Systematic Review on the Efficacy and Safety of Oral Janus Kinase Inhibitors for the Treatment of Atopic Dermatitis.

Background: Atopic dermatitis is a chronic, relapsing and remitting disease that can be difficult to treat despite a recently approved biologic therapy targeting IL-4/IL-13 receptor. Oral janus kinase inhibitors (JAKi) represent a novel therapeutic class of targeted therapy to treat moderate-to-severe atopic dermatitis (AD). Objective: To review the efficacy, safety, and pharmacokinetic characteristics of oral JAKi in the treatment of AD. Methods: A PRISMA systematic review was conducted using MEDLINE, EMBASE (Ovid), and PubMed databases for studies assessing the efficacy, safety, and/or pharmacokinetic properties of oral forms of JAKi in the treatment of AD in pediatric or adult populations from inception to June 2021. Results: 496 papers were reviewed. Of 28 articles that underwent full text screening, 11 met our inclusion criteria for final qualitative review. Four studies examined abrocitinib; three studies examined baricitinib; three examined upadacitinib and one examined gusacitinib (ASN002). Significant clinical efficacy and a reassuring safety profile was reported for all JAKi agents reviewed. Rapid symptom control was reported for abrocitinib, baricitinib and upadacitinib. Limitations: Given the relatively limited evidence for each JAKi and the differences in patient eligibility criteria between studies, the data was not deemed suitable for a meta-analysis at this time. Conclusion: Given their ability to achieve rapid symptom control with a reassuring safety profile, we recommend considering the use of JAKi as a reliable systemic treatment option for adult patients with moderate-to-severe AD, who are unresponsive to topical or skin directed treatments.
Competing Interests: MB an advisory board member and speaker for AbbVie, Amgen, Leo Pharma, and Janssen; a speaker for Astellas and Merck; and an investigator for AbbVie, Astellas, Amgen, Leo Pharma, Novartis, Janssen, Sun Pharma, Lilly, Pfizer, and Celgene; LF an investigator for Pfizer, Amgen, Leo, and received honoraria as speaker and participant of advisory boards from the same companies. She is also a speaker for Pierre Fabre and Galderma; MG has been an investigator, speaker or advisory board member for Abbvie, Akros, Amgen, Arcutis, Boehringer Ingelheim, BMS, Celgene, Dermira, Dermavant, Galderma, GSK, Eli Lilly, Incyte, Janssen, Kyowa Kirin, Leo Pharma, Medimmune, Merck, Novartis, Pfizer, Regeneron, Sanofi Genzyme, Sun Pharmaceuticals, UCB, Valeant/Bausch; LG has been a consultant, advisory board member, speaker and clinical trials principal investigator for AbbVie, Eli Lilly, LaRoche Posay, Leo Pharma, Pfizer and Roche, and a consultant, advisory board member and speaker for Bausch Health, Johnson & Johnson, and Sanofi Aventis. SH has been a consultant and/or advisor and/or investigator for or received honoraria from Abbvie, Akros, Altius Healthcare, Amgen, Aralez, Arcutis, Bausch Health, Biopharma, BMS, Boehringer-Ingelheim, Celgene, Coherus, Concert Pharma, Cutanea, Dermira, Galderma, Glenmark, Incyte, Janssen, Leo, Lilly, Novartis, Pedia-Pharm, Pfizer, Regeneron, Sandoz, Sanofi, Sun Pharma, UCB; HH has been a consultant and/or advisor and/or investigator for or received honoraria from Abbvie, Amgen, Arcutis, Bausch Health, Boerhinger Ingelheim, Bristol Meyers Squibb, Celgene, Dermavant, Dermira, DS Biopharma, Eli Lilly, Galderma, GlaxoSmithKline, Incyte, Janssen, Leo Pharma, Medimmune, Merck, Novartis, Pfizer, Regeneron, Sanofi, Sun Pharma, and UCB; PL has been a consultant and/or advisor and/or investigator for or received honoraria from Abbvie, Amgen, Aralez, Bausch Health, Boehringer-Ingelheim, Celgene, Dermira, Galderma, Janssen, Leo, Lilly, Novartis, Pfizer, Regeneron, Sanofi, Sun Pharma; DM has been a consultant and/or investigator and/or speaker for Abbvie, Celgene, Janssen, Leo Pharma, Lilly, Novartis, Pfizer, Regeneron, Sanofi, UCB; MW reports having received honoraria for ad board participation from Novartis, Sun Pharma and Pfizer; JY has been a speaker, consultant, and investigator for AbbVie, Allergan, Amgen, Arcutis, Astellas, Bausch Health, Boehringer Ingelheim, Bristol Meyers Squibb, Celgene, Centocor, Coherus, Dermavant, Dermira, Forward, Galderma, GlaxoSmithKline, Incyte, Janssen, Kyowa, Leo Pharma, Lilly, Medimmune, Merck, Novartis, Pfizer, Regeneron, Roche, Sandoz, Sanofi Genzyme, Sun Pharma, Takeda, UCB, and Xenon. CL was a consultant, speaker, and advisory board member for Amgen, Pfizer, AbbVie, Janssen, Novartis, and Celgene, and was an investigator for Amgen, Pfizer, AbbVie, Janssen, Lilly, Novartis, and Celgene. Dr Poulin was a speaker and advisory board member for AbbVie, Amgen, and Janssen, and was an investigator for AbbVie, Amgen, Celgene, Centocor, Lilly, Galderma, Incyte, Sun Pharma, Janssen, Leo Pharma, Merck, Novartis, Pfizer, and Roche; IVL received grant funding from Novartis, Merck, AbbVie, and Bristol Myers Squibb and honoraria from Janssen, Bausch, Galderma, Novartis, Pfizer, Sun Pharmaceuticals, Johnson & Johnson, and Actelion. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2021 Le, Berman-Rosa, Ghazawi, Bourcier, Fiorillo, Gooderham, Guenther, Hanna, Hong, Landells, Lansang, Marcoux, Wiseman, Yeung, Lynde and Litvinov.)