Dataset Information

Application of Topical Phosphodiesterase 4 Inhibitors in Mild to Moderate Atopic Dermatitis: A Systematic Review and Meta-analysis.

ABSTRACT: Importance:Topical medication is the central treatment for patients with atopic dermatitis (AD), but the options are limited. Phosphodiesterase 4 (PDE4) inhibitors are a new candidate for AD therapy. Objective:To evaluate the efficacy and safety of topical PDE4 inhibitors in mild to moderate AD. Data Sources:Clinical trials were identified from MEDLINE, Embase, Cochrane Controlled Register of Trials, Chinese medical databases (Wanfang, Chinese National Knowledge Infrastructure, Chinese Biomedical Literature Database, and China Science and Technology Journal Database), ClinicalTrials.gov, and other trial registries from inception to August 15, 2018. No restrictions on languages were placed. Study Selection:Only double-blind randomized clinical trials with topical PDE4 inhibitors vs topical vehicle treatment for patients with mild to moderate AD were included. Data Extraction and Synthesis:Two reviewers independently extracted study features, intervention details, and outcomes. A meta-analysis was performed using the random-effects model. The Cochrane Collaboration's risk of bias assessment tool was used to assess the risk of bias. Funnel plots and Egger tests were used to assess the publication bias. Main Outcomes and Measures:Changes from baseline in target lesion score were expressed in terms of standardized mean differences (SMDs) with 95% CIs. Outcomes of investigators' assessment and safety were expressed in terms of relative risk with 95% CIs. Results:Seven studies were identified, which included 1869 patients with mild to moderate AD. Overall, compared with the topical vehicle control, topical application of PDE4 inhibitors was associated with a significant decrease in target lesion score (SMD -0.40; 95% CI, -0.61 to -0.18; P?

SUBMITTER: Yang H

PROVIDER: S-EPMC6507295 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Application of Topical Phosphodiesterase 4 Inhibitors in Mild to Moderate Atopic Dermatitis: A Systematic Review and Meta-analysis.

Yang Huan H Wang Ji J Zhang Xin X Zhang Yan Y Qin Zi-Li ZL Wang Hua H Luo Xiao-Yan XY

JAMA dermatology 20190501 5

<h4>Importance</h4>Topical medication is the central treatment for patients with atopic dermatitis (AD), but the options are limited. Phosphodiesterase 4 (PDE4) inhibitors are a new candidate for AD therapy.<h4>Objective</h4>To evaluate the efficacy and safety of topical PDE4 inhibitors in mild to moderate AD.<h4>Data sources</h4>Clinical trials were identified from MEDLINE, Embase, Cochrane Controlled Register of Trials, Chinese medical databases (Wanfang, Chinese National Knowledge Infrastruct ...[more]

PMID: 30916723

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Project description:Objective Evaluate the safety profile and tolerability of topical phosphodiesterase 4 (PDE4) inhibitors versus vehicle as treatment for atopic dermatitis in published studies. Methods A search was performed in Medline/PubMed, Web of Science, and Cochrane Library databases on September 27, 2021, by 1 evaluator, without restrictions on publication dates or languages. Terms such as atopic dermatitis, phosphodiesterase 4 inhibitors, calcineurin inhibitors, and randomized controlled trials were included. The database searches were carried out by 1 evaluator. The titles and abstracts were reviewed for the identification and evaluation of potentially eligible studies. Study selection was made by two reviewers, so there was no intra-examiner statistic at the study selection step. The full-text articles were reviewed to determine whether or not they would be included in the systematic review. Global analyses, which included studies with both unclear and low risk of bias and subanalyses of studies with a low risk of bias were performed. Results Out of 237 identified articles, 14 clinical trials were included in the meta-analysis. In global analyses of studies with low and unclear risk of bias, topical treatment with PDE4 inhibitors did not differ from vehicle treatment in global treatment emergent adverse events (relative risk = 0.99; 95% CI, 0.87–1.14; P = 0.94) or in serious emergent adverse events appearance (relative risk = 0.92; 95% CI, 0.39–2.20; P = 0.86). In subanalyses of studies with a low risk of bias, a reduced rate of atopic dermatitis exacerbation was observed in PDE4 inhibitors compared with the vehicle (relative risk = 0.62; 95% CI, 0.39-0.98; P = 0.04) and risk of pain at the application site was confirmed (relative risk = 2.59; 95% CI, 1.27–5.28; P = 0.01). Conclusions PDE4 inhibitors did not show differences from vehicle treatment in treatment emergent adverse events or serious emergent adverse events incidence. In studies with low risk of bias, PDE4 inhibitors had a statistically significant risk of producing pain and reduced occurrence of atopic dermatitis exacerbation.

Project description:IntroductionCrisaborole topical ointment, 2%, is a nonsteroidal, topical anti-inflammatory phosphodiesterase-4 (PDE4) inhibitor that is approved for the treatment of mild-to-moderate atopic dermatitis (AD). The objective of the current analysis was to compare the efficacy of crisaborole 2% relative to pimecrolimus 1%, tacrolimus 0.03% and tacrolimus 0.1% in patients aged ≥ 2 years with mild-to-moderate AD by comparing improvement in Investigator's Static Global Assessment scores ( (ISGA scores of 0/1 indicating "clear or almost clear"). ISGA was selected as the primary efficacy outcome given the US Food and Drug Administration's recommendations on the use of ISGA for assessment of global severity in AD and to align with efficacy measurements in the crisaborole registration trials. Safety endpoints could not be analyzed due to differences in outcome definitions across studies.MethodsEfficacy of crisaborole was evaluated using individual patient data (IPD) from two pivotal phase III randomized controlled trials (RCTs), and efficacy of comparators was evaluated using published RCTs included in a previous network meta-analysis. Vehicle controls were not comparable due to differences in ingredients and population imbalance and, therefore, an unanchored matching-adjusted indirect comparison (MAIC) was used, which reweighted IPD for crisaborole to estimate absolute response in comparator populations.ResultsThe odds of achieving an improvement in ISGA score was higher with crisaborole 2% versus pimecrolimus 1% (odds ratio [OR] 2.03; 95% confidence interval [CI] 1.45-2.85; effective sample size = 627, reduced from 1021; p value < 0.001) and for crisaborole 2% versus tacrolimus 0.03% (OR 1.50; 95% CI 1.09-2.05; effective sample size = 311, reduced from 1021; p = 0.012).ConclusionThe unanchored MAIC suggests that the odds of achieving an improvement in ISGA score is greater with crisaborole 2% than with pimecrolimus 1% or tacrolimus 0.03% in patients aged ≥ 2 years with mild-to-moderate AD. These results are consistent with findings from the previously published network meta-analysis, which used a different methodology for performing indirect treatment comparisons.

Project description:IntroductionThe comparative efficacy of targeted systemic therapies for moderate to severe atopic dermatitis (AD) has not been systematically assessed using recent phase 3 data. This network meta-analysis assesses the comparative efficacy of targeted systemic therapies without the addition of topical corticosteroids (TCS) and/or topical calcineurin inhibitors (TCI) in adults with moderate to severe AD.MethodsThe systematic literature review searched through 17 May 2021 for phase 3/4 trials with upadacitinib, interleukin-4 (IL-4), interleukin-13 (IL-13), or JAK inhibitors compared with placebo or active intervention for adults and adolescents with moderate to severe AD with inadequate response to TCS/TCI or for whom TCS/TCI was medically inadvisable, without restrictions on year or region. Researchers assessed data using PRISMA guidelines. The proportion of patients achieving trial co-primary endpoints [Investigator Global Assessment (IGA) score of 0 or 1 (clear or almost clear) and reduction of ≥ 2 points from baseline; proportion of patients achieving Eczema Area and Severity Index (EASI) improvement ≥ 75% from baseline (EASI-75)]; EASI improvement ≥ 90% from baseline (EASI-90); and ≥ 4-point improvement on Pruritus Numerical Rating Scale from baseline (ΔNRS ≥ 4) were evaluated using Bayesian network meta-analysis.ResultsOf 3415 initially identified records, network meta-analysis (NMA) ultimately included 6 records representing 9 unique studies. Two upadacitinib trials were also included. Eleven clinical trials including 6254 patients were analyzed. Upadacitinib 30 mg daily was the most efficacious therapy across all endpoints at the primary endpoint (week 12 or 16) and at earlier timepoints, followed by upadacitinib 15 mg daily and abrocitinib 200 mg daily.DiscussionMany factors need to be considered for treatment selection for AD. These findings can help healthcare providers when personalizing a patient's treatment.ConclusionUpadacitinib 30 mg daily, upadacitinib 15 mg daily, and abrocitinib 200 mg daily may be the most efficacious targeted systemic therapies over 12-16 weeks of therapy in AD.

Project description:IntroductionThere is a need to compare efficacy and safety profiles of crisaborole ointment, 2%, versus other topical treatments across randomized clinical trials (RCTs). We performed this review/network meta-analysis to evaluate the comparative efficacy and safety of crisaborole versus other topical pharmacologic therapies for mild-to-moderate atopic dermatitis (AD) among patients aged ≥ 2 years.MethodsSearches were conducted in MEDLINE, Embase, the Cochrane Collection Central Register of Clinical Trials, and the Database of Abstracts of Reviews of Effects using Ovid to identify English language articles reporting RCTs of topical anti-inflammatory agents in patients aged ≥ 2 years with mild-to-moderate AD published between inception and 10 March 2020. This review used a prespecified protocol with eligibility criteria for population, interventions, comparisons, outcomes, and study design. Efficacy was evaluated using the Investigator's Static Global Assessment (ISGA) of clear (0) or almost clear (1) and expressed by hazard ratios (HR) with 95% credible intervals.ResultsPatients treated with crisaborole or tacrolimus ointment, 0.1% or 0.03%, versus vehicle alone were significantly more likely to achieve ISGA 0/1 at 28-42 days, with the greatest point estimate observed for the crisaborole comparison (hazard ratio: 2.07; 95% credible interval 1.76 to - 2.36; probability HR above 1 [p better]: 100.0%). Patients were also more likely to achieve ISGA 0/1 with crisaborole than with pimecrolimus cream, 1% (HR: 1.62; 95% credible interval 1.04-2.48; p better: 98.3%). While network meta-analysis for safety was not feasible because of data limitations, crisaborole pivotal studies (AD-301/AD-302) showed crisaborole was well tolerated.ConclusionsCrisaborole was shown to be superior to vehicle and pimecrolimus and comparable to tacrolimus, 0.1% or 0.03%, with respect to ISGA 0/1 at 28-42 days in patients aged ≥ 2 years with mild-to-moderate AD. This evaluation of comparative efficacy of crisaborole further supports use of crisaborole as an effective therapeutic option in this population.

Dataset Information

Application of Topical Phosphodiesterase 4 Inhibitors in Mild to Moderate Atopic Dermatitis: A Systematic Review and Meta-analysis.

Publications

Application of Topical Phosphodiesterase 4 Inhibitors in Mild to Moderate Atopic Dermatitis: A Systematic Review and Meta-analysis.

Similar Datasets

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