Deucravacitinib, a Tyrosine Kinase 2 Inhibitor, in Systemic Lupus Erythematosus: A Phase II, Randomized, Double-Blind, Placebo-Controlled Trial

Eric Morand; Marilyn Pike; Joan T. Merrill; Ronald van Vollenhoven; Victoria P. Werth; Coburn Hobar; Nikolay Delev; Vaishali Shah; Brian Sharkey; Thomas Wegman; Ian Catlett; Subhashis Banerjee; Shalabh Singhal

doi:10.1002/art.42391

Deucravacitinib, a Tyrosine Kinase 2 Inhibitor, in Systemic Lupus Erythematosus: A Phase II, Randomized, Double-Blind, Placebo-Controlled Trial

Eric Morand, Marilyn Pike, Joan T. Merrill, Ronald van Vollenhoven, Victoria P. Werth, Coburn Hobar, Nikolay Delev, Vaishali Shah, Brian Sharkey, Thomas Wegman, Ian Catlett, Subhashis Banerjee, Shalabh Singhal

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Abstract

Objective: To assess the efficacy and safety of deucravacitinib, an oral, selective, allosteric inhibitor of TYK2, in a phase II trial in adult patients with active systemic lupus erythematosus (SLE). Methods: Adults with active SLE were enrolled from 162 sites in 17 countries. Patients (n = 363) were randomized 1:1:1:1 to receive deucravacitinib 3 mg twice daily, 6 mg twice daily, 12 mg once daily, or placebo. The primary end point was SLE Responder Index 4 (SRI-4) response at week 32. Secondary outcomes assessed at week 48 included SRI-4, British Isles Lupus Assessment Group–based Composite Lupus Assessment (BICLA) response, Cutaneous Lupus Erythematosus Disease Area and Severity Index 50 (CLASI-50), Lupus Low Disease Activity State (LLDAS), and improvements in active (swollen plus tender), swollen, and tender joint counts. Results: At week 32, the percentage of patients achieving SRI-4 response was 34% with placebo compared to 58% with deucravacitinib 3 mg twice daily (odds ratio [OR] 2.8 [95% confidence interval (95% CI) 1.5, 5.1]; P < 0.001 versus placebo), 50% with 6 mg twice daily (OR 1.9 [95% CI 1.0, 3.4]; P = 0.02 versus placebo), and 45% with 12 mg once daily (OR 1.6 [95% CI 0.8, 2.9]; nominal P = 0.08 versus placebo). Response rates were higher with deucravacitinib treatment for BICLA, CLASI-50, LLDAS, and joint counts compared to placebo. Rates of adverse events were similar across groups, except higher rates of infections and cutaneous events, including rash and acne, with deucravacitinib treatment. Rates of serious adverse events were comparable, with no deaths, opportunistic infections, tuberculosis infections, major adverse cardiovascular events, or thrombotic events reported. Conclusion: Deucravacitinib treatment elicited higher response rates for SRI-4 and other end points compared with placebo, with an acceptable safety profile, in adult patients with active SLE.

Original language	English
Pages (from-to)	242-252
Number of pages	11
Journal	Arthritis & Rheumatology
Volume	75
Issue number	2
DOIs	https://doi.org/10.1002/art.42391
Publication status	Published - Feb 2023

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10.1002/art.42391Licence: CC BY-NC

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Morand, E., Pike, M., Merrill, J. T., van Vollenhoven, R., Werth, V. P., Hobar, C., Delev, N., Shah, V., Sharkey, B., Wegman, T., Catlett, I., Banerjee, S., & Singhal, S. (2023). Deucravacitinib, a Tyrosine Kinase 2 Inhibitor, in Systemic Lupus Erythematosus: A Phase II, Randomized, Double-Blind, Placebo-Controlled Trial. Arthritis & Rheumatology, 75(2), 242-252. https://doi.org/10.1002/art.42391

@article{5d84287500a14a2dbada6f2b4dff4bc8,

title = "Deucravacitinib, a Tyrosine Kinase 2 Inhibitor, in Systemic Lupus Erythematosus: A Phase II, Randomized, Double-Blind, Placebo-Controlled Trial",

abstract = "Objective: To assess the efficacy and safety of deucravacitinib, an oral, selective, allosteric inhibitor of TYK2, in a phase II trial in adult patients with active systemic lupus erythematosus (SLE). Methods: Adults with active SLE were enrolled from 162 sites in 17 countries. Patients (n = 363) were randomized 1:1:1:1 to receive deucravacitinib 3 mg twice daily, 6 mg twice daily, 12 mg once daily, or placebo. The primary end point was SLE Responder Index 4 (SRI-4) response at week 32. Secondary outcomes assessed at week 48 included SRI-4, British Isles Lupus Assessment Group–based Composite Lupus Assessment (BICLA) response, Cutaneous Lupus Erythematosus Disease Area and Severity Index 50 (CLASI-50), Lupus Low Disease Activity State (LLDAS), and improvements in active (swollen plus tender), swollen, and tender joint counts. Results: At week 32, the percentage of patients achieving SRI-4 response was 34\% with placebo compared to 58\% with deucravacitinib 3 mg twice daily (odds ratio [OR] 2.8 [95\% confidence interval (95\% CI) 1.5, 5.1]; P < 0.001 versus placebo), 50\% with 6 mg twice daily (OR 1.9 [95\% CI 1.0, 3.4]; P = 0.02 versus placebo), and 45\% with 12 mg once daily (OR 1.6 [95\% CI 0.8, 2.9]; nominal P = 0.08 versus placebo). Response rates were higher with deucravacitinib treatment for BICLA, CLASI-50, LLDAS, and joint counts compared to placebo. Rates of adverse events were similar across groups, except higher rates of infections and cutaneous events, including rash and acne, with deucravacitinib treatment. Rates of serious adverse events were comparable, with no deaths, opportunistic infections, tuberculosis infections, major adverse cardiovascular events, or thrombotic events reported. Conclusion: Deucravacitinib treatment elicited higher response rates for SRI-4 and other end points compared with placebo, with an acceptable safety profile, in adult patients with active SLE.",

author = "Eric Morand and Marilyn Pike and Merrill, \{Joan T.\} and \{van Vollenhoven\}, Ronald and Werth, \{Victoria P.\} and Coburn Hobar and Nikolay Delev and Vaishali Shah and Brian Sharkey and Thomas Wegman and Ian Catlett and Subhashis Banerjee and Shalabh Singhal",

note = "Funding Information: Bristol Myers Squibb designed the trial, participated in the collection, analysis, and interpretation of the data along with external authors, and paid for professional writing assistance. There were confidentiality agreements between the authors and the sponsor. All authors had full access to the trial data, participated in the interpretation of the data and development of the draft, approved the final draft before submission, and vouch for adherence of the trial to the protocol, completeness and accuracy of the data and analyses, and reporting of adverse events. Publication of this article was not contingent upon approval by Bristol Myers Squibb. Medical writing and editorial assistance were provided by Julianne Hatfield, PhD, of Peloton Advantage, LLC, an OPEN Health company, and funded by Bristol Myers Squibb. Publisher Copyright: {\textcopyright} 2022 The Authors. Arthritis \& Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.",

year = "2023",

month = feb,

doi = "10.1002/art.42391",

language = "English",

volume = "75",

pages = "242--252",

journal = "Arthritis \& Rheumatology",

issn = "2326-5191",

publisher = "John Wiley \& Sons",

number = "2",

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Morand, E, Pike, M, Merrill, JT, van Vollenhoven, R, Werth, VP, Hobar, C, Delev, N, Shah, V, Sharkey, B, Wegman, T, Catlett, I, Banerjee, S & Singhal, S 2023, 'Deucravacitinib, a Tyrosine Kinase 2 Inhibitor, in Systemic Lupus Erythematosus: A Phase II, Randomized, Double-Blind, Placebo-Controlled Trial', Arthritis & Rheumatology, vol. 75, no. 2, pp. 242-252. https://doi.org/10.1002/art.42391

TY - JOUR

T1 - Deucravacitinib, a Tyrosine Kinase 2 Inhibitor, in Systemic Lupus Erythematosus

T2 - A Phase II, Randomized, Double-Blind, Placebo-Controlled Trial

AU - Morand, Eric

AU - Pike, Marilyn

AU - Merrill, Joan T.

AU - van Vollenhoven, Ronald

AU - Werth, Victoria P.

AU - Hobar, Coburn

AU - Delev, Nikolay

AU - Shah, Vaishali

AU - Sharkey, Brian

AU - Wegman, Thomas

AU - Catlett, Ian

AU - Banerjee, Subhashis

AU - Singhal, Shalabh

N1 - Funding Information: Bristol Myers Squibb designed the trial, participated in the collection, analysis, and interpretation of the data along with external authors, and paid for professional writing assistance. There were confidentiality agreements between the authors and the sponsor. All authors had full access to the trial data, participated in the interpretation of the data and development of the draft, approved the final draft before submission, and vouch for adherence of the trial to the protocol, completeness and accuracy of the data and analyses, and reporting of adverse events. Publication of this article was not contingent upon approval by Bristol Myers Squibb. Medical writing and editorial assistance were provided by Julianne Hatfield, PhD, of Peloton Advantage, LLC, an OPEN Health company, and funded by Bristol Myers Squibb. Publisher Copyright: © 2022 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.

PY - 2023/2

Y1 - 2023/2

N2 - Objective: To assess the efficacy and safety of deucravacitinib, an oral, selective, allosteric inhibitor of TYK2, in a phase II trial in adult patients with active systemic lupus erythematosus (SLE). Methods: Adults with active SLE were enrolled from 162 sites in 17 countries. Patients (n = 363) were randomized 1:1:1:1 to receive deucravacitinib 3 mg twice daily, 6 mg twice daily, 12 mg once daily, or placebo. The primary end point was SLE Responder Index 4 (SRI-4) response at week 32. Secondary outcomes assessed at week 48 included SRI-4, British Isles Lupus Assessment Group–based Composite Lupus Assessment (BICLA) response, Cutaneous Lupus Erythematosus Disease Area and Severity Index 50 (CLASI-50), Lupus Low Disease Activity State (LLDAS), and improvements in active (swollen plus tender), swollen, and tender joint counts. Results: At week 32, the percentage of patients achieving SRI-4 response was 34% with placebo compared to 58% with deucravacitinib 3 mg twice daily (odds ratio [OR] 2.8 [95% confidence interval (95% CI) 1.5, 5.1]; P < 0.001 versus placebo), 50% with 6 mg twice daily (OR 1.9 [95% CI 1.0, 3.4]; P = 0.02 versus placebo), and 45% with 12 mg once daily (OR 1.6 [95% CI 0.8, 2.9]; nominal P = 0.08 versus placebo). Response rates were higher with deucravacitinib treatment for BICLA, CLASI-50, LLDAS, and joint counts compared to placebo. Rates of adverse events were similar across groups, except higher rates of infections and cutaneous events, including rash and acne, with deucravacitinib treatment. Rates of serious adverse events were comparable, with no deaths, opportunistic infections, tuberculosis infections, major adverse cardiovascular events, or thrombotic events reported. Conclusion: Deucravacitinib treatment elicited higher response rates for SRI-4 and other end points compared with placebo, with an acceptable safety profile, in adult patients with active SLE.

AB - Objective: To assess the efficacy and safety of deucravacitinib, an oral, selective, allosteric inhibitor of TYK2, in a phase II trial in adult patients with active systemic lupus erythematosus (SLE). Methods: Adults with active SLE were enrolled from 162 sites in 17 countries. Patients (n = 363) were randomized 1:1:1:1 to receive deucravacitinib 3 mg twice daily, 6 mg twice daily, 12 mg once daily, or placebo. The primary end point was SLE Responder Index 4 (SRI-4) response at week 32. Secondary outcomes assessed at week 48 included SRI-4, British Isles Lupus Assessment Group–based Composite Lupus Assessment (BICLA) response, Cutaneous Lupus Erythematosus Disease Area and Severity Index 50 (CLASI-50), Lupus Low Disease Activity State (LLDAS), and improvements in active (swollen plus tender), swollen, and tender joint counts. Results: At week 32, the percentage of patients achieving SRI-4 response was 34% with placebo compared to 58% with deucravacitinib 3 mg twice daily (odds ratio [OR] 2.8 [95% confidence interval (95% CI) 1.5, 5.1]; P < 0.001 versus placebo), 50% with 6 mg twice daily (OR 1.9 [95% CI 1.0, 3.4]; P = 0.02 versus placebo), and 45% with 12 mg once daily (OR 1.6 [95% CI 0.8, 2.9]; nominal P = 0.08 versus placebo). Response rates were higher with deucravacitinib treatment for BICLA, CLASI-50, LLDAS, and joint counts compared to placebo. Rates of adverse events were similar across groups, except higher rates of infections and cutaneous events, including rash and acne, with deucravacitinib treatment. Rates of serious adverse events were comparable, with no deaths, opportunistic infections, tuberculosis infections, major adverse cardiovascular events, or thrombotic events reported. Conclusion: Deucravacitinib treatment elicited higher response rates for SRI-4 and other end points compared with placebo, with an acceptable safety profile, in adult patients with active SLE.

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U2 - 10.1002/art.42391

DO - 10.1002/art.42391

M3 - Article

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AN - SCOPUS:85143212168

SN - 2326-5191

VL - 75

SP - 242

EP - 252

JO - Arthritis & Rheumatology

JF - Arthritis & Rheumatology

IS - 2

ER -

Deucravacitinib, a Tyrosine Kinase 2 Inhibitor, in Systemic Lupus Erythematosus: A Phase II, Randomized, Double-Blind, Placebo-Controlled Trial

Abstract

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Plain Language Summary of the PAISLEY study: deucravacitinib as a treatment for people with systemic lupus erythematosus

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