Comparative efficacy and safety of systemic therapies used in moderate‐to‐severe atopic dermatitis: a systematic literature review and network meta‐analysis

Silverberg, Jonathan I.; Thyssen, Jacob P.; Fahrbach, Kyle; Mickle, Kristin; Cappelleri, Joseph C.; Romero, William; Cameron, Michael C.; Myers, Daniela E.; Clibborn, Claire; DiBonaventura, Marco

doi:10.1111/jdv.17351

Cited by 87 publications

(68 citation statements)

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“…The increased effectiveness of dupilumab in clinical practice was reflected in a higher number of patients who achieved EASI-50 and a higher reduction in SCORAD and DLQI. Clinical improvement with dupilumab was similar to that observed in previous studies in real-life settings (achieving EASI-50 in around 80% at week 12–16) [ 31 , 32 , 33 ] and higher than in clinical trials [ 34 ]. As in previous studies, we found that dupilumab improves patient quality of life [ 35 ].…”

Section: Discussionsupporting

confidence: 86%

Dupilumab Improves Skin Barrier Function in Adults with Atopic Dermatitis: A Prospective Observational Study

Montero‐Vílchez

Rodríguez-Pozo

Díaz-Calvillo

et al. 2022

JCM

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Epidermal barrier dysfunction plays an important role in atopic dermatitis (AD). The difficulty of objectively assessing AD severity and the introduction of new biologicals into clinical practice highlight the need to find parameters to monitor clinical outcomes. The aim of this study is to evaluate the impact of dupilumab on skin barrier function and compare it with other treatments in patients with AD. A prospective observational study was conducted in adults with AD treated with topical corticosteroids (TCS), cyclosporine, or dupilumab. The main outcome measures after 16 weeks of treatment were Eczema Area and Severity (EASI)-50 (50% improvement in EASI), and transepidermal water loss (TEWL)-50 (50% improvement in TEWL). Forty-six patients with AD were included in the study. The proportion of patients who achieved EASI-50 at week 16 was significantly higher in patients receiving dupilumab (81.8% vs. 28.6% vs. 40%, p = 0.004). In eczematous lesions, TEWL decreased in patients receiving dupilumab (31.02 vs. 12.10 g·h−1·m−2, p < 0.001) and TCS (25.30 vs. 14.88 g·h−1·m−2, p = 0.047). The proportion of patients who achieved TEWL-50 at week 16 was higher for dupilumab than for cyclosporine or TCS. Temperature only decreased in the dupilumab group. Stratum corneum hydration increased in eczematous lesions and non-involved skin only in patients with dupilumab. In conclusion, dupilumab improves skin barrier function in patients with AD better than TCS or cyclosporine, both in eczematous lesions and in non-lesioned skin.

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Section: Discussionsupporting

confidence: 86%

Dupilumab Improves Skin Barrier Function in Adults with Atopic Dermatitis: A Prospective Observational Study

Montero‐Vílchez

Rodríguez-Pozo

Díaz-Calvillo

et al. 2022

JCM

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“…This indirect comparison analysis found that baricitinib and dupilumab might have similar efficacy across EASI75, ≥ 4-point improvement in itch NRS, and DLQI improvement (baricitinib 4 mg) after 16 weeks of treatment, confirming the findings of a recently published network meta-analysis (NMA) and extending them to an earlier time point (week 4) [ 14 ].…”

Section: Discussionsupporting

confidence: 85%

Indirect Treatment Comparison of Baricitinib versus Dupilumab in Adults with Moderate-to-Severe Atopic Dermatitis

Bruin‐Weller

Serra‐Baldrich²,

Barbarot³

et al. 2022

Dermatol Ther (Heidelb)

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Introduction Indirect treatment comparison was used to compare approved doses of baricitinib and dupilumab for treating adult patients with moderate-to-severe atopic dermatitis (AD) who are candidates for systemic therapy. Methods Baricitinib and dupilumab were compared (Bucher method) at weeks 4 and 16. Performance in combination with topical corticosteroids (TCS) was analyzed in patients with inadequate response or inadvisable to topical therapies (population A) and cyclosporine (population B). Population A was additionally examined as monotherapy. Results For the Eczema Area and Severity Index (EASI) 75, baricitinib and dupilumab were similar. A ≥ 4-point improvement in itch numerical rating scale (NRS) was significantly more likely with baricitinib 4 mg than dupilumab in population A as monotherapy (RR = 2.62, 95% CI 1.22, 5.61, p = 0.013) and in TCS combination at week 4. These differences were not significant by week 16. For the Dermatology Life Quality Index (DLQI), baricitinib 4 mg and dupilumab were similar on mean difference in change from baseline (MDcfb), though some differences were seen between baricitinib 2 mg and dupilumab at week 16 for the population A monotherapy (MDcfb = 2.05, 95% CI 0.53, 3.56, p = 0.016) and TCS combination therapy (MDcfb = 2.48, 95% CI 0.46, 4.50, p = 0.016) groups, and in population B (MDcfb = 3.38 95% CI 1.18, 5.58, p = 0.003). Conclusions Baricitinib potentially offers more rapid improvement in itch while providing similar efficacy on EASI75 and DLQI outcomes compared with dupilumab.

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“…Silverberg et al. published an NMA comparing systemic therapies in monotherapy and combination therapy for AD but did not include data after October 2019, and so excluded the phase 3 upadacitinib trial program [ 46 ]. This analysis focused only on targeted therapies studied as monotherapy and considered the primary endpoints used in clinical trials (IGA 0/1 and EASI-75) and itch, the hallmark symptom of AD.…”

Section: Discussionmentioning

confidence: 99%

Comparative Efficacy of Targeted Systemic Therapies for Moderate to Severe Atopic Dermatitis without Topical Corticosteroids: Systematic Review and Network Meta-analysis

Silverberg

Hong

Thyssen

et al. 2022

Dermatol Ther (Heidelb)

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Introduction The 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. Methods The 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. Results Of 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. Discussion Many factors need to be considered for treatment selection for AD. These findings can help healthcare providers when personalizing a patient’s treatment. Conclusion Upadacitinib 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. Supplementary Information The online version contains supplementary material available at 10.1007/s13555-022-00721-1.

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Comparative efficacy and safety of systemic therapies used in moderate‐to‐severe atopic dermatitis: a systematic literature review and network meta‐analysis

Cited by 87 publications

References 50 publications

Dupilumab Improves Skin Barrier Function in Adults with Atopic Dermatitis: A Prospective Observational Study

Dupilumab Improves Skin Barrier Function in Adults with Atopic Dermatitis: A Prospective Observational Study

Indirect Treatment Comparison of Baricitinib versus Dupilumab in Adults with Moderate-to-Severe Atopic Dermatitis

Comparative Efficacy of Targeted Systemic Therapies for Moderate to Severe Atopic Dermatitis without Topical Corticosteroids: Systematic Review and Network Meta-analysis

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