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Wednesday, June 18, 2025

Dupilumab for Atopic Dermatitis Linked to Increased Risk of Psoriasis

 

  • The use of dupilumab for the treatment of atopic dermatitis was associated with an increased risk of psoriasis compared with other systemic agents.
  • The association between dupilumab and psoriasis was further supported by validation in patients with asthma without atopic dermatitis.
  • This suggests that dupilumab may act as a trigger in promoting psoriasis.

The use of dupilumab (Dupixent) for the treatment of atopic dermatitis was associated with an increased risk of psoriasis compared with other systemic agents, according to a retrospective cohort study.

Among over 19,000 matched patients, the 3-year cumulative incidence of psoriasis was 2.86% with dupilumab versus 1.79% with other systemic agents (P<0.001), with a number needed to harm of 94, reported Chun-Ying Wu, MD, MPH, PhD, of National Yang Ming Chiao Tung University in Taipei, Taiwan, and colleagues in JAMA Dermatologyopens in a new tab or window

The dupilumab cohort had an increased risk for psoriasis (HR 1.58, 95% CI 1.25-1.99), although the risk for psoriatic arthritis (PsA) was not significant (HR 1.97, 95% CI 0.75-5.18).

Key findings of subgroup analyses included an observed increased psoriasis risk in patients without atopic comorbidities (HR 1.42, 95% CI 1.06-1.89) and those with pretreatment immunoglobulin E (IgE) levels less than 0.048 mg/dL (HR 1.59, 95% CI 1.26-2.01).

The association between dupilumab and psoriasis was further supported by validation in patients with asthma without atopic dermatitis (HR 2.13, 95% CI 1.38-3.31), the authors noted.

"Since psoriasis prevalence in general AD [atopic dermatitis] populations ranges from 0.3% to 12.6%, the dupilumab cohort's psoriasis rate, although higher than the control cohort, remained within this range," Wu and team wrote. "This suggests that dupilumab may act more as a trigger rather than a decisive factor in promoting psoriatic eruption in patients with AD."

"Recent proposals suggest that AD and psoriasis may exist on a spectrumopens in a new tab or window, with varying Th2-Th17 polarization associated with overlapping disease features," they explained. "Because IL [interleukin]-4 and IL-13 negatively regulate Th17 function, their blockade by dupilumab may skew immune responses toward Th17-driven inflammation, potentially triggering psoriasis."

However, "such an immune shift following dupilumab may not be straightforward in all patients," they added.

Danilo C. Del Campo, MD, of the Chicago Skin Clinic, told MedPage Today that "this immune shift from Th2 to Th17 dominance is certainly something we have seen in private practice, and it's encouraging to see it supported by a large, well-designed cohort study."

"That said, I do not see this as practice-changing at this point," he added. "Dupilumab remains an effective and well-tolerated option for many patients with moderate-to-severe atopic dermatitis. Awareness of this potential risk can help guide monitoring and patient counseling, particularly in those with a personal or family history of psoriasis."

Shoshana Marmon, MD, PhD, of New York Medical College in Valhalla, told MedPage Today that "the observed association between dupilumab and psoriasis in patients with asthma (but not atopic dermatitis) supports a likely drug-related trigger related to this shift in immune balance. While the absolute risk remains low, clinicians should be aware of this potential adverse effect, particularly in patients 60 years or older, without atopic comorbidities, or with lower baseline IgE levels."

"Though relatively rare, this paradoxical reaction highlights the need for increased clinical awareness when evaluating new-onset psoriasiform lesions in patients receiving dupilumab," she noted. "Clinicians should remain aware of this risk but balance it against dupilumab's strong efficacy in treating moderate-to-severe atopic dermatitis."

Observations of arthritis and enthesitis resembling PsA following dupilumab initiation also support a possible connection to a psoriatic disease phenotype, Wu and colleagues said. However, observational dataopens in a new tab or window link more than a quarter of musculoskeletal events to non-inflammatory causes; thus, "identifying the role of PsA in inflammatory cases remains challenging. As psoriatic skin lesions often precede PsA, patients may discontinue dupilumab after developing psoriasis, preventing further progression. If PsA occurs first, the absence of skin symptoms may lead to a missed diagnosis."

This population-based retrospective cohort study included adults with atopic dermatitis from the TriNetX Global Collaborative Network. Propensity score matching at a 1:1 ratio was based on age, sex, race, comorbidities, laboratory measurements, and prior medications.

Wu and colleagues analyzed 19,720 patients, 9,860 who were prescribed dupilumab and 9,860 who were prescribed other systemic agents (corticosteroids, methotrexate, cyclosporine, azathioprine, or mycophenolate mofetil). Mean age in both groups was 44.8, 55.2% were women, 50.2% were white, 18.2% were Black, and 10.2% were Asian.

Due to the observational nature of the study, the authors could only report an increased risk of psoriasis in patients receiving dupilumab without establishing causality, which was a limitation.

Disclosures

This work was supported in part by the National Science Technology Council of Taiwan and Taichung Veterans General Hospital.

The study authors had no disclosures.

Del Campo and Marmon had no disclosures.

Primary Source

JAMA Dermatology

Source Reference: opens in a new tab or windowLin T-L, et al "Psoriasis risk in patients with atopic dermatitis treated with dupilumab" JAMA Dermatol 2025; DOI: 10.1001/jamadermatol.2025.1578.


https://www.medpagetoday.com/dermatology/psoriasis/116153

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