Methods: Efficacy outcomes of interest were clinical response, clinical remission and mucosal healing at week 6 (induction phase); and clinical remission, durable clinical response, durable clinical remission, mucosal healing and glucocorticoid-free remission at week 52 (maintenance phase). Differences in outcome rates between vedolizumab and placebo in Asian countries (Hong Kong, India, Malaysia, Singapore, South Korea, and Taiwan) were assessed using descriptive analyses, and efficacy and safety compared between Asian and non-Asian countries.
Results: During induction, in Asian countries (n = 58), clinical response rates at week 6 with vedolizumab and placebo were 55.2% and 24.1%, respectively (difference 31.0%; 95% confidence interval: 7.2%-54.9%). In non-Asian countries (n = 316), response rates at week 6 with vedolizumab and placebo were 45.9% and 25.8%, respectively. During maintenance, in Asian countries, clinical remission rates at 52 weeks with vedolizumab administered every 8 weeks, vedolizumab administered every 4 weeks and placebo were 9.1%, 36.8%, and 31.6%, respectively; corresponding rates for mucosal healing were 45.5%, 47.4%, and 47.4%, respectively. Vedolizumab was well-tolerated; adverse event frequency was comparable in Asian and non-Asian countries.
Conclusions: In patients from Asian countries, the efficacy and safety of vedolizumab in treatment of UC were broadly consistent with that in the overall study population.
METHODS AND ANALYSIS: At least 51 patients with an acute GPP flare will be randomised 2:1 to receive a single 900 mg intravenous dose of spesolimab or placebo and followed for up to 28 weeks. The primary endpoint is a Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) pustulation subscore of 0 (pustule clearance) at Week 1. The key secondary endpoint is a GPPGA score of 0 or 1 (clear or almost clear) at Week 1. Safety will be assessed over the study duration by the occurrence of treatment-emergent adverse events. Blood and skin biopsies will be collected to assess biomarkers. Superiority of spesolimab over placebo in the proportion of patients achieving the primary and key secondary endpoints will be evaluated.
ETHICS AND DISSEMINATION: The study complies with the ethical principles of the Declaration of Helsinki, the International Council for Harmonisation's Good Clinical Practice and local regulations. Ethics committee approvals have been obtained for each centre from all participating countries and are listed in online supplementary file 1. Primary results will be published in a peer-reviewed journal.
TRIAL REGISTRATION DETAILS: ClinicalTrials.gov identifier: NCT03782792; Pre-results.
METHODS: We conducted a retrospective analysis of data collected in the Pan-Asian Resuscitation Outcomes Study (PAROS) registry. We included OHCA cases from seven communities (Japan, South Korea, Malaysia, Singapore, Taiwan, Thailand, and United Arab Emirates) between January 2009 and December 2012. Paediatric cases, cases that were conveyed by non-emergency medical services (EMS), and cases with incomplete records were excluded from the study.
RESULTS: The RACA score showed similar discrimination performance as the original German study and various European validation studies. However, it had poor calibration with the original constant regression coefficient, which was primarily due to the low ROSC rate (8.2%) in the PAROS cohort. The calibration performance of RACA significantly improved after the constant coefficient was modified to adjust for the disparity in ROSC rates between Asia and Europe.
CONCLUSION: This is the largest validation study of the RACA score. RACA consistently performs well in both Pan-Asian and European communities and can thus be a valuable tool for evaluating EMS systems. However, to implement it, the constant coefficient has to be modified in the RACA formula with local historical data.