D1.246 - Characterization of Unmet Need for Targeted Precision Medication in Atopic Dermatitis Due to Inadequate Response or Adverse Reactions to Dupilumab

While dupilumab has significantly advanced the treatment of moderate-to-severe atopic dermatitis (AD), a meaningful subset of patients experience incomplete disease control, loss of response over time, or adverse reactions. These patterns suggest underlying clinical and immunological heterogeneity. Characterizing response patterns may define unmet therapeutic needs and identify populations who may benefit from alternative or differently targeted precision therapies.

A retrospective chart review was conducted using electronic medical records from tertiary academic dermatology and allergy clinics. Patients with AD treated with dupilumab were evaluated for treatment response and adverse reactions. Treatment discontinuation, waning efficacy, adverse event profiles, and atopic comorbidities were evaluated.

For this interim report, 461 AD patient charts were reviewed, including 224* well-controlled patients and 237 patients with inadequate response and/or adverse events. Among the latter group, 157 were partial responders, 12 partial responders with adverse reactions, 32 with only adverse reactions, 29 non-responders, and 7 non-responders with adverse reaction. The most common adverse reactions were conjunctivitis (32), injection site reaction (7), psoriasiform dermatitis (3) and skin sloughing (1). 

Seventy-nine patients discontinued dupilumab, most commonly due to adverse reaction (23), partial response (22), no response (18), adverse event with no response (2), needle phobia (2), and drug cost/insurance issues (4). Average time to discontinuation was 19.41 months. Waning efficacy occurred in 57 patients at a mean of 16.7 months after treatment initiation, with 34 reporting symptom recurrence between doses an average of 4.7 days prior to the next injection. The most common waning symptoms were recurrent flares (37), persistent pruritus (12), and persistent flares (11). One patient experienced intermittent impetigo. Additionally, 33% of patients had no atopic comorbidities, with 71% of these patients being partial responders.

Analysis of clinician-reported outcomes was planned, but many charts lacked these scores, limiting reliable analysis.

*Distribution was not planned - this was a result of a random selection of AD charts.

A substantial portion of the AD population on dupilumab experience inadequate response, particularly those without comorbidities, reflecting disease clinical and immunological heterogeneity. The incidence of adverse reactions, especially conjunctivitis, highlights the necessity for other targeted therapies. These findings highlight an unmet need and support further investigation into immunologic and clinical predictors of treatment response.