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

Abstract

Introduction The treatment landscape for moderate-to-severe atopic dermatitis (AD) continues to expand. This network meta-analysis (NMA) updates a previously conducted NMA to include data from the most recent phase 3 trials to assess 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 Data from recent phase 3 monotherapy trials of lebrikizumab, ADvocate1 (NCT04146363) and ADvocate2 (NCT04178967), were included in the analyses, along with other eligible phase 3/4 randomized placebo-controlled trials for abrocitinib, baricitinib, dupilumab, tralokinumab, and upadacitinib identified through a systemic literature review in Silverberg et al. (Dermatol Ther (Heidelb) 12(5):1181–1196, 2022 ). The proportion of patients achieving Eczema Area and Severity Index (EASI) improvement ≥ 90% from baseline (EASI-90), EASI improvement ≥ 75% from baseline (EASI-75), ≥ 4-point improvement on Pruritus Numerical Rating Scale from baseline (ΔNRS ≥ 4), and Investigator Global Assessment (IGA) score of 0 or 1 (clear or almost clear) and reduction of ≥ 2 points from baseline (IGA 0/1) were evaluated using a Bayesian network meta-analysis. Results The updated NMA analyzed 13 unique placebo-controlled trials involving 7105 patients in 32 arms across 6 targeted therapies. Upadacitinib 30 mg was the most efficacious therapy across all endpoints at the primary timepoint (week 12 or 16) and at earlier timepoints, generally followed by abrocitinib 200 mg, upadacitinib 15 mg, dupilumab 300 mg, and lebrikizumab 250 mg or abrocitinib 100 mg. Baricitinib 2 mg and tralokinumab were generally ranked lower across outcomes. Conclusions Many factors need to be considered for treatment selection for AD, especially as new treatments continue to emerge. After incorporating recent placebo-controlled phase 3 data of lebrikizumab, upadacitinib 30 mg, upadacitinib 15 mg, and abrocitinib 200 mg remain the most efficacious targeted systemic therapies over 12–16 weeks of therapy in AD. These updated findings can help healthcare providers when creating a patient’s personalized treatment plan. Supplementary Information The online version contains supplementary material available at 10.1007/s13555-023-01000-3.

Systemic Immunomodulatory Treatments for Atopic Dermatitis

“…The findings of this NMA are largely consistent with the findings of other recently published systematic reviews with NMA of systemic treatments for atopic dermatitis . Chu et al used a GRADE minimally contextualized approach to create categories of medications based on their relative efficacy.…”

“…They found statistical differences in overall adverse events between medications, whereas we did not detect important differences in withdrawals due to adverse events or serious adverse events, which are less common. The NMA by Silverberg et al was limited to studies of new targeted agents used without concomitant topical corticosteroids. Although that approach may improve transitivity compared to the more inclusive approach we used, we did not find any substantial differences with our secondary analyses limited to studies allowing vs not allowing concomitant topical anti-inflammatory therapy.…”

Matching-Adjusted Indirect Comparison of the Efficacy at Week 32 of Tralokinumab and Dupilumab in the Treatment of Moderate-to-Severe Atopic Dermatitis

“…Recent network meta-analyses of tralokinumab and dupilumab phase 3 trials have analysed data at 16 weeks of treatment [ 12 , 13 ]. One limitation of comparisons over 16 weeks is that differences in study design can have a particularly large impact in the early weeks of clinical trials.…”

“…In the absence of head-to-head data, indirect comparison methods can be used to compare therapies [ 11 ]. To date, indirect comparisons assessing the relative efficacy of tralokinumab and dupilumab have been reported up to 16 weeks of treatment [ 12 , 13 ]. However, a comparison at 16 weeks may be too early in the course of treatment to fully assess the benefits of these therapies, given that response to treatment may continue to improve with additional time, and that AD is a chronic disease [ 14 ].…”

Real-world Experience of Abrocitinib Treatment in Patients with Atopic Dermatitis and Hand Eczema: Up to 28-week Results from the BioDay Registry

“…Important to note is that a subgroup of upa-NR ( n = 6) previously received 15 mg upadacitinib, and that these patients were all treated with abrocitinib 200 mg. Due to the small numbers it was not possible to perform subgroup analyses. Results of a systematic literature review and network meta-analyses of clinical trials suggested that the EASI response was highest for upadacitinib 30 mg and abrocitinib 200 mg compared with all other treatments ( 33 ). Future studies should include a larger sample size of patients who previously failed on upadacitinib 30 mg, in order to confirm the findings of the current study.…”