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Arthritis & rheumatology (Hoboken, N.J.)
Sep, 2024;76 (9): 1397-1407.

Phase 2 Trial of Deucravacitinib in Psoriatic Arthritis: Biomarkers Associated With Disease Activity, Pharmacodynamics, and Clinical Responses.

Oliver FitzGerald, Dafna D Gladman, Philip J Mease, Christopher Ritchlin, Josef S Smolen, Lu Gao, Yanhua Hu, Miroslawa Nowak, Subhashis Banerjee, Ian Catlett
Author Information
  1. Oliver FitzGerald: University College Dublin, Dublin, Ireland. ORCID
  2. Dafna D Gladman: University of Toronto, Toronto, Ontario, Canada. ORCID
  3. Philip J Mease: Swedish Medical Center, Seattle, Washington. ORCID
  4. Christopher Ritchlin: University of Rochester Medical Center, Rochester, New York. ORCID
  5. Josef S Smolen: Medical University of Vienna and Hietzing Hospital, Vienna, Austria. ORCID
  6. Lu Gao: Bristol Myers Squibb, Princeton, New Jersey.
  7. Yanhua Hu: Bristol Myers Squibb, Princeton, New Jersey.
  8. Miroslawa Nowak: Bristol Myers Squibb, Princeton, New Jersey.
  9. Subhashis Banerjee: Bristol Myers Squibb, Princeton, New Jersey.
  10. Ian Catlett: Bristol Myers Squibb, Princeton, New Jersey.
PMID: 38770592 DOI: 10.1002/art.42921

Abstract

OBJECTIVE: Our objective was to evaluate the association of serum biomarkers with baseline psoriatic arthritis (PsA) disease activity, pharmacodynamic effects of deucravacitinib on biomarker levels, and the relationship between biomarkers and clinical responses to deucravacitinib.
METHODS: The phase 2 trial (ClinicalTrials.gov identifier: NCT03881059) randomly assigned 203 patients with PsA 1:1:1 to placebo, deucravacitinib at 6 mg once daily (QD), or deucravacitinib at 12 mg QD. Serum biomarkers associated with the interleukin 23 (IL-23) pathway (IL-17A, β-defensin [BD-2], and IL-19), type I interferon pathway, inflammation, and collagen matrix turnover were measured by immunoassay. Clinical responses (≥75% improvement from baseline in the Psoriasis Area and Severity Index [PASI75] and ≥20% improvement from baseline in American College of Rheumatology criteria [ACR20] responses) were measured at week 16. Hematologic variables were also assessed.
RESULTS: IL-17A, BD-2, and IL-19 had a modest association with PASI scores (r = 0.4, r = 0.56, and r = 0.5, respectively) at baseline. In deucravacitinib groups, IL-17A, BD-2, IL-19, C-X-C motif ligand 9 (CXCL9), CXCL10, C-reactive protein, matrix metalloproteinase 3, and collagen type 4 degradation marker levels were significantly reduced at week 16 versus baseline (P < 0.01); higher levels of IL-23 pathway-associated biomarkers predicted higher PASI75 and ACR20 response rates in deucravacitinib-treated patients. Significantly higher PASI75 response rates were seen in patients with high baseline IL-17A (odds ratio 15.76) and BD-2 levels (odds ratio 15.41) versus low baseline IL-17A and BD-2 levels. Changes in hematologic variables that are characteristic of JAK inhibition were not observed with deucravacitinib.
CONCLUSION: Deucravacitinib significantly impacted biomarkers associated with Tyk2 signaling pathways of key inflammatory cytokines, including IL-23 and type I interferon, and those related to collagen matrix turnover. These biomarkers may predict treatment responses to deucravacitinib.

Associated Data

ClinicalTrials.gov | NCT03881059

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Grants

  1. /Bristol-Myers Squibb

MeSH Term

Humans
Arthritis, Psoriatic
Male
Biomarkers
Female
Middle Aged
Adult
Interleukin-17
Treatment Outcome
beta-Defensins
Severity of Illness Index
Matrix Metalloproteinase 3
Double-Blind Method
Chemokine CXCL10
Interleukin-23

Chemicals

Biomarkers
Interleukin-17
beta-Defensins
Matrix Metalloproteinase 3
IL17A protein, human
Chemokine CXCL10
Interleukin-23
CXCL10 protein, human
Journal Article Clinical Trial, Phase II Randomized Controlled Trial

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