Biologics and JAK inhibitors for atopic manifestations in inborn errors of immunity: a systematic review.

BACKGROUND

Atopy might be the initial or dominant manifestation in patients with inborn errors of immunity (IEIs). Biologics and Janus kinase (JAK) inhibitors have emerged as targeted options for atopic disorders in IEIs refractory to conventional treatment.

METHODS

We conducted a systematic review of PubMed, Web of Science, and Scopus for human studies reporting biologics or JAK inhibitors used specifically to treat atopic manifestations in IEIs. Data on genotypes, clinical phenotypes, treatments, outcomes, adverse events, and laboratory changes were extracted and synthesized. The databases were last searched in April 2026. Study quality was appraised with the Joanna Briggs Institute checklists and the certainty of evidence was rated following GRADE principles.

RESULTS

Eighty-one studies comprising 172 patients were included. The most common IEIs were STAT3 loss-of-function (LOF) disease (n = 52, 30.2%), Netherton syndrome (n = 32, 18.6%), and DOCK8 deficiency (n = 19, 11.0%). Dupilumab (n = 120, 69.8%) was the most frequently reported agent, followed by JAK inhibitors (n = 21, 12.2%) and omalizumab (n = 16, 9.3%). A complete or major clinical response was described in most published patients treated with dupilumab, together with improvement in skin disease in some patients. Omalizumab was also associated with a favorable outcome in atopic dermatitis and asthma, with steroid-sparing effects and few reported adverse events. Responses to JAK inhibitors were most often described in patients with JAK-STAT pathway defects, although adverse events such as anemia were reported in some cases. All proportions are descriptive frequencies among published patients with available outcome information and are not estimates of treatment effectiveness.

CONCLUSION

Published case reports and small series suggest that biologics and JAK inhibitors may provide clinically meaningful control of selected atopic or atopic-like manifestations in some patients with IEIs. Dupilumab has the largest published experience, while JAK inhibitors may be particularly relevant when the underlying disorder involves JAK-STAT pathway activation. Due to the lack of evidence, treatment should remain individualized, genotype-informed, and accompanied by careful infection surveillance and longitudinal outcome assessment.