Long-term safety and tolerability of apremilast in patients with psoriasis: Pooled safety analysis for ≥156 weeks from 2 phase 3, randomized, controlled trials (ESTEEM 1 and 2)

Randomized, controlled trials demonstrated efficacy and safety of apremilast for moderate-to-severe plaque psoriasis and psoriatic arthritis. Assess long-term safety of oral apremilast in psoriasis patients. Safety findings are reported for 0 to ≥156 weeks from the Efficacy and Safety Trial Evaluati...

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Veröffentlicht in:Journal of the American Academy of Dermatology Jg. 77; H. 2; S. 310 - 317.e1
Hauptverfasser: Crowley, Jeffrey, Thaçi, Diamant, Joly, Pascal, Peris, Ketty, Papp, Kim A., Goncalves, Joana, Day, Robert M., Chen, Rongdean, Shah, Kamal, Ferrándiz, Carlos, Cather, Jennifer C.
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States Elsevier Inc 01.08.2017
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ISSN:0190-9622, 1097-6787, 1097-6787
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Abstract Randomized, controlled trials demonstrated efficacy and safety of apremilast for moderate-to-severe plaque psoriasis and psoriatic arthritis. Assess long-term safety of oral apremilast in psoriasis patients. Safety findings are reported for 0 to ≥156 weeks from the Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis (ESTEEM) 1 and 2. The 0 to ≥156–week apremilast-exposure period included 1184 patients treated twice daily with apremilast 30 mg (1902.2 patient-years). During 0 to ≤52 weeks, the adverse events (AEs) that occurred in ≥5% of patients included diarrhea, nausea, upper respiratory tract infection, nasopharyngitis, tension headache, and headache. From 0 to ≥156 weeks, no new AEs (affecting ≥5% of the population) were reported. AEs, serious AEs, and study drug discontinuations caused by AEs did not increase with long-term exposure. During the 0 to ≥156–week period, the rates of major cardiac events (exposure-adjusted incidence rate [EAIR] 0.5/100 patient-years), malignancies (EAIR 1.2/100 patient-years), depression (EAIR 1.8/100 patient-years), or suicide attempts (EAIR 0.1/100 patient-years) did not increase in comparison with the rates found during the 0 to ≤52–week period. No serious opportunistic infections, reactivation of tuberculosis, or clinically meaningful effects on laboratory measurements were reported. This study had a high dropout rate (21% of patients ongoing >156 weeks); most were unrelated to safety concerns. Apremilast demonstrated an acceptable safety profile and was generally well tolerated for ≥156 weeks.
AbstractList Randomized, controlled trials demonstrated efficacy and safety of apremilast for moderate-to-severe plaque psoriasis and psoriatic arthritis. Assess long-term safety of oral apremilast in psoriasis patients. Safety findings are reported for 0 to ≥156 weeks from the Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis (ESTEEM) 1 and 2. The 0 to ≥156-week apremilast-exposure period included 1184 patients treated twice daily with apremilast 30 mg (1902.2 patient-years). During 0 to ≤52 weeks, the adverse events (AEs) that occurred in ≥5% of patients included diarrhea, nausea, upper respiratory tract infection, nasopharyngitis, tension headache, and headache. From 0 to ≥156 weeks, no new AEs (affecting ≥5% of the population) were reported. AEs, serious AEs, and study drug discontinuations caused by AEs did not increase with long-term exposure. During the 0 to ≥156-week period, the rates of major cardiac events (exposure-adjusted incidence rate [EAIR] 0.5/100 patient-years), malignancies (EAIR 1.2/100 patient-years), depression (EAIR 1.8/100 patient-years), or suicide attempts (EAIR 0.1/100 patient-years) did not increase in comparison with the rates found during the 0 to ≤52-week period. No serious opportunistic infections, reactivation of tuberculosis, or clinically meaningful effects on laboratory measurements were reported. This study had a high dropout rate (21% of patients ongoing >156 weeks); most were unrelated to safety concerns. Apremilast demonstrated an acceptable safety profile and was generally well tolerated for ≥156 weeks.
Background Randomized, controlled trials demonstrated efficacy and safety of apremilast for moderate-to-severe plaque psoriasis and psoriatic arthritis. Objective Assess long-term safety of oral apremilast in psoriasis patients. Methods Safety findings are reported for 0 to ≥156 weeks from the Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis (ESTEEM) 1 and 2. Results The 0 to ≥156–week apremilast-exposure period included 1184 patients treated twice daily with apremilast 30 mg (1902.2 patient-years). During 0 to ≤52 weeks, the adverse events (AEs) that occurred in ≥5% of patients included diarrhea, nausea, upper respiratory tract infection, nasopharyngitis, tension headache, and headache. From 0 to ≥156 weeks, no new AEs (affecting ≥5% of the population) were reported. AEs, serious AEs, and study drug discontinuations caused by AEs did not increase with long-term exposure. During the 0 to ≥156–week period, the rates of major cardiac events (exposure-adjusted incidence rate [EAIR] 0.5/100 patient-years), malignancies (EAIR 1.2/100 patient-years), depression (EAIR 1.8/100 patient-years), or suicide attempts (EAIR 0.1/100 patient-years) did not increase in comparison with the rates found during the 0 to ≤52–week period. No serious opportunistic infections, reactivation of tuberculosis, or clinically meaningful effects on laboratory measurements were reported. Limitations This study had a high dropout rate (21% of patients ongoing >156 weeks); most were unrelated to safety concerns. Conclusions Apremilast demonstrated an acceptable safety profile and was generally well tolerated for ≥156 weeks.
Randomized, controlled trials demonstrated efficacy and safety of apremilast for moderate-to-severe plaque psoriasis and psoriatic arthritis.BACKGROUNDRandomized, controlled trials demonstrated efficacy and safety of apremilast for moderate-to-severe plaque psoriasis and psoriatic arthritis.Assess long-term safety of oral apremilast in psoriasis patients.OBJECTIVEAssess long-term safety of oral apremilast in psoriasis patients.Safety findings are reported for 0 to ≥156 weeks from the Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis (ESTEEM) 1 and 2.METHODSSafety findings are reported for 0 to ≥156 weeks from the Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis (ESTEEM) 1 and 2.The 0 to ≥156-week apremilast-exposure period included 1184 patients treated twice daily with apremilast 30 mg (1902.2 patient-years). During 0 to ≤52 weeks, the adverse events (AEs) that occurred in ≥5% of patients included diarrhea, nausea, upper respiratory tract infection, nasopharyngitis, tension headache, and headache. From 0 to ≥156 weeks, no new AEs (affecting ≥5% of the population) were reported. AEs, serious AEs, and study drug discontinuations caused by AEs did not increase with long-term exposure. During the 0 to ≥156-week period, the rates of major cardiac events (exposure-adjusted incidence rate [EAIR] 0.5/100 patient-years), malignancies (EAIR 1.2/100 patient-years), depression (EAIR 1.8/100 patient-years), or suicide attempts (EAIR 0.1/100 patient-years) did not increase in comparison with the rates found during the 0 to ≤52-week period. No serious opportunistic infections, reactivation of tuberculosis, or clinically meaningful effects on laboratory measurements were reported.RESULTSThe 0 to ≥156-week apremilast-exposure period included 1184 patients treated twice daily with apremilast 30 mg (1902.2 patient-years). During 0 to ≤52 weeks, the adverse events (AEs) that occurred in ≥5% of patients included diarrhea, nausea, upper respiratory tract infection, nasopharyngitis, tension headache, and headache. From 0 to ≥156 weeks, no new AEs (affecting ≥5% of the population) were reported. AEs, serious AEs, and study drug discontinuations caused by AEs did not increase with long-term exposure. During the 0 to ≥156-week period, the rates of major cardiac events (exposure-adjusted incidence rate [EAIR] 0.5/100 patient-years), malignancies (EAIR 1.2/100 patient-years), depression (EAIR 1.8/100 patient-years), or suicide attempts (EAIR 0.1/100 patient-years) did not increase in comparison with the rates found during the 0 to ≤52-week period. No serious opportunistic infections, reactivation of tuberculosis, or clinically meaningful effects on laboratory measurements were reported.This study had a high dropout rate (21% of patients ongoing >156 weeks); most were unrelated to safety concerns.LIMITATIONSThis study had a high dropout rate (21% of patients ongoing >156 weeks); most were unrelated to safety concerns.Apremilast demonstrated an acceptable safety profile and was generally well tolerated for ≥156 weeks.CONCLUSIONSApremilast demonstrated an acceptable safety profile and was generally well tolerated for ≥156 weeks.
Background: Randomized, controlled trials demonstrated efficacy and safety of apremilast for moderate-to-severe plaque psoriasis and psoriatic arthritis.Objective: Assess long-term safety of oral apremilast in psoriasis patients.Methods: Safety findings are reported for 0 to ≥156 weeks from the Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis (ESTEEM) 1 and 2.Results: The 0 to ≥156–week apremilast-exposure period included 1184 patients treated twice daily with apremilast 30 mg (1902.2 patient-years). During 0 to ≤52 weeks, the adverse events (AEs) that occurred in ≥5% of patients included diarrhea, nausea, upper respiratory tract infection, nasopharyngitis, tension headache, and headache. From 0 to ≥156 weeks, no new AEs (affecting ≥5% of the population) were reported. AEs, serious AEs, and study drug discontinuations caused by AEs did not increase with long-term exposure. During the 0 to ≥156–week period, the rates of major cardiac events (exposure-adjusted incidence rate [EAIR] 0.5/100 patient-years), malignancies (EAIR 1.2/100 patient-years), depression (EAIR 1.8/100 patient-years), or suicide attempts (EAIR 0.1/100 patient-years) did not increase in comparison with the rates found during the 0 to ≤52–week period. No serious opportunistic infections, reactivation of tuberculosis, or clinically meaningful effects on laboratory measurements were reported.Limitations: This study had a high dropout rate (21% of patients ongoing >156 weeks); most were unrelated to safety concerns.Conclusions: Apremilast demonstrated an acceptable safety profile and was generally well tolerated for ≥156 weeks.
Author Joly, Pascal
Goncalves, Joana
Shah, Kamal
Chen, Rongdean
Cather, Jennifer C.
Thaçi, Diamant
Day, Robert M.
Crowley, Jeffrey
Peris, Ketty
Ferrándiz, Carlos
Papp, Kim A.
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  fullname: Thaçi, Diamant
  organization: Comprehensive Center for Inflammation Medicine, University Hospital Schleswig-Holstein, Campus Lübeck, Germany
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  givenname: Pascal
  surname: Joly
  fullname: Joly, Pascal
  organization: Department of Dermatology, Hôpital Charles Nicolle, Université de Rouen, Rouen, France
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  givenname: Ketty
  surname: Peris
  fullname: Peris, Ketty
  organization: Catholic University of Rome, Rome, Italy
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  givenname: Kim A.
  surname: Papp
  fullname: Papp, Kim A.
  organization: Probity Medical Research, Waterloo, Ontario, Canada
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  surname: Goncalves
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  organization: Celgene Corporation, Summit, New Jersy
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  surname: Day
  fullname: Day, Robert M.
  organization: Celgene Corporation, Summit, New Jersy
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  givenname: Rongdean
  surname: Chen
  fullname: Chen, Rongdean
  organization: Celgene Corporation, Summit, New Jersy
– sequence: 9
  givenname: Kamal
  surname: Shah
  fullname: Shah, Kamal
  organization: Celgene Corporation, Summit, New Jersy
– sequence: 10
  givenname: Carlos
  surname: Ferrándiz
  fullname: Ferrándiz, Carlos
  organization: Hospital Universitario Germans Trias i Pujol, Badalona, Universidad Autónoma de Barcelona, Barcelona, Spain
– sequence: 11
  givenname: Jennifer C.
  surname: Cather
  fullname: Cather, Jennifer C.
  organization: Modern Research Associates, Dallas, Texas
BackLink https://www.ncbi.nlm.nih.gov/pubmed/28416342$$D View this record in MEDLINE/PubMed
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ContentType Journal Article
Copyright 2017 American Academy of Dermatology, Inc.
American Academy of Dermatology, Inc.
Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.
licence_http://creativecommons.org/publicdomain/zero
Copyright_xml – notice: 2017 American Academy of Dermatology, Inc.
– notice: American Academy of Dermatology, Inc.
– notice: Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.
– notice: licence_http://creativecommons.org/publicdomain/zero
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ISSN 0190-9622
1097-6787
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Issue 2
Keywords clinical trial
ESTEEM
GI
AE
EAIR
psoriasis
safety
PDE4
phosphodiesterase 4 inhibitor
psoriatic arthritis
apremilast
TB
Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis
tuberculosis
adverse event
gastrointestinal
exposure-adjusted incidence rate
phosphodiesterase 4
Language English
License This is an open access article under the CC BY-NC-ND license.
Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.
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  ident: 10.1016/j.jaad.2017.01.052_bib13
  article-title: Longterm (52-week) results of a phase III randomized, controlled trial of apremilast in patients with psoriatic arthritis
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  article-title: Apremilast is a selective PDE4 inhibitor with regulatory effects on innate immunity
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SSID ssj0009437
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Snippet Randomized, controlled trials demonstrated efficacy and safety of apremilast for moderate-to-severe plaque psoriasis and psoriatic arthritis. Assess long-term...
Background Randomized, controlled trials demonstrated efficacy and safety of apremilast for moderate-to-severe plaque psoriasis and psoriatic arthritis....
Randomized, controlled trials demonstrated efficacy and safety of apremilast for moderate-to-severe plaque psoriasis and psoriatic...
Background: Randomized, controlled trials demonstrated efficacy and safety of apremilast for moderate-to-severe plaque psoriasis and psoriatic...
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SubjectTerms Adult
Anti-Inflammatory Agents, Non-Steroidal - adverse effects
apremilast
Cardiovascular Diseases - epidemiology
clinical trial
Depression - epidemiology
Dermatology
Diarrhea - chemically induced
ESTEEM
Female
Headache - chemically induced
Human health and pathology
Humans
Immunology
Immunotherapy
Incidence
Life Sciences
Male
Middle Aged
Nasopharyngitis - chemically induced
Nausea - chemically induced
Neoplasms - epidemiology
phosphodiesterase 4 inhibitor
psoriasis
Psoriasis - drug therapy
psoriatic arthritis
Respiratory Tract Infections - chemically induced
Rhumatology and musculoskeletal system
safety
Santé publique et épidémiologie
Suicide, Attempted - statistics & numerical data
Tension-Type Headache - chemically induced
Thalidomide - adverse effects
Thalidomide - analogs & derivatives
Time Factors
Title Long-term safety and tolerability of apremilast in patients with psoriasis: Pooled safety analysis for ≥156 weeks from 2 phase 3, randomized, controlled trials (ESTEEM 1 and 2)
URI https://www.clinicalkey.com/#!/content/1-s2.0-S0190962217301469
https://www.clinicalkey.es/playcontent/1-s2.0-S0190962217301469
https://dx.doi.org/10.1016/j.jaad.2017.01.052
https://www.ncbi.nlm.nih.gov/pubmed/28416342
https://www.proquest.com/docview/1889386406
https://hal.science/hal-02467951
Volume 77
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