Influence of pathogenic filaggrin variants on dupilumab treatment in atopic dermatitis

Background: Pathogenic variants in filaggrin (FLG) are associated with an increased risk of atopic dermatitis (AD). Objective: We evaluated the influence of FLG variants on the effectiveness of dupilumab treatment in AD. Methods: This prospective observational study included adult AD patients treated with dupilumab from the BioDay registry. FLG was analyzed with single-molecule molecular inversion probe-targeted sequencing. Novel mutations were confirmed by Sanger sequencing. Eczema Area and Severity Index (EASI), Investigator Global Assessment (IGA), numeric rating scale (NRS) pruritus, Dermatology Quality of Life Index (DLQI), and Patient-Oriented Eczema Measure (POEM) were assessed at baseline and at weeks 16 and 52. The study was registered at ClinicalTrials.gov as NCT03549416. Results: Genetic analysis of the 285 included patients showed biallelic pathogenic variants (FLG-/-) in 41 (14%), monoallelic pathogenic variants (FLG-/+) in 64 (23%), and wild-type alleles (FLG(+/+)) in 180 patients (63%). Three novel pathogenic variants were found. We observed no clinically relevant differences in EASI, IGA, NRS pruritus, DLQI, or total POEM scores for patients with and without pathogenic FLG variants at all time points. The FLG(-/-) group showed significantly higher POEM flaking and dryness scores at week 16 (P <.001 and P = .002, respectively) and week 52 (P < .001 and P = .016, respectively) compared to FLG( + / +) as well as significant differences compared to FLG( - / +) , while differences in delta scores were nonsignificant. Conclusion: The effectiveness of dupilumab treatment in AD patients was not influenced by pathogenic FLG variants. However, patients with biallelic pathogenic FLG variants tended to have drier skin before and during dupilumab treatment compared to patients with monoallelic pathogenic variants or wild -type alleles. (J Allergy Clin Immunol 2024;153:1155-61.)