Adverse events of Dupilumab in adults with moderate-to-severe atopic dermatitis: A meta-analysis

doi:10.1016/j.intimp.2017.11.031

International Immunopharmacology

Volume 54, January 2018, Pages 303-310

https://doi.org/10.1016/j.intimp.2017.11.031 Get rights and content

Highlights

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Dupilumab moderately reduced the risk of skin infection and the exacerbation of AD.
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Dupilumab slightly increased the risk of headache.
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Dupilumab moderately increased the risk of injection-site reaction and conjunctivitis.
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Dupilumab had little effect on upper respiration infection.

Abstract

Background

Dupilumab, a fully human monoclonal antibody against interleukin-4 receptor alpha, inhibits the signals of interleukin-4 and interleukin-13, and has also shown significant efficacy in patients with moderate-to-severe atopic dermatitis (AD), while the effect of it on adverse events remains controversial.

Objective

To assess the influence of dupilumab on adverse events in adults with moderate-to-severe AD.

Method

Randomised controlled trials (RCTs) that compared dupilumab with a placebo for patients with moderate-to-severe AD were searched in the MEDLINE, EMBASE, Web of Science and Cochrane databases. The outcome of the study was the incidence of adverse events during the observation period.

Results

Eight RCTs were analysed in this study. Meta-analysis showed that patients treated with dupilumab had a lower risk of skin infection (risk ratio [RR] 0.54; 95% confidence interval [CI] 0.42–0.69) and exacerbation of AD (RR 0.44, 95% CI 0.34–0.59), but had a higher risk of injection-site reaction (RR 2.24, 95% CI 1.68–2.99), headache (RR 1.47, 95% CI 1.05–2.06), and conjunctivitis (RR 2.64, 95% CI 1.79–3.89) than did patients treated with a placebo. Nasopharyngitis, urinary tract infection, upper respiratory tract infection, and herpes virus infection were found balanced in dupilumab groups and placebo groups.

Conclusion

Dupilumab moderately reduced the risk of skin infection and the exacerbation of AD, slightly increased the risk of headache, and moderately increased the risk of injection-site reaction and conjunctivitis, but had little effect on other infections in adults with moderate-to-severe AD.

Introduction

Atopic dermatitis (AD) is a chronic, incurable disease characterised by robust type 2 helper T cell (Th2)-mediated immune responses to many environmental antigens, refractory pruritus and susceptibility to skin infection [1]. The prevalence of this disease is about 3% to 10% in adults and up to 20% in children [2], [3], [4], [5]; 20% of the patients have moderate-to-severe AD [1], for which previous therapies, such as cyclosporine, have limited efficacy, numerous side effects and also increase the risk of infection [6], [7], [8], [9]. Thus, it is necessary to find new therapies for patients with moderate-to-severe cases [10], [11], [9].

Dupilumab, a monoclonal antibody aimed at interleukin (IL)-4 receptor alpha, inhibits the signals of IL-4 and IL-13, which are type 2 cytokines that may be important drivers of atopic or allergic diseases such as AD and allergic asthma [12], [13], [14], [15], [16], [17]. Several clinical studies on dupilumab have shown significant efficacy in adults with moderate-to-severe AD and it has also recently been approved by the US Food and Drug Administration as a new systemic therapy for this disease. However, the effect of it on adverse events in adults with this disease remains controversial [6], [13], [14], [18], [16]. The purpose of this study was to estimate the influence of dupilumab on adverse events in adult patients with moderate-to-severe AD.

Section snippets

Methods and materials

This work was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement [19].

Search results

The electronic searches retrieved 261 articles, of which 138 remained after removing duplicates. Two authors screened these articles and excluded 107 records based on title and abstract information. Finally, four articles (eight trials) were included for full analysis (Fig. 1). A total of 27 studies were excluded because they were duplicate reports/subanalyses (n = 20) or were only published in conference abstracts (n = 7).

Character of included studies

All studies included in this work were placebo-controlled randomised

Discussion

Previous therapies for adult patients with moderate-to-severe AD have had limited efficacy, with many adverse effects and an increased risk of infection [6], [8], [9]. Dupilumab, a new therapy, has shown significantly reduced symptoms and signs in previous studies [6], [13], [14], [18], but its adverse effects remain controversial [6], [13], [14].

We previously considered that secondary infections were the most worrying side effect of dupilumab. However, we found that dupilumab reduced the risk

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Recently, Jak inhibitors such as baricitinib, upadacitinib, and abrocitinib were approved for the treatment of atopic dermatitis (AD) in addition to biologics, including dupilumab, tralokinumab, and nemolizumab. The increase in treatment options can be a benefit to patients with AD. Meanwhile, it could make it difficult for physicians to choose the best treatment among those treatment options. Biologics and Jak inhibitors differ in efficacy, safety, route of administration, and whether or not there is a concern about immunogenicity in addition to the evidence on comorbidities. Among the three Jak inhibitors, the degree of inhibition of signal transducer and activator of transcription differs in each Jak inhibitor. Therefore, the efficacy and safety profiles of the three Jak inhibitors are different. Physicians who treat patients with AD with Jak inhibitors and biologics need to understand the current evidence and choose the best treatment for individual patients. In this review, we discuss how integrating knowledge of the mechanisms of action of Jak inhibitors and biologics, the potential significant adverse events of these drugs, and the age and comorbidities of the patient can help achieve optimal clinical benefit for patients with moderate-to-severe AD refractory to topical agents.
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^☆: Funding: This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sector.

¹: First author.

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Adverse events of Dupilumab in adults with moderate-to-severe atopic dermatitis: A meta-analysis☆

Highlights

Abstract

Background

Objective

Method

Results

Conclusion

Introduction

Section snippets

Methods and materials

Search results

Character of included studies

Discussion

J. Allergy Clin. Immunol.

J. Am. Acad. Dermatol.

Lancet

J. Allergy Clin. Immunol.

J. Am. Acad. Dermatol.

J. Invest. Dermatol.

Clin. Immunol. (Orlando, Fla)

Epidemiology of atopic dermatitis: a review

Allergy Asthma Proc.

Quality of life of children with atopic dermatitis and their families

Curr. Opin. Allergy Clin. Immunol.

Prevalence of atopic dermatitis in Japanese adults

Br. J. Dermatol.

Global variations in prevalence of eczema symptoms in children from ISAAC Phase Three

J. Allergy Clin. Immunol.

Two phase 3 trials of Dupilumab versus placebo in atopic dermatitis

N. Engl. J. Med.