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POS1027 EFFICACY AND SAFETY OF GUSELKUMAB, A MONOCLONAL ANTIBODY SPECIFIC TO THE p19-SUBUNIT OF INTERLEUKIN-23, THROUGH 2 YEARS: RESULTS FROM A PHASE 3, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY CONDUCTED IN BIOLOGIC-NAÏVE PATIENTS WITH ACTIVE PSORIATIC ARTHRITIS
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  1. I. Mcinnes1,
  2. P. Rahman2,
  3. A. B. Gottlieb3,
  4. E. C. Hsia4,5,
  5. A. Kollmeier4,
  6. X. L. Xu4,
  7. S. Sheng6,
  8. Y. Jiang6,
  9. M. Shawi7,
  10. S. D. Chakravarty8,9,
  11. D. Van der Heijde10,
  12. P. J. Mease11
  1. 1University of Glasgow, Institute of Infection, Immunity and Inflammation, Glasgow, United Kingdom
  2. 2Memorial University of Newfoundland, Craig L Dobbin Genetics Research Centre, St. John’s, Canada
  3. 3Icahn School of Medicine Mt. Sinai, Dermatology, New York, United States of America
  4. 4Janssen Research & Development, LLC, Immunology, Spring House, United States of America
  5. 5University of Pennsylvania Medical Center, Rheumatology, Philadelphia, United States of America
  6. 6Janssen Research & Development, LLC, Biostatistics, Spring House, United States of America
  7. 7Janssen Scientific Affairs, LLC, Immunology, Horsham, United States of America
  8. 8Janssen Scientific Affairs, LLC, Immunology, Horsham, United States of America
  9. 9Drexel University College of Medicine, Rheumatology, Philadelphia, United States of America
  10. 10Leiden University Medical Center, Rheumatology, Leiden, Netherlands
  11. 11Swedish Medical Center/Providence St. Joseph Health and University of Washington, Rheumatology Research, Seattle, United States of America

Abstract

Background: Guselkumab (GUS), a selective IL-23 inhibitor dosed every 4 or 8 weeks (Q4W or Q8W), demonstrated efficacy for joint and skin symptoms, inhibition of structural damage progression (Q4W), and safety vs. placebo (PBO) through Week 24 (W24) of the Ph3, double-blind, PBO-controlled trial in biologic-naïve pts with PsA (DISCOVER-2).1 Favorable benefit-risk was also seen through 1 year.2

Objectives: To assess GUS efficacy and safety through 2 years.

Methods: Biologic-naïve adults with active PsA (≥5 swollen joint count [SJC] + ≥5 tender joint count [TJC]; CRP ≥0.6 mg/dL) were randomized (1:1:1) to GUS 100 mg Q4W; GUS 100 mg at W0, W4, Q8W; or PBO with crossover to GUS 100 mg Q4W (PBO→Q4W) at W24. Clinical efficacy (ACR/PASI/IGA/HAQ-DI) was assessed in the modified intention to treat (mITT) population through W100 with missing data imputation (nonresponse for categorical endpoints; no change/multiple imputation for continuous endpoints). Observed PsA-modified van der Heijde Sharp (vdH-S) scores derived from blinded radiographic images collected at W0, W24, W52, W100 (or at discontinuation [d/c]) and adverse events (AEs) through W112 were collected.

Results: 712/739 (96%) randomized pts continued study agent at W24; 687/739 (93%) continued at W52; 652/739 (88%) completed W100. ACR20 response rates in the mITT population continued to increase after W24, and at W100 were 76% for Q4W and 74% for Q8W (Figure 1). Similar response patterns were seen for ACR50/70, HAQ-DI and PASI90/100 (Table 1), and IGA0/1 and PASI75 response rates were consistent through W100 in pts randomized to Q4W and Q8W; W100 data for PBO→Q4W pts were consistent with pts treated with Q4W and Q8W (Table 1). GUS improvements in SF-36 PCS/MCS at W52 also persisted through W100 (data not shown). Low rates of radiographic progression (as measured by PsA-modified vdH-S scores) were observed during W52-100 for Q4W (n=227; 0.75) and Q8W (n=232; 0.46). In the PBO→Q4W group (n=228), radiographic progression was 1.12 during W0-24 (while on PBO), 0.51 during W24-100 (while on Q4W), and 0.13 during W52-100. Through W112, the incidences of AEs, serious AEs (SAEs), AEs leading to d/c, infections, serious infections, and injection site reactions were generally consistent with the PBO-controlled period and through 1 year. Of the pts in the Q4W (n=245), Q8W (n=248), and PBO→Q4W (n=238) groups, 9%, 9% and 7% had ≥1 SAE; 2%, 3% and 3% had ≥1 serious infection; 2 Q8W pts (fungal esophagitis, disseminated herpes zoster) and 1 PBO→Q4W pt (listeria meningitis) had opportunistic infections; 1 PBO→Q4W pt died (road traffic accident); 1 PBO-randomized pt had IBD; no pt had anaphylactic or serum sickness reaction, or active TB.

Conclusion: In biologic-naïve PsA pts, GUS improvements in joint and skin symptoms, physical function, and low rates of radiographic progression persisted through 2 years. GUS safety in PsA through 2 years was comparable with safety at 6 months and 1 year, similar between Q4W and Q8W, and consistent with GUS safety in psoriasis.

References: [1]Mease PJ. Lancet. 2020 Apr 4;395(10230):1126-1136. [2] McInnes IB. Arthritis Rheumatol. 2020 Oct 11. doi: 10.1002/art.41553.

Table 1.

Efficacy Through W100 (NRI)

Disclosure of Interests: Iain McInnes Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Gilead, 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, Alice B Gottlieb Consultant of: Avotres Therapeutics, Beiersdorf, Boehringer Ingelheim, Bristol-Myers Squibb Co, Incyte, Janssen, LEO Pharma, Eli Lilly, Novartis, Sun Pharmaceutical Industries Inc, UCB, and Xbiotech, Grant/research support from: Boehringer Ingelheim, Incyte, Janssen, Novartis, Sun Pharmaceuticals Industries Inc, UCB, and Xbiotech, Elizabeth C Hsia Shareholder of: Johnson & Johnson, Employee of: Janssen Research and Development, LLC, Alexa Kollmeier Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Xie L Xu Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Shihong Sheng Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Yusang Jiang Employee of: Cytel, Inc. providing statistical support (funded by Janssen), May Shawi Shareholder of: Johnson & Johnson, Employee of: Janssen Scientific Affairs, LLC, Soumya D Chakravarty Shareholder of: Johnson & Johnson, Employee of: Janssen Scientific Affairs, LLC, Désirée van der Heijde Paid instructor for: Director of Imaging and Rheumatology BV, Consultant of: AbbVie, Amgen, Astellas, AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Celgene, Cyxone, Daiichi, Eisai, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, and UCB, Philip J Mease Speakers bureau: Boehringer Ingelheim and GlaxoSmithKline, Grant/research support from: AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, SUN, and UCB.

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