Background
Secukinumab demonstrated sustained efficacy in patients with ankylosing spondylitis (AS) through 5 years in pivotal Phase III studies. Here, we present efficacy and safety results (52-week) of secukinumab in patients with AS from the MEASURE 5 study.
Methods
MEASURE 5 was a 52-week, Phase III, China-centric study. Eligible patients were randomly assigned (2:1) to receive subcutaneous secukinumab 150 mg or placebo weekly for the first five doses and then once every 4 weeks (q4w). All placebo patients switched to secukinumab 150 mg q4w starting at Week 16. Primary endpoint was Assessments of SpondyloArthritis international Society (ASAS) 20 at Week 16. Randomization was stratified by region (China
vs
. non-China).
Results
Of 458 patients (secukinumab 150 mg,
N
= 305; placebo,
N
= 153) randomized, 327 (71.4%) were from China and 131 (28.6%) were not from China. Of these, 97.7% and 97.4% patients completed Week 16 and 91.1% and 95.3% (placebo-secukinumab) patients completed Week 52 of treatment. The primary endpoint was met; secukinumab significantly improved ASAS20 response at Week 16
vs.
placebo (58.4%
vs.
36.6%;
P
< 0.0001); corresponding rate in the Chinese population was 56.0%
vs.
38.5% (
P
< 0.01). All secondary efficacy endpoints significantly improved with secukinumab 150 mg in the overall population at Week 16; responses were maintained with a trend toward increased efficacy from Week 16 to 52. No new or unexpected safety signals were reported up to Week 52.
Conclusions
Secukinumab 150 mg demonstrated rapid and significant improvement in signs and symptoms of AS. Secukinumab was well tolerated and the safety profile was consistent with previous reports. Efficacy and safety results were comparable between the overall and Chinese populations.
Trial registration
ClinicalTrials.gov, NCT02896127;
https://clinicaltrials.gov/ct2/show/NCT02896127?term=NCT02896127&draw=2&rank=1
.
Background
The extracellular vesicles (EVs) traffic constitutes an essential pathway of cellular communication. And the molecules in EVs produced by procaryotes help in maintaining homeostasis, addressing microbial imbalance and infections, and regulating the immune system. Despite the fact that Clostridium butyricum (C. butyricum) is commonly used for treating ulcerative colitis (UC), the potential role of C. butyricum-secreted EVs in commensals-host crosstalk remains unclear.
Results
Here, we performed flow cytometry, western blot, immunohistochemistry and 16S rRNA analysis to explore the role of C. butyricum-derived EVs on macrophage polarization and gut microbiota composition in a dextran sulfate sodium (DSS)-induced UC mouse model. The antibiotic cocktail-induced microbiome depletion and faecal transplantations were used to further investigate the mechanisms by which EVs regulate macrophage balance. Our findings showed that C. butyricum-derived EVs improved the remission of murine colitis and polarized the transformation of macrophages to the M2 type. Furthermore, C. butyricum-derived EVs restored gut dysbiosis and altered the relative abundance of Helicobacter, Escherichia-Shigella, Lactobacillus, Akkermansia and Bacteroides, which, in turn, faecal transplantations from EVs-treated mice relieved the symptoms of UC and improved the impact of EVs on the reprogramming of the M2 macrophages.
Conclusion
C. butyricum-derived EVs could protect against DSS-induced colitis by regulating the repolarization of M2 macrophages and remodelling the composition of gut microbiota, suggesting the potential efficacy of EVs from commensal and probiotic Clostridium species against UC.
We expounded the effect of intravenous arginine on the healing of human skin graft donor sites. This randomized study was double blind and controlled by placebos from October 2012 to May 2015. Nine patients were selected into the arginine group and 10 were selected into the control group. There was no significance in age, weight, BMI, CRP, albumin and total plasma protein in arginine and control groups. Angiogenesis, re-epithelialization and neutrophil influx of wound healing were measured. The concentrations of plasma amino acid were measured to evaluate our intervention. In our study, plasma arginine and ornithine concentrations in arginine group were the highest after arginine-treated at 2 days. Supplementation of intravenous arginine could not affect on healing of human skin graft donor sites, improve angiogenesis, reepithelialization or neutrophil influx in rats.
Article Info
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