Effectiveness and Safety of Dupilumab in Children Under 6 Years of Age with Moderate-to-Severe Atopic Dermatitis: A Retrospective Real-World Study.

INTRODUCTION: Dupilumab has recently been shown to be effective in children under 6 years of age with atopic dermatitis (AD). Nevertheless, real-life and long-term follow-up data are scarce. We aimed to assess the effectiveness, safety, and long-term outcomes of dupilumab in a daily-practice setting in this age group. METHOD: This was a retrospective observational cohort study. Only patients with 16 or more weeks of treatment were included in the analysis. The proportion of patients who achieved ≥75% or 90% reduction from baseline EASI (EASI75 and EASI90, respectively) and the percentage of patients who achieved vIGA 0-1 were analyzed at 4, 16, 48, 72, and 96 weeks (when available). Adverse events were recorded during follow-up. RESULTS: A total of 19 patients <6 years old with moderate-to-severe AD were included in the cohort, with a median age of 4.7 years (range: 2.6-5.9). The median weeks on dupilumab were 51.3 (IQR: 24.6-79.3). EASI75 was achieved in 11/19 patients (57.9%) at w4, 16/19 (84.2%) at w16, 9/12 (75%) at w48, 6/6 (100%) at w72, and in 2/2 (100%) at week 96. The objective of vIGA 0-1 was reached by 10/19 patients (51.6%) at w4, by 14/19 (73.7%) at w16, by 9/12 (75%) at w48, by 5/6 (83.3%) at w72, and by 2/2 (100%) at w96. Dupilumab was discontinued in 3 patients (15.8%) due to loss of response. One patient developed a paradoxical palmo-plantar eruption. We found no cases of conjunctivitis, facial erythema, or injection-site reactions related to dupilumab. CONCLUSIONS: Dupilumab was effective and safe in our cohort of patients with moderate-to-severe AD under 6 years of age. Response was maintained in the long term in most patients with longer follow-up. Its adverse effect profile was similar to that found in older children and adults.

Real-world Performance of a New Strategy for Off-Label Use of Guselkumab in Moderate to Severe Psoriasis: Super-Responder Patients as the Epitome of Efficacy and Optimisation.

BACKGROUND: Guselkumab is a drug used to treat moderate to severe plaque psoriasis. However, real-life clinical data on its off-label use are limited, especially regarding the optimal drug dosage regimen for different patient profiles. OBJECTIVE: The main objective of this real-world, single-centre, retrospective study was to identify the off-label guselkumab dosing regimen used in clinical practice. The study also aimed to evaluate the drug's efficacy, safety, and survival, as well as the proportion of super-responders (SR) based on a newly proposed definition. METHODS: The study included 69 patients who started treatment with guselkumab between March 2019 and July 2021. Patients were followed up until April 2022, during which time their efficacy, safety, persistence, and use of guselkumab were recorded. Patients were aged ≥  18 years and had moderate to severe plaque psoriasis. RESULTS: The mean disease duration was 18.6 years, and 59% of patients had received at least one biologic treatment before guselkumab with a mean of 1.3 biologics per patient. The initial absolute Psoriasis Area and Severity Index (PASI) was 10.1 and decreased to 2.1 between Week 11-20 without significant changes in the PASI value throughout the 90 weeks of follow-up. The cumulative probability of drug survival was 93.5% at Week 52. No differences were found in terms of efficacy and survival associated with the off-label drug dosage regimens compared to the doses described in the Summary of Product Characteristics (SmPC). The greatest adjustments in the drug administration regimen were achieved in the subgroups of bio-naïve and SR patients, with a reduction in the number of administrations by 40% and 47% compared to the regimen described in the SmPC. Super-response to guselkumab was mainly associated with patients naïve to previous biologic treatment. CONCLUSION: The study demonstrated that off-label use of guselkumab was safe and effective in real-life clinical practice. The findings suggest that adjustments to the drug administration regimen may be necessary to optimise its use in different patient profiles, especially in SR and bio-naïve patients. Further studies are needed to confirm these findings.

Human monkeypox outbreak: Epidemiological data and therapeutic potential of topical cidofovir in a prospective cohort study.

BACKGROUND: Human monkeypox has become increasingly frequent worldwide since the outbreak was first reported in May 2022. OBJECTIVES: As cidofovir is effective against vaccinia and other Orthopoxvirus diseases, we hypothesize that its topical use could be an effective treatment for monkeypox skin lesions, avoiding the adverse effects of systemic administration. METHODS: We conducted a prospective study to collect data on the clinical and virologic course of patients with monkeypox. All patients were offered symptomatic treatment. They were also offered treatment with topical cidofovir on a compassionate use basis. Twelve patients received treatment with topical cidofovir 1%, while the others received only symptomatic treatment. Prospective visits were scheduled for the collection of clinical and virological data. RESULTS: Lesions cleared quicker in the cidofovir-treated group (hazard ratio, 4.572; P = .0039). The median time to resolution was 12 (11.5-15) and 18 (16-21) days, respectively. On day 14, polymerase chain reaction-positive skin lesions were detected in 10% of the cidofovir sample, compared with 62.5% of the non-treated group (P = .019). Local adverse effects were frequent (50%), especially in the anogenital region. No systemic adverse effects were reported. LIMITATIONS: The study is not a clinical trial and lacks a placebo-controlled arm. DISCUSSION: Topical cidofovir is a potentially relevant therapy in patients with skin lesions but mild systemic involvement. Reducing time to resolution could shorten isolation time and improve the cosmetic impact in areas such as the face.