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SAT0402 (2020)
EFFICACY AND SAFETY OF GUSELKUMAB, A MONOCLONAL ANTIBODY SPECIFIC TO THE P19-SUBUNIT OF INTERLEUKIN-23, THROUGH WEEK 52 OF A PHASE 3, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY CONDUCTED IN BIOLOGIC-NAÏVE PATIENTS WITH ACTIVE PSORIATIC ARTHRITIS
I. Mcinnes1, P. Rahman2, A. B. Gottlieb3, E. C. Hsia4,5, A. Kollmeier4, X. L. Xu4, R. A. Subramanian4, P. Agarwal4, S. Sheng4, Y. Jiang4, B. Zhou4, D. Van der Heijde6, P. J. Mease7
1Univ Glasgow, Glasgow, United Kingdom
2Memorial Univ Newfoundland, St John’s, Canada
3Icahn School of Med Mt Sinai, New York, United States of America
4Janssen Research & Development, LLC, Spring House, United States of America
5U Penn Med Ctr, Philadelphia, United States of America
6Leiden Univ Medical Ctr, Leiden, Netherlands
7Swedish Med Ctr/Providence St Joseph Health and U Wash School of Med, Seattle, United States of America

Background: Guselkumab (GUS), a monoclonal antibody that specifically binds to the p19-subunit of IL-23, is approved to treat psoriasis. Through Week24 (W24) of the Ph3, double-blind, placebo (PBO)-controlled trial in biologic-naïve pts with active PsA (DISCOVER-2), GUS every 4 or 8 weeks (Q4W or Q8W) demonstrated efficacy for joint & skin symptoms and inhibition of structural damage progression (Q4W), and was well tolerated.


Objectives: Assess GUS efficacy and safety through W52.


Methods: Biologic-naïve adults with active PsA (≥5 swollen+≥5 tender joints; CRP ≥0.6mg/dL) were randomized (1:1:1) to GUS 100 mg Q4W; GUS 100 mg at W0, W4, Q8W; or PBO. At W24, PBO pts crossed over to GUS 100 mg Q4W (PBO X Q4W). ACR response rates at W52, based on nonresponder imputation (NRI) for missing data and as observed in pts who continued study agent at W24, are shown. Observed data for additional endpoints, including PsA-modified van der Heijde Sharp (vdH-S) scores derived from blinded radiographic images collected at W0, W24, W52 (or at d/c) and scored in a new Read Campaign, are shown.


Results: 712/739 (96.3%) randomized & treated pts continued study agent at W24; 689/739 (93.2%) completed Wk52. NRI ACR20 response rates continued to increase after W24, and at W52 were 70.6% for GUS Q4W and 74.6% for GUS Q8W ( Fig 1A ). Similar response patterns were observed for the more stringent ACR50/70 criteria ( Fig 1C ,E). Observed ACR (Fig, 1B,D,F), IGA, PASI & MDA/VLDA responses; dactylitis & enthesitis resolution; and mean improvements in HAQ-DI and SF-36 PCS/MCS scores were also sustained through W52 in pts receiving Q4W & Q8W; W52 data for PBO X Q4W pts were generally consistent with other GUS-treated pts ( Fig 1 , Table 1 ). Changes in vdH-S scores were similar for W24-52 (0.62) and W0-24 (0.46) for Q4W; less radiographic progression occurred from W24-52 v W0-24 for Q8W (0.23 v 0.73) & PBO X Q4W (0.25 v 1.00). In 731 GUS-treated pts, 4.2% had SAEs; 1.2% had serious infections; no pt died; and no pt had IBD, opportunistic infections or active TB, or anaphylactic or serum sickness-like reactions.

Observed Efficacy 1

GUS Q4W GUS Q8W PBO X (W0-24 ) GUS Q4W (W24-52 )
Data are % unless otherwise stated W24 W52 W24 W52 W24 W52
Dactylitis at W0, n 116 111 107 105 95 93
Resolution 68.1 81.1 60.7 81.9 41.1 78.5
Enthesitis at W0, n 165 160 151 148 172 168
Resolution 45.5 60.0 57.6 65.5 32.6 67.3
≥3% BSA psoriasis, IGA ≥2 at W0, n 176 173 172 170 176 172
IGA 0/1 + ≥2-grade decrease 71.0 84.4 72.1 77.1 19.9 84.3
PASI75 81.8 91.9 80.8 88.8 23.3 88.4
PASI90 63.6 81.5 70.3 77.1 10.2 76.7
PASI100 46.6 61.3 46.5 54.7 2.8 55.2
HAQ-DI, n 234 229 238 234 237 230
Mean change -0.4 -0.5 -0.4 -0.5 -0.2 -0.4
SF-36 scores, n (mean change) 234 229 238 234 237 230
Physical Component - PCS 7.2 9.0 7.8 9.5 3.8 8.1
Mental Component - MCS 4.1 4.1 4.5 4.5 2.2 4.3
MDA/VLDA , n 234 228 238 234 238 231
MDA 19.7 36.8 26.5 32.9 6.3 31.6
VLDA 5.1 12.2 2 4.6 3 17.1 1.3 6.9

1 Randomized pts still on study agent at W24; 2 N=229; 3 N=237


Conclusion: In biologic-naïve pts with active PsA, GUS elicited sustained improvements in joint & skin symptoms; inhibition of radiographic progression & improvements in physical function, quality of life & composite indices through W52. GUS safety in PsA was similar at W24 1 & W52 and consistent with GUS safety in psoriasis.


REFERENCES:

[1]Mease P (A#L13), Arthritis Rheumatol 2019;71(suppl 10)


Acknowledgments: None


Disclosure of Interests: Iain McInnes Grant/research support from: Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Janssen, and UCB, Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Gilead, Janssen, Novartis, Pfizer, and UCB, Proton Rahman Grant/research support from: Janssen and Novartis, Consultant of: Abbott, AbbVie, Amgen, BMS, Celgene, Lilly, Janssen, Novartis, and Pfizer., Speakers bureau: Abbott, AbbVie, Amgen, BMS, Celgene, Lilly, Janssen, Novartis, Pfizer, Alice B Gottlieb Grant/research support from:: Research grants, consultation fees, or speaker honoraria for lectures from: Pfizer, AbbVie, BMS, Lilly, MSD, Novartis, Roche, Sanofi, Sandoz, Nordic, Celltrion and UCB., Consultant of:: Research grants, consultation fees, or speaker honoraria for lectures from: Pfizer, AbbVie, BMS, Lilly, MSD, Novartis, Roche, Sanofi, Sandoz, Nordic, Celltrion and UCB., Speakers bureau:: Research grants, consultation fees, or speaker honoraria for lectures from: Pfizer, AbbVie, BMS, Lilly, MSD, Novartis, Roche, Sanofi, Sandoz, Nordic, Celltrion and UCB., Elizabeth C Hsia Shareholder of: Johnson & Johnson, Employee of: Janssen Research & 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, Ramanand A Subramanian Employee of: Janssen Research & Development, LLC, Prasheen Agarwal Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Shihong Sheng Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Yusang Jiang: None declared, Bei Zhou Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Désirée van der Heijde Consultant of: AbbVie, Amgen, Astellas, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Cyxone, Daiichi, Eisai, Eli-Lilly, Galapagos, Gilead Sciences, Inc., Glaxo-Smith-Kline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, UCB Pharma; Director of Imaging Rheumatology BV, Philip J Mease Grant/research support from: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB – grant/research support, Consultant of: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB – consultant, Speakers bureau: Abbott, Amgen, Biogen Idec, BMS, Eli Lilly, Genentech, Janssen, Pfizer, UCB – speakers bureau

Citation: Ann Rheum Dis, volume 79, supplement 1, year 2020, page 1148
Session: Psoriatic arthritis (Poster Presentations)