No abstract

Background For adolescent patients (aged ≥ 12 to < 18 years) with uncontrolled moderate-to-severe atopic dermatitis (AD), 16 weeks of treatment with dupilumab resulted in substantial clinical benefit compared with placebo, with an acceptable safety profile. However, long-term data on the approved dose regimens of dupilumab in adolescents with AD are lacking. Objectives This open-label extension study (LIBERTY AD PED-OLE, NCT02612454) reports the long-term safety, efficacy, and pharmacokinetics of dupilumab in adolescents with moderate-to-severe AD who had participated in dupilumab parent trials. Methods Patients enrolled under the original study protocol received subcutaneous dupilumab according to a weight-based regimen (2 or 4 mg/kg every week). Following protocol amendment, patients were switched to subcutaneous dupilumab 300 mg every 4 weeks (q4w) irrespective of weight, and newly enrolled patients were started on dupilumab 300 mg q4w. Patients with an inadequate clinical response (Investigator’s Global Assessment [IGA] score of 0/1 was not reached) to the q4w regimen could be uptitrated to the approved dupilumab dose regimens of 200 or 300 mg every 2 weeks (body weight < 60 or ≥ 60 kg, respectively). Patients whose IGA score of 0/1 was maintained continuously for a 12-week period after week 40 were discontinued from dupilumab, monitored for relapse, and re-initiated on dupilumab if required. Results Data for 294 patients (mean age 14.7 years) were analyzed, 102 (34.7%) of whom had completed the 52-week visit at the database lock. The dupilumab long-term safety profile was comparable to that seen in adults and consistent with the known safety profile. Most treatment-emergent adverse events were mild/moderate. By week 52, 42.7% of patients had an IGA score of 0/1 (clear/almost clear), and 93.1%, 81.2%, and 56.4%, respectively, had at least a 50%, 75%, or 90% improvement in Eczema Area and Severity Index (EASI). Most (70.9%) patients required uptitration to the approved dupilumab dose regimen. The proportions of uptitrated patients with an IGA score of 0/1 or 75% improvement in EASI increased over time, reaching 35.7% and 51.9%, respectively, 48 weeks after the first uptitration visit. By week 52, 29.4% of patients had clear/almost clear skin sustained for 12 weeks and had stopped medication; 56.7% relapsed and were subsequently re-initiated on treatment, with a mean time to re-initiation of 17.5 (± standard deviation 17.3) weeks. Conclusions Consistent with results seen with short-term treatment, long-term treatment with dupilumab showed an acceptable safety profile while providing incremental clinical benefit with continued treatment over time. The high proportion of patients who needed uptitration because of inadequate response to q4w dosing supports the q2w dose regimen as optimal for this age group. Finally, the majority of patients who stopped medication after having clear/a...

Boehringer Ingelheim Pharmaceuticals, Inc. (BIPI) provided funding for this study. Yu and Devercelli are currently salaried employees of BIPI. Wu, Chuang, Wang, Pan, and Benjamin are currently employees of Evidera, which provides consulting and other research services to pharmaceutical, device, government, and nongovernment organizations. In their salaried positions, they work with a variety of companies and organizations and are precluded from receiving payment or honoraria directly from these organizations for services rendered. Evidera received funding from BIPI to conduct the analysis. Coultas was previously a paid consultant of BIPI. The contents do not represent the views of the Department of Veterans Affairs or the U.S. government. This manuscript does not contain clinical studies or patient data. The authors have full control of all primary data, and they agree to allow the journal to review their data if requested. All authors meet the criteria for authorship as recommended by the International Committee of Medical Journal Editors, and they are fully responsible for all content and editorial decisions and were involved at all stages of manuscript development. The manuscript was drafted by Benjamin, Wu, and Yu and revised by Wang, Pan, Yu, Coultas, and Devercelli. The study was designed by Yu, Wu, Chuang, Wang, Benjamin, and Coultas. Statistical analysis was conducted by Wu, Chuang, and Wang. Senior review was provided by Coultas and Devercelli.

Outpatient visits during the 30 days after discharge were associated with a lower hospital readmission risk during the following 90 days. Assertive hospital discharge planning to secure outpatient visits after hospital discharge is needed for these patient populations.