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The British Journal of Dermatology Oct 2023Atopic dermatitis (AD) is an inflammatory skin disease with significant unmet need. Blockade of the OX40-OX40 ligand (OX40L) costimulation pathway by targeting OX40L on... (Randomized Controlled Trial)
Randomized Controlled Trial
Safety and efficacy of amlitelimab, a fully human nondepleting, noncytotoxic anti-OX40 ligand monoclonal antibody, in atopic dermatitis: results of a phase IIa randomized placebo-controlled trial.
BACKGROUND
Atopic dermatitis (AD) is an inflammatory skin disease with significant unmet need. Blockade of the OX40-OX40 ligand (OX40L) costimulation pathway by targeting OX40L on antigen-presenting cells (APCs) with a fully human noncytotoxic, nondepleting anti-OX40L monoclonal antibody (amlitelimab; SAR445229; KY1005) is a novel way to modulate persistent inflammation.
OBJECTIVES
To assess the safety and efficacy of amlitelimab over 16 weeks in adults with AD in a phase IIa double-blind placebo-controlled study.
METHODS
The study was conducted at 19 hospitals in Germany, Poland, Spain and the UK. Eligible patients with moderate-to-severe AD were randomized (1 : 1 : 1) to low-dose intravenous (IV) amlitelimab (200 mg), high-dose IV amlitelimab (500 mg) or placebo, followed by three maintenance doses (50% of loading dose) at 4, 8 and 12 weeks, with safety follow-up to week 36. The co-primary endpoints were the incidence of treatment-emergent adverse events (all patients who received ≥ 1 dose of the study drug) and mean percentage change in Eczema Area and Severity Index (EASI) to week 16 (full analysis set).
RESULTS
Between 13 December 2018 and 12 May 2020, 89 patients were randomly assigned to low- (n = 29) or high-dose amlitelimab (n = 30) or placebo (n = 29), of whom 88 proceeded to treatment [37 women (42%), 51 (58%) men; mean (SD) age 33.6 (11.9) years]. Amlitelimab was generally well tolerated with an unremarkable safety profile; no hypersensitivity events were reported. For the primary endpoint, the least square mean percentage change in EASI from baseline to week 16 was -80.12% [95% confidence interval (CI) -95.55 to -64.68; P = 0.009 vs. placebo] and -69.97% (95% CI -85.04 to -54.60; P = 0.07 vs. placebo) for the low- (n = 27) and high-dose (n = 27) amlitelimab groups, respectively, vs. -49.37% (95% CI -66.02 to -32.72) for placebo (n = 24). Numerically greater reductions in EASI were observed for amlitelimab vs. placebo from weeks 2 to 16.
CONCLUSIONS
Novel targeting of OX40L-expressing APCs with amlitelimab was well tolerated and resulted in clinically meaningful improvements in AD.
Topics: Adult; Male; Humans; Female; Dermatitis, Atopic; Treatment Outcome; Antibodies, Monoclonal; Injections, Subcutaneous; Germany; Antineoplastic Agents; Double-Blind Method; Severity of Illness Index
PubMed: 37463508
DOI: 10.1093/bjd/ljad240 -
American Journal of Clinical Dermatology Jul 2023Acute generalized exanthematous pustulosis (AGEP) is a rare, acute, severe cutaneous adverse reaction mainly attributed to drugs, although other triggers, including... (Review)
Review
Acute generalized exanthematous pustulosis (AGEP) is a rare, acute, severe cutaneous adverse reaction mainly attributed to drugs, although other triggers, including infections, vaccinations, ingestion of various substances, and spider bites, have also been described. AGEP is characterized by the development of edema and erythema followed by the eruption of multiple punctate, non-follicular, sterile pustules and subsequent desquamation. AGEP typically has a rapid onset and prompt resolution within a few weeks. The differential diagnoses for AGEP are broad and include infectious, inflammatory, and drug-induced etiologies. Diagnosis of AGEP depends on both clinical and histologic criteria, as cases of overlap with other disease processes have been reported. Management includes removal of the offending drug or treatment of the underlying cause, if necessary, and supportive care, as AGEP is a self-limited disease. This review aims to provide an overview and update on the epidemiology, pathogenesis, reported precipitating factors, differentials, diagnosis, and management of AGEP.
Topics: Humans; Acute Generalized Exanthematous Pustulosis; Diagnosis, Differential; Skin; Exanthema; Erythema
PubMed: 37156992
DOI: 10.1007/s40257-023-00779-3 -
Allergologie Select 2023Not available.
Guideline for allergological diagnosis of drug hypersensitivity reactions: S2k Guideline of the German Society for Allergology and Clinical Immunology (DGAKI) in cooperation with the German Dermatological Society (DDG), the Association of German Allergologists (ÄDA), the German Society for...
Not available.
PubMed: 37705676
DOI: 10.5414/ALX02422E -
JAMA Internal Medicine Aug 2023
Topics: Humans; Penicillins; Drug Hypersensitivity; Clinical Decision-Making; Hypersensitivity; Anti-Bacterial Agents; Skin Tests
PubMed: 37338869
DOI: 10.1001/jamainternmed.2023.1572 -
European Journal of Hospital Pharmacy :... Dec 2023
Topics: Anesthesia; Adverse Drug Reaction Reporting Systems
PubMed: 38151284
DOI: 10.1136/ejhpharm-2023-004051