Psoriasis, a systemic condition often viewed solely from a dermatological lens, is associated with various comorbidities, including metabolic syndrome, heart disease, depression, inflammatory bowel disease, and arthritis, among others. However, the fragmented nature of healthcare today makes it challenging to provide integrated care that addresses these concurrent conditions. Clinicians may find it difficult to manage these comorbidities effectively while ensuring follow-up and treatment coordination. Nevertheless, with careful attention, systemic therapies, including biologics, can often address multiple aspects of the disease, including related comorbidities like obesity and depression.
Obesity and Psoriasis: A Complex Relationship
Obesity is a common comorbidity among psoriasis patients, and while FDA-approved psoriasis treatments are not typically adjusted based on body weight, research has shown that weight reduction can improve biologic response in some cases. In a clinical trial, patients on biologic therapy (including infliximab, adalimumab, etanercept, or ustekinumab) who followed a low-calorie diet (≤1000 calories) for 24 weeks experienced a mean 84% improvement in their Psoriasis Area and Severity Index (PASI) score, compared to a 59.3% improvement in the control group. This data suggests that weight loss could enhance treatment outcomes for psoriasis patients, although dietary modifications may be difficult to discuss in a clinical setting. Nevertheless, with appropriate counseling, weight management can be integrated into patient care.
For patients with obesity, prescribing glucagon-like peptide (GLP)-1 agonists may be a viable option. While currently approved for managing diabetes and obesity, GLP-1 agonists have also shown promise in psoriasis treatment. A small-scale study of psoriasis patients with type 2 diabetes revealed that treatment with GLP-1 therapy resulted in a significant decrease in PASI scores, from a mean of 14.02 to 2.40 after 12 weeks. Additionally, the treatment group showed lower tissue expression of IL-17 and IL-23—markers involved in psoriasis inflammation—while no significant reduction in tumor necrosis factor-α levels was observed.
Dermatologists unfamiliar with GLP-1 agonists can consider referring patients to an endocrinologist or primary care physician. Interestingly, Eli Lilly, maker of ixekizumab, has launched a program allowing dermatologists to prescribe tirzepatide (a GLP-1 agonist) to obese patients undergoing treatment with ixekizumab. This collaborative approach can help manage both psoriasis and obesity concurrently.
Alternatively, IL-23 inhibitors, such as guselkumab and risankizumab, have shown consistent efficacy in patients with obesity. Guselkumab, in particular, demonstrated higher PASI 90 and PASI 100 responses in heavier patients compared to secukinumab in the phase 3 ECLIPSE study. Similarly, risankizumab has shown superior outcomes across various weight categories when compared to ustekinumab, making IL-23 inhibitors an appealing option for managing both obesity and psoriasis.
The Intersection of Depression and Psoriasis
Patients with chronic inflammatory diseases, including psoriasis, often experience psychiatric comorbidities such as depression and anxiety. Depression, in particular, is prevalent among those with psoriasis, and evidence suggests that inflammatory mediators such as IL-17 may play a role in its pathogenesis. This brings attention to the potential psychiatric side effects of biologic therapies, notably brodalumab, an IL-17 receptor antagonist.
Brodalumab carries a black box warning for suicidality, but the connection between the drug and suicide risk has been questioned. Research indicates that blockade of the IL-17A receptor leads to a fourfold increase in circulating IL-17 levels, which generally normalize within 30 days post-dose. Notably, three of the four suicides linked to brodalumab occurred within this 30-day window. While this does not establish causality, it raises important questions about the relationship between IL-17 levels and psychiatric symptoms, including depression.
Further studies have indicated elevated IL-17 levels in patients with depressive disorders, with some showing a decrease in these levels after treatment with selective serotonin reuptake inhibitors (SSRIs). Although findings remain inconsistent, several models suggest that IL-17 may contribute to neuroinflammation and potentially disrupt the blood-brain barrier, thus affecting brain function and mood regulation.
Given this, psoriasis patients should be routinely screened for depression using tools such as the Patient Health Questionnaire-2 (PHQ-2), with close attention paid to suicidality risks. If depression is identified and suicidality is not a concern, biologic therapies such as IL-17 blockers (ixekizumab, bimekizumab, secukinumab) may be considered. It is crucial, however, to involve psychiatry and primary care providers in managing patients with significant psychiatric symptoms, as some psychiatric medications can exacerbate psoriasis.
Interestingly, some studies have shown that antidepressant use may have a protective effect on psoriasis. A population-based cohort study from Taiwan found that patients with major depressive disorder who received antidepressants were less likely to develop psoriasis compared to those who did not receive such treatment. Though not definitive, these results underscore the importance of addressing both dermatological and psychiatric care in psoriasis patients.
A Comprehensive Approach to Psoriasis Treatment
Psoriasis should be recognized as a systemic disease with wide-reaching impacts on a patient’s overall health. While clinicians may not always be able to address every issue, tailoring treatment to a patient’s specific comorbidities—such as obesity and depression—can significantly improve outcomes. The growing range of biologic therapies and other systemic treatments provides opportunities to manage psoriasis in a more holistic manner, considering not just the skin but the broader health challenges that may accompany the disease.
Dr. Karan Lal, DO, MS, FAAD, is a dual fellowship-trained pediatric and cosmetic dermatologist practicing at Affiliated Dermatology in Scottsdale, Arizona, and a member of the Dermatology Times editorial advisory board.
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