Eric L. Simpson, Lawrence F. Eichenfield, Javier Alonso-Llamazares, Zoe D. Draelos, Laura K. Ferris, Seth B. Forman, Melinda Gooderham, Mercedes E. Gonzalez, Adelaide A. Hebert, Leon H. Kircik, Mark Lomaga, Angela Moore, Kim A. Papp, Vimal H. Prajapati, Diane Hanna, Scott Snyder, David Krupa, Patrick Burnett, Erin Almaraz, Robert C. Higham, David H. Chu, David R. Berk
{"title":"Roflumilast Cream, 0.15%, for Atopic Dermatitis in Adults and Children","authors":"Eric L. Simpson, Lawrence F. Eichenfield, Javier Alonso-Llamazares, Zoe D. Draelos, Laura K. Ferris, Seth B. Forman, Melinda Gooderham, Mercedes E. Gonzalez, Adelaide A. Hebert, Leon H. Kircik, Mark Lomaga, Angela Moore, Kim A. Papp, Vimal H. Prajapati, Diane Hanna, Scott Snyder, David Krupa, Patrick Burnett, Erin Almaraz, Robert C. Higham, David H. Chu, David R. Berk","doi":"10.1001/jamadermatol.2024.3121","DOIUrl":null,"url":null,"abstract":"ImportanceSafe, effective, and well-tolerated topical treatment options available for long-term use in patients with atopic dermatitis (AD) are limited and associated with low adherence rates.ObjectiveTo evaluate efficacy and safety of once-daily roflumilast cream, 0.15%, vs vehicle cream in patients with AD.Design, Setting, and ParticipantsTwo phase 3, randomized, double-blind, vehicle-controlled trials (Interventional Trial Evaluating Roflumilast Cream for the Treatment of Atopic Dermatitis 1 and 2 [INTEGUMENT-1 and INTEGUMENT-2]), included patients from sites in the US, Canada, and Poland. Participants were 6 years or older with mild to moderate AD based on Validated Global Assessment for Atopic Dermatitis (assessed on a 5-point scale ranging from 0 [clear] to 4 [severe]).InterventionPatients were randomized 2:1 to receive roflumilast cream, 0.15%, or vehicle cream once daily for 4 weeks.Main Outcomes and MeasuresThe primary efficacy end point was Validated Investigator Global Assessment for Atopic Dermatitis success at week 4, defined as a score of 0 or 1 plus at least a 2-grade improvement from baseline. Secondary end points included Eczema Area and Severity Index and Worst Itch Numeric Rating Scale. Safety and local tolerability were also evaluated.ResultsAmong 1337 patients (654 patients in INTEGUMENT-1 and 683 patients in INTEGUMENT-2), the mean (SD) age was 27.7 (19.2) years, and 761 participants (56.9%) were female. The mean body surface area involved was 13.6% (SD = 11.6%; range, 3.0% to 88.0%). Significantly more patients treated with roflumilast than vehicle achieved the primary end point (INTEGUMENT-1: 32.0% vs 15.2%, respectively; <jats:italic>P</jats:italic> &amp;lt; .001; INTEGUMENT-2: 28.9% vs 12.0%, respectively; <jats:italic>P</jats:italic> &amp;lt; .001). At week 4, statistically significant differences favoring roflumilast also occurred for the achievement of at least 75% reduction in the Eczema Area and Severity Index (INTEGUMENT-1: 43.2% vs 22.0%, respectively; <jats:italic>P</jats:italic> &amp;lt; .001; INTEGUMENT-2: 42.0% vs 19.7%, respectively; <jats:italic>P</jats:italic> &amp;lt; .001). Roflumilast was well tolerated with low rates of treatment-emergent adverse events. At each time point, investigators noted no signs of irritation at the application site in 885 patients who were treated with roflumilast (≥95%), and 885 patients who were treated with roflumilast (90%) reported no or mild sensation at the application site.Conclusions and RelevanceIn 2 phase 3 trials enrolling adults and children, once-daily roflumilast cream, 0.15%, improved AD relative to vehicle cream, based on multiple efficacy end points, with favorable safety and tolerability.Trial RegistrationClinicalTrials.gov Identifiers: <jats:ext-link xmlns:xlink=\"http://www.w3.org/1999/xlink\" ext-link-type=\"uri\" xlink:href=\"https://clinicaltrials.gov/study/NCT04773587?id=NCT04773587&amp;amp;rank=1\">NCT04773587</jats:ext-link>, <jats:ext-link xmlns:xlink=\"http://www.w3.org/1999/xlink\" ext-link-type=\"uri\" xlink:href=\"https://clinicaltrials.gov/study/NCT04773600?id=NCT04773600&amp;amp;rank=1\">NCT04773600</jats:ext-link>","PeriodicalId":14734,"journal":{"name":"JAMA dermatology","volume":null,"pages":null},"PeriodicalIF":11.5000,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"JAMA dermatology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1001/jamadermatol.2024.3121","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"DERMATOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
ImportanceSafe, effective, and well-tolerated topical treatment options available for long-term use in patients with atopic dermatitis (AD) are limited and associated with low adherence rates.ObjectiveTo evaluate efficacy and safety of once-daily roflumilast cream, 0.15%, vs vehicle cream in patients with AD.Design, Setting, and ParticipantsTwo phase 3, randomized, double-blind, vehicle-controlled trials (Interventional Trial Evaluating Roflumilast Cream for the Treatment of Atopic Dermatitis 1 and 2 [INTEGUMENT-1 and INTEGUMENT-2]), included patients from sites in the US, Canada, and Poland. Participants were 6 years or older with mild to moderate AD based on Validated Global Assessment for Atopic Dermatitis (assessed on a 5-point scale ranging from 0 [clear] to 4 [severe]).InterventionPatients were randomized 2:1 to receive roflumilast cream, 0.15%, or vehicle cream once daily for 4 weeks.Main Outcomes and MeasuresThe primary efficacy end point was Validated Investigator Global Assessment for Atopic Dermatitis success at week 4, defined as a score of 0 or 1 plus at least a 2-grade improvement from baseline. Secondary end points included Eczema Area and Severity Index and Worst Itch Numeric Rating Scale. Safety and local tolerability were also evaluated.ResultsAmong 1337 patients (654 patients in INTEGUMENT-1 and 683 patients in INTEGUMENT-2), the mean (SD) age was 27.7 (19.2) years, and 761 participants (56.9%) were female. The mean body surface area involved was 13.6% (SD = 11.6%; range, 3.0% to 88.0%). Significantly more patients treated with roflumilast than vehicle achieved the primary end point (INTEGUMENT-1: 32.0% vs 15.2%, respectively; P &lt; .001; INTEGUMENT-2: 28.9% vs 12.0%, respectively; P &lt; .001). At week 4, statistically significant differences favoring roflumilast also occurred for the achievement of at least 75% reduction in the Eczema Area and Severity Index (INTEGUMENT-1: 43.2% vs 22.0%, respectively; P &lt; .001; INTEGUMENT-2: 42.0% vs 19.7%, respectively; P &lt; .001). Roflumilast was well tolerated with low rates of treatment-emergent adverse events. At each time point, investigators noted no signs of irritation at the application site in 885 patients who were treated with roflumilast (≥95%), and 885 patients who were treated with roflumilast (90%) reported no or mild sensation at the application site.Conclusions and RelevanceIn 2 phase 3 trials enrolling adults and children, once-daily roflumilast cream, 0.15%, improved AD relative to vehicle cream, based on multiple efficacy end points, with favorable safety and tolerability.Trial RegistrationClinicalTrials.gov Identifiers: NCT04773587, NCT04773600
期刊介绍:
JAMA Dermatology is an international peer-reviewed journal that has been in continuous publication since 1882. It began publication by the American Medical Association in 1920 as Archives of Dermatology and Syphilology. The journal publishes material that helps in the development and testing of the effectiveness of diagnosis and treatment in medical and surgical dermatology, pediatric and geriatric dermatology, and oncologic and aesthetic dermatologic surgery.
JAMA Dermatology is a member of the JAMA Network, a consortium of peer-reviewed, general medical and specialty publications. It is published online weekly, every Wednesday, and in 12 print/online issues a year. The mission of the journal is to elevate the art and science of health and diseases of skin, hair, nails, and mucous membranes, and their treatment, with the aim of enabling dermatologists to deliver evidence-based, high-value medical and surgical dermatologic care.
The journal publishes a broad range of innovative studies and trials that shift research and clinical practice paradigms, expand the understanding of the burden of dermatologic diseases and key outcomes, improve the practice of dermatology, and ensure equitable care to all patients. It also features research and opinion examining ethical, moral, socioeconomic, educational, and political issues relevant to dermatologists, aiming to enable ongoing improvement to the workforce, scope of practice, and the training of future dermatologists.
JAMA Dermatology aims to be a leader in developing initiatives to improve diversity, equity, and inclusion within the specialty and within dermatology medical publishing.