Reference: JAMA Dermatol. 2025 Jun 18:e251578 early online
Practice Point: Clinical resolution of moderate-to-severe eczema with dupilumab comes at a cost: an increased risk of developing psoriasis.
EBM Pearl: Don’t let yourself (or your patients) be led astray by mistaking a relative measure of effect for absolute risk. In the case of dupilumab for eczema, the 60% increased risk of developing psoriasis equates to an absolute risk increase of 1%.
Dermatologists, close your ears. In primary care, rashes without a slam-dunk clinical diagnosis often follow the treatment sequence of a) topical steroid followed by b) topical antifungal followed by c) referral to derm if the rash isn’t gone by then. Eczema, also known as atopic dermatitis, is no exception. Eczema is commonly seen in primary care offices, but many patients with moderate-to-severe eczema still end up seeing a dermatologist who will prescribe more powerful agents such as biologics, corticosteroids, methotrexate, conventional immunosuppressants, and/or ultraviolet light therapy. The biologic dupilumab has been FDA approved to treat moderate-to-severe eczema since 2017 and is strongly recommended for this indication because of its high potential for complete symptomatic resolution (NNT of 3-5 at 16 weeks). The same cannot be said for other systemic treatments, which on average offer moderate clinical improvement (but not resolution) in about 60% of people treated.
However, new cases of psoriasis seemed to be popping up in patients taking dupilumab for eczema as well as other indications, an adverse event not observed during clinical trials. Because eczema and psoriasis are driven by distinct, and at times opposing, immune pathways, it was thought that the conditions would not coexist in the same person. However, stranger things have happened, and both conditions have been documented in a small subset of patients. In an effort to sort out what essentially comes down to nature vs. nurture, investigators designed a population-based retrospective cohort study to take a closer look.
In this recent JAMA Dermatology study using data from the TriNetX Global Collaborative Network, researchers identified over 200,000 patients diagnosed with moderate-to-severe eczema and followed them for 3 years. Approximately 90,000 patients were eligible for propensity-score matching based on age, sex, race, comorbidities, laboratory findings, and prior antihistamine use. Following propensity matching, two well-balanced cohorts were created, each consisting of around 10,000 patients: One group received dupilumab, and the other group was treated with nonbiologic systemic agents, including corticosteroids, methotrexate, cyclosporine, azathioprine, or mycophenolate mofetil. This design aimed to mimic the conditions of a randomized controlled trial as best it could and allowed for a quasi-causal inference.
Results demonstrated a 3-year cumulative incidence of psoriasis in 2.9% of patients taking dupilumab vs. 1.8% of those treated with other systemic agents (hazard ratio 1.58, 95% CI 1.25-1.99). This translates to an NNH of 94.
The risk of developing a new, potentially worse, condition is kind of a big deal. But how big? Given an NNT of 3-5, for every 25 patients who achieve resolution of their eczema with dupilumab, 1 patient will develop psoriasis. That’s quite a trade-off. On a population level, a high NNH paired with a low NNT gets a green light for continued use. But for the patients who do develop iatrogenic psoriasis, the likelihood of harm is 100%. That’s the tricky part. And without more long-term data, we also don’t know whether the psoriasis will recede with cessation of the drug or become a chronic condition with all its known morbidities.
While we can’t say with complete certainty that dupilumab causes psoriasis in some people who take it for moderate-to-severe eczema, the propensity-matching executed in this study gets us pretty close to being able to draw that conclusion. And while close usually only counts in horseshoes and hand grenades, sometimes it’s the best we get in clinical medicine. In this case, the key is bringing up the potential for harm with patients before prescribing it, and specifically speaking in terms of absolute risk. Hearing about a nearly 60% increased risk hits different than being told your risk of psoriasis goes from 2% to 3%. Some patients may be willing to take the risk, but we better be darn sure our patients understand the actual risk before agreeing to the treatment, particularly when other options are available.
For more information, see the topic Atopic Dermatitis in Adults in DynaMed.
DynaMed EBM Focus Editorial Team
This EBM Focus was written by Katharine DeGeorge, MD, MS, Senior Deputy Editor at DynaMed and Associate Professor of Family Medicine at the University of Virginia. Edited by Alan Ehrlich, MD, FAAFP, Executive Editor at DynaMed and Associate Professor in Family Medicine at the University of Massachusetts Medical School; Dan Randall, MD, MPH, FACP, Senior Deputy Editor at DynaMed; Gayle Sulik, PhD, Senior Medical Editor and Team Lead for Palliative Care at DynaMed; McKenzie Ferguson, PharmD, BCPS, Senior Clinical Writer at DynaMed; Rich Lamkin, MPH, MPAS, PA-C, Clinical Writer at DynaMed; Matthew Lavoie, BA, Senior Medical Copyeditor at DynaMed; Hannah Ekeh, MA, Senior Associate Editor II at DynaMed; and Jennifer Wallace, BA, Senior Associate Editor at DynaMed.