Short-, mid- and long-term efficacy of dupilumab in moderate to severe atopic dermatitis: a real life multicenter Italian study on 2576 patients.

BACKGROUND: The efficacy and safety of dupilumab in atopic dermatitis (AD) have been defined in clinical trials but limited real-world evidence on long term treatment outcomes are currently available to inform clinical decisions. OBJECTIVES: to describe long-term effectiveness and safety of dupilumab up to 48 months in patients with moderate-to-severe AD. METHODS: a multicenter, retrospective, dynamic cohort study was conducted to assess long term effectiveness and safety of dupilumab in patients with moderate to severe AD in a real-world setting. Predictors of minimal disease activity (MDA) optimal treatment target criteria (defined as the simultaneous achievement of EASI90, itch NRS score ≤1, sleep NRS score ≤1 and DLQI ≤1) were investigated. RESULTS: 2576 patients were enrolled from June 2018 to July 2022. MDA optimal treatment target criteria were achieved by 506 (21.91%), 769 (40.63%), 628 (50.36%), 330 (55.37%) and 58 (54.72%) of those that reached 4, 12, 24, 36 and 48 months of follow-up, respectively. Logistic regression revealed a negative effect on MDA achievement for conjunctivitis and food allergy at all timepoints. Adverse events (AE) were mild and were observed in 373 (15.78%), 166 (7.02%), 83 (6.43%), 27 (4.50%) and 5 (4.55%) of those that reached 4, 12, 24, 36 and 48 months of follow-up. Conjunctivitis was the most frequently reported AE during the available follow-up. AE led to treatment discontinuation in <1% of patients during the evaluated time periods. CONCLUSION: High long-term effectiveness and safety of dupilumab were confirmed in this dynamic cohort of patients with moderate to severe AD, regardless of clinical phenotype and course at baseline. Further research will be needed to investigate the effect of Th2 comorbidities and disease duration on the response to dupilumab and other newer therapeutics for AD.

Contact allergy to SIDAPA baseline series allergens in patients with eyelid dermatitis: An Italian multicentre study.

BACKGROUND: Eyelid dermatitis is a frequent reason of dermatological consultation. Its aetiology is not univocal, being contact dermatitis, both allergic and irritant, the most frequent. The primary sources of allergen exposure include cosmetics, metals, and topical medications, from direct, indirect, or airborne contact. OBJECTIVES: To define the frequency of positive patch test reactions to SIDAPA baseline series allergens, to document positive allergens, and to precise the final diagnosis in patients with eyelid involvement. METHODS: A total of 8557 consecutive patients from 12 Italian Dermatology Clinics underwent patch testing with SIDAPA baseline series in 2018 and 2019. Patients were divided into two groups: (i) with eyelid involvement with or without other involved sites (E-Group) and (ii) without eyelid involvement (NE-Group). The final diagnosis and the frequency of positive relevant patch test reactions were evaluated. RESULTS: E-Group consisted of 688 patients (females 78.6%, mean age 45.3 years), 8.0% of 8557 consecutively patch-tested patients. The final diagnosis in E-Group was ADC in 42.4%, ICD in 34.2%, and AD in 30.5%. The highest reaction rates were elicited by nickel sulphate and methylchloroisothiazolinone/methylisothiazolinone in both E-Group and NE-Group, even if these allergens were significantly more frequently positive in NE-Group patients than in E-Group ones. Positive patch test reactions to fragrance Mix II, dimethylaminopropylamine, and sorbitan sesquiolate were significantly more frequent in E-Group patients than in NE-Group ones. CONCLUSIONS: Eyelid dermatitis is a frequent dermatological complaint. Allergic contact dermatitis is the most frequent diagnosis commonly caused by nickel sulphate, isothiazolinones, and fragrances. The surfactants dimethylaminopropylamine and sorbitan sesquioleate are emerging causes of eyelid allergic contact dermatitis.

Association between maternal dupilumab exposure and pregnancy outcomes in patients with moderate-to-severe atopic dermatitis: A nationwide retrospective cohort study.

BACKGROUND: There is limited epidemiological evidence on outcomes associated with dupilumab exposure during pregnancy; monitoring pregnancy outcomes in large populations is required. OBJECTIVE: To investigate the potential association between exposure to dupilumab in pregnant women with atopic dermatitis and any adverse pregnancy, neonatal, congenital and post-partum outcomes. METHODS: We performed a multicentre retrospective cohort study across 19 Italian tertiary referral hospital. Childbearing women were eligible if aged 18-49 years and carried out the pregnancy between 1 October 2018 and 1 September 2022. RESULTS: We retrospectively screened records of 5062 patients receiving dupilumab regardless of age and gender, identifying 951 female atopic dermatitis patients of childbearing age, 29 of whom had been exposed to the drug during pregnancy (3%). The median duration of dupilumab treatment prior to conception was 22.5 weeks (range: 3-118). The median time of exposure to the drug during pregnancy was 6 weeks (range: 2-24). All the documented pregnancies were unplanned, and the drug was discontinued in all cases once pregnancy status was reported. The comparison of the study cohort and the control group found no significant drug-associated risk for adverse pregnancy, congenital, neonatal or post-partum outcomes. The absence of a statistically significant effect of exposure on the event was confirmed by bivariate analysis and multivariate analysis adjusted for other confounding factors. CONCLUSIONS: This cohort of pregnant patients exposed to dupilumab adds to the existing evidence concerning the safety of biologic agents in pregnancy. No safety issues were identified regarding the primary outcome assessed. In clinical practice, these data provide reassurance in case of dupilumab exposure during the first trimester. However, the continuous use of dupilumab throughout pregnancy warrants further research.