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A survey was conducted to evaluate how clinicians worldwide manage scabies. The survey included different scenarios and settings, and most respondents were dermatologists. The study found that there was a wide variation in the first-line treatment proposed depending on the scenario, with oral ivermectin and permethrin 5% cream being the most popular choices. The study also highlighted the lack of consensus on treatment recommendations and the widespread use of decontamination measures, despite their questionable value. The limitations of the study included the use of a vignette-based survey and the predominantly dermatologist participants from high-income settings. Further research is needed to assess the effectiveness of different treatments and approaches in various locations and healthcare settings. [Extracted from the article]

Introduction/Background Targeting and binding OX40 ligand (OX40L) expressed on antigen-presenting cells may inhibit the persistent immune response that drives atopic dermatitis (AD) pathophysiology. Amlitelimab (SAR445229; KY1005) is a potential first-in-class, fully human, non-depleting anti-OX40L monoclonal antibody that blocks OX40L-OX40 interactions and has shown efficacy and an acceptable safety profile in a Phase 2a trial in adults with moderate-to-severe AD. Here, we present 24-week efficacy and safety results (Part 1) from an ongoing dose-ranging Phase 2b trial. The study remains blinded to individual patient data (Part 2 ongoing). Objectives: To evaluate the efficacy and safety of amlitelimab in adults with moderate-to-severe AD. Methods: STREAM-AD (NCT05131477) is a 52-week, randomised, double-blinded, placebo-controlled Phase 2b monotherapy trial. This study is designed with 2 parts (double-blind throughout): a 24-week treatment period (Part 1, completed and presented here) and a 36-week maintenance/withdrawal period (Part 2, ongoing). Adults (18 to <75 years; n=390) with moderate-to-severe AD were randomised 1:1:1:1:1 to receive subcutaneous amlitelimab Q4W (250 mg with 500 mg loading dose [LD], n=77; 250 mg without LD, n=78; 125 mg without LD, n=77; or 62.5 mg without LD, n=79) or placebo Q4W (n=79). The primary endpoint was percentage change in Eczema Area and Severity Index (EASI) from baseline at Week 16. Key secondary endpoints included percentage change in EASI at Week 24 and percentage of patients with at least 75% reduction from baseline in EASI (EASI-75), percentage of patients with Investigator Global Assessment response of 0 (clear) or 1 (almost clear) and a reduction from baseline of ≥2 points (IGA 0/1), and proportion of patients with a weekly average reduction of Peak Pruritus Numerical Rating Scale (PP-NRS) ≥4 points from baseline. The primary efficacy analysis included all randomised patients who completed Week 24 or discontinued treatment or study prior to Week 24 visit (n=390), whereas the safety analysis included all treated patients (n=388). Results: Treatment with amlitelimab resulted in statistically significant improvements in percentage change in EASI from baseline to Week 16 compared to placebo for all four doses studied. The 250 mg with LD group had the numerically highest response versus placebo at Week 16, with a least-squares mean change from baseline of -32.1% (95% CI: -43.9, -20.3; P<0.0001); the remaining groups without LD had the following responses versus placebo: 250 mg, -27.3 (95% CI: -39.1, -15.6; P<0.0001); 125 mg, -22.2 (95% CI: -34.0, -10.4; P=0.0002); and 62.5 mg, -30.2 (95% CI: -41.9, -18.5; P<0.0001). There were also clinically meaningful improvements in all key secondary efficacy outcome measures, with all amlitelimab dose groups demonstrating nominally significant (P<0.05) efficacy versus placebo for EASI-75, IGA 0/1, and PP-NRS =4, except 250 mg (no LD) in IGA 0/1 at Week 16 (P=0.0562). Continued improvements were generally observed through Week 24 in primary and key secondary efficacy outcomes. Amlitelimab was well tolerated across all dose groups, with no safety concerns identified. Conclusions: In this dose-ranging Phase 2b trial of amlitelimab in adults with moderate-to-severe AD, amlitelimab demonstrated clinically meaningful efficacy over 24 weeks with an acceptable safety profile across all four dose groups. [ABSTRACT FROM AUTHOR]

Introduction/Background Amlitelimab is a fully human, nondepleting anti-OX40 Ligand (OX40L) monoclonal antibody that blocks OX40L-OX40 interactions. In addition to an acceptable safety profile, phase 2a and 2b trials showed the clinical efficacy of amlitelimab in achieving lesional and symptomatic (pruritus) endpoints and demonstrating a continued durable response when patients with moderate-to-severe atopic dermatitis (AD) were withdrawn from amlitelimab during a 28-week period, suggesting the viability of extended interval dosing (every 12 weeks [Q12W]). Objectives Phase 3 clinical trials will determine the efficacy and safety of amlitelimab every four weeks (Q4W) and Q12W dosing in patients with moderate-to-severe AD with various treatment histories. Methods OCEANA phase 3 clinical trials (COAST 1, COAST 2, SHORE, AQUA, and ESTUARY) are multinational, multicenter, randomized, double-blind, parallel group, placebo-controlled trials evaluating efficacy and safety of subcutaneous amlitelimab with two different dosing regimens. Key inclusion criteria for COAST 1/2, SHORE, and AQUA include: adults and adolescents (≥12 years old) having AD ≥1 year with inadequate response to topical treatments (within 6 months before screening) and/or systemic treatment (within 12 months before screening), validated Investigator Global Assessment scale for Atopic Dermatitis (vIGA-AD) baseline score of 3 or 4, Eczema Area and Severity Index (EASI) baseline score of ≥16, AD involvement of ≥10% of body surface area at baseline, and weekly average Peak Pruritus Numerical Rating Scale score of ≥4. COAST 1/2 are 24-week monotherapy studies, while SHORE is a 24-week study with background topical corticosteroids (TCSs) and topical calcineurin inhibitors (TCIs). AQUA is a 36-week study with background TCSs and TCIs that exclusively includes participants with an inadequate response to prior treatment with AD biologics or oral Janus kinase inhibitors. Primary endpoints for COAST 1/2, SHORE, and AQUA include vIGA-AD 0/1 and a reduction from baseline of ≥2 points (for US and US reference countries) and vIGA-AD 0/1 and EASI-75 (for Japan, EU, and EU reference countries). Adult patients ≥40 kg will be randomized to amlitelimab 250 mg Q4W + 500 mg loading dose (LD), amlitelimab 250 mg Q12W + 500 mg LD, or placebo; dose will be adjusted for patients <40 kg. Trials have a 2- to 4-week screening period. Primary endpoints will be evaluated at Week 24 for COAST 1/2 and SHORE and at Week 36 for AQUA, with expected enrollment of 420, 420, 496, and 249 patients in each study, respectively. Patients who have completed COAST 1/2 or SHORE can elect to enter the ESTUARY blinded extension study; patients completing AQUA can enter RIVER-AD, an open-label long-term study. Upon entering ESTUARY, clinical responders previously on 250 mg Q4W +LD will be randomized to 250 mg Q4W, 250 mg Q12W, or treatment withdrawal (placebo), while nonresponders will continue on 250 mg Q4W. Clinical responders previously on 250 mg Q12W +LD will be randomized to 250 mg Q12W or treatment withdrawal (placebo), while nonresponders will be randomized to 250 mg Q12W or 250 mg Q4W. Clinical responders previously on placebo will continue placebo, while nonresponders on placebo will receive amlitelimab 250 mg Q4W +LD. Participants not entering the ESTUARY or RIVER-AD trials will be included in a 16-week safety follow-up. ESTUARY and RIVER-AD will evaluate long-term safety and efficacy. Biopsies and blood samples will be collected at various timepoints in the OCEANA phase 3 trials. Results Enrollment for the OCEANA phase 3 trials began Q4 2023. COAST 1/2, SHORE, and AQUA trials are expected to be completed in 2026. Conclusions Results of the clinical trials should provide further evidence demonstrating the efficacy and safety of amlitelimab in treating moderate-to-severe AD using two different dosing regimens, including an extended dosing regimen, in patients with various treatment histories. [ABSTRACT FROM AUTHOR]

Background Amlitelimab is a fully-human, non-depleting, anti-OX40 ligand (OX40L) monoclonal antibody that binds to OX40L on antigen-presenting cells. Amlitelimab blocks the interaction of OX40L with OX40 on activated T-cells, inhibiting T-cell dependent inflammation without depleting T-cells. Objective To evaluate the efficacy and safety of amlitelimab (Part 1), and explore the maintenance of clinical response over a 28-Week period (Part 2) in patients with moderate-to-severe AD. Methods STREAM-AD (NCT05131477), was a randomized, double-blind, placebo-controlled Phase 2b trial, that included a 24-Week, double-blind, treatment period (Part 1), a 28-Week maintenance/withdrawal period (Part 2), and a 16-Week safety follow-up. In Part 1, adult participants were randomized 1:1:1:1:1 to subcutaneous amlitelimab Q4W (250mg with 500mg loading dose [+ LD], n=77; 250mg, n=78; 125mg, n=77; 62.5mg, n=79) or placebo Q4W (n=79). In Part 2, Clinical responders (defined as those achieving EASI-75 and/or IGA 0/1 at Week-24) in Part 1, were rerandomized 3:1 to withdraw or continue pre-Week 24 Q4W dose (250mg + LD, n=34 [withdrawal]/n=13 [continuing]; 250mg, n=28/n=12; 125mg, n=33/n=12; 62.5mg, n=35/n=7; placebo responders continuing placebo, n=16), and were followed to Week-52 to evaluate maintenance of clinical response. Primary efficacy endpoint was percent change in EASI from baseline at Week-16. Key secondary endpoints were proportion of patients achieving IGA 0/1, EASI-75, PP-RNS≥4. The statistical analysis was performed using two methods: 1) imputing the endpoint as nonresponder after rescue medication use (NRI); and 2) including all measurements regardless of rescue use (treatment policy). Results Out of 390 participants enrolled in Part 1, 190 entered Part 2. In Part 1, all four doses of amlitelimab demonstrated statistically significant improvements in percent change in EASI from baseline to Week-16 vs placebo; the highest response was seen with 250mg + LD group. Clinically meaningful improvements in key secondary endpoints were observed at Week-16, with continued improvements through Week-24. In Part 2, maintenance of EASI-75 and/or IGA 0/1 response at Week-52 was observed in 59%, 63%, 55%, and 66% of clinical responders withdrawn from 250mg + LD, 250mg, 125mg, and 62.5mg, respectively (NRI). Using treatment policy, 77%, 82%, 67%, and 74% maintained response off-drug, respectively. Those continuing amlitelimab treatment had numerically higher maintenance response rates. AD-related biomarkers were reduced during Part 1 and remained decreased over Part 2. Amlitelimab was well tolerated across all dose groups, with no new safety concerns identified during the 52-Weeks. Conclusion Clinically meaningful efficacy with amlitelimab was demonstrated over 52-Weeks, with an acceptable safety profile. Clinical responses were maintained in most patients 28-Weeks after treatment discontinuation. [ABSTRACT FROM AUTHOR]

We highlight the absence of high-level evidence from dose-ranging studies regarding the use of oral ivermectin in susceptible parasitic diseases. We provide published data supporting the use of a higher dosage regimen of ivermectin in malaria and difficult-to-treat head lice, and announce an ongoing randomized clinical trial in severe scabies.

Thermal burns can occur during seizure. This diagnosis can be difficult in case of atypical lesions, even more if the epilepsy is unknown and in case of seizures with loss of consciousness and/or an unwitnessed epileptic attack. We report two cases of cutaneous bullous lesions initially misdiagnosed as severe acute cutaneous adverse reactions (generalized bullous fixed drug eruption and Stevens-Johnson syndrome). In the two cases, the clinical aspect, necrotic evolution, and absence of obvious attributable medication allowed to revert to the diagnosis of burns due to boiling water revealing previously unknown epilepsy. For both, surgical management with skin graft was performed, and antiepileptic treatment was introduced. Facing unexplained burns, occult epilepsy should be investigated. Questioning of patient and relatives is crucial. [ABSTRACT FROM AUTHOR]

Scabies is one of the most common skin diseases worldwide, affecting 150-200 million people yearly. Scabies affects young children in particular, and has the greatest impact in poor overcrowded living conditions. The burden of the disease is now well characterized, including group A Streptococcus and Staphylococcus aureus bacterial superinfections, with reports of nephritis, acute rheumatic fever, or fatal invasive sepsis secondary to scabies. Management of scabies remains largely suboptimal from diagnosis to treatment, and progress in the development of new therapeutic measures leading to cure is urgently needed. This review gives an overview of the current limitations in the management of scabies, an update on recent advances, and outlines prospects for potential improvements. [ABSTRACT FROM AUTHOR]