BACKGROUND: Disease-modifying therapies have been approved for the treatment of relapsing multiple sclerosis (RMS). The present study aims to examine the safety of teriflunomide in Chinese patients with RMS. METHODS: This non-randomized, multi-center, 24-week, prospective study enrolled RMS patients with variant (c.421C>A) or wild type ABCG2 who received once-daily oral teriflunomide 14 mg. The primary endpoint was the relationship between ABCG2 polymorphisms and teriflunomide exposure over 24 weeks. Safety was assessed over the 24-week treatment with teriflunomide. RESULTS: Eighty-two patients were assigned to variant ( n  = 42) and wild type groups ( n  = 40), respectively. Geometric mean and geometric standard deviation (SD) of pre-dose concentration (variant, 54.9 [38.0] μg/mL; wild type, 49.1 [32.0] μg/mL) and area under plasma concentration-time curve over a dosing interval (AUC tau ) (variant, 1731.3 [769.0] μg∙h/mL; wild type, 1564.5 [1053.0] μg∙h/mL) values at steady state were approximately similar between the two groups. Safety profile was similar and well tolerated across variant and wild type groups in terms of rates of treatment emergent adverse events (TEAE), treatment-related TEAE, grade ≥3 TEAE, and serious adverse events (AEs). No new specific safety concerns or deaths were reported in the study. CONCLUSION: ABCG2 polymorphisms did not affect the steady-state exposure of teriflunomide, suggesting a similar efficacy and safety profile between variant and wild type RMS patients. REGISTRATION NCT04410965, https://clinicaltrials.gov .
Humans ; Crotonates/adverse effects* ; Toluidines/adverse effects* ; Nitriles ; Hydroxybutyrates ; Female ; Male ; Adult ; ATP Binding Cassette Transporter, Subfamily G, Member 2/genetics* ; Middle Aged ; Multiple Sclerosis, Relapsing-Remitting/genetics* ; Prospective Studies ; Young Adult ; Neoplasm Proteins/genetics* ; East Asian People

Objective To investigate the clinical value of noninvasive monitoring technique in intracranial hemorrhage and secondary brain edema after operation for traumatic brain injury (TBI).Methods A retrospective case-series analysis was done on 196 TBI patients (128 males and 68 females,aged 18-60 years old,median age 36.5 years old) admitted from January 2014 to December 2015 and treated surgically with simultaneous implantation of intracranial pressure (ICP) probe.There were 89 patients with Glasgow coma score (GCS) 6-8 points and 107 with GCS 9-12 points.The values of ICP were recorded.The changes of cerebral electrical impedance (CEI) were monitored in all patients through the BORN-BE noninvasive monitor.Results The disturbance factor of the BORN-BE noninvasive monitor in brain edema in the cerebral stage exhibited a strongly positive correlation with ICP (R =0.954,R2 =0.910,P ＜ 0.05).All the rebleeding occurred within 24 hours after operation in the study.The disturbance factor showed a significant reduction in the bleeding side,which exhibited a strongly negative correlation with the volume of cerebral hemorrhage (R =-0.982,R2 =0.964,P ＜ 0.05).Conclusion After operation for TBI,the ICE changes from dynamic noninvasive monitor can reflect the severity of brain edema digitally,indicating that the postoperative rebleeding and its volume may play an important role in selection of optimal treatment.