fetching data ...

POS0074 (2022)
IMMUNOLOGICAL DIFFERENCES BETWEEN PsA PATIENTS WHO ARE TUMOR NECROSIS FACTOR INHIBITOR-NAIVE AND WHO HAVE INADEQUATE RESPONSE TO TUMOR NECROSIS FACTOR INHIBITORS
S. Siebert1, L. Coates2, G. Schett3, S. P. Raychaudhuri4, W. Chen5, S. Gao5, S. D. Chakravarty6,7, M. Shawi8, F. Lavie9, E. Theander10, M. Neuhold11, A. Kollmeier12, X. L. Xu12, P. Rahman13, P. J. Mease14, A. Deodhar15
1University of Glasgow, Institute of Infection, Immunity and Inflammation, Glasgow, United Kingdom
2University of Oxford, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Oxford, United Kingdom
3FAU Erlangen-Nürnburg, Internal Medicine 3, Erlangen, Germany
4University of California Davis, School of Medicine, Rheumatology, Allergy, and Clinical Immunology, Mather, United States of America
5Janssen Research & Development, LLC, Immunology, Spring House, United States of America
6Janssen Scientific Affairs, LLC, Immunology, Horsham, United States of America
7Drexel University College of Medicine, Rheumatology, Philadelphia, United States of America
8Janssen Pharmaceutical Companies of Johnson & Johnson, Immunology Global Medical Affairs, Horsham, United States of America
9Janssen Cilag Global Medical Affairs, Immunology Global Medical Affairs, Issy-les-Moulineaux, France
10Janssen Scientific Affairs, LLC, Immunology, Solna, Sweden
11Janssen Scientific Affairs, LLC, Immunology, Zug, Switzerland
12Janssen Research & Development, LLC, Immunology, San Diego, United States of America
13Memorial University of Newfoundland, Craig L. Dobbin Genetics Research Centre, St. John’s, Canada
14Swedish Medical Center/Providence St. Joseph Health and University of Washington, Rheumatology Research, Seattle, United States of America
15Oregon Health & Science University, Division of Arthritis and Rheumatic Diseases, Portland, United States of America

Background: A better understanding of the immunological differences between psoriatic arthritis (PsA) patients (pts) who are tumor necrosis factor inhibitor (TNFi)-naïve & who have inadequate response to TNFi (TNFi-IR) may guide treatment choices. In DISCOVER-1, benefit of the IL-23p19 subunit inhibitor guselkumab (GUS) every-four-weeks (Q4W) & Q8W vs placebo (PBO) in improving PsA signs & symptoms was seen in adults with active PsA. 1 The Ph3b COSMOS study of GUS Q8W vs PBO in TNFi-IR PsA pts corroborated these findings. 2


Objectives: Assess baseline (BL) molecular differences between TNFi-naïve & -IR PsA pts & investigate GUS pharmacodynamic (PD) effect on cytokine expression over time in these cohorts.


Methods: Serum samples collected from consenting biomarker substudy pts in DISCOVER-1 1 (TNFi-naïve [n=101] & -IR [n=17]), DISCOVER-2 3 (TNFi-naïve [n=150]), & COSMOS 2 (TNFi-IR [n=76]) were analyzed for selected serum cytokine levels. TNFi-IR pts in this post-hoc analysis had active PsA & discontinued 1-2 TNFi due to inadequate efficacy; these pts required a TNFi-specific washout period prior to starting GUS. PD effect of GUS Q8W on cytokine levels was assessed. Differential BL cytokine expression, associations between BL cytokine levels & clinical response (Psoriasis [PsO] Area & Severity Index 75% improvement from BL [PASI75] & American College of Rheumatology 20% improvement [ACR20]), & GUS effect on cytokine levels were analyzed with a General linear model & Spearman linear regression.


Results: BL pt demographics, disease characteristics, & conventional synthetic disease-modifying antirheumatic drug (csDMARD) use were comparable between TNFi-naïve (DISCOVER-1 & -2, N=251) & -IR (DISCOVER-1 & COSMOS, N=93) pts, with differences in mean PASI score (8.9 v 12.5), swollen joint count (SJC) (11.7 v 10.3), PsA duration (5.8 v 9.8 yrs), & PsO duration (16.7 v 20.4 yrs; Table 1 ). BL serum IL-22 & TNFα levels for pooled treatment groups were higher in TNFi-IR than -naïve pts (p<0.05). At W24, GUS reduced IL-22, IL-17A/F, IL-6, C-reactive protein (CRP), & serum amyloid A protein to similar levels in both cohorts (p<0.05; Figure 1 ). W24 PASI75 responders had higher BL IL-17F levels with GUS in both cohorts (p<0.05) & higher IL-22 levels in TNFi-IR pts only (p<0.05). A trend of upregulated BL IL-22 expression in W24 ACR20 responders was seen for TNFi-IR pts with GUS (p=0.07).

BL demographics, disease characteristics, & drug use in TNFi-naïve & -IR cohorts with available cytokine data in DISCOVER-1&2 & COSMOS.*

TNFi-naïve (N=251) TNFi-IR (N=93)
Age [yrs] 47.2 (11.3) 48.5 (11.1)
Female, n (%) 132 (52.6) 46 (49.5)
Body mass index [kg/m 2 ] 29.6 (6.1) 30.3 (6.4)
Median (range) CRP [mg/dL] 0.9 (0.0-12.9) 1.0 (0.0-13.2)
Log2 IL-22 / TNFα [pg/mL] 2.0 (1.4) / 1.1 (0.6) 2.5 (1.5) / 1.9 (1.2)
Log2 IL-17A / F [pg/mL] -0.4 (1.5) / 1.7 (1.5) -0.1 (1.7) / 2.0 (1.6)
SJC [0-66] 11.7 (7.1) 10.3 (8.3)
TJC [0-68] 20.3 (13.1) 20.6 (14.2)
PsA duration [yrs] 5.8 (5.9) 9.8 (8.2)
PsO duration [yrs] 16.7 (12.8) 20.4 (12.0)
PsO Body surface area (%) 14.8 (18.6) 19.1 (21.3)
Investigator’s Global Assessment score [0-4] 2.3 (0.9) 2.3 (1.0)
PASI score [0-72] 8.9 (10.6) 12.5 (12.0)
Enthesitis [Y], n (%) 160 (63.7) 58 (62.4)
csDMARD use [Y], n (%) 164 (65.3) 62 (66.7)
Corticosteroid use (Y), n (%) 45 (17.9) 19 (20.4)
Methotrexate use [Y], n (%) 136 (54.2) 54 (58.1)

Data are mean (SD) unless otherwise noted. *Pts with serum CRP level ≥0.3 mg/dL, SJC ≥3, & TJC ≥3 (to mimic D1 inclusion criteria 1 ). TJC = tender joint count


Conclusion: Elevated BL IL-22 expression & association between BL IL-22 levels & W24 PASI75 response, & a W24 trend for an association between upregulated BL IL-22 & ACR20 response, in TNFi-IR pts seen in this exploratory analysis may suggest increased involvement of the IL-23 pathway in TNFi-IR pts. GUS showed comparable & significant PD effects for TNFi-naïve & -IR pts, consistent with observed clinical responses.


REFERENCES:

[1]Deodhar A, et al. Lancet. 2020;395:1115-25.

[2]Coates LC, et al. Ann Rheum Dis. 2021;80:140-1.

[3]Mease P, et al. Lancet. 2020;395:1126-36.


Disclosure of Interests: Stefan Siebert Speakers bureau: AbbVie, Biogen, GSK, Janssen, Novartis, UCB, Grant/research support from: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, GSK, Janssen, Novartis, and UCB, Laura Coates Speakers bureau: AbbVie, Amgen, Biogen, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Medac, Novartis, Pfizer and UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Gilead, Galapagos, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, Georg Schett Speakers bureau: AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Gilead, Janssen, Novartis, and UCB, Siba P Raychaudhuri Speakers bureau: AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, SUN Pharma, and UCB, Consultant of: AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, SUN Pharma, and UCB, Grant/research support from: AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, SUN Pharma, and UCB, Warner Chen Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC (a wholly owned subsidiary of Johnson & Johnson), Sheng Gao Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC (a wholly owned subsidiary of Johnson & Johnson), Soumya D Chakravarty Shareholder of: Johnson & Johnson, Employee of: Janssen Scientific Affairs, LLC (a wholly owned subsidiary of Johnson & Johnson), May Shawi Shareholder of: Johnson & Johnson, Employee of: Janssen Pharmaceutical Companies of Johnson & Johnson, Frederic Lavie Shareholder of: Johnson & Johnson, Employee of: Janssen Pharmaceutical Companies of Johnson & Johnson, Elke Theander Shareholder of: Johnson & Johnson, Employee of: Janssen Scientific Affairs, LLC (a wholly owned subsidiary of Johnson & Johnson), Marlies Neuhold Shareholder of: Johnson & Johnson, Employee of: Janssen Scientific Affairs, LLC (a wholly owned subsidiary of Johnson & Johnson), Alexa Kollmeier Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC (a wholly owned subsidiary of Johnson & Johnson), Xie L Xu Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC (a wholly owned subsidiary of Johnson & Johnson), Proton Rahman Consultant of: AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, and UCB, Grant/research support from: Janssen and Novartis, Philip J Mease Speakers bureau: AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer, Sun Pharma, and UCB, Consultant of: AbbVie, Aclaris, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, GSK, Inmagene, Janssen, Novartis, Pfizer, Sun Pharma, and UCB, Grant/research support from: AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, Sun Pharma, and UCB, Atul Deodhar Speakers bureau: AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Amgen, Aurinia, Bristol Myers Squibb, Celgene, Eli Lilly, GSK, Janssen, MoonLake, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Eli Lilly, GSK, Novartis, Pfizer, and UCB

Citation: , volume 81, supplement 1, year 2022, page 254
Session: New therapeutic avenues in psoriatic arthritis (Poster Tours)