Dupilumab Safety and Efficacy in a Phase III Open-Label Extension Trial in Children 6-11 Years of Age with Severe Atopic Dermatitis.

BACKGROUND: For children aged 6-11 years with uncontrolled severe atopic dermatitis (AD), 16 weeks of treatment with dupilumab resulted in substantial clinical benefit compared with placebo with an acceptable safety profile. However, longer-term safety and efficacy data are important to inform longitudinal AD management. OBJECTIVES: This analysis of data from an open-label extension study (LIBERTY AD PED-OLE, NCT02612454) reports the long-term safety, efficacy, and pharmacokinetics of dupilumab in children with severe AD who had participated in the pivotal dupilumab LIBERTY AD PEDS study (NCT03345914). METHODS: Enrolled patients initially received subcutaneous dupilumab 300 mg every 4 weeks (q4w). The q4w regimen could be uptitrated to dupilumab dose regimens of 200 or 300 mg every 2 weeks (q2w; for body weight < 60 or ≥ 60 kg, respectively) for patients who did not achieve an Investigators Global Assessment (IGA) score of 0/1 (clear/almost clear skin) at week 16, or prior to week 16 as rescue treatment. Additional patients were uptitrated to a weight-tiered q2w regimen following a protocol amendment. Patients who maintained an IGA score of 0/1 continuously for a 12-week period after week 40 discontinued dupilumab. They were monitored for relapse and were reinitiated on dupilumab if required. RESULTS: Data for 321 patients (mean age 8.6 years) were analyzed, 254 (79%) of whom had completed the scheduled 52-week visit at the database lock. Most treatment-emergent adverse events were mild/moderate. By week 52, 41% of patients achieved an IGA score of 0/1, and 97%, 82%, and 50%, respectively, had at least a 50%, 75%, and 90% improvement from the parent study baseline in Eczema Area and Severity Index (EASI). By week 52, 29% of patients in the overall population had clear/almost clear skin sustained for 12 weeks and had stopped medication; of these, 40% relapsed and were subsequently reinitiated on treatment, with a mean time to reinitiation of 13.5 (standard deviation 5.2) weeks. Following reinitiation of dupilumab, 41% of the patients with evaluable data at the time of database lock had regained an IGA 0/1 clinical response. CONCLUSIONS: Consistent with results seen in adults and adolescents, long-term treatment with dupilumab in children aged 6-11 years with severe AD showed an acceptable safety profile and incremental clinical benefit. A substantial proportion of children who stopped dupilumab treatment after achieving clear/almost clear skin subsequently experienced disease recurrence, and required reinitiation of dupilumab, suggesting that continuous treatment may be necessary for maintenance of clinical benefit. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT02612454

The effect of dupilumab on caregiver- and patient-reported outcomes in young children with moderate-to-severe atopic dermatitis: results from a placebo-controlled, phase 3 study

Background: Moderate-to-severe atopic dermatitis (AD) greatly impacts children/82 caregivers.Objective: Evaluate the impact of treatment with dupilumab on caregiver- and patient-reported AD symptoms and quality of life (QoL) in young children.Methods: In the LIBERTY AD PRESCHOOL (randomized, placebo-controlled) study, children aged 6 months to 5 years with moderate-to-severe AD received dupilumab or placebo plus low-potency topical corticosteroids for 16 weeks. This post-hoc analysis assessed the change from baseline to week 16 in caregiver-reported outcome measures of AD symptoms (e.g., itch and sleep) and QoL of patients and their caregivers/families.Results: Dupilumab (n = 83) vs placebo (n = 79) provided significant improvements in caregiver reported AD symptoms and QoL. Significant improvements were seen as early as week 4 and sustained through the end of the study. Additionally, dupilumab vs placebo provided rapid and significant improvement in QoL measures for the patients caregivers/families.Limitations: Few patients aged <2 years; significance only reported for pre-specified endpoints; Infant's Dermatitis QoL Index severity strata adopted from Children's Dermatology Life Quality Index.Conclusion: Dupilumab improved AD symptoms and QoL in patients and their caregivers/families

Baricitinib in adult patients with moderate-to-severe atopic dermatitis: A phase 2 parallel, double-blinded, randomized placebo-controlled multiple-dose study

© 2018 Background: Baricitinib, an oral selective inhibitor of Janus kinase 1 and Janus kinase 2, modulates proinflammatory cytokine signaling. Objectives: The efficacy and safety of baricitinib were evaluated in patients with moderate-to-severe atopic dermatitis (AD). Methods: In this phase 2, randomized, double-blind, placebo-controlled study, 124 patients with moderate-to-severe AD applied topical corticosteroids (TCSs) for 4 weeks before randomization to once-daily placebo, 2 mg of baricitinib, or 4 mg of baricitinib for 16 weeks. Use of TCSs was permitted during the study. The primary outcome was the proportion of patients achieving at least a 50% reduction in the Eczema Area and Severity Index (EASI-50) compared with placebo. Results: Significantly more patients who received baricitinib, 4 mg, achieved EASI-50 than did patients receiving placebo (61% vs 37% [P =.027]) at 16 weeks. The difference between the proportion of patients receiving baricitinib, 2 or 4 mg, who achieved EASI-50 and the proportion of patients receiving placebo and achieving EASI-50 was significant as early as week 4. Baricitinib also improved pruritus and sleep loss. Treatment-emergent adverse events were reported in 24 of the patients receiving placebo (49%), 17 of those receiving 2 mg of baricitinib (46%), and 27 of those receiving 4 mg of baricitinib (71%). Limitations: A TCS standardization period before randomization reduced disease severity, limiting the ability to compare results with those of baricitinib monotherapy. Longer studies are required to confirm baricitinib\u27s efficacy and safety in patients with AD. Conclusions: Baricitinib used with TCSs reduced inflammation and pruritus in patients with moderate-to-severe AD

Efficacy and safety of dupilumab treatment with concomitant topical corticosteroids in children aged 6 months to 5 years with severe atopic dermatitis

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