The objective of this study was to assess the effect of secukinumab, a monoclonal antibody that inhibits interleukin (IL)-17A, on number of new active brain magnetic resonance imaging (MRI) lesions in subjects with relapsing-remitting multiple sclerosis (MS). Subjects (N = 73) were randomized 1:1 to secukinumab 10 mg/kg or placebo by intravenous infusion at weeks 0, 2, 4, 8, 12, 16, and 20. MRI scans were obtained within 30 days prior to randomization, on a monthly basis during the treatment period, and at study completion. The primary endpoint was the cumulative number of combined unique active lesions (CUAL) observed on brain MRI scans from week 4 to week 24. Compared with placebo, secukinumab non-significantly reduced the number of CUAL observed on 4-weekly MRI from week 4 to 24 (primary endpoint) by 49 % (95 % CI -10 to 77 %; P = 0.087) and significantly reduced the number of cumulative new gadolinium-enhancing T1 lesions by 67 % (31-84 %, P = 0.003). CUAL reductions were progressively greater from week 4 (1 %) to week 16 (49 %) and persisted until end-study (50 %). There were no serious adverse events; the adverse event rate was comparable to placebo (53 versus 49 %), although mild-to-moderate infection was somewhat more frequent (37 versus 23 %). This proof-of-concept study provides the first evidence that blocking IL-17A with an antibody may reduce MRI lesion activity in MS. Further studies are needed to confirm this finding and determine the magnitude of effect.

for the Glatiramer Acetate Clinical Trial to Assess Equivalence With Copaxone (GATE) Study Group IMPORTANCE The patents for the first approved treatments for relapsing-remitting multiple sclerosis are expiring, creating the opportunity to develop generic alternatives.OBJECTIVE To evaluate in the Glatiramer Acetate Clinical Trial to Assess Equivalence With Copaxone (GATE) study whether generic glatiramer acetate (hereafter generic drug) is equivalent to the originator brand glatiramer acetate (hereafter brand drug) product, as measured by imaging and clinical end points, safety, and tolerability. DESIGN, SETTING, AND PARTICIPANTS Randomized, multicenter, double-blind, active and placebo-controlled phase 3 trial. The setting included academic medical centers and clinical practices. Participants were patients with relapsing-remitting multiple sclerosis 18 to 55 years old with at least 1 relapse in the prior year and 1 to 15 gadolinium-enhancing brain magnetic resonance imaging lesions. They were randomized between December 7, 2011, and March 21, 2013. The last participant completed follow-up December 2, 2013.INTERVENTIONS Participants were randomized 4.3:4.3:1 to receive generic glatiramer acetate (20 mg), brand glatiramer acetate (20 mg), or placebo by daily subcutaneous injection for 9 months. MAIN OUTCOMES AND MEASURESThe primary end point was the total number of gadolinium-enhancing lesions during months 7, 8, and 9. Additional end points included other magnetic resonance imaging parameters, annualized relapse rate, and Expanded Disability Status Scale score. Safety and tolerability were assessed by monitoring adverse events, injection site reactions, and laboratory test results. RESULTSIn total, 794 participants were randomized and treated with generic drug (n = 353), brand drug (n = 357), or placebo (n = 84). The estimated mean numbers of gadolinium-enhancing lesions with generic drug and brand drug were lower than with placebo (ratio, 0.488; 95% CI, 0.365-0.651; P < .001), confirming study sensitivity. For gadolinium-enhancing lesions, the estimated ratio of generic drug to brand drug was 1.095 (95% CI, 0.883-1.360), which was within the predefined equivalence margin of 0.727 to 1.375. The incidence, spectrum, and severity of reported adverse events, including injection site reactions, were similar in the generic drug and brand drug groups. CONCLUSIONS AND RELEVANCEAs treatment for relapsing-remitting multiple sclerosis, glatiramer acetate generic drug and brand drug had equivalent efficacy, safety, and tolerability.TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01489254

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Although the predefined noninferiority criterion was not met, abobotulinumtoxinA solution for injection was similarly effective to freeze-dried abobotulinumtoxinA in reducing Toronto Western Spasmodic Torticollis Rating Scale total scores with a similar safety profile. AbobotulinumtoxinA solution for injection efficacy was maintained with chronic open-label treatment, and this novel formulation may add convenience as well as dosing accuracy to treatment with abobotulinumtoxinA. © 2016 International Parkinson and Movement Disorder Society.

Background:Open-label 15-month follow-up of the double-blind, placebo-controlled Glatiramer Acetate clinical Trial to assess Equivalence with Copaxone® (GATE) trial.Objective:To evaluate efficacy, safety, and tolerability of prolonged generic glatiramer acetate (GTR) treatment and to evaluate efficacy, safety, and tolerability of switching from brand glatiramer acetate (GA) to GTR treatment.Methods:A total of 729 patients received GTR 20 mg/mL daily. Safety was assessed at months 12, 15, 18, 21, and 24 and Expanded Disability Status Scale and magnetic resonance imaging (MRI) scans at months 12, 18, and 24. The presence of glatiramer anti-drug antibodies (ADAs) was tested at baseline and months 1, 3, 6, 9, 12, 18, and 24.Results:The mean number of gadolinium-enhancing lesions in the GTR/GTR and GA/GTR groups was similar at months 12, 18, and 24. The change in other MRI parameters was also similar in the GTR/GTR and GA/GTR groups. The annualized relapse rate (ARR) did not differ between the GTR/GTR and GA/GTR groups, 0.21 and 0.24, respectively. The incidence, spectrum, and severity of reported adverse events did not differ between the GTR/GTR and GA/GTR groups. Glatiramer ADA titers were similar in the GTR/GTR and GA/GTR groups.Conclusion:Efficacy and safety of GTR is maintained over 2 years. Additionally, switching from GA to GTR is safe and well tolerated.

Autism spectrum disorders (ASD) are disorders of psychic development characterized by the difficulties of social interaction and stereotyped and repetitive patterns of behavior. Rather often they are accompanied by disturbances of speech, intelligence, and adaptive behavior. Pathogenesis of ASD is still poorly studied. MRI with its latest modalities is a modern diagnostic method enabling medical providers to evaluate structural, metabolic, and functional features of brain development in this pathology. The aim of the study was to assess the capabilities of functional MRI (fMRI) in determining pathophysiological mechanisms of delay in speech development in ASD. Materials and Methods. A brief review of international studies is given in the article. Our own results of examining 6 preschool children with one of the ASD forms-early childhood autism and speech disorders, and 6 children of the comparison group without autism and language disturbances are also presented using fMRI and a block design paradigm to analyze speech perception patterns. Results. In all children with normal speech development, bilateral symmetric spread of activation along the cortex of the entire superior temporal gyri was revealed whereas children with autism showed lateralized and limited involvement of the auditory cortex. Sevoflurane anesthesia did not influence the character of auditory zone activation. Conclusion. The possibility of using fMRI with application of the paradigm for speech understanding to study the individual features of brain functioning in children with autism has been demonstrated. The revealed objective instrumental signs of brain activity differences in the children with autism compared to the healthy children allow the fMRI data to be considered as a potential biomarker of this disease. It has also been shown that the possibility to carry out this examination under general anesthesia makes it more acceptable and convenient for patients with childhood autism.

In rehabilitation of patients who have lost their ability to move independently due to the paralysis of lower limbs, using exoskeletons is a perspective direction. In recent years a great number of robotic devices improving walking of people with lower paraparesis have been developed. However, their comparison is hindered since there are no standardized approaches to the assessment of their efficiency and safety. In this review, general principles of evaluating external robotic devices have been presented, and methods of determining safety and convenience of exoskeleton usage have been analyzed. Assessment of qualitative and quantitative parameters of exoskeletonassisted walking has also been considered. The characteristic of the questionnaires, standard tests and biochemical investigations, which are used in approbation of exoskeletal devices in people with paraplegia has been presented. Possible ways of evaluating energy expenditure when moving in exoskeletons are shown. The need of elaborating a unified evaluation strategy of walking in exoskeletons has been substantiated.Key words: exoskeleton; assessment of walking; approbation of exoskeleton devices; paralysis of the lower limbs.

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