Influence of pathogenic filaggrin variants on dupilumab treatment in atopic dermatitis

Abstract

Listen

Translate article

BackgroundPathogenic variants in filaggrin (FLG) are associated with an increased risk of atopic dermatitis (AD). ObjectiveTo evaluate the influence of FLG variants on the effectiveness of dupilumab treatment in AD. MethodsThis prospective observational study included adult AD patients treated with dupilumab from the BioDay Registry. FLG was analysed with smMIP 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, week 16 and 52. ResultsGenetic analysis of 285 included patients showed bi-allelic pathogenic variants (FLG-/-) in n=41 (14%), mono-allelic pathogenic variants (FLG-/+) in n=64 (23%) and wild-type alleles (FLG+/+) in n=180 (63%). Three novel pathogenic variants were found. We observed no clinically relevant differences in EASI, IGA, NRS pruritus, DLQI and 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<0.001 and p=0.002, respectively) and 52 (p<0.001 and p=0.016, respectively) compared to FLG+/+, and also significant differences compared with FLG-/+, while differences in delta scores were non-significant. ConclusionThis study suggests that the effectiveness of dupilumab treatment in AD patients was not influenced by pathogenic FLG variants. However, patients with bi-allelic pathogenic FLG variants tended to have a drier skin before and during dupilumab treatment compared to patients with mono-allelic pathogenic variants or wild-type alleles.