Dupilumab provides clinically meaningful responses in children aged 6–11 years with severe atopic dermatitis: post hoc analysis results from a phase III trial

Background: Children with severe atopic dermatitis (AD) have a multidimensional disease burden. Objective: Here we assess the clinically meaningful improvements in AD signs, symptoms, and quality of life (QoL) in children aged 6–11 years with severe AD treated with dupilumab compared with placebo. Methods: R668-AD-1652 LIBERTY AD PEDS was a randomized, double-blinded, placebo-controlled, parallel-group, phase III clinical trial of dupilumab with concomitant topical corticosteroids (TCS) in children aged 6–11 years with severe AD. This post hoc analysis focuses on 304 patients receiving either dupilumab or placebo with TCS and assessed the percentage of patients considered responsive to dupilumab treatment at week 16. Results: At week 16, almost all patients receiving dupilumab + TCS (95%) demonstrated clinically meaningful improvements in AD signs, symptoms, or QoL compared with placebo + TCS (61%, p < 0.0001). Significant improvements were seen as early as week 2 and sustained through the end of the study in the full analysis set (FAS) and the subgroup of patients with an Investigator’s Global Assessment score greater than 1 at week 16. Limitations: Limitations include the post hoc nature of the analysis and that some outcomes were not prespecified; the small number of patients in some subgroups potentially limits generalizability of findings. Conclusion: Treatment with dupilumab provides significant and sustained improvements within 2 weeks in AD signs, symptoms, and QoL in almost all children with severe AD, including those who did not achieve clear or almost clear skin by week 16. Trial Registration: NCT03345914. [MediaObject not available: see fulltext.

Infections in children aged 6 months to 5 years treated with dupilumab in a placebo-controlled clinical trial of moderate-to-severe atopic dermatitis

Background: Patients with atopic dermatitis (AD), particularly infants and young children, are at greater risk of developing skin infections. In this study, we assessed infection rates in AD patients aged 6 months to 5 years treated with dupilumab. Methods: In LIBERTY AD PRESCHOOL, a double-blind, placebo-controlled, phase III clinical trial, children aged 6 months to 5 years with moderate-to-severe AD were randomized 1:1 to subcutaneous dupilumab or placebo, with concomitant low-potency topical corticosteroids, every 4 weeks for 16 weeks. Exposure-adjusted infection rates were used to compare treatment groups. Results: The analysis included 162 patients, of whom 83 received dupilumab and 79 received placebo. Total infection rates were not significantly different between the dupilumab and placebo groups (rate ratio [RR] 0.75, 95% CI 0.48–1.19; p = 0.223). Non-herpetic adjudicated skin infections and bacterial infections were significantly less frequent with dupilumab versus placebo (non-herpetic skin infections: RR 0.46, 95% CI 0.21–0.99; p = 0.047; bacterial infections: RR 0.09, 95% CI 0.01–0.67; p = 0.019), and the number of patients using systemic anti-infective medication was significantly lower in the dupilumab group (RR 0.52, 95% CI 0.30–0.89; p = 0.019). There were no significant differences in the number of herpetic infections between the dupilumab and placebo groups (RR 1.17, 95% CI 0.31–4.35; p = 0.817). The number of patients with two or more infection events was significantly higher in the placebo group (RR 0.29, 95% CI 0.12–0.68; p = 0.004), and no severe or serious infections (including eczema herpeticum) were observed among patients receiving dupilumab. Conclusions: These data suggest that dupilumab treatment in infants and children younger than 6 years with AD does not increase overall risk of infections and is associated with a reduced risk of bacterial and non-herpetic skin infections compared with placebo, resulting in a reduced need for anti-infective medication. Trial Registration: The trial was registered with ClinicalTrials.gov with ID number NCT03346434 on November 17, 2017. Infographic: [Figure not available: see fulltext.

Infections in children and adolescents treated with dupilumab in pediatric clinical trials for atopic dermatitis—a pooled analysis of trial data

Background/Objective Patients with moderate-to-severe atopic dermatitis (AD) have increased risk of cutaneous and extracutaneous infections. Dupilumab has previously been associated with reduced risk of serious/severe infections and non-herpetic skin infections in adults with moderate-to-severe AD. This analysis assessed infection rates with dupilumab versus placebo in pediatric patients with moderate-to-severe and severe AD participating in clinical trials. Methods This is a pooled analysis from two 16-week, randomized, placebo-controlled, phase 3 clinical trials of dupilumab: monotherapy in adolescents aged 12–17 years with moderate-to-severe AD (LIBERTY AD ADOL, NCT03054428) and with concomitant topical corticosteroids in children aged 6–11 years with severe AD (LIBERTY AD PEDS, NCT03345914). Data were pooled according to treatment received: placebo/approved dupilumab doses/other studied dupilumab doses/all dupilumab doses. Exposure-adjusted rates (patients with ≥1 event per 100 patient-years [nP/100 PY]) were used to compare treatment groups. Results Overall, 612 patients were included: 205 received placebo and 407 received dupilumab (261 received approved dupilumab doses and 146 received other studied dupilumab doses). Overall infection rates were numerically lower with dupilumab versus placebo (nP/100 PY: placebo, 227; approved dupilumab, 173; other dupilumab, 206; all dupilumab, 184). Total skin infections were numerically less frequent in all dupilumab-treated groups versus placebo (nP/100 PY: placebo, 67; approved dupilumab, 30; other dupilumab, 46; all dupilumab, 36). Conclusions These data suggest that dupilumab treatment in children and adolescents with AD does not increase infection risk overall and is associated with lower rates of skin infections compared with placebo

Using natural language processing to evaluate the suitability of Adult Attachment Interviews for coding secure base script knowledge

The primary objective of this study is to explore the use of natural language processing to automate the evaluation of the suitability of Adult Attachment Interview (AAI) transcripts for coding secure base script (SBS) knowledge. Suitability refers to the appropriateness of an AAI transcript for assessing SBS knowledge, considering factors such as probing for specific events and privacy of the interview setting

Low-Frequency Type-II Radio Detections and Coronagraph Data Employed to Describe and Forecast the Propagation of 71 CMEs/Shocks

The vulnerability of technology on which present society relies demands that a solar event, its time of arrival at Earth, and its degree of geoeffectiveness be promptly forecasted. Motivated by improving predictions of arrival times at Earth of shocks driven by coronal mass ejections (CMEs), we have analyzed 71 Earth-directed events in different stages of their propagation. The study is primarily based on approximated locations of interplanetary (IP) shocks derived from type II radio emissions detected by the Wind/WAVES experiment during 1997-2007. Distance-time diagrams resulting from the combination of white-light corona, IP type II radio, and in situ data lead to the formulation of descriptive profiles of each CME's journey toward Earth. Furthermore, two different methods to track and predict the location of CME-driven IP shocks are presented. The linear method, solely based on Wind/WAVES data, arises after key modifications to a pre-existing technique that linearly projects the drifting low-frequency type II emissions to 1 AU. This upgraded method improves forecasts of shock arrival time by almost 50%. The second predictive method is proposed on the basis of information derived from the descriptive profiles, and relies on a single CME height-time point and on low-frequency type II radio emissions to obtain an approximate value of the shock arrival time at Earth. In addition, we discuss results on CME-radio emission associations, characteristics of IP propagation, and the relative success of the forecasting methods.Comment: Solar Physics; Accepted for publication 2015-Apr-2