Dupilumab had an acceptable long-term safety and efficacy for adolescents with moderate to severe atopic dermatitis (AD), according to data from an open-label extension (OLE) phase 3 trial published in the American Journal of Clinical Dermatology.
For adolescents (aged 12 to 18 years) with moderate to severe AD enrolled in the LIBERTY AD PED-OLE study, investigators initially administered subcutaneous dupilumab 2 to 4 mg/kg once weekly, then amended the protocol to 300 mg dupilumab every 4 weeks regardless of patient weight; newly enrolled participants also treated with 300 mg dupilumab every 4 weeks. They increased the dose to 200 to 300 mg dupilumab, based on body weight, every 2 weeks if a patient did not exhibit an adequate response to the 4-week regimen, ie, not achieving an Investigator’s Global Assessment (IGA) score of 0/1, by week 16. Patients with an IGA score of 0/1 maintained continuously for 12 weeks after week 40 of treatment were discontinued from dupilumab, monitored for relapse, and restarted on dupilumab if needed.
The primary outcome was the incidence and rate (patients per 100 patient-years [100PY] and/or events per 100PY) of treatment-emergent adverse events (TEAE) through the last study visit. Secondary outcomes included the percentage of patients with an IGA of 0/1 per visit until week 52, and the percentage of patients with an Eczema Area and Severity Index (EASI)-75 (> 75% reduction in EASI from baseline of parent study) per visit until week 52.
Investigators analyzed data from 294 patients enrolled in the study, 34.7% of whom completed the full 52-week study period. Patients’ mean age was 14.7 years, 69% were White and 56.8% were men. Most (61.9%) patients had previously tried 1 or more systemic immunosuppressive medication for AD besides dupilumab.
Dupilumab’s safety profile was consistent with its profile seen in adults, with 73.8% of patients reporting 1 or more TEAE, most of which were mild or moderate and transient. Of 370.2 events per 100PY reported, 39.3 events per 100PY were considered related to treatment, 3.9 events per 100PY were severe, and 1.6 events per 100PY were serious. All serious TEAEs resolved over time. There were 6 TEAEs of special interest which included severe viral conjunctivitis, severe allergic conjunctivitis, mild atopic keratoconjunctivitis, mild suicidal ideation, moderate depression, and moderate allergic reaction to egg. The most frequent TEAEs reported were nasopharyngitis (20.4%), AD (19%), upper respiratory tract infection (11.9%), and headache (8.8%).
By week 52, 42.7% of patients had an IGA score of 0/1 (clear/almost clear), and 93.1% and 83.1% had at least a 50% or 75% improvement in EASI, respectively. In addition, 29.4% of patients had an IGA score of 0/1 sustained for 12 weeks and had stopped dupilumab treatment; 56.7% of these patients relapsed and restarted treatment. Patients exhibited AD improvement regardless of baseline body weight. Patients also reported improved health-related quality of life, with 86.4% having a 6-point or more improvement in Children’s Dermatology Life Quality Index (CDLQI) by week 52.
Most (70.9%) of 289 patients at week 16 required an increase in the titration of their doses to every 2 weeks.
The pharmacokinetic profile showed that mean trough concentrations of functional dupilumab for patients receiving 300 mg every 4 weeks reached a steady-state of about 20 mg/L by week 16, which was maintained through week 52. Mean concentrations were higher in patients uptitrated to 200 to 300 mg every 2 weeks.
The study was limited by nonrandomization, the inclusion of patients from 3 different parent trials, and nonstandardized use of concomitant topical corticosteroids.
Based on the percentage of patients who required uptitration for clinical effectiveness, the study authors wrote that “the approved q2w dose regimen is optimal for adolescents in the corresponding weight groups.”
Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures. This research was supported by Sanofi and Regeneron Pharmaceuticals, Inc. Please see the original reference for a full list of disclosures.
Pakhchanian H, Khan H, Raker R, et al. COVID-19 outcomes in patients with dermatomyositis: A registry-based cohort analysis. Semin Arthritis Rheum. Published online May 28, 2022. doi:10.1016/j.semarthrit.2022.152034