Comparison of Binary Efficacy Outcomes of Systemic Immunomodulatory Treatments for Atopic Dermatitis

Atopic dermatitis (AD) has seen a massive change in therapeutic management over the past several years. In about half a decade of time, we have gone from no approved targeted therapies for moderate-severe atopic dermatitis to four in the USA (with an additional option globally). We are now arriving at a point where we have multiple effective medications to discuss with patients at every clinical encounter. Naturally, questions about comparative efficacy arise through those discussions, although, as with most dermatologic therapies, head-to-head comparison is limited. Systematic reviews with network meta-analyses attempt to address this problem and design statistical models to allow for some degree of comparison among placebo-controlled trials, with obvious limitations based on often very different study designs and populations. The authors of this paper spent several years building a “living” systematic review of AD treatments that is constantly updated with new trial data, and they have previously reported on continuous measures of signs, symptoms, and quality of life. Those data suggested that upadacitinib 30 mg and abrocitinib 200 mg were among the most effective therapeutic options. However, while these kinds of endpoints allow for robust comparison, they are infrequently utilized for regulatory approval, package inserts, and promotional material.

In this manuscript, the authors conducted a similar type of systematic review and network meta-analysis but, instead, focused on binary endpoints that were commonly used as regularly endpoints in pivotal randomized controlled trials, including Eczema Area Severity Index (EASI) improvement of 50% (EASI-50), 75% (EASI-75), and 90% (EASI-90), as well as IGA success (clear/almost clear with ≥2 grade improvement). These endpoints are most familiar to clinicians. They found that these data supported their previous findings and showed highest efficacy for upadacitinib 30 mg and abrocitinib 200 mg, followed by upadacitinib 15 mg, dupilumab, and abrocitinib 100 mg, and then followed by baricitinib 4 mg and 2 mg and tralokinumab. These findings are helpful for clinicians looking to explain relative efficacy of the individual treatment options, but it’s important to note that efficacy is only one part of therapeutic shared decision making — safety and patient preference are of equal importance in the discussion. Additionally, these analyses are limited by placebo-controlled data up to 16 weeks, which may not be an optimal measure of efficacy for a chronic disease that requires chronic treatment. Additionally, these data do not inform us about long-term disease control, which is a composite concept that involves many distinct clinician- and patient-centered domains. Nevertheless, despite these limitations, the findings should enhance efficacy-related discussions between healthcare providers and patients.