Biologics changed severe eczema. About a third of patients reach clear or near-clear skin

For moderate-to-severe atopic dermatitis, the arrival of targeted biologics and oral JAK inhibitors since 2017 is the largest change in eczema treatment in a generation. It is also a change whose size is routinely overstated: in the trials that won dupilumab its approval, roughly a third of patients reached clear or almost clear skin at four months. That is a transformation for those patients, and it leaves the majority short of the endpoint.

The pivotal trials

SOLO 1 and SOLO 2 were two identically designed randomised, placebo-controlled phase 3 trials in adults with moderate-to-severe atopic dermatitis whose disease was inadequately controlled by topical treatment [s2]. SOLO 1 enrolled 671 patients and SOLO 2 enrolled 708, randomised 1:1:1 to subcutaneous dupilumab 300 mg weekly, the same dose every other week alternating with placebo, or placebo, for 16 weeks [s2].

The primary outcome was a score of 0 or 1 — clear or almost clear — on the Investigator's Global Assessment together with a reduction of at least two points from baseline. In SOLO 1 that was reached by 85 patients (38%) on every-other-week dupilumab and 83 (37%) on weekly dupilumab, against 23 (10%) on placebo. In SOLO 2 the figures were 84 (36%), 87 (36%) and 20 (8%) [s2]. Significantly more patients on each dupilumab regimen also achieved at least 75% improvement on the Eczema Area and Severity Index [s2].

The trials also measured things eczema trials had historically neglected. Dupilumab improved itch, quality of life, and symptoms of anxiety and depression compared with placebo [s2]. Against that, injection-site reactions and conjunctivitis were more frequent in the dupilumab groups [s2]. Sixteen weeks is short, and the authors said plainly that longer trials were needed to assess long-term effectiveness and safety [s2].

What happens when you compare the newer drugs with each other

Almost none of these medications have been tested head to head. A living systematic review and network meta-analysis run by a research group that updates it as new trials appear has become the default answer to "which one is better", and its most recent published update covers 97 randomised trials totalling 24,679 patients, searched through 3 November 2023 [s1].

The structural weakness in that comparison is stated in the paper. The network plots "reflect the predominance of placebo-controlled trials, with few direct connections between approved therapies", and lebrikizumab — the newest entrant at the time of the update — was connected to every network only through placebo [s1]. That means the comparison between two drugs a patient might actually be choosing between is often computed indirectly, from how each performed against a placebo arm in a separate trial.

With that caveat, the findings were narrow. Against dupilumab, lebrikizumab showed no important difference in Eczema Area and Severity Index score (mean difference −2.0, 95% credible interval −4.5 to 0.3, moderate certainty), in the Patient Oriented Eczema Measure (−1.1, −2.5 to 0.2), in the Dermatology Life Quality Index (−0.2, −2.1 to 1.6), or in peak itch on a numeric rating scale (0.1, −0.4 to 0.6, high certainty) over 16 weeks [s1].

On the binary outcomes the same comparison tilted the other way. Dupilumab had higher odds than lebrikizumab of achieving 50% improvement in the severity index (odds ratio 1.4, 1.0 to 2.0), 75% improvement (1.4, 1.0 to 1.9), 90% improvement (1.5, 1.1 to 2.2) and global assessment success (1.3, 0.9 to 1.9) [s1]. Continuous and binary measures of the same trials pointing in slightly different directions is a familiar problem in this literature, and the review reports both rather than choosing.

Across the wider network, high-dose upadacitinib and abrocitinib — both oral JAK inhibitors — showed the numerically highest relative efficacy, consistent with earlier updates of the same review [s1].

What the review could not answer

Safety is where this analysis runs out. The review reports that low event rates limited useful comparisons, and that results for serious adverse events and withdrawals due to adverse events remain imprecise with wide credible intervals [s1]. Comparisons between the newer drugs and older systemic treatments such as methotrexate were likewise imprecise [s1].

That gap matters more for the JAK inhibitors than for the antibody drugs, because the JAK class carries regulatory safety labelling derived from studies in other diseases, and 16-week placebo-controlled eczema trials are not designed to detect the events those labels concern. Nothing in this network meta-analysis resolves that question in either direction.

How to read a result like this

Three things are established. Dupilumab produces clear or almost clear skin in about a third of adults with moderate-to-severe disease at 16 weeks, against roughly one in ten on placebo [s2]. The newer targeted drugs perform similarly to each other on continuous severity scores, with the oral JAK inhibitors ranking numerically highest [s1]. And the comparative safety evidence between them does not yet exist at useful precision [s1].

What is not established is how any of them perform over years rather than months, and how they compare when a patient's actual choice is between two active drugs rather than between one drug and a placebo. The review continues to update as trials report; the honest position is that it is answering a question that the trial literature has not yet been designed to answer.

This article is informational and is not medical advice.

Sources

• [s1] Systemic Immunomodulatory Treatments for Atopic Dermatitis: Living Systematic Review and Network Meta-Analysis Update — JAMA Dermatology, published online 17 July 2024. https://doi.org/10.1001/jamadermatol.2024.2192
• [s2] Two Phase 3 Trials of Dupilumab versus Placebo in Atopic Dermatitis — New England Journal of Medicine, published online 30 September 2016. https://doi.org/10.1056/NEJMoa1610020