LAUSR

Brepocitinib (PF-06700841) is a small-molecule dual inhibitor of tyrosine kinase 2 and Janus kinase (JAK)1 previously administered orally in trials of other inflammatory dermatoses. In this issue of the BJD, Landis and coauthors report the results of a phase IIb study of brepocitinib cream vs. vehicle in mild-to-moderate eczema. Major advances have been made in the treatment of more severe eczema, with biologics and oral JAK inhibitors being approved in recent years. Progress has been more incremental for topical treatments used to treat eczema of mild and moderate severity, which, although it may be less burdensome for individual patients, is much more common at the population level. Topical corticosteroids are relatively inexpensive and are safe and effective for most people when used appropriately, but more efficacious options for mild or moderate eczema with favourable safety profiles would be welcome. While this phase IIb study cannot provide the level of evidence needed to place brepocitinib cream in that clinical context, it is a necessary preliminary step. Participants (n = 292) were randomized to one of eight groups: once-daily brepocitinib 3%, 1%, 0 3%, 0 1% or vehicle; or twice-daily brepocitinib 1%, 0 3% or vehicle. Across both clinicianand patient-reported effectiveness outcomes, brepocitinib was reported to be more effective than vehicle, with a suggestion of a dose–response relationship. It is difficult to estimate the magnitude of benefit as the 90% confidence intervals given indicate substantial imprecision, which is to be expected where the sample is divided across so many treatment arms. Regarding safety, while the paper presents the median plasma concentration of brepocitinib assessed weekly throughout the study, the clinical interpretation is lacking. Clarification is needed on how the systemic absorption of brepocitinib compares with that of other topical JAK inhibitors, which carry US Food and Drug Administration class-effect black boxed warnings for blood clots, serious infections, cardiovascular events and cancer. The question remains, as raised in response to another, similar trial, of how brepocitinib compares with the standard of care in mild-to-moderate eczema. Ideally, future phase III studies will include an active comparator, such as a moderate-potency topical corticosteroid. As of now (22 August 2022), a search of ClinicalTrials.gov did not reveal any information posted about what larger, phase III studies for brepocitinib cream for eczema may look like. In any case, as Landis and coauthors reported data aligning with the established Harmonising Outcome Measures for Eczema core outcome set, we hope to include brepocitinib cream in our proposed network meta-analyses of the comparative efficacy and safety of topical anti-inflammatory treatments for eczema. We look forward to well-powered phase III studies with longer treatment duration, active comparators and cost–benefit analyses, to determine whether brepocitinib will be a viable, accessible treatment option for people with mild-to-moderate eczema treated in community settings.