Reviewing Complex Cases: Special Issues in AD Comorbidities

In the second round of breakout sessions at the Horizons in Advanced Practice meeting in Las Vegas, Nevada, Omar Noor, MD, FAAD; Douglas DiRuggiero, DMSc, MHS, PA-C; and Lakshi Aldredge, MSN, ANP-BC, DCNP, FAANP, focused on common challenges and innovations in treating plaque psoriasis and atopic dermatitis (AD). To foster collaboration and discussion around the cases, the meeting attendees were divided into 3 groups, with each Horizons chair moderating a session.

Special Issues in Comorbidities

In the first breakout room, DiRuggiero​ discussed the case of a woman aged 27 years who had eczematous lesions covering more than 20% of her body surface area (BSA). Although the lesions were also present elsewhere, the patient had erythema and excoriations primarily on her arms, legs, and torso. The patient reported the condition adversely impacted her quality of life. For instance, she had intense pruritus, causing sleep disturbances. The physical nature of the disease combined with lack of sleep affected her work, as she experienced a loss of confidence. The patient also reported recent asthma exacerbations, primarily during high-pollen seasons.

A medical history revealed a long-term course of illness. She reported that she had experienced moderate to severe AD since childhood. Similarly, the patient noted a 10-year history of asthma and allergic rhinitis. Additional discussions of quality of life and mental health status revealed that AD has had a significant negative impact. The history also noted that her asthma is often aggravated when she experiences episodes of worsening AD. Moreover, seasonality has more recently played a role.

The patient has been treated for AD and asthma by another clinician. She has been prescribed emollients and topical corticosteroids to use as needed for the AD. For the asthma, she uses an inhaled corticosteroid daily. The patient also used a short-acting β-agonist as needed, and oral corticosteroids were prescribed when she experienced asthma exacerbations.

To best help this patient, the clinician discussed her treatment goals, DiRuggiero said. She explained she is a teacher, and the AD negatively impacts her social interactions and confidence in the classroom. The patient also expressed concern about the long-term consequences of using steroids and noted that she is interested in a more sustainable approach. Because asthma has also become a distressing issue, she is interested in achieving long-term control of both the AD and asthma symptoms.

DiRuggiero paused to discuss the case and its implications. He asked the group to consider the variables, including multiple comorbidities in assessing patients and developing appropriate long-term strategies. 

Exploring Pathophysiology and Treatment Options

To better answer the questions around treatment strategy, DiRuggiero reviewed the pathophysiology of atopic disease and the role of biologics. The type 2 inflammation pathway involves cytokines IL-4, IL-5, IL-13, and IL-31, he explained. Consequences of dysregulation and disease associated with this pathway include allergies, anaphylaxis, type 2 asthma, AD, chronic obstructive pulmonary disease (COPD)with type 2 inflammation, and chronic rhinosinusitis with nasal polyps (CRSwNP).¹ 

Although IL-4 and IL-13 have overlapping functions, they are not redundant, he explained. “IL-4 drives T-cell differentiation in the early steps of AD, while ​IL-13 affects peripheral tissue cells and is involved in later steps of immune response,” he told attendees. “Dual blockade (IL-4/IL-13) targets multiple steps in AD cascade to provide rapid and sustained therapeutic response​.” Thus, targeting IL-4 allows for early intervention in the AD pathogenesis.²

DiRuggiero noted several agents target IL-13: dupilumab (Dupixent; Sanofi and Regeneron), tralokinumab (Adbry; LEO Pharma), and lebrikizumab (Ebglyss; Lilly). Both tralokinumab and lebrikizumab are indicated for treating AD in patients 12 years and older. Dupilumab also targets IL-4, he added, and thus has been proven safe and effective for additional conditions (eg, asthma in patients 6 years or older, CRSwNP in patients 12 years or older; eosinophilic esophagitis in patients aged 1 year or older; prurigo nodularis in patients 18 years and older; and COPD in patients 18 years and older).

In exploring how dupilumab works, DiRuggiero also presented 2-year interim real-world data from the PROSE registry on its effectiveness in treating AD. This study included patients with​ moderate to severe AD for 12 years or longer (N= 764), 50% of which were naive to systemic AD treatment(s) (ie, no prior biologics). Data showed rapid and sustained improvement across several measures, including BSA affected by AD, Eczema Area and Severity Index (EASI) scores, and the Dermatology Life Quality Index. The agent was considered relatively safe, with conjunctivitis (2.4%) and AD (1.7%)​ as the most common adverse events​(AEs) and only 2.1% serious AEs, he reported.^3,4

Choosing and Monitoring Treatment

In looking at the PROSE registry data, DiRuggiero asked attendees to consider several important points: How do you decide between systemic treatment like dupilumab vs topical treatments, and under which circumstances would you choose a combination? And, when you do choose dupilumab, what strategies can be used to monitor and manage potential AEs?

After a brief discussion, DiRuggieroreturned to the case he had presented earlier. The patient and clinician considered her history and medical comorbidities and decided to initiate treatment with dupilumab. Her treatment protocol included a 600-mg subcutaneous loading dose of dupilumab followed by 300 mg once every 2 weeks. She also continued the daily emollient use and was prescribed triamcinolone 0.1% cream.

At 16 weeks, there was a 70% reduction in her EASI score, he told attendees. She reported reduced pruritus, which also helped improve her sleep. She did not experience asthma exacerbation; in fact, she reported less use of short-acting β2-agonists with physical activity​. Her quality of life and mental health improved, and she reported better work performance and social interactions. The patient experienced mild conjunctivitis due to the treatment; it was managed with artificial tears and a consultation with an ophthalmologist. 

According to DiRuggiero, the case demonstrated when dupilumab is a good choice for patients with comorbid asthma and AD. A good medical history and probing questions can often lead clinicians to a clear treatment path.

References

1. Haddad EB, Cyr SL, Arima K, McDonald RA, Levit NA, Nestle FO. Current and emerging strategies to inhibit type 2 inflammation in atopic dermatitis. Dermatol Ther (Heidelb). 2022;12(7):1501-1533. doi:10.1007/s13555-022-00737-7

2. Chiricozzi A, Maurelli M, Peris K, Girolomoni G. Targeting IL-4 for the treatment of atopic dermatitis. Immunotargets Ther. 2020;9:151-156. doi:10.2147/ITT.S260370

3. Simpson EL, Lockshin B, Lee LW, Chen Z, Daoud M, Korotzer A. Real-world effectiveness of dupilumab in adult and adolescent patients with atopic dermatitis: 2-year interim data from the PROSE Registry. Dermatol Ther (Heidelb). 2024;14(1):261-270. doi:10.1007/s13555-023-01061-4

4. Bagel J, Nguyen TQ, Lima H, et al. Baseline demographics and severity and burden of atopic dermatitis in adult patients initiating dupilumab treatment in a real-world registry (PROSE). Dermatol Ther (Heidelb). 2022;12(6):1417-1430. doi:10.1007/s13555-022-00742-w