Integrated Safety Analysis of Abrocitinib for the Treatment of Moderate-to-Severe Atopic Dermatitis From the Phase II and Phase III Clinical Trial Program

Eric L Simpson; Jonathan I Silverberg; Audrey Nosbaum; Kevin L Winthrop; Emma Guttman-Yassky; Karin M Hoffmeister; Alexander Egeberg; Hernan Valdez; Min Zhang; Saleem A Farooqui; William Romero; Andrew J Thorpe; Ricardo Rojo; Susan Johnson

doi:10.1007/s40257-021-00618-3

Integrated Safety Analysis of Abrocitinib for the Treatment of Moderate-to-Severe Atopic Dermatitis From the Phase II and Phase III Clinical Trial Program

Eric L Simpson, Jonathan I Silverberg, Audrey Nosbaum, Kevin L Winthrop, Emma Guttman-Yassky, Karin M Hoffmeister, Alexander Egeberg, Hernan Valdez, Min Zhang, Saleem A Farooqui, William Romero, Andrew J Thorpe, Ricardo Rojo, Susan Johnson

Dermatology, Department of

Abstract

BACKGROUND: Pivotal phase III studies demonstrated that abrocitinib, an oral, once-daily, JAK1-selective inhibitor, is effective treatment for moderate-to-severe atopic dermatitis (AD) as monotherapy and in combination with topical therapy.

OBJECTIVE: The aim of this study was to evaluate the long-term safety of abrocitinib 200 mg and 100 mg in an integrated analysis of a phase IIb study, four phase III studies, and one long-term extension study.

METHODS: Two cohorts were analyzed: a placebo-controlled cohort from 12- to 16-week studies and an all-abrocitinib cohort including patients who received one or more abrocitinib doses. Adverse events (AEs) of interest and laboratory data are reported.

RESULTS: Total exposure in the all-abrocitinib cohort (n = 2856) was 1614 patient-years (PY); exposure was ≥ 24 weeks in 1248 patients and ≥ 48 weeks in 606 (maximum 108 weeks). In the placebo-controlled cohort (n = 1540), dose-related AEs (200 mg, 100 mg, placebo) were nausea (14.6%, 6.1%, 2.0%), headache (7.8%, 5.9%, 3.5%), and acne (4.7%, 1.6%, 0%). Platelet count was reduced transiently in a dose-dependent manner; 2/2718 patients (200-mg group) had confirmed platelet counts of < 50 × 103/mm3 at week 4. Incidence rates (IRs) were 2.33/100PY and 2.65/100 PY for serious infection, 4.34/100PY and 2.04/100PY for herpes zoster, and 11.83/100PY and 8.73/100PY for herpes simplex in the 200-mg and 100-mg groups, respectively. IRs for nonmelanoma skin cancer, other malignancies, and major adverse cardiovascular events were < 0.5/100PY for both doses. Five venous thromboembolism events occurred (IR 0.30/100PY), all in the 200-mg group. There were three deaths due to gastric carcinoma (diagnosed at day 43), sudden death, and COVID-19.

CONCLUSION: Abrocitinib, with proper patient and dose selection, has a manageable tolerability and longer-term safety profile appropriate for long-term use in patients with moderate-to-severe AD.

TRIAL REGISTRIES: ClinicalTrials.gov: NCT02780167, NCT03349060, NCT03575871, NCT03720470, NCT03627767, NCT03422822.

Original language	English
Journal	American Journal of Clinical Dermatology
Volume	22
Issue number	5
Pages (from-to)	693-707
Number of pages	15
ISSN	1175-0561
DOIs	https://doi.org/10.1007/s40257-021-00618-3
Publication status	Published - Sep 2021

Keywords

Acne Vulgaris/chemically induced
Adolescent
Adult
Aged
Cardiovascular Diseases/epidemiology
Cholesterol, HDL/blood
Cholesterol, LDL/blood
Dermatitis, Atopic/drug therapy
Female
Headache/chemically induced
Herpes Simplex/epidemiology
Herpes Zoster/epidemiology
Humans
Incidence
Infections/epidemiology
Lymphocyte Count
Male
Middle Aged
Nausea/chemically induced
Platelet Count
Protein Kinase Inhibitors/administration & dosage
Pyrimidines/administration & dosage
Risk Factors
Skin Neoplasms/epidemiology
Sulfonamides/administration & dosage
Time Factors
Venous Thromboembolism/epidemiology
Young Adult

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10.1007/s40257-021-00618-3

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Simpson, E. L., Silverberg, J. I., Nosbaum, A., Winthrop, K. L., Guttman-Yassky, E., Hoffmeister, K. M., Egeberg, A., Valdez, H., Zhang, M., Farooqui, S. A., Romero, W., Thorpe, A. J., Rojo, R., & Johnson, S. (2021). Integrated Safety Analysis of Abrocitinib for the Treatment of Moderate-to-Severe Atopic Dermatitis From the Phase II and Phase III Clinical Trial Program. American Journal of Clinical Dermatology, 22(5), 693-707. https://doi.org/10.1007/s40257-021-00618-3

Integrated Safety Analysis of Abrocitinib for the Treatment of Moderate-to-Severe Atopic Dermatitis From the Phase II and Phase III Clinical Trial Program. / Simpson, Eric L; Silverberg, Jonathan I; Nosbaum, Audrey et al.

In: American Journal of Clinical Dermatology, Vol. 22, No. 5, 09.2021, p. 693-707.

Research output: Contribution to journal › Journal article › Research › peer-review

Simpson, EL, Silverberg, JI, Nosbaum, A, Winthrop, KL, Guttman-Yassky, E, Hoffmeister, KM, Egeberg, A, Valdez, H, Zhang, M, Farooqui, SA, Romero, W, Thorpe, AJ, Rojo, R & Johnson, S 2021, 'Integrated Safety Analysis of Abrocitinib for the Treatment of Moderate-to-Severe Atopic Dermatitis From the Phase II and Phase III Clinical Trial Program', American Journal of Clinical Dermatology, vol. 22, no. 5, pp. 693-707. https://doi.org/10.1007/s40257-021-00618-3

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title = "Integrated Safety Analysis of Abrocitinib for the Treatment of Moderate-to-Severe Atopic Dermatitis From the Phase II and Phase III Clinical Trial Program",

abstract = "BACKGROUND: Pivotal phase III studies demonstrated that abrocitinib, an oral, once-daily, JAK1-selective inhibitor, is effective treatment for moderate-to-severe atopic dermatitis (AD) as monotherapy and in combination with topical therapy.OBJECTIVE: The aim of this study was to evaluate the long-term safety of abrocitinib 200 mg and 100 mg in an integrated analysis of a phase IIb study, four phase III studies, and one long-term extension study.METHODS: Two cohorts were analyzed: a placebo-controlled cohort from 12- to 16-week studies and an all-abrocitinib cohort including patients who received one or more abrocitinib doses. Adverse events (AEs) of interest and laboratory data are reported.RESULTS: Total exposure in the all-abrocitinib cohort (n = 2856) was 1614 patient-years (PY); exposure was ≥ 24 weeks in 1248 patients and ≥ 48 weeks in 606 (maximum 108 weeks). In the placebo-controlled cohort (n = 1540), dose-related AEs (200 mg, 100 mg, placebo) were nausea (14.6%, 6.1%, 2.0%), headache (7.8%, 5.9%, 3.5%), and acne (4.7%, 1.6%, 0%). Platelet count was reduced transiently in a dose-dependent manner; 2/2718 patients (200-mg group) had confirmed platelet counts of < 50 × 103/mm3 at week 4. Incidence rates (IRs) were 2.33/100PY and 2.65/100 PY for serious infection, 4.34/100PY and 2.04/100PY for herpes zoster, and 11.83/100PY and 8.73/100PY for herpes simplex in the 200-mg and 100-mg groups, respectively. IRs for nonmelanoma skin cancer, other malignancies, and major adverse cardiovascular events were < 0.5/100PY for both doses. Five venous thromboembolism events occurred (IR 0.30/100PY), all in the 200-mg group. There were three deaths due to gastric carcinoma (diagnosed at day 43), sudden death, and COVID-19.CONCLUSION: Abrocitinib, with proper patient and dose selection, has a manageable tolerability and longer-term safety profile appropriate for long-term use in patients with moderate-to-severe AD.TRIAL REGISTRIES: ClinicalTrials.gov: NCT02780167, NCT03349060, NCT03575871, NCT03720470, NCT03627767, NCT03422822.",

keywords = "Acne Vulgaris/chemically induced, Adolescent, Adult, Aged, Cardiovascular Diseases/epidemiology, Cholesterol, HDL/blood, Cholesterol, LDL/blood, Dermatitis, Atopic/drug therapy, Female, Headache/chemically induced, Herpes Simplex/epidemiology, Herpes Zoster/epidemiology, Humans, Incidence, Infections/epidemiology, Lymphocyte Count, Male, Middle Aged, Nausea/chemically induced, Platelet Count, Protein Kinase Inhibitors/administration & dosage, Pyrimidines/administration & dosage, Risk Factors, Skin Neoplasms/epidemiology, Sulfonamides/administration & dosage, Time Factors, Venous Thromboembolism/epidemiology, Young Adult",

author = "Simpson, {Eric L} and Silverberg, {Jonathan I} and Audrey Nosbaum and Winthrop, {Kevin L} and Emma Guttman-Yassky and Hoffmeister, {Karin M} and Alexander Egeberg and Hernan Valdez and Min Zhang and Farooqui, {Saleem A} and William Romero and Thorpe, {Andrew J} and Ricardo Rojo and Susan Johnson",

note = "{\textcopyright} 2021. The Author(s).",

year = "2021",

month = sep,

doi = "10.1007/s40257-021-00618-3",

language = "English",

volume = "22",

pages = "693--707",

journal = "American Journal of Clinical Dermatology",

issn = "1175-0561",

publisher = "Adis International Ltd",

number = "5",

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TY - JOUR

T1 - Integrated Safety Analysis of Abrocitinib for the Treatment of Moderate-to-Severe Atopic Dermatitis From the Phase II and Phase III Clinical Trial Program

AU - Simpson, Eric L

AU - Silverberg, Jonathan I

AU - Nosbaum, Audrey

AU - Winthrop, Kevin L

AU - Guttman-Yassky, Emma

AU - Hoffmeister, Karin M

AU - Egeberg, Alexander

AU - Valdez, Hernan

AU - Zhang, Min

AU - Farooqui, Saleem A

AU - Romero, William

AU - Thorpe, Andrew J

AU - Rojo, Ricardo

AU - Johnson, Susan

PY - 2021/9

Y1 - 2021/9

N2 - BACKGROUND: Pivotal phase III studies demonstrated that abrocitinib, an oral, once-daily, JAK1-selective inhibitor, is effective treatment for moderate-to-severe atopic dermatitis (AD) as monotherapy and in combination with topical therapy.OBJECTIVE: The aim of this study was to evaluate the long-term safety of abrocitinib 200 mg and 100 mg in an integrated analysis of a phase IIb study, four phase III studies, and one long-term extension study.METHODS: Two cohorts were analyzed: a placebo-controlled cohort from 12- to 16-week studies and an all-abrocitinib cohort including patients who received one or more abrocitinib doses. Adverse events (AEs) of interest and laboratory data are reported.RESULTS: Total exposure in the all-abrocitinib cohort (n = 2856) was 1614 patient-years (PY); exposure was ≥ 24 weeks in 1248 patients and ≥ 48 weeks in 606 (maximum 108 weeks). In the placebo-controlled cohort (n = 1540), dose-related AEs (200 mg, 100 mg, placebo) were nausea (14.6%, 6.1%, 2.0%), headache (7.8%, 5.9%, 3.5%), and acne (4.7%, 1.6%, 0%). Platelet count was reduced transiently in a dose-dependent manner; 2/2718 patients (200-mg group) had confirmed platelet counts of < 50 × 103/mm3 at week 4. Incidence rates (IRs) were 2.33/100PY and 2.65/100 PY for serious infection, 4.34/100PY and 2.04/100PY for herpes zoster, and 11.83/100PY and 8.73/100PY for herpes simplex in the 200-mg and 100-mg groups, respectively. IRs for nonmelanoma skin cancer, other malignancies, and major adverse cardiovascular events were < 0.5/100PY for both doses. Five venous thromboembolism events occurred (IR 0.30/100PY), all in the 200-mg group. There were three deaths due to gastric carcinoma (diagnosed at day 43), sudden death, and COVID-19.CONCLUSION: Abrocitinib, with proper patient and dose selection, has a manageable tolerability and longer-term safety profile appropriate for long-term use in patients with moderate-to-severe AD.TRIAL REGISTRIES: ClinicalTrials.gov: NCT02780167, NCT03349060, NCT03575871, NCT03720470, NCT03627767, NCT03422822.

AB - BACKGROUND: Pivotal phase III studies demonstrated that abrocitinib, an oral, once-daily, JAK1-selective inhibitor, is effective treatment for moderate-to-severe atopic dermatitis (AD) as monotherapy and in combination with topical therapy.OBJECTIVE: The aim of this study was to evaluate the long-term safety of abrocitinib 200 mg and 100 mg in an integrated analysis of a phase IIb study, four phase III studies, and one long-term extension study.METHODS: Two cohorts were analyzed: a placebo-controlled cohort from 12- to 16-week studies and an all-abrocitinib cohort including patients who received one or more abrocitinib doses. Adverse events (AEs) of interest and laboratory data are reported.RESULTS: Total exposure in the all-abrocitinib cohort (n = 2856) was 1614 patient-years (PY); exposure was ≥ 24 weeks in 1248 patients and ≥ 48 weeks in 606 (maximum 108 weeks). In the placebo-controlled cohort (n = 1540), dose-related AEs (200 mg, 100 mg, placebo) were nausea (14.6%, 6.1%, 2.0%), headache (7.8%, 5.9%, 3.5%), and acne (4.7%, 1.6%, 0%). Platelet count was reduced transiently in a dose-dependent manner; 2/2718 patients (200-mg group) had confirmed platelet counts of < 50 × 103/mm3 at week 4. Incidence rates (IRs) were 2.33/100PY and 2.65/100 PY for serious infection, 4.34/100PY and 2.04/100PY for herpes zoster, and 11.83/100PY and 8.73/100PY for herpes simplex in the 200-mg and 100-mg groups, respectively. IRs for nonmelanoma skin cancer, other malignancies, and major adverse cardiovascular events were < 0.5/100PY for both doses. Five venous thromboembolism events occurred (IR 0.30/100PY), all in the 200-mg group. There were three deaths due to gastric carcinoma (diagnosed at day 43), sudden death, and COVID-19.CONCLUSION: Abrocitinib, with proper patient and dose selection, has a manageable tolerability and longer-term safety profile appropriate for long-term use in patients with moderate-to-severe AD.TRIAL REGISTRIES: ClinicalTrials.gov: NCT02780167, NCT03349060, NCT03575871, NCT03720470, NCT03627767, NCT03422822.

KW - Acne Vulgaris/chemically induced

KW - Adolescent

KW - Adult

KW - Aged

KW - Cardiovascular Diseases/epidemiology

KW - Cholesterol, HDL/blood

KW - Cholesterol, LDL/blood

KW - Dermatitis, Atopic/drug therapy

KW - Female

KW - Headache/chemically induced

KW - Herpes Simplex/epidemiology

KW - Herpes Zoster/epidemiology

KW - Humans

KW - Incidence

KW - Infections/epidemiology

KW - Lymphocyte Count

KW - Male

KW - Middle Aged

KW - Nausea/chemically induced

KW - Platelet Count

KW - Protein Kinase Inhibitors/administration & dosage

KW - Pyrimidines/administration & dosage

KW - Risk Factors

KW - Skin Neoplasms/epidemiology

KW - Sulfonamides/administration & dosage

KW - Time Factors

KW - Venous Thromboembolism/epidemiology

KW - Young Adult

UR - http://www.scopus.com/inward/record.url?scp=85112827883&partnerID=8YFLogxK

U2 - 10.1007/s40257-021-00618-3

DO - 10.1007/s40257-021-00618-3

M3 - Journal article

C2 - 34406619

VL - 22

SP - 693

EP - 707

JO - American Journal of Clinical Dermatology

JF - American Journal of Clinical Dermatology

SN - 1175-0561

IS - 5

ER -

Integrated Safety Analysis of Abrocitinib for the Treatment of Moderate-to-Severe Atopic Dermatitis From the Phase II and Phase III Clinical Trial Program

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