Efficacy and safety of topically applied therapeutic ammonia oxidising bacteria in adults with mild-to-moderate atopic dermatitis and moderate-to-severe pruritus: a randomised, double-blind, placebo-controlled, dose-ranging, phase 2b trial.

Background: Topical anti-inflammatory therapy is a cornerstone of treatment for atopic dermatitis (AD). However, many unmet needs remain with existing therapies. B244 is a live topical biotherapeutic being tested for the reduction of pruritus and improvement of eczema signs in patients with AD. We aimed to assess the safety and efficacy of B244, compared to vehicle, for patients with mild-to-moderate AD and moderate-to-severe pruritus. Methods: In this randomised, placebo-controlled, double-blind phase 2b trial, adults aged 18-65 years with mild-to-moderate AD and moderate-to-severe pruritus were enrolled across 56 sites in the USA. Patients were randomised 1:1:1 into a low-dose (optical density at 600 nm [OD] 5.0), high-dose (OD 20.0), or vehicle group for the 4-week treatment period and a 4 week follow-up period. Patients were instructed to apply the topical spray twice daily throughout the treatment period. Randomisation was centrally based (random alternating blocks of 6 and 3) and stratified by site. All participants, investigators, and those assessing outcomes were blinded to the treatment group assignments. The primary endpoint was the mean change in pruritus as measured by the Worst Itch Numeric Rating Scale (WI-NRS) at 4 weeks. Safety was tracked throughout the study. Primary efficacy analyses included the modified intent-to-treat (mITT) population, encompassing those who received at least one dose of study drug and attended at least one post-baseline visit. The safety population included all participants who received at least one does of study drug. This study is registered with ClinicalTrials.gov, NCT04490109. Findings: Between June 4, 2020 and October 22, 2021, 547 eligible patients were enrolled. All study endpoints were meaningfully improved with B244 compared to vehicle. The WI-NRS score was reduced by 34% (-2.8 B244 vs -2.1 placebo, p = 0.014 and p = 0.015 for OD 20.0 and OD 5.0), from a baseline score of >8. B244 was well tolerated with no serious adverse events (SAEs); treatment-emergent adverse events (TEAEs) and treatment related TEAEs were low in incidence, mild in severity, and transient. 33 (18%) of 180 patients given B244 OD 5.0, 29 (16%) of 180 patients given B244 OD 20.0, and 17 (9%) of 186 patients given placebo reported treatment-emergent adverse events; headache was the most frequent (3%, 2%, and 1%, respectively). Interpretation: B244 was well tolerated and demonstrated improved efficacy compared to vehicle in all primary, secondary, and exploratory endpoints and should be further developed as a novel, natural, fast-acting topical spray treatment option for AD and associated pruritus. Funding: AOBiome Therapeutics.

Child and parent secondary outcomes in stepped care versus standard care treatment for childhood trauma.

INTRODUCTION: Stepped care trauma-focused cognitive behavioral therapy (SC-TF-CBT) is comparable in efficacy to standard TF-CBT for child posttraumatic stress symptoms (PTSS), but less is known about the effectiveness of SC-TF-CBT on child and parent secondary outcomes. The aim of this community-based randomized clinical trial was to compare child- and caregiver-secondary outcomes among SC-TF-CBT versus TF-CBT participants. METHODS: Children (ages 4 to 12) with PTSS and their caregivers were randomly assigned to either SC-TF-CBT (n = 91) or TF-CBT (n = 92). Secondary child (internalizing and externalizing behavior problems, anger outburst and sleep disturbances) and parent outcomes (PTSS, depression symptoms, and parenting stress) were measured at baseline, post-treatment and 6- and 12-month follow-up. RESULTS: There were comparable changes at all-time points in child and caregiver secondary outcomes. Non-inferiority tests indicated that for completers and intent-to-treat samples, SC-TF-CBT was non-inferior to TF-CBT for all outcomes except parenting stress at 6-months. The analysis with completers did not support non-inferiority at post-treatment for internalizing and externalizing problems and at 6- and 12-month follow-up assessments for externalizing problems, but the intent-to-treat analysis did support non-inferiority. LIMITATIONS: Limitations included modest rates of attrition, excluding in vivo component for standard TF-CBT, parent-only assessments, and no control condition. CONCLUSIONS: SC-TF-CBT is an effective alternative treatment method although parents with high stress may need more support and children with externalizing problems may need more standard TF-CBT sessions.

Parents' Perception of Stepped Care and Standard Care Trauma-Focused Cognitive Behavioral Therapy for Young Children.

Delivery systems other than in-office therapist-led treatments are needed to address treatment barriers such as accessibility, efficiency, costs, and parents wanting an active role in helping their child. To address these barriers, stepped care trauma focused-cognitive behavioral therapy (SC-TF-CBT) was developed as a parent-led, therapist-assisted therapy that occurs primarily at-home so that fewer in-office sessions are required. The current study examines caregivers' perceptions of parent-led (SC-TF-CBT) and therapist-led (TF-CBT) treatment. Participants consisted of 52 parents/care-givers (25-68 years) of young trauma-exposed children (3-7 years) who were randomly assigned to SC-TF-CBT (n = 34) or to TF-CBT (n = 18). Data were collected at mid-and post-treatment via interviews inquiring about what participants liked, disliked, found most helpful, and found least helpful about the treatment. Results indicated that parents/caregivers favored relaxation skills, affect modulation and expression skills, the trauma narrative, and parenting skills across both conditions. The majority of parents/caregivers in SC-TF-CBT favored the at-home parent-child meetings and the workbook that guides the parent-led treatment, and there were suggestions for improving the workbook. Reported disliked and least helpful aspects of treatments were minimal across conditions, but themes that emerged that will need further exploration included the content and structure, and implementation difficulties for both conditions. Collectively, these results highlight the positive impact that a parent-led, therapist-assisted treatment could have in terms of providing caregivers with more tools to help their child after trauma and reduce barriers to treatment.

Parents' and children's perception of parent-led Trauma-Focused Cognitive Behavioral Therapy.

This study explored parent and child experiences of a parent-led, therapist-assisted treatment during Step One of Stepped Care Trauma-Focused Cognitive Behavioral Therapy (TF-CBT). Seventeen parents/guardians and 16 children who were between the ages of 8 and 12 years were interviewed after Step One and six weeks after the completion of a maintenance phase about their perceptions of the parent-led, therapist-assisted treatment. Participants were asked what they liked and disliked about the treatment as well as what they found to be most and least helpful. Generally, parents and children liked the treatment and found it helpful. In terms of treatment components, children indicated that the relaxation exercises were the most liked/helpful component (62.5%) followed by trauma narrative activities (56.3%). A few children (18.8%) did not like or found least helpful the trauma narrative component as they wanted to avoid talking or thinking about the trauma. Parents indicated that the parent-child meetings were the most liked/helpful (82.4%) followed by the Stepping Together workbook (58.8%) and relaxation exercises (52.9%). Some parents (23.5%) noted that the workbook seemed too repetitive and some parents (17.6%) at times were uncertain if they were leading the parent-child meetings the best way. Parent-led, therapist-assisted TF-CBT may be an acceptable type of service delivery for both parents and children, although more research is needed.