ReviewReal-world evidence of dupilumab efficacy and risk of adverse events: A systematic review and meta-analysis
Introduction
Atopic dermatitis is a chronic inflammatory pruritic skin disease affecting approximately 3% to 5% of adults.1 Most atopic dermatitis patients are managed with education, trigger avoidance, emollients, topical anti-inflammatory agents, and light therapy, but moderate to severe atopic dermatitis requires additional systemic immunosuppressive or biologic therapy.
Dupilumab is a monoclonal antibody that blocks the interleukin (IL) 4 receptor α and thereby inhibits signaling of IL-4 and IL-13.2,3 Clinical trials of dupilumab have shown clinically meaningful reductions in signs and symptoms of atopic dermatitis and an acceptable safety profile.4, 5, 6
In 2017 and 2019, the Food and Drug Administration and European Medicines Agency approved dupilumab for treatment of adult and adolescent patients, respectively, with moderate to severe atopic dermatitis. The Food and Drug Administration approved dupilumab for patients whose disease is not adequately controlled with topical therapies or for use when these therapies are not advisable, and the European Medicines Agency approved dupilumab for patients who are candidates for systemic therapy.
Clinical trials have strict eligibility criteria, which may prohibit the inclusion of patients with multiple morbidities, and certain patient profiles may not have been represented,6 which may further limit the generalizability of these trials. Clinicians rely on real-world data generated after launch of dupilumab to sufficiently appreciate risk and benefits of the medication.
In this systematic review and meta-analysis, we examined evidence of the efficacy and safety profile of dupilumab in atopic dermatitis after marketing.
Section snippets
Materials and methods
Before the study began, a protocol was registered on PROSPERO.
The systematic review and meta-analysis was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines.7 Two authors (A.-S.H. and N.L.) independently searched the databases PubMed and EMBASE from inception through October 2019, using the search term “dupilumab.” Additionally, all abstracts from the 28th European Academy of Dermatology and Venereology Congress were screened.
Results
The search process yielded 1236 nonduplicate studies. Twenty-four publications were included, covering 22 unique studies and 3303 atopic dermatitis patients (Supplemental Fig 1). Studies originated from Asia (n = 1),9 Europe (n = 13),10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 the Middle East (n = 1),25 and North America (n = 7).26, 27, 28, 29, 30, 31, 32 Twenty studies examined adults,9, 10, 11, 12, 13, 14, 15,17,18,20, 21, 22, 23, 24, 25, 26, 27,29,30,32 1 adults and children,31
Main findings
This systematic review and meta-analysis provided real-world efficacy and safety data for dupilumab therapy in adults with atopic dermatitis. Most data were generated in Europe and the United States and had relatively short follow-up time. Dupilumab was effective and well tolerated, but ocular adverse events were commonly reported and were the main reason for discontinuation.
Interpretation
The efficacy of dupilumab treatment in atopic dermatitis patients was overall consistent with results of clinical trials.
Limitations
Limited data in terms of size and follow-up time were available, which may result in underestimations or overestimations of the efficacy of dupilumab and reporting of important adverse events. Most studies were conducted in Europe and North America, limiting generalization. Monitoring bias is a concern because investigators may have treated patients more frequently for the purpose of collecting data on dupilumab. This may improve adherence among patients. Because of the nature of real-world
Conclusion
According to real-world data, the efficacy of dupilumab to treat adult atopic dermatitis was successful, with no short-term safety signals besides conjunctivitis, blepharitis, injection site reactions, and herpes simplex virus. There is a continuous need for registries to monitor common and uncommon serious adverse events.
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Funding sources: None.
Conflicts of interest: Dr Loft has been an honorary speaker for Eli Lilly and Janssen Cilag. Dr Silverberg has been an investigator for AbbVie, AnaptysBio, Arena, Asana, Boehringer Ingelheim, Dermira, Dermavant, DS Biopharma, Eli Lilly, Galderma, GlaxoSmithKline, Glenmark, Kiniksa, Leo Pharma, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc, and Sanofi; has been a consultant for AbbVie, Eli Lilly, Galderma, Incyte, Kiniksa, Leo Pharma, Menlo Therapeutics, Pfizer, Realm, Regeneron Pharmaceuticals, Inc, and Sanofi; and has been a speaker for Regeneron Pharmaceuticals, Inc and Sanofi. Dr Guttman-Yassky is an employee of Mount Sinai and has received research funds (grants paid to the institution) from AbbVie, Almirall, Amgen, AnaptysBio, Asana Biosciences, Boehringer Ingelheim, Celgene, Dermavant, DS Biopharma, Eli Lilly, Galderma, Ichnos Sciences, Innovaderm, Janssen, Kiniska, Kyowa Kirin, Leo Pharma, Novan, Pfizer, Ralexar, Regeneron, Sienna Biopharma, UCB, and Union Therapeutics; and is also a consultant for AbbVie, Almirall, Amgen, Arena Pharmaceuticals, Asana Biosciences, AstraZeneca Biopharmaceuticals, Boehringer Ingelheim, Cara Therapeutics, Celgene, Concert, DBV, Dermira, DS Biopharma, Eli Lilly, EMD Serono, Escalier, Galderma, Ichnos Sciences, Kyowa Kirin, Leo Pharma, Mitsubishi Tanabe, Pandion Therapeutics, Pfizer, RAPT Therapeutics, Regeneron, Sanofi, Sienna Biopharma, and Union Therapeutics. Dr Thyssen has attended advisory boards for Sanofi-Genzyme, Regeneron, AbbVie, Pfizer, Union Therapeutics, and Eli Lilly & Co; has received speaker honoraria from Leo Pharma, Regeneron, AbbVie and Sanofi-Genzyme; and been an investigator for Sanofi-Genzyme, Eli Lilly & Co, Leo Pharma, Pfizer, and AbbVie. Dr. Halling has no conflicts of interest to declare.
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