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AB0538 (2021)
POOLED SAFETY RESULTS FROM TWO PHASE-3 TRIALS OF GUSELKUMAB IN PATIENTS WITH PSORIATIC ARTHRITIS THROUGH 1 YEAR
C. T. Ritchlin1, P. Rahman2, P. Helliwell3, W. H. Boehncke4, I. Mcinnes5, A. B. Gottlieb6, S. Kafka7, A. Kollmeier8, E. C. Hsia8,9, X. L. Xu8, M. Shawi10, S. Sheng11, P. Agarwal11, B. Zhou11, P. Ramachandran12, P. J. Mease13
1University of Rochester, School of Medicine and Dentistry, Rochester, United States of America
2Memorial University of Newfoundland, Disicpline of Medicine, Faculty of Medicine, St. Johns, Canada
3University of Leeds, Clinical Rheumatology, Leeds, United Kingdom
4Geneva University Hospitals, Department of Dermatology, Geneva, Switzerland
5University of Glasgow, Director of Dermatology, Glasgow, United Kingdom
6Icahn School of Medicine/Mt Sinai, Department of Dermatology, New York, United States of America
7Janssen Scientific Affairs, MED GROUP RHEUM TA, Horsham, United States of America
8Janssen Research & Development, LJ IMMUNOLOGY CLINIC, Spring House, United States of America
9University of Pennsylvania Medical Center, Division of Rheumatology, Philadelphia, United States of America
10Janssen Scientific Affairs, GMA COMMERCIAL OPS, Horsham, United States of America
11Janssen Research & Development, CLINICAL BIOSTATS PA, Spring House, United States of America
12Janssen Research & Development, MSA US PA, Spring House, United States of America
13Swedish Medical Center/Providence St Joseph Health and University of Washington School of Medicine, Department of Internal Medicine, Seatle, United States of America

Background: DISCOVER 1 & 2, two double-blind, phase-3, psoriatic arthritis (PsA) trials of guselkumab (GUS, an IL-23 inhibitor), demonstrated significant improvement with GUS vs placebo (PBO) in signs and symptoms of PsA, with good tolerability, at week (w) 24 during the PBO-controlled period. 1,2 Beyond w24, all patients (pts) switched to GUS. Continued treatment maintained efficacy through w52. 3,4


Objectives: To describe pooled safety results from the DISCOVER 1 & 2 trials through 1-year of GUS treatment.


Methods: Adults with active PsA (DISCOVER 1: ≥3 tender/swollen joints and C-Reactive protein [CRP] ≥0.3 mg/dL; DISCOVER 2: ≥5 tender/swollen joints and CRP ≥0.6 mg/dL) were randomized to subcutaneous GUS 100 mg at w0, w4, then every 8 w (q8w); GUS 100 mg q4w; or PBO. At w24, PBO pts switched to GUS 100 mg q4w. Pts were biologic naive except ~30% pts in DISCOVER 1. Safety was reported through w60 in DISCOVER 1 and through w52 in DISCOVER 2.


Results: Baseline characteristics were similar between treatment groups in the pooled studies. Through w24 and 1 year, numbers of pts per 100 patient years with ≥1 event were similar among treatment groups for adverse events (AEs), serious AEs, infections, serious infections, and discontinuations due to AE ( Table 1 ). At 1 year, there were no cases of active tuberculosis, opportunistic infections (including candida), or inflammatory bowel disease in GUS-treated pts; 2 deaths in PBO pts; and low incidences that were similar across treatment groups for malignancy, major adverse cardiac events, and injection-site reactions. Incidence of anti-GUS antibodies was 4.5%, and most were not neutralizing. Mild elevations in serum hepatic transaminases and decreases in neutrophil counts were consistent at 1 year with the results at w24 ( Table 1 ).


Conclusion: GUS regimens of q8w and q4w were well tolerated in PsA pts through 1 year of treatment in the phase-3 DISCOVER trials, consistent with the w24 results. No meaningful differences between incidences of AEs were reported in the q8w and q4w groups. The safety profile of GUS in PsA pts is generally comparable with the previously established safety profile of GUS.


REFERENCES:

[1]Deodhar A et al. Lancet. 2020;395:1115

[2]Mease P et al. Lancet. 2020;395:1126

[3]Ritchlin C et al. EULAR 2020 # SAT0397

[4]McInnes I et al. EULAR 2020 # SAT0402

Number of Patients with AEs per 100 PY and Incidence of AEs of Interest

Time Period 24 Weeks 1 Year*
Treatment Group PBO GUS SC 100 mg PBO to GUS ‡ GUS SC 100 mg
Dosing Schedule Matching q8w q4w GUS Combined † q4w q8w q4w GUS Combined ‡
N 372 375 373 748 352 375 373 1100
Total PY Follow-Up 173 173 172 346 204 384 385 589
Patients with AEs per 100 PY, n (95% CI )
≥1 AE 143 (123, 166) 148 (127, 171) 154 (132, 178) 151 (136, 167) 92 (77, 108) 114 (100, 130) 115 (101, 131) 109 (100, 117)
≥1 Serious AE 7.1 (3.7, 12) 4.1 (1.6, 8.4) 4.7 (2.0, 9.3) 4.4 (2.5, 7.3) 7.0 (3.8, 11.8) 4.8 (2.9, 7.6) 4.0 (2.2, 6.6) 4.9 (3.6, 6.6)
≥1 Infection 50 (39, 62) 47 (37, 59) 52 (42, 65) 49 (42, 58) 39 (31, 49) 41 (34, 48) 38 (31, 45) 39 (35, 44)
≥1 Serious Infection 1.7 (0.4, 5.1) 0.6 (0.0, 3.2) 1.8 (0.4, 5.1) 1.2 (0.3, 3.0) 2.5 (0.8, 5.8) 1.3 (0.4, 3.1) 0.8 (0.2, 2.3) 1.3 (0.7, 2.3)
Discontinued due to AE 4.1 (1.6, 8.4) 2.9 (1.0, 6.8) 4.7 (2.0, 9.3) 3.8 (2.0, 6.5) 3.5 (1.4, 7.1) 2.1 (0.9, 4.1) 2.6 (1.3, 4.8) 2.6 (1.7, 3.8)
AEs of Interest § , n (% )
Death 2 (0.5) 0 0 0 0 0 0 0
Malignancy 1 (0.3) 2 (0.5) 0 2 (0.3) 1 (0.3) 2 (0.5) 0 3 (0.3)
Major Adverse Cardiac Events 1 (0.3) 0 1 (0.3) 1 (0.1) 0 0 1 (0.3) 1 (0.1)
Opportunistic Infections 0 0 0 0 0 0 0 0
Tuberculosis 0 0 0 0 0 0 0 0
Inflammatory Bowel Disease 1 (0.3) 0 0 0 0 0 0 0
Injection-Site Reaction 1 (0.3) 5 (1.3) 4 (1.1) 9 (1.2) 4 (1.1) 6 (1.6) 9 (2.4) 19 (1.7)
Anti-GUS Antibody + - 6/373 (1.6) 9/371 (2.4) 15/744 (2.0) 14/350 (4.0) 18/373 (4.8) 17/371 (4.6) 49/1094 (4.5)

*Through w60 for DISCOVER 1 and w52 for DISCOVER 2; † Combined GUS q8w and q4w; ‡ For patients who switched from PBO to GUS, only data on and after first GUS administration were included in this group; § PBO N=370.

AE, adverse event; CI, confidence interval; GUS, guselkumab; PBO, placebo; PY, patient year; q4w, every 4 weeks; q8w, every 8 weeks; SC, subcutaneous; w, week


Disclosure of Interests: Christopher T. Ritchlin Grant/research support from: Received grant/research support from UCB Pharma, AbbVie, Amgen, consultation fees from UCB Pharma, Amgen, AbbVie, Lilly, Pfizer, Novartis, Gilead, Janssen, Proton Rahman Speakers bureau: Received speakers fees from Abbott, AbbVie, Amgen, BMS, Celgene, Lilly, Janssen, Novartis, Pfizer, Grant/research support from: Received grant/research support from Janssen and Novartis, consultation fees from Abbott, AbbVie, Amgen, BMS, Celgene, Lilly, Janssen, Novartis, and Pfizer., Philip Helliwell Consultant of: Consultation fees paid to charity (AbbVie, Amgen, Pfizer, UCB) or himself (Celgene, Galapagos), Grant/research support from: Received grants/research support paid to charity (AbbVie, Janssen, Novartis), Wolf-Henning Boehncke Consultant of: Received consultation fees from Janssen, Grant/research support from: Received grant/research support from Janssen Research & Development, LLC, Iain McInnes Consultant of: Received consultation fees from AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Gilead, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: Received grant/research support from Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Janssen, and UCB, Alice B Gottlieb Speakers bureau: Received speakers fees from Pfizer, AbbVie, BMS, Lilly, MSD, Novartis, Roche, Sanofi, Sandoz, Nordic, Celltrion and UCB, Consultant of: Received consultation fees from Pfizer, AbbVie, BMS, Lilly, MSD, Novartis, Roche, Sanofi, Sandoz, Nordic, Celltrion and UCB, Grant/research support from: Received grant/research support from Pfizer, AbbVie, BMS, Lilly, MSD, Novartis, Roche, Sanofi, Sandoz, Nordic, Celltrion and UCB, Shelly Kafka Shareholder of: Shareholder of Johnson & Johnson, Employee of: Employee of Janssen Research & Development, LLC, Alexa Kollmeier Shareholder of: Shareholder of Johnson & Johnson, Employee of: Employee of Janssen Research & Development, LLC, Elizabeth C Hsia Shareholder of: Shareholder of Johnson & Johnson, Employee of: Employee of Janssen Research & Development, LLC, Xie L Xu Shareholder of: Shareholder of Johnson & Johnson, Employee of: Employee of Janssen Research & Development, LLC, May Shawi Shareholder of: Shareholder of Johnson & Johnson, Employee of: Employee of Janssen Research & Development, LLC, Shihong Sheng Shareholder of: Shareholder of Johnson & Johnson, Employee of: Employee of Janssen Research & Development, LLC, Prasheen Agarwal Shareholder of: Shareholder of Johnson & Johnson, Employee of: Employee of Janssen Research & Development, LLC, Bei Zhou Shareholder of: Shareholder of Johnson & Johnson, Employee of: Employee of Janssen Research & Development, LLC, Paraneedharan Ramachandran Shareholder of: Shareholder of Johnson & Johnson, Employee of: Employee of Janssen Research & Development, LLC, Philip J Mease Speakers bureau: Received speakers fees from Abbott, Amgen, Biogen Idec, BMS, Eli Lilly, Genentech, Janssen, Pfizer, UCB – speakers bureau, Consultant of: Received consultation fees from Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB, Grant/research support from: Received grant/research support from Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB.

Citation: Ann Rheum Dis, volume 80, supplement 1, year 2021, page 1300
Session: Psoriatic arthritis – treatment (Publication Only)