Evidence map›Paper›PMID 39283417›Full record

ArticleDermatology and therapy2024

Pharmacodynamic Response to Deucravacitinib, an Oral, Selective, Allosteric TYK2 Inhibitor, in a Global, Phase 2, Randomized, Double-Blind, Placebo-Controlled Psoriasis Trial.

Ian M Catlett, Lu Gao, Yanhua Hu, Subhashis Banerjee, James G Krueger

Registry-linked trialAbstract read
In one paragraph

Article in Dermatology and therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02931838 (A Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Phase 2 Study to Evaluate the Clinical Efficacy and Safety of BMS-986165 in Subjects With Moderate to Severe Psoriasis), which is not on this map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT02931838 phase2completednot on this map

A Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Phase 2 Study to Evaluate the Clinical Efficacy and Safety of BMS-986165 in Subjects With Moderate to Severe Psoriasis

TypeinterventionalSponsorBristol-Myers SquibbRan2016 to 2017Enrolled268ConditionsPsoriasisArmsBMS-986165, Placebo for BMS-986165
3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors.

Ian M CatlettBristol Myers Squibb, 3401 Princeton Pike, Lawrenceville, NJ, 08648, USA.ORCID http://orcid.org/0000-0001-6220-2626
Lu GaoBristol Myers Squibb, 3401 Princeton Pike, Lawrenceville, NJ, 08648, USA. Lu.Gao@bms.com.ORCID https://orcid.org/0000-0002-2206-5476
Yanhua HuBristol Myers Squibb, 3401 Princeton Pike, Lawrenceville, NJ, 08648, USA.ORCID http://orcid.org/0000-0002-8149-5636
Subhashis BanerjeeBristol Myers Squibb, 3401 Princeton Pike, Lawrenceville, NJ, 08648, USA.ORCID http://orcid.org/0009-0000-1365-5207
James G KruegerThe Rockefeller University, New York, NY, USA.ORCID http://orcid.org/0000-0002-3775-1778

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundPsoriasis, a chronic, immune-mediated, inflammatory disease, affects 2‒3% of the population. Tyrosine kinase 2 (TYK2) mediates cytokine signaling involved in adaptive [interleukin (IL)-12, IL-23] and innate (type-I interferons) immune responses; IL-23-driven T-helper (Th)17 pathways play a key role in chronic inflammation in psoriasis. In a phase 2 trial, deucravacitinib, an oral, selective, allosteric TYK2 inhibitor, reduced IL-23/Th17 and type-I interferon pathway expression in the skin of patients with moderate to severe plaque psoriasis, reductions that were accompanied by clinical improvement of psoriatic lesions.

objectivesThe aim of this study was to identify biomarkers of psoriatic disease in serum from patients enrolled in the phase 2 trial and to assess the effects of deucravacitinib on those biomarkers.

methodsSerum biomarkers from Olink proteomics and other quantitative assays were evaluated for a pharmacodynamic response to deucravacitinib treatment and correlation with psoriasis disease activity measures.

resultsSerum biomarkers associated with the IL-23/Th17 pathway [IL-17A, IL-17C, IL-19, IL-20, beta-defensin, and peptidase inhibitor 3 (PI3)] were upregulated in patients with psoriasis versus healthy controls. Deucravacitinib treatment reduced IL-17A (adjusted mean change from baseline at Day 85; 12 mg once daily versus placebo; -0.240 versus -0.067), IL-17C (-14.850 versus -1.664), IL-19 (-96.445 versus -8.119), IL-20 (-0.265 versus -0.064), beta-defensin (-65,025.443 versus -7553.961), and PI3 (-14.005 versus -1.360) expression. Reductions in serum biomarker expression occurred in a dose- and time-dependent manner, with significant reductions from baseline seen with deucravacitinib doses ≥ 3 mg twice daily (P ≤ 0.05). Biomarker expression correlated with disease activity measures such as Psoriasis Area and Severity Index (PASI) at baseline. Biomarker expression also correlated with PASI scores at Week 12.

conclusionIL-23/Th17 pathway expression in the serum of patients with psoriasis is an indicator of disease activity and response to deucravacitinib treatment. TRIAL REGISTRATION NUMBER: NCT02931838.

Indexed as

CytokineDeucravacitinibPharmacodynamicsPsoriasisTyrosine kinase 2

Identifiers

PMID39283417
PMCPMC11480296

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.