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Isotretinoin Laboratory Monitoring in Acne TreatmentA Delphi Consensus Study

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Key Points

Question  What is the optimal approach to laboratory monitoring for otherwise healthy patients treated with isotretinoin for acne?

Findings  In this modified Delphi consensus study administered to 22 international dermatologist experts in acne, consensus was achieved for checking alanine aminotransferase and triglycerides at baseline and peak dose. Consensus was achieved for not checking complete blood cell count or basic metabolic panel parameters, among others.

Meaning  Given the wide variation in practice patterns, these results provide data to guide clinical practice and guideline development to optimize laboratory monitoring for patients treated with isotretinoin for acne.

Abstract

Importance  Although isotretinoin may rarely be associated with laboratory abnormalities such as hypertriglyceridemia, the optimal approach to laboratory monitoring is uncertain, and there is wide variation in clinical practice.

Objective  To establish a consensus for isotretinoin laboratory monitoring among a diverse, international cohort of clinical and research experts in acne.

Design, Setting, and Participants  Using a modified electronic Delphi process, 4 rounds of anonymous electronic surveys were administered from 2021 to 2022. For laboratory tests reaching consensus (≥70% agreement) for inclusion, questions regarding more time-specific monitoring throughout isotretinoin therapy were asked in subsequent rounds. The participants were international board-certified dermatologist acne experts who were selected on a voluntary basis based on involvement in acne-related professional organizations and research.

Main Outcomes and Measures  The primary outcome measured was whether participants could reach consensus on key isotretinoin laboratory monitoring parameters.

Results  The 22 participants from 5 continents had a mean (SD) time in practice of 23.7 (11.6) years and represented a variety of practice settings. Throughout the 4-round study, participation rates ranged from 90% to 100%. Consensus was achieved for the following: check alanine aminotransferase within a month prior to initiation (89.5%) and at peak dose (89.5%) but not monthly (76.2%) or after treatment completion (73.7%); check triglycerides within a month prior to initiation (89.5%) and at peak dose (78.9%) but not monthly (84.2%) or after treatment completion (73.7%); do not check complete blood cell count or basic metabolic panel parameters at any point during isotretinoin treatment (all >70%); do not check gamma-glutamyl transferase (78.9%), bilirubin (81.0%), albumin (72.7%), total protein (72.7%), low-density lipoprotein (73.7%), high-density lipoprotein (73.7%), or C-reactive protein (77.3%).

Conclusions and Relevance  This Delphi study identified a core set of laboratory tests that should be evaluated prior to and during treatment with isotretinoin. These results provide valuable data to guide clinical practice and clinical guideline development to optimize laboratory monitoring in patients treated with isotretinoin.

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Article Information

Accepted for Publication: April 19, 2022.

Published Online: June 15, 2022. doi:10.1001/jamadermatol.2022.2044

Corresponding Author: Arash Mostaghimi, MD, MPA, MPH, Department of Dermatology, Brigham and Women’s Hospital, 221 Longwood Ave, Boston, MA 02115 (amostaghimi@bwh.harvard.edu).

Author Contributions: Drs Mostaghimi and Barbieri had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Drs Barbieri and Mostaghimi contributed equally to the work.

Concept and design: Xia, Han, Faletsky, Baldwin, Dréno, Goh, Kircik, Mann, Webster, Thiboutot, Zaenglein, Barbieri, Mostaghimi.

Acquisition, analysis, or interpretation of data: Xia, Han, Baldwin, Beleznay, Bettoli, Goh, Stein Gold, Gollnick, Herane, Kang, Kircik, Nast, Oon, See, Tollefson, Webster, Zip, Tan, Tapper, Thiboutot, Zaenglein, Barbieri, Mostaghimi.

Drafting of the manuscript: Xia, Stein Gold, Oon, Zip, Barbieri, Mostaghimi.

Critical revision of the manuscript for important intellectual content: Xia, Han, Faletsky, Baldwin, Beleznay, Bettoli, Dréno, Goh, Stein Gold, Gollnick, Herane, Kang, Kircik, Mann, Nast, Oon, See, Tollefson, Webster, Tan, Tapper, Thiboutot, Zaenglein, Barbieri, Mostaghimi.

Statistical analysis: Goh, Barbieri, Mostaghimi.

Administrative, technical, or material support: Han, Faletsky, Baldwin, Beleznay, Kang, Mann, Nast, Oon, Webster, Thiboutot, Mostaghimi.

Supervision: Bettoli, Dréno, Goh, Stein Gold, Kircik, Mann, Webster, Barbieri, Mostaghimi.

Conflict of Interest Disclosures: Mr Xia reported receiving grants from the Boston University School of Medicine Medical Student Summer Research Program during the conduct of the study. Dr Baldwin reported receiving speaking fees from Sun Pharma outside the submitted work. Dr. Beleznay has acted as an advisor, consultant, investigator, and/or speaker for: AbbVie, Allergan, Bausch Health, CeraVe, Cipher, Galderma, Johnson & Johnson, La Roche Posay, LEO Pharma, L’Oréal, Procter & Gamble, Revance, Sanofi, SkinCeuticals, and Vichy. Dr. Bettoli has acted as consultant, advisory board member, research investigator and received honoraria from AbbVie, Baiersdorf, Bioderma, Biogena, Difa-Cooper, Galderma, GSK, ICF, LEO Pharma, L’Oréal, Meda, Menarini-Relife, Mylan, Novartis, Pharcos-Biodue, UCB Pharma, and received research support (funds to institution) from AbbVie. Dr Dréno reported receiving personal fees from Galderma during the conduct of the study. Dr. Goh is a medical advisory member of Cantabria Lab (Spain) and a member of the photoprotection panel at La Roche-Posay. Dr Stein Gold reported receiving personal fees from Sun Pharma, grants from Galderma, personal fees from Galderma, personal fees from Almirall, and grants from Ortho outside the submitted work. Dr. Herane has done research or been a speaker for Galderma, ISDIN, Vichy, La Roche Posay, and Abbott. Dr. Kang has served as a consultant or an advisory board member for Allergan, CeraVe, Galderma, and Unilever. Dr. Kircik has served either as an investigator, consultant, advisory board member, or speaker for Abbott, AbbVie, Ablynx, Aclaris, Amcambis, Allergan, Almirall, Amgen, Anacor Pharma, Anaptys, Arcutis, Arena, Assos Pharma, Astellas Pharma, Asubio, Bausch Health, Berlex Laboratories, Biogen-Idec, Biolife, Biopelle, Bristol Myers Squibb, Boehringer Ingelheim, Breckinridge Pharma, Cassiopea, Centocor, Cellceutix, Cipher, Coherus, Colbar, Combinatrix, Connectics Corporation, Coria, Dermavant, Dermira, Dermik Laboratories, Dow Pharmaceutical Sciences, Dr. Reddy’s Lab, Dusa, Embil Pharma, Eli Lilly, EOS, Exeltis, Ferndale Laboratories, Foamix, Ferrer, Galderma, Genentech, GlaxoSmithKline, Glenmark, Health Point, Idera, Incyte, Intendis, Innocutis, Innovail, Isdin, Johnson & Johnson, Kyowakirin, Laboratory Skin Care, Leo, L’Oréal, 3M, Maruho, Medical International Technologies, Merck, Medicis Pharma, Merz, Nano Bio, Novartis AG, Noven Pharma, Nucryst Pharma, Obagi, Onset, OrthoNeutrogena, PediaPharma, Pfizer, Promius, PuraCap, PharmaDerm, QLT, Quinnova, Quatrix, Regeneron, Sanofi, Serono, SkinMedica, Stiefel Laboratories, Sun Pharma, Taro, TolerRx, Triax, UCB, Valeant Pharma, Warner-Chilcott, XenoPort, and ZAGE; and Dr Kircik reported receiving personal fees from Sun Pharma during the conduct of the study. Dr. Mann has served as an investigator for Amgen, Celgene, and Target PharmaSolutions. Dr Oon reported receiving speaker fees and advisory board membership and researcher from Galderma, Janssen, and Novartis; she has also been a clinical investigator for Pfizer, as well as a speaker and advisory board member for AbbVie, Eli Lilly, and Leo Pharma. Dr. See has served either as an investigator, consultant, advisory board member, or speaker for Allergan, Galderma, La Roche Posay, Mayne Pharma, Next Science, and Viatris. Dr. Webster has received support from Galderma, Accure, and Hovione. Dr. Zip has served as an advisor and/or speaker for Amgen, Bausch Health, Loreal, Sun pharma, UCB, Leo Pharma, AbbVie, Galderma, Sanofi Genzyme, Janssen, Calgene, and Lilly. Dr. Zaenglein has served as an advisor for Cassiopea, Dermata, Sol-Gel, Verrica and has received research grants from AbbVie, Dermavant, Galderma and Incyte. She is co-editor of Pediatric Dermatology. Dr. Tan is an advisor, consultant, investigator, and/or speaker for: Allergan, Bausch, Boots Walgreens, Botanix, Cipher, Cutera, Dermavant, Galderma, Leo, L’Oréal, Novartis, Pfizer, and Sun Pharma. Dr Tapper has received research support from Bausch, Gilead, and Novo Nordisk, and has previously consulted for Allergan, Novartis, Novo Nordisk, Axcella, Kaleido, Mallinckrodt, Takeda, and Bausch outside the submitted work. Dr. Thiboutot reported serving as a consultant for Galderma and Novartis. Dr Mostaghimi reported receiving grants and personal fees from Pfizer, personal fees from Eli Lilly, personal fees and licensing from Concert, personal fees from Bioniz, holds equity and advisory board membership from Hims & Hers and Figure 1, personal fees from Digital Diagnostics, and personal fees from AbbVie outside the submitted work. No other disclosures were reported.

Disclaimer: John Barbieri, MD, MBA, and Arash Mostaghimi, MD, MPA, MPH, are Associate Editors of JAMA Dermatology, and Dr Barbieri is also Evidence-based Practice Editor, but they were not involved in any of the decisions regarding review of the manuscript or its acceptance.

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