Citations

Background Rhabdomyolysis is a complex and potentially life-threatening syndrome characterized by the rapid breakdown of damaged skeletal muscle. Despite its clinical significance, universally accepted diagnostic criteria and standardized management guidelines are lacking. Methods A cross-sectional online survey about the current diagnostic approach, assessment of risk factors and severity, and management of follow-up of rhabdomyolysis was conducted among clinicians across Europe, Australia, and the USA. Results Fifty-four respondents from 16 countries completed the survey. Results revealed considerable variability in hospital admission practices, and patient follow-up. Some agreement was found in the frequent use of genetic and neurophysiological testing in as diagnostic tools. The survey revealed no consensus on which CK-level would be considered cut-off levels for rhabdomyolysis. Conclusions The survey found little to no coherent approach to diagnosing, assessment of severity, nor follow-up of rhabdomyolysis among respondents who were primarily neurologists and pediatric neurologists. It highlights the need for international guidelines in the diagnostic process, treatment and follow-up of rhabdomyolysis as well as a universally agreed definition of rhabdomyolysis.

Background: Losmapimod is an orally administered small molecule and selective p38α/β mitogen-activated protein kinase (MAPK) inhibitor able to reduce aberrant expression of DUX4 in vitro and thereby potentially slowing disease progression in patients with facioscapulohumeral muscular dystrophy (FSHD). Objective: This global, randomized, placebo-controlled, double-blind phase 3 study in patients with FSHD1 and FSHD2 examined the efficacy and safety of losmapimod over a 48-week treatment period compared to placebo (NCT05397470, EUDRACT 2022-000389-16). Methods: The primary endpoint was change in quantification of reachable workspace (RWS) expressed as relative surface area (RSA). Other endpoints included measures of muscle composition (fat content and lean muscle) using magnetic resonance imaging (MRI), muscle strength using quantitative dynamometry, and quality of life measures. Results: 130 participants received losmapimod and 130 participants received placebo, with 252 participants completing the 48-week treatment period. There were no statistically significant differences between groups in change in RSA and all secondary efficacy endpoints from baseline to Week 48. Losmapimod treatment was well-tolerated, and most adverse events were mild. Conclusions: Losmapimod was generally well tolerated with a favorable safety profile at a dose of 15 mg twice daily. Although none of the efficacy endpoints were met, study design and data from the study may inform future studies of FSHD therapies.