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 .

Effective treatment of osteomyelitis remains a formidable clinical challenge. The rapid emergence of multidrug-resistant bacteria has renewed interest in developing antimicrobial biomaterials using antiseptic silver ions to treat osteomyelitis. However, inadequate local retention and severe cytotoxic effects have limited the clinical use of ionic silver for bone grafts. We recently developed novel porous nano-hydroxyapatite/polyamide 66 (nHP66)-based nanoscaffold materials containing varied concentrations of silver ions (Ag+) (TA-nHAPA66) and oxidized titanium (TiO2), which was added as a second binary element to enhance antibacterial activity and biocompatibility. In this study, we establish a large cohort of rabbit model of experimental osteomyelitis and investigate the in vivo antimicrobial and therapeutic effects of TA-nHP66 biomaterials and their in vivo silver release kinetics. We find the TA-nHP66 scaffolds exhibit potent antibacterial activities against E. coli and S. aureus, support cell adhesion and cell proliferation of pre-osteoblasts, and stimulate osteogenic regulator/marker expression. Moreover, the TA2-nHP66 scaffold exerts potent antibacterial/anti-inflammation effects in vivo and promotes bone formation at the lesion site of osteomyelitis. We further demonstrate that TA2-nHP66 exhibits excellent biosafety profile without apparent systemic toxicities. Therefore, the TA-nHP66 scaffold biomaterials may be further explored as an effective adjuvant therapy for infected bone defects and/or osteomyelitis debridement.

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The effect of 1,25-dihydroxyvitamin D3 [1,25(OH)(2)D3] on two leukemia cell lines, K562 and SHI-1, and its relation to the expression of different subtypes of polypeptide: N-acetylgalactosaminyltransferase (pp-GalNAc-T) was studied. With morphological and cell flow-cytometric method, it was found that 1,25(OH)(2)D3 induced the differentiation of both leukemia cell lines toward monocytic lineage, but not affected the cell growth and apoptosis. The expressions of different subtypes of pp-GalNAc-T, the initial glycosyltransferase in O-glycan synthesis, were studied with RT-PCR before and after the treatment of different concentrations of 1,25(OH)(2)D3. Among fourteen subtypes of pp-GalNAc-T (T1 approximately T14), K562 cells obviously expressed pp-GalNAc-T2, T4, T5, T7 (T2 was the highest) and SHI-1 cells apparently expressed pp-GalNAcT1, T2, T3 and T4 (T4 was the highest) only. After K562 cells were treated 1, 25(OH)(2)D3 for 72 h, pp-GalNAc-T2, T4, T5, T7 were increased in a dose dependent manner. In contrast, pp-GalNAc-T1 and T2, especially T1, were up-regulated in SHI-1 cells by 1,25(OH)(2)D3, but T3 was unchanged and T4 was down-regulated. The different alterations of pp-GalNAc-Ts in these two cell lines were probably related to the different structural changes of O-glycans during 1,25(OH)(2)D3 induced differentiation.