A 52-Week Retrospective Italian Study of Flare Characteristics in Adult Atopic Dermatitis Patients Receiving JAK Inhibitors

Background: Atopic dermatitis (AD) flares occurring during treatment with Janus kinase inhibitors (JAKi) remain insufficiently characterized outside randomized clinical trials. Real-world evidence on their incidence, clinical presentation, predictors, and management is limited. Methods: This multicenter retrospective study analyzed adult patients with moderate-to-severe AD treated in routine clinical practice with upadacitinib, abrocitinib, or baricitinib over a 52-week period. The incidence, timing, anatomical distribution, predictors, laboratory findings, and management strategies of AD flares were evaluated. Results: Among 332 patients, 79 (23.8%) experienced at least one flare, resulting in 94 flare events. Flares occurred after a mean of 39 weeks of therapy and most frequently involved the head, neck, and upper limbs. A flare was defined as a clinically relevant worsening of AD, evidenced by increased Eczema Area and Severity Index (EASI), Dermatology Life Quality Index (DLQI), or pruritus numerical rating scale (P-NRS) scores, requiring therapeutic adjustment, including initiation or intensification of topical corticosteroids, use of systemic corticosteroids, or modification of systemic treatment. The longest flare-free interval was observed in patients receiving upadacitinib 15 mg. Flares were significantly more frequent during colder months. Compared with patients without flares, those who developed flares had higher baseline EASI, DLQI, and P-NRS scores and a greater prevalence of atopic multimorbidity, associated with a more than twofold increased risk of flare. Laboratory changes observed at flare onset differed among JAKi and reflected drug-specific biological profiles rather than flare severity. All flares required topical corticosteroids, while systemic corticosteroids were used in 24% of cases. Therapeutic adjustments, including dose escalation or treatment switching, were frequently required in patients with inadequate disease control. Conclusions: Although JAKi are highly effective in the management of moderate-to-severe AD, disease flares remain clinically relevant during long-term treatment. Higher baseline disease severity, atopic multimorbidity, and seasonal factors increase flare risk, underscoring the importance of personalized monitoring and management strategies for patients receiving JAKi therapy.