AB0532 MAINTENANCE OF RESPONSE THROUGH 5 YEARS OF CONTINUOUS GUSELKUMAB TREATMENT: RESULTS FROM THE PHASE-3 VOYAGE 1 TRIAL
Authors: C. E. M. Griffiths, K. Papp, M. Song, M. Miller, Y. You, Y. K. Shen, A. Blauvelt
Journal: Annals of the Rheumatic Diseases (2021)

Background: VOYAGE 1, a phase-3, double-blinded, placebo- and active comparator-controlled study evaluated the efficacy and safety of guselkumab (GUS; a fully human anti-interleukin-23 monoclonal antibody) in patients with moderate-to-severe plaque psoriasis. 1,2,3 Objectives: To assess the efficacy and safety through 5 years of continuous GUS treatment. Methods: In VOYAGE 1, patients were randomized to GUS 100 mg at Weeks 0, 4, 12, then every 8 weeks (q8w); placebo at Weeks 0, 4, 12 followed by GUS 100 mg at Weeks 16, 20 then q8w; or adalimumab 80 mg at Week 0, 40 mg at Week 1, then 40 mg every 2 weeks (q2w) through Week 47. At Week 52, all patients continued open-label GUS through Week 252. Efficacy assessments included proportions of patients achieving ≥90% or 100% improvement in Psoriasis Area and Severity Index (PASI 90, PASI 100), and Investigator’s Global Assessment scores of cleared/minimal or cleared (IGA 0/1, IGA 0). Three statistical methods were used to analyze efficacy: prespecified Treatment Failure Rules (TFR), Nonresponder Imputation (NRI), and As Observed (OBS). For TFR analyses, patients who discontinued study agent due to lack of efficacy, worsening of psoriasis, or use of a protocol-prohibited psoriasis treatment were considered nonresponders. For NRI analyses, patients with missing efficacy data (regardless of the reason) after application of TFR were counted as nonresponders. For OBS analyses, missing data were not imputed. Safety was assessed through Week 264. Results: Among a total of 494 patients randomized to GUS at Week 0 (N=329) and placebo patients who crossed over to GUS at Week 16 (N=165), 76.9% (380/494) continued study agent through Week 252. PASI 90 responses were well-maintained with up to 5 years of continuous GUS use. At Week 52, PASI 90 response rates were 79.7%, 75.5%, and 80.6% based on TFR, NRI, and OBS analyses, respectively; corresponding rates at Week 252 were 84.1%, 66.6%, and 86.6%. Likewise, PASI 100, IGA 0/1, and IGA 0 responses were maintained from Week 52 through Week 252 (Table 1). Efficacy was also maintained through Week 252 in patients randomized to GUS at Week 0 (N=329). Through the end of the study for all patients (GUS group and adalimumab→GUS crossover group; N=774), the proportion of patients reporting at least one adverse event (AE), serious AE, or discontinuation due to AEs were 87.7%, 16.4%, and 6.1%, respectively. Rates of AEs of interest through Week 264 were as follows: serious infections (2.8%), malignancies (nonmelanoma skin cancer [1.7%]; cancer other than nonmelanoma skin cancer [2.3%]), major adverse cardiovascular events (1.0%), and suicidal ideation and behavior (0.6%). Conclusion: High efficacy response rates were maintained (regardless of the method used to analyze data) and no new safety concerns were identified through 5 years of continuous GUS treatment in VOYAGE 1. References: [1]Blauvelt A et al. J Am Acad Derm 2017;76:405-417 [2]Griffiths CEM et al. J Drugs Dermatol 2018;17:826-832 [3]Griffiths CEM et al. J Dermatol Treat 2020;13:1-9 Table 1. Proportion of Patients in the GUS Group a Achieving Clinical Responses by Analysis Type at Week 52 and Week 252 Week 52 Week 252 TFR (N=468) (%) NRI (N=494)(%) OBS (N=463) (%) TFR (N=391) (%) NRI (N=494) (%) OBS (N=380) (%) PASI 90 77.9 75.5 80.6 84.1 66.6 86.6 PASI 100 49.7 46.6 49.7 52.7 41.7 54.2 IGA 0 84.6 80.2 85.5 82.4 65.2 84.7 IGA 0 53.3 50.8 54.2 54.7 43.3 56.3 GUS, guselkumab; IGA, Investigator’s Global Assessment; NRI, nonresponder imputation method; OBS, As Observed method; PASI, Psoriasis Area and Severity Index; TFR, treatment failure rules method a Includes patients randomized to GUS and placebo patients who crossed over to GUS at Week 16 Disclosure of Interests: Christopher E.M. Griffiths Speakers bureau: AbbVie, Eli Lilly, Janssen, Leo, Novartis, Pfizer, Sandoz, and Sun Pharma, Consultant of: AbbVie, Eli Lilly, Janssen, Leo, Novartis, Pfizer, Sandoz, and Sun Pharma, Grant/research support from: AbbVie, Eli Lilly, Janssen, Leo, Novartis, Pfizer, Sandoz, and Sun Pharma, Kim Papp Speakers bureau: AbbVie, Amgen, Astellas, Baxalta, Baxter, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Centocor, Dermira, Eli Lilly, Forward Pharma, Galderma, Genentech, GlaxoSmithKline, Janssen, Kyowa-Hakko Kirin, Leo Pharma, MedImmune, Merck-Serono, Merck Sharp &amp; Dohme, Novartis, Pfizer, Regeneron, Roche, Sanofi-Genzyme, Stiefel, Sun Pharma, Takeda, UCB, and Valeant, Consultant of: AbbVie, Amgen, Astellas, Baxalta, Baxter, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Centocor, Dermira, Eli Lilly, Forward Pharma, Galderma, Genentech, GlaxoSmithKline, Janssen, Kyowa-Hakko Kirin, Leo Pharma, MedImmune, Merck-Serono, Merck Sharp &amp; Dohme, Novartis, Pfizer, Regeneron, Roche, Sanofi-Genzyme, Stiefel, Sun Pharma, Takeda, UCB, and Valeant, Grant/research support from: AbbVie, Amgen, Astellas, Baxalta, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Centocor, Dermira, Eli Lilly, Galderma, Genentech, GlaxoSmithKline, Janssen, Kyowa-Hakko Kirin, Leo Pharma, MedImmune, Merck-Serono, Merck Sharp &amp; Dohme, Novartis, Pfizer, Regeneron, Roche, Sanofi-Genzyme, Stiefel, Takeda, UCB, and Valeant, Michael Song Shareholder of: Johnson and Johnson, Employee of: Janssen Research &amp; Development, LLC, Megan Miller Shareholder of: Johnson and Johnson, Employee of: Janssen Research &amp; Development, LLC, Yin You Shareholder of: Johnson and Johnson, Employee of: Janssen Research &amp; Development, LLC, Yaung-Kaung Shen Shareholder of: Johnson and Johnson, Employee of: Janssen Research &amp; Development, LLC, Andrew Blauvelt Speakers bureau: AbbVie, Consultant of: AbbVie, Aclaris, Almirall, Arena, Athenex, Boehringer Ingelheim, Bristol-Myers Squibb, Dermavant, Dermira, Eli Lilly, FLX Bio, Forte, Galderma, Janssen, Leo, Novartis, Ortho, Pfizer, Regeneron, Sandoz, Sanofi Genzyme, Sun Pharma, and UCB Pharma.