer, Sun Pharmaceutical, and UCB Pharma, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Celgene, Eli Lilly, Janssen, LEO Pharma, Merck, Novartis, Pizer, Sun Pharmaceutical, and UCB Pharma, 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, Christopher E.M. Griffiths Speakers bureau: AbbVie, Amgen, Almirall, BMS, Boehringer Ingelheim Celgene, Janssen, LEO Pharma, Lilly, Novartis, Pfizer, Sun Pharma, UCB Pharma., Consultant of: AbbVie, Amgen, Almirall, BMS, Boehringer Ingelheim Celgene, Janssen, LEO Pharma, Lilly, Novartis, Pfizer, Sun Pharma, UCB Pharma., Grant/research support from: AbbVie, Amgen, Almirall, BMS, Boehringer Ingelheim Celgene, Janssen, LEO Pharma, Lilly, Novartis, Pfizer, Sun Pharma, UCB Pharma., May Shawi Shareholder of: Johnson &amp; Johnson, Employee of: Janssen Global Services, LLC, Ya-Wen Yang Shareholder of: Johnson &amp; Johnson, Employee of: Janssen Global Services, LLC, Elizabeth C Hsia Shareholder of: Johnson &amp; Johnson, Employee of: Janssen Research &amp; Development, LLC, Alexa Kollmeier Shareholder of: Johnson &amp; Johnson, Employee of: Janssen Research &amp; Development, LLC, Xie L Xu Shareholder of: Johnson &amp; Johnson, Employee of: Janssen Research &amp; Development, LLC, Miwa Izutsu Shareholder of: Johnson &amp; Johnson, Employee of: Janssen Research &amp; Development, LLC, Paraneedharan Ramachandran Shareholder of: Johnson &amp; Johnson, Employee of: Janssen Research &amp; Development, LLC, Shihong Sheng Shareholder of: Johnson &amp; Johnson, Employee of: Janssen Research &amp; Development, LLC, Yin You Shareholder of: Johnson &amp; Johnson, Employee of: Janssen Research &amp; Development, LLC, Megan Miller Shareholder of: Johnson &amp; Johnson, Employee of: Janssen Research &amp; Development, LLC, Christopher T. Ritchlin Consultant of: AbbVie, Amgen, Gilead, Janssen, Lilly, Novartis, Pfizer, and UCB Pharma, Grant/research support from: AbbVie, Amgen, and UCB Pharma, Iain McInnes Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Gilead, and Janssen, Novartis, Pfizer, and UCB, Grant/research support from: Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Janssen, and UCB, Proton Rahman Speakers bureau: AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, Roche, and UCB, Grant/research support from: Janssen and Novartis.