Dupilumab linked to reduced risks for psychiatric disorders in atopic dermatitis
Key takeaways:
- Social stigma and pruritus impact the mental health of patients with atopic dermatitis.
- Reduced risks persisted across subgroups including age, sex, race and atopic comorbidities.
Patients with dupilumab prescriptions for their atopic dermatitis had lower risks for psychiatric and sleep disorders than those prescribed other treatments, according to a study published in Annals of Allergy, Asthma & Immunology.
These risks were even lower for Black or African American patients, Teng-Li Lin, MD, department of dermatology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, and colleagues wrote.
Psychiatric and sleep disorders may develop with atopic dermatitis not only due to its social stigmatization and pruritus, the researchers said, but also because its persistent inflammation and dysregulated cytokines contribute to neuropsychological dysfunction and disrupted circadian rhythm.
By targeting the IL-4 beta receptor and IL-13, the researchers said, dupilumab (Dupixent; Sanofi, Regeneron) manages atopic dermatitis and improves depression and anxiety, but evidence about its impact on mental health and sleep remains scant, the researchers said.
The study included data from adults with at least two diagnoses of atopic dermatitis, spaced 30 days apart, in the Global Collaborative Network in the TriNetX database.
The patients in the dupilumab group (n = 6,114; mean age at index, 40.3 years) were prescribed the biologic. The conventional group (n = 6,114; mean age at index, 41.5 years) were prescribed systemic corticosteroids or traditional immunomodulators.
During the follow-up period (median, 3 years), diagnoses for the dupilumab and conventional group included:
- anxiety: 4.2% vs. 4.8%;
- depressive disorders: 2.8% vs. 3.4% (P = .041);
- adjustment disorders: 0.7% vs. 1.2% (P = .011);
- sleep disorders: 3.4% vs. 3.8%; and
- ADHD: 0.8% vs. 0.7%.
Based on Kaplan-Meier analyses, 3-year cumulative incidences of these diagnoses in the dupilumab and conventional groups included:
- anxiety: 6.52% vs. 8.51% (P = .001);
- depressive disorders: 4.5% vs. 6.25% (P = .001);
- adjustment disorders: 1.25% vs. 2.17% (P = .001);
- sleep disorders: 5.4% vs. 6.83% (P = .008); and
- ADHD: 1.24% vs. 1.32%.
Hazard ratios in the dupilumab group based on Cox regression analysis included 0.756 (95% CI, 0.639-0.894) for anxiety, 0.704 (95% CI, 0.575-0.863) for depressive disorders, 0.535 (95% CI, 0.367-0.779) for adjustment disorders and 0.777 (95% CI, 0.645-0.937) for sleep disorders, which indicate significantly attenuated risks, the researchers said, whereas risks for ADHD between the groups were similar.
Also, the researchers noted that results remained consistent when the follow-up period was extended through 5 years. Further, associations between dupilumab and reduced risks for anxiety and depressive, adjustment and sleep disorders persisted across almost all subgroup analyses based on age, sex, race and atopic comorbidities.
However, there were no decreased risks for sleep disorders among patients aged 65 years and older with dupilumab, which the researchers attributed to the more complex factors that affect sleep among this age group.
But Black or African American subgroups (approximately 15% of each group) saw a more pronounced protective effect with dupilumab for anxiety (HR = 0.414; 95% CI, 0.268-0.641), depressive disorders (HR = 0.4; 95% CI, 0.296-0.627), adjustment disorders (HR = 0.228; 95% CI, 0.085-0.612) and sleep disorders (HR = 0.623; 95% CI, 0.396-0.981).
The researchers suggested that the more pronounced type 2 inflammation and the lesser involvement of the TH1/TH17 axes in atopic dermatitis among Black and African American patients may explain why dupilumab is more effective in treating atopic dermatitis and its subsequent comorbidities among these populations.
These risk reductions also persisted in the dupilumab group despite the presence of atopic comorbidities as well, with uniform results based on specific comorbidities, the researchers continued, although patients who did not have any atopic comorbidities saw even lower risks with dupilumab.
Nine different sensitivity analyses supported these results as well, the researchers said.
In one model, which required at least three coding records, hazard ratios with dupilumab included 0.602 for anxiety, 0.634 for depressive disorders, 0.504 for adjustment disorders, 0.87 for ADHD, and 0.598 for sleep disorders.
In another model that included patients with previous psychiatric and sleep disorders, hazard ratios for medical visits for existing or newly occurring issues included 0.805 for anxiety, 0.872 for depressive disorders, 0.765 for adjustment disorders, 0.733 for ADHD, and 0.908 for sleep disorders.
Based on these findings, the researchers concluded that patients with dupilumab prescriptions for atopic dermatitis have reduced risks for psychiatric and sleep disorders compared with those prescribed systemic corticosteroids or traditional immunomodulators.
But even though these risks fell with dupilumab, the researchers continued, the slight decreases in incidence for these outcomes indicate that physicians need to consider other factors beyond atopic dermatitis treatment in psychiatric and sleep disorders.
“We are encouraged to see this study by Lin et al as the relationship of mental health and eczema treatment is an important one for the NEA [National Eczema Association] community,” Wendy Smith Begolka, MBS, chief strategy officer-research, medical and community affairs, NEA, told Healio.
“We’ve shown in our own research that improvement in mental health doesn’t always parallel improvement in AD symptoms,” she continued. “This research provides helpful insights for healthcare providers and patients as they look to achieve holistic eczema care."
Perspective
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These findings are not surprising and are significant. In essence, physical and mental health go hand in hand. When one declines, so does the other. Another example is that sertraline in patients with cardiovascular diseases helps improve cardiac function. With regard more to significance, this study validates that the human body is a complex organism with many interrelated processes that we still don’t fully understand.
I do not have any patients with atopic dermatitis, but I do have many with chronic medical conditions, and the rate of anxiety and depression is quite high. Physicians treating atopic dermatitis should specifically ask patients about how their atopic dermatitis affects their mood and sense of self. An alternative would be to use screening tools such as the Patient Health Questionnaire, or PHQ-9, for depression and the General Anxiety Disorder-7, or GAD-7, for anxiety, but asking the question is what counts.
If a study aims to determine a true causal relationship between dupilumab and psychiatric conditions, then it needs to be conducted with control and study patients who have mild depression, anxiety and sleep issues compared with patients taking antidepressants.
Professor of Psychiatry and Human Behavior and Director of Emergency and Consultation Liaison Psychiatry, University of California, Irvine
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