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Psoriatic arthritis
Efficacy and safety of selective TYK2 inhibitor, deucravacitinib, in a phase II trial in psoriatic arthritis
  1. Philip J Mease1,
  2. Atul A Deodhar2,
  3. Désirée van der Heijde3,
  4. Frank Behrens4,
  5. Alan J Kivitz5,
  6. Jeffrey Neal6,
  7. Jonghyeon Kim7,
  8. Shalabh Singhal7,
  9. Miroslawa Nowak7,
  10. Subhashis Banerjee7
  1. 1 Swedish Medical Center/Providence St. Joseph Health and University of Washington, Seattle, Washington, USA
  2. 2 Oregon Health & Science University, Portland, Oregon, USA
  3. 3 Leiden University Medical Center, Leiden, The Netherlands
  4. 4 Rheumatology and Fraunhofer Institute, Translational Medicine and Pharmacology (ITMP) & Fraunhofer Cluster of Excellence Immune-Mediated Diseases (CIMD), Goethe University, Frankfurt, Germany
  5. 5 Department of Rheumatology, Altoona Center for Clinical Research, Duncansville, Pennsylvania, USA
  6. 6 Arthritis Center of Lexington, University of Kentucky School of Medicine, Lexington, Kentucky, USA
  7. 7 Bristol Myers Squibb, Princeton, New Jersey, USA
  1. Correspondence to Dr Philip J Mease, Rheumatology Research, Swedish Medical Center, Seattle, WA 98109, USA; pmease{at}philipmease.com

Abstract

Objective To evaluate the efficacy and safety of an oral selective tyrosine kinase 2 (TYK2) inhibitor, deucravacitinib, in patients with active psoriatic arthritis (PsA).

Methods In this double-blind, phase II trial, 203 patients with PsA were randomised 1:1:1 to placebo, deucravacitinib 6 mg once a day or 12 mg once a day. The primary endpoint was American College of Rheumatology-20 (ACR-20) response at week 16.

Results ACR-20 response was significantly higher with deucravacitinib 6 mg once a day (52.9%, p=0.0134) and 12 mg once a day (62.7%, p=0.0004) versus placebo (31.8%) at week 16. Both deucravacitinib doses resulted in significant improvements versus placebo (p≤0.05) in the multiplicity-controlled secondary endpoints of change from baseline in Health Assessment Questionnaire-Disability Index and Short Form-36 Physical Component Summary score and in Psoriasis Area and Severity Index-75 response. Improvements were also seen in multiple exploratory endpoints with deucravacitinib treatment. The most common adverse events (AEs) (≥5%) in deucravacitinib-treated patients were nasopharyngitis, upper respiratory tract infection, sinusitis, bronchitis, rash, headache and diarrhoea. There were no serious AEs and no occurrence of herpes zoster, opportunistic infections and major adverse cardiovascular events, or differences versus placebo in mean changes in laboratory parameters with deucravacitinib treatment.

Conclusions Treatment with the selective TYK2 inhibitor deucravacitinib was well tolerated and resulted in greater improvements than placebo in ACR-20, multiplicity-controlled secondary endpoints and other exploratory efficacy measures in patients with PsA. Larger trials over longer periods of time with deucravacitinib are warranted to confirm its safety profile and benefits in PsA.

Trial registration number NCT03881059.

  • arthritis
  • psoriatic
  • inflammation
  • therapeutics

Data availability statement

Data are available upon reasonable request. Bristol Myers Squibb’s policy on data sharing is found at https://www.bms.com/researchers-and-partners/independent-research/data-sharing-request-process.html

https://creativecommons.org/licenses/by/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/.

https://doi.org/10.1136/annrheumdis-2021-221664

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    Data availability statement

    Data are available upon reasonable request. Bristol Myers Squibb’s policy on data sharing is found at https://www.bms.com/researchers-and-partners/independent-research/data-sharing-request-process.html

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    Footnotes

    • Handling editor Josef S Smolen

    • Contributors PJM: study design and study investigator. AAD, DvdH, MN: study design. FB, AJK, JN: collection and assembly of data. JK: data analysis. SB: study design, data analysis and manuscript preparation. All authors interpreted the data, reviewed and revised the manuscript, and gave final approval to submit the manuscript for publication.

    • Funding This study was sponsored by Bristol Myers Squibb. The sponsor designed the trial, provided the trial drug and placebo, conducted blinded safety monitoring, developed the analysis plan, analysed the results, and funded professional writing assistance. A contract research organisation (PRA Health Sciences, Raleigh, North Carolina) conducted the trial under the direction of the sponsor, and medical writers paid by the sponsor wrote the first draft of the manuscript. All authors had full access to the trial data, reviewed and approved the manuscript before submission, and vouch for the adherence of the trial to the protocol, the completeness and accuracy of the data and analyses, and the reporting of AEs. There were confidentiality agreements between the authors and the sponsor.

    • Competing interests PJM: research grants: AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Novartis, Pfizer, SUN Pharma and UCB; consulting and/or speaker fees: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Novartis, Pfizer, SUN Pharma and UCB. AAD: consulting and/or advisory boards: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Galapagos, GlaxoSmithKline, Janssen, Novartis, Pfizer and UCB; research grants: AbbVie, Eli Lilly, GlaxoSmithKline, Novartis, Pfizer and UCB. DvdH: consulting fees: AbbVie, Amgen, Astellas, AstraZeneca, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Cyxone, Daiichi, Eisai, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda and UCB Pharma; Director: Imaging Rheumatology. FB: research grants: Pfizer, Janssen, Chugai, Celgene and Roche; consultancies/speaker fees: Pfizer, AbbVie, Sanofi, Lilly, Novartis, Genzyme, Boehringer, Janssen, MSD, Celgene, Roche, Chugai, Bristol Myers Squibb and UCB Pharma. AJK: shareholder: Pfizer, Sanofi, GlaxoSmithKline, Gilead Sciences and Novartis; paid consultant: AbbVie, Boehringer Ingelheim, Flexion, Janssen, Pfizer, Sanofi, Regeneron, SUN Pharma Advanced Research and Gilead Sciences; speakers bureau: Celgene, Merck, Lilly, Novartis, Pfizer, Sanofi, Genzyme, Flexion and AbbVie. JN: research grants to foundation: AbbVie, Amgen, Eli Lilly, Genentech, Novartis, UCB, Pfizer, Gilead and Bristol Myers Squibb. SS, MN, SB: employees and shareholders of Bristol Myers Squibb. JK: employee of Bristol Myers Squibb at time of the study conduct.

    • Provenance and peer review Not commissioned; externally peer reviewed.

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