Efficacy and Safety of Teriflunomide in Chinese Patients with Relapsing Forms of Multiple Sclerosis: A Subgroup Analysis of the Phase 3 TOWER Study

Background:Disease-modifying therapy is the standard treatment for patients with multiple sclerosis (MS)in remission.The primary objective of the current analysis was to assess the efficacy and safety of two teriflunomide doses (7mg and 14mg)in the subgroup of Chinese patients with relapsing MS included in the TOWER study. Methods:TOWER was a multicenter,multinational,randomized, double-blind,parallel-group (three groups),placebo-controlled study.This subgroup analysis includes 148 Chinese patients randomized to receive either teriflunomide 7mg (n =51), teriflunomide 14mg (n=43),or placebo (n=54). Results:Of the 148patients in the intent-to-treat population, adjusted annualized-relapse rates were 0.63(95% confidence interval [CI]:0.44,0.92)in the placebo group,0.48(95%CI:0.33, 0.70)in the teriflunomide 7mg group,and 0.18(95%CI:0.09,0.36)in the terifltmomide 14mg group;this corresponded to a significant relative risk reduction in the teriflunomide 14mg group versus placebo (-71.2%,P =0.0012).Terifiunomide 14mg also tended to reduce 12-week confirmed disability worsening by 68.1% compared with placebo (hazard ratio:0.319,P =0.1194).There were no differences across all treatment groups in the proportion of patients with treatment-emergent adverse events (TEAEs;72.2% in the placebo group,74.5%in the teriflunomide 7mg group,and 69.8% in the teriflunomide 14mg group);corresponding proportions for serious adverse events were 11.1%,3.9%,and 11.6%,respectively.The most frequently reported TEAEs with teriflunomide versus placebo were neutropenia,increased alanine aminotransferase,and hair thinning. Conclusions:Teriflunomide was as effective and safe in the Chinese subpopulation as it was in the overall population of patients in the TOWER trial.Teriflunomide has the potential to meet unmet medical needs for MS patients in China.

Clinical Features of Patients with Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorders

Background： Neuromyelitis optica spectrum disorder （NMOSD） was long believed to be an aggressive form of multiple sclerosis （MS）. This study aimed to describe the clinical features of patients with MS and NMOSD to assist in differential diagnoses in clinical practice. Methods： Data including the patients＇ serum and cerebrospinal fluid （CSF） tests, image findings, and clinical information from 175 patients with MS or NMOSD at Xuanwu Hospital, Capital Medical University from November 2012 to May 2014 were collected and analyzed retrospectively. An enzyme-linked immunosorbent assay was performed to detect the myelin oligodendrocyte glycoprotein （MOG） autoantibodies in CSF and serum. Cell-based assays were used to detect aquaporin-4-antibody （AQP4-Ab）. The Chi-square test was used to compare the categorical variables. Wilcoxon rank sum test was peribrmed to analyze the continuous variables. Results： Totally 85 MS patients （49%） and 90 NMOSD patients （51%） were enrolled, including 124 （71%） women and 51 （29%） men. Fewer MS patients （6%） had autoinamune diseases compared to NMOSD （19%） （x2= 6.9, P 〈 0.01 ）. Patients with NMOSD had higher Expanded Disability Status Scale scores （3.5 [3]） than MS group （2 [2]） （x2= -3.69, P 〈 0.01）. The CSF levels of white cell count and protein in both two groups were slightly elevated titan the normal range, without significant difference between each other. Positivity of serum AQP4-Ab in NMOSD patients was higher than that in MS patients （MS： 0, NMOSD： 67%; x2= 63.9, P 〈 0.01 ）. Oligoclonal bands in CSF among NMOSD patients were remarkably lower than that among MS （MS： 59%, NMOSD： 20%; x2= 25.7, P 〈 0.01）. No significant difference of MOG autoantibodies was found between the two groups. Conclusion： The different CSF features combined with clinical, magnetic resonance imaging, and serum characteristics between Chinese patients with MS and NMOSD could assist in the differential diagnosis.

Depressive severity associated with cesarean section in young depressed individuals

This cross-sectional study recruited consecutively 347 patients (178 males,169 females) aged 19 to 30 years with a diagnosis of MDD according to Diagnostic and Statistical Manual of Mental Disorders,Fifth Edition (DSM-V) criteria who underwent in-person interviews,the mini international neuropsychiatric interview,and physical examinations by experienced psychiatrists at Division of Neuropsychiatry,Department of Neurology,Xuanwu Hospital of Capital Medical University (Beijing,China) between August 20,2015,and December 28,2018.All patients were excluded with anemia,thyroid dysfunction,mental retardation,neurologic conditions,bipolar disorders,schizophrenia,and other mental disorders.Depressive symptoms were assessed with the Hamilton rating scale for depression (HAMD-17) by three experienced psychological testing technicians who were blinded to all subjects' birth delivery types at the Neuropsychological Center of Department of Neurology of Xuanwu Hospital.The study was conducted in accordance with the Declaration of Helsinki and was approved by the Ethics Committee of Xuanwu Hospital.As a retrospective study and data analysis were performed anonymously,this study was exempt from the informed consent from patients.

A Novel SLC2OA2 Mutation Associated with Familial Idiopathic Basal Ganglia Calcification and Analysis of the Genotype-Phenotype Association in Chinese Patients

Background： Idiopathic basal ganglia calcification （IBGC） is a genetic disorder characterized by bilateral basal ganglia calcification and neural degeneration. In this study, we reported a new SLC2OA2 mutation of IBGC and reviewed relevant literature to explore the association between phenotypes and genotypes in Chinese IBGC patients. Methods： Clinical information of the proband and her relatives were collected comprehensively. Blood samples of both the patient and her father were obtained, and genetic screening related to IBGC was performed using second generation sequencing with their consent. Findings were confirmed by Sanger sequencing. Polyphen-2 was used to predict the potential association between mutations and disease. Then, we retrieved literatures of Chinese IBGC patients and explored the association between phenotype and genotype. Results： A novel mutation was identified through genetic testing, and it is suggested to be a damage mutation predicted by Polyphen-2. Through literature review, we tbund that SLC2OA2 mutation is the most common cause for IBGC in China. Its hot spot regions are mainly on the 1^st and 8th exons; the second common one is PDGFB where the hot spot covered a length of 220-230 bp localized on the 2^nd exon; moreover, Chinese IBGC patients featured early-onset, more severe movement disorder and relatively mild cognitive impairment compared with those in other countries. Conclusions： There is significant heterogeneity both in phenotype and genotype in Chinese IBGC patients. Further research of pathogenic mechanism of IBGC is required to eventually develop precise treatment for individuals who suffered this disease.