Systemic treatments for eczema: a network meta-analysis

Sawangjit, Ratree; Dilokthornsakul, Piyameth; Lloyd-Lavery, Antonia; Chua, Sean Kai Jie; Lai, Nai Ming; Dellavalle, R.; Chaiyakunapruk, Nathorn

doi:10.1002/14651858.cd013206

Cited by 22 publications

(31 citation statements)

References 126 publications

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“…JAK inhibitors show higher efficacy than Dupilumab, but indeed a higher risk of adverse effects. These data confirm previous results reported in literature [37,38].…”

Section: Discussionsupporting

confidence: 93%

Short-Term Effectiveness and Safety of Biologics and Small Molecule Drugs for Moderate to Severe Atopic Dermatitis: A Systematic Review and Network Meta-Analysis

Pereyra‐Rodriguez

Alcantara-Luna

Domínguez-Cruz

et al. 2021

Life

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Background: Some Network Meta-analysis (NMA) has been published regarding atopic dermatitis (AD). These studies have considered drugs under investigation both in monotheraphy or in combination with topical corticosteroids, as well as systemic immunosuppressant therapies. The objective of this study is to evaluate the efficacy and safety of biological agents and small molecules in AD. Methods: A systematic review and NMA of biologics agents and small molecules in AD was performed. A literature search was performed using MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials for clinical trials and systematic reviews between January 2000 and 19 December 2020. Only randomized clinical trials (RCTs) were included. It was limited to English language and adult human subjects. Two networks were evaluated: monotherapy and combination with TCS. The two primary outcomes were Eczema Area and Severity Index (EASI) 75 and EASI 90 change from baseline to week 12–16, depending on source study cut-off. The Cochrane’s Risk of Bias tool 2011 update was used to analyze the risk of bias, focused on the primary objectives. Results: 30 RCTs (included in 26 publications) were included in the systematic review. Finally, 23 RCTs were included in the quantitative analysis (14 RCTs including 3582 patients in monotherapy; and 9 RCTs including 3686 patients with TCS). In monotherapy, a higher percentage of patients achieving EASI-75 was obtained with Upadacitinib 30 mg [OR: 18.90 (13.94; 25.62)] followed by Abrocitinib 200 mg [OR = 11.26 (7.02; 18.05)] and Upadacitinib 15 mg [OR: 10.89 (8.13; 14.59)]. These results were also observed in studies where the use of topical corticosteroid (TCS) was allowed (OR Upadacitinib 30 mg = 9.43; OR Abrocitinib 200 mg = 6.12; OR Upadacitinib 15 mg = 5.20). Regarding IGA, the percentage of patients achieving IGA0/1 was higher with both doses of Upadacitinib 30 mg [OR: 19.13 (13.14; 27.85)] and 15 mg [OR = 10.95 (7.52; 15.94). In studies where the use of TCS were allowed, however, the dose of Abrocitinib 200 mg [OR = 6.10 (3.94; 9.44)] showed higher efficacy than Upadacitinib 15 mg [OR = 5.47 (3.57; 8.41)]. Regarding safety, the drugs with the highest probability of presenting adverse effects were the Janus kinases (JAK) inhibitors, Upadacitinib and Abrocitinib in monotherapy and Baricitinib in combination with TCS. Discussion: Some risks of bias have been found, which must be taken into account when interpreting the results. The funnel plot shows a possible publication bias that may underestimate the efficacy of drugs. Upadacitinib and Abrocitinib are the drugs with the highest efficacy, both in monotherapy and in association with TCS. However, they were also those associated with the highest risk of adverse effects, showing monoclonal antibodies better safety profile. Limitations: We have included molecules still in the development phase as well studies completed and presented at conferences and with data available in Trialsgov® but not published yet. Several molecules’ development had included a small number of patients from 12 to 17 years of age, without being able to differentiate the results from the adult population. Other: Founding: None. PROSPERO database registration number CRD42021225793.

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“…JAK inhibitors show higher efficacy than Dupilumab, but indeed a higher risk of adverse effects. These data confirm previous results reported in literature [37,38].…”

Section: Discussionsupporting

confidence: 93%

Short-Term Effectiveness and Safety of Biologics and Small Molecule Drugs for Moderate to Severe Atopic Dermatitis: A Systematic Review and Network Meta-Analysis

Pereyra‐Rodriguez

Alcantara-Luna

Domínguez-Cruz

et al. 2021

Life

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“…Randomized clinical trials and network meta-analyses can be helpful for patients and clinicians to understand the relative efficacy and safety of treatments, 4,5 but the populations included in randomized clinical trials (RCTs) for AD are often limited. In a systematic review, a third of AD systemic therapy trials had explicit upper age limits, and 70% had other exclusion criteria that would preferentially exclude older adults 6 .…”

Section: Capsule Summarymentioning

confidence: 99%

Systemic Therapy for Atopic Dermatitis in Older Adults and Adults With Comorbidities: A Scoping Review and International Eczema Council Survey

Drucker¹,

Lam²,

Flohr³

et al. 2022

Dermatitis

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Background: Clinical trials of systemic therapies for atopic dermatitis (AD) often exclude patients based on age and comorbidities.Objectives: We conducted a scoping review of observational studies and survey of International Eczema Council (IEC) members on the treatment of AD in patients with liver disease, renal disease, viral hepatitis, HIV, or history of malignancy.Methods: We searched MEDLINE via Ovid, Embase via Ovid, and Web of Science from inception to September 14, 2020. We mapped the available evidence on the use of cyclosporine, methotrexate, azathioprine, mycophenolate, systemic corticosteroids, and dupilumab for AD in older adults (≥65 years) and adults with the previously mentioned comorbidities. We surveyed IEC members on their preferred systemic medications for each patient population.Results: We identified 25 studies on the use of systemic medications in special populations of adults with AD. Although IEC members preferred dupilumab as the first-line systemic agent across all special populations, many could not identify viable third-line systemic therapy options for some populations.

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“…133 In a Cochrane review, Dupilumab has been indicated as the most effective biological treatment for eczema. 134 With such credentials, the drug has been approved both in America and Europe for treating AD over 12 years. A trial is also ongoing to evaluate a possible synergy between Dupilumab and anti-IL-33 (REGN3500).…”

Section: Atopic Dermatitismentioning

confidence: 99%

“…The only significant side effect was conjunctivitis 133 . In a Cochrane review, Dupilumab has been indicated as the most effective biological treatment for eczema 134 . With such credentials, the drug has been approved both in America and Europe for treating AD over 12 years.…”

Section: Monoclonal Antibodies Showing Promise In Clinical Trials For Food Allergy‐related Conditionsmentioning

confidence: 99%

The use of biologics in food allergy

Fiocchi

Vickery

Wood

2021

Clin Experimental Allergy

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Background Food allergy continues to pose problems due to its increased frequency and its increasingly high severity. In this context, alongside the traditional avoidance strategies of allergenic foods and desensitization through the cautious progression of exposure to foods in the context of oral immunotherapy (OIT), alternative strategies have made their way in the last decades. We review the possibilities of intervention in food allergy with the use of biological drugs capable of interfering with the synthesis of IgE, with their mechanisms of action, or with complex biological mechanisms that lead to the establishment of a food allergy. Methods Repeated Entrez PubMed searches using the template algorithm “Food allergy” and “biologics” or “Omalizumab” or “Dupilumab” or “milk desensitization” or “oral tolerance induction” or “oral immunotherapy” or “Etokimab” or “Tezepelumab” or “Quilizumab” or “Ligelizumab” or “Tralokinumab” or “Nemolizumab” or “Mepolizumab” or “Reslizumab” or “Benralizumab”. The authors’ clinical experience in paediatric allergy units of University hospitals was also drawn upon. Results The landscape in this context has changed dramatically over the past 10 years. We have acquired knowledge mainly on the effect of different types of anti‐IgE treatments in poliallergic patients with food allergy, and in patients treated with OIT. However, other mediators are being targeted by specific biologic treatments. Among them, the alarmins Il‐33 and TSLP, IL‐4 and IL‐13, eosinophil‐related molecules as IL‐6, IL‐8, IL‐10, IL‐12, and mostly IL‐5, and integrins involved in the pathogenesis of eosinophilic gastrointestinal diseases (EGIDs), as SIGLEC‐8. Conclusions The ever‐better knowledge of the mechanisms of food allergy allowing these developments will improve not only the perspective of patients with the most serious immediate food allergies such as anaphylaxis, but also those of patients with related diseases such as atopic dermatitis, eosinophilic esophagitis, and EGIDs. Biologics are also intended to complement OIT strategies that have developed over the years.

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Systemic treatments for eczema: a network meta-analysis

Cited by 22 publications

References 126 publications

Short-Term Effectiveness and Safety of Biologics and Small Molecule Drugs for Moderate to Severe Atopic Dermatitis: A Systematic Review and Network Meta-Analysis

Short-Term Effectiveness and Safety of Biologics and Small Molecule Drugs for Moderate to Severe Atopic Dermatitis: A Systematic Review and Network Meta-Analysis

Systemic Therapy for Atopic Dermatitis in Older Adults and Adults With Comorbidities: A Scoping Review and International Eczema Council Survey

The use of biologics in food allergy

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