TARGETED SAFETY ANALYSES OF GUSELKUMAB: LONG-TERM RESULTS FROM RANDOMIZED CLINICAL TRIALS IN PATIENTS WITH ACTIVE PSORIATIC ARTHRITIS AND MODERATE TO SEVERE PSORIASIS

BackgroundGuselkumab (GUS) demonstrated efficacy and a favorable safety profile in active PsA in the Phase (Ph) 21 and Ph3 DISCOVER-1&2 trials2,3 and in moderate-to-severe plaque psoriasis (PsO) in the Ph3 VOYAGE-1&2 trials.4,5ObjectivesTo assess long-term safety of GUS across PsA/PsO trials.MethodsUsing pooled safety data through 2 years (yrs) from PsA trials (N=1229; GUS 100 mg every 4/8 weeks [Q4W/Q8W])1-3 and through 5 yrs from PsO trials (N=1721; GUS 100 mg Q8W),4,5 incidences of serious adverse events (SAEs); gastrointestinal (GI)-related SAEs and other targeted AEs; including candidiasis, uveitis, and opportunistic infections (OIs) were evaluated. Incidence rates (IRs) were calculated as the number of events per 100 pt-yrs (PY) of follow-up with 95% CI. Patients (pts) with an IBD history were not excluded in PsA/PsO trials. Max exposure duration was W100 for PsA trials and W252 for PsO trials.ResultsThe PsA and PsO populations had comparable mean age and BMI. IRs of SAEs and GI-related SAEs were generally similar between GUS- and PBO-treated pts during PBO-controlled periods, and between PsA pts receiving GUS Q4W/Q8W for up to 2 yrs and PsO pts receiving GUS Q8W for up to 5 yrs (Table 1). IRs of other targeted AEs of interest were low. OIs did not occur in PsO pts and were infrequent in PsA pts (Table 1). Candidal infections were infrequent and non-serious. Iridocyclitis was reported in 1 PBO- and 1 GUS Q8W-treated PsA pt. No exacerbations or new onset of IBD or active tuberculosis was reported in GUS-treated PsA/PsO pts.Table 1.Targeted AEs of InterestPooled PsA*Pooled PsOThrough 2 YrsThrough 5 YrsGUS 100 mg Q4W (N=373)GUS 100 mg Q8W (N=475)PBO→GUS 100 mg Q4W (N=352)aPBO→GUS 100 mg Q8W (N=29)aGUS Combined (N=1229)GUS 100 mg Q8W (N=1221)bADA→GUS 100 mg Q8W (N=500)cGUS Combined (N=1721)Total PY645748461171871525419127166Mean PY1.71.61.30.61.54.33.84.2Events/100 PY (95% CI)Overall SAEs4.65(3.14, 6.64)6.42(4.73, 8.51)5.86(3.86, 8.52)0.00(0.00, 17.24)5.61(4.59, 6.79)5.18(4.58, 5.83)4.55(3.64, 5.61)5.01(4.50, 5.56)GI-related SAEs0.46(0.10, 1.36)0.27(0.03, 0.97)0.00 (0.00, 0.65)0.00(0.00, 17.24)0.27(0.09, 0.62)0.44(0.28, 0.66)0.42(0.18, 0.82)0.43(0.29, 0.61)OIsd0.00(0.00, 0.46)0.27(0.03, 0.97)0.22(0.01, 1.21)0.00(0.00, 17.24)0.16(0.03, 0.47)0.00(0.00, 0.06)0.00(0.00, 0.16)0.00(0.00, 0.04)Candida infections0.31(0.04, 1.12)0.00(0.00, 0.40)0.00(0.00, 0.65)0.00(0.00, 17.24)0.11(0.01, 0.39)0.49(0.32, 0.73)0.52(0.25, 0.96)0.50(0.35, 0.70)Non-pathogen specific fungal infections, suspicious for candida0.00(0.00, 0.46)0.27(0.03, 0.97)0.00(0.00, 0.65)0.00(0.00, 17.24)0.11(0.01, 0.39)0.11(0.04, 0.25)0.16(0.03, 0.46)0.13(0.06, 0.24)Uveitis/ Iridocyclitis0.00(0.00, 0.46)0.13(0.00, 0.75)0.00(0.00, 0.65)0.00(0.00, 17.24)0.05(0.00, 0.30)0.00(0.00, 0.06)0.00(0.00, 0.16)0.00(0.00, 0.04)*In PsA Ph2, data after early escape at W16 were excluded. AEs are coded using MedDRA Version 23.1aFor PBO→GUS, data on/after 1st GUS administration were includedbPBO crossover pts were included in GUS column after crossover to GUScEvents prior to GUS (ADA events) were excluded. Only includes pts randomized to ADA at W0 and crossed over to GUS at/after W52 for VOYAGE-1 & W28 for VOYAGE-2dHerpes zoster disseminated, fungal oesophagitis, and meningitis listeria (1 each)ADA=AdalimumabConclusionIRs of SAEs; GI-related SAEs; and AEs of interest including candidiasis, uveitis, and OIs were low, or no cases were reported. No new safety concerns were identified with GUS treatment through 2 yrs and 5 yrs of follow-up in the pooled PsA and PsO trials, respectively, supporting a durable and favorable GUS safety profile consistent between pts with active PsA and moderate-to-severe PsO.References[1]Deodhar A, et al. Lancet. 2018;391:2213-2224.[2]Deodhar A, et al. Lancet. 2020;395:1115-1125.[3]Mease PJ, et al. Lancet. 2020;395:1126-1136.[4]Blauvelt A, et al. J Am Acad Dermatol. 2017;76:405-417.[5]Reich K, et al. J Am Acad Dermatol. 2017;76:418-431.Disclosure of InterestsPhilip J Mease Speakers bureau: AbbVie, Aclaris, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Celgene, Crescendo Bioscience, Genentech, Inmagene, Janssen, Lilly, Merck, Novartis, Pfizer, SUN Pharma, and UCB, Consultant of: AbbVie, Aclaris, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Celgene, Crescendo Bioscience, Genentech, Inmagene, Janssen, Lilly, Merck, Novartis, Pfizer, SUN Pharma, and UCB, Grant/research support from: AbbVie, Aclaris, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Celgene, Crescendo Bioscience, Genentech, Inmagene, Janssen, Lilly, Merck, Novartis, Pfizer, SUN Pharma, and UCB, Peter Foley Speakers bureau: AbbVie, Celgene, Janssen, Eli Lilly, Merck, Novartis, Pfizer, Valeant, Galderma, GlaxoSmithKline, Leo Pharma, and Roche, Paid instructor for: (Advisory boards) AbbVie, Amgen, Aslan, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Janssen, Eli Lilly, Merck, Novartis, Pfizer, Sun Pharma, UCB Pharma, Valeant, Galderma, GlaxoSmithKline, Leo Pharma, and Sanofi, Consultant of: Janssen, Eli Lilly, Novartis, Pfizer, UCB Pharma, Bristol-Myers Squibb, Galderma, Leo Pharma, and Roche; investigator for AbbVie, Amgen, AstraZeneca, Arcutis, Aslan, Boehringer Ingelheim, Celgene, Hexima, Janssen, Eli Lilly, Merck, Novartis, Pfizer, Sun Pharma, UCB Pharma, Valeant, Bristol-Myers Squibb, Celtaxsys, CSL, Cutanea, Dermira, Galderma, Genentech, GlaxoSmithKline, Leo Pharma, Regeneron Pharmaceuticals Inc, Reistone, Roche, and Sanofi, Grant/research support from: AbbVie, Amgen, Celgene, Janssen, Leo Pharma, Eli Lilly, Merck, Novartis, Pfizer, Sanofi, and Sun Pharma; travel grants from AbbVie, Janssen, Eli Lilly, Merck, Novartis, Pfizer, Galderma, Leo Pharma, Roche, Sun Pharma, and Sanofi; served as speaker for or received honoraria from AbbVie, Celgene, Janssen, Eli Lilly, Merck, Novartis, Pfizer, Valeant, Galderma, GlaxoSmithKline, Leo Pharma, and Roche, Kristian Reich Speakers bureau: Abbvie, Affibody, Amgen, Biogen, Boehringer Ingelheim Pharma, Bristol Myers Squibb, Celgene, Centocor, Covagen, Eli Lilly, Forward Pharma, Galderma, GlaxoSmithKline, Janssen-Cilag, Leo, Medac, Merck Sharp & Dohme Corp., Novartis, Ocean Pharma, Pfizer, Regeneron, Sanofi, Takeda, UCB Pharma, and Xenoport, Paid instructor for: Abbvie, Affibody, Amgen, Biogen, Boehringer Ingelheim Pharma, Bristol Myers Squibb, Celgene, Centocor, Covagen, Eli Lilly, Forward Pharma, Galderma, GlaxoSmithKline, Janssen-Cilag, Leo, Medac, Merck Sharp & Dohme Corp., Novartis, Ocean Pharma, Pfizer, Regeneron, Sanofi, Takeda, UCB Pharma, and Xenoport, Consultant of: Participated in clinical trials sponsored by Abbvie, Affibody, Amgen, Biogen, Boehringer Ingelheim Pharma, Bristol Myers Squibb, Celgene, Centocor, Covagen, Eli Lilly, Forward Pharma, Galderma, GlaxoSmithKline, Janssen-Cilag, Leo, Medac, Merck Sharp & Dohme Corp., Novartis, Ocean Pharma, Pfizer, Regeneron, Sanofi, Takeda, UCB Pharma, and Xenoport, Soumya D Chakravarty Employee of: Janssen Scientific Affairs, LLC and may own stock or stock options in Johnson & Johnson, May Shawi Employee of: Janssen Global Services, LLC and may own stock or stock options in Johnson & Johnson, Ya-Wen Yang Employee of: Janssen Global Services, LLC and may own stock or stock options in Johnson & Johnson, Megan Miller Employee of: Janssen Research & Development, LLC and may own stock or stock options in Johnson & Johnson, Alexa Kollmeier Employee of: Janssen Research & Development, LLC and may own stock or stock options in Johnson & Johnson, Xie L Xu Employee of: Janssen Research & Development, LLC and may own stock or stock options in Johnson & Johnson, Jenny Yu Employee of: Janssen Research & Development, LLC and may own stock or stock options in Johnson & Johnson, Yanli Wang Employee of: Janssen Research & Development, LLC and may own stock or stock options in Johnson & Johnson, Shihong Sheng Employee of: Janssen Research & Development, LLC and may own stock or stock options in Johnson & Johnson, Yin You Employee of: Janssen Research & Development, LLC and may own stock or stock options in Johnson & Johnson, Iain McInnes Consultant of: AbbVie, Bristol-Myers Squibb, Boehringer-Ingelheim, Celgene, Eli Lilly, Gilead, Janssen, Novartis and UCB., Grant/research support from: Astra Zeneca, Bristol-Myers Squibb, Celgene, Janssen, Lilly, Novartis, and UCB