Does Antiepileptic Drug Clearance Change During Pregnancy?
In pregnant women, antiepileptic drug (AED) clearance significantly changes by the first trimester for levetiracetam and by the second trimester for oxcarbazepine and topiramate, according to a study published September 25 in Neurology. This prospective, observational study included 40 women with epilepsy who were planning to conceive or were fewer than 16 weeks pregnant and who chose to continue their AEDs during pregnancy. Drug clearance values were obtained by blood draw at baseline and during pregnancy. Mean maximal clearances were 1.71 times the baseline clearance for levetiracetam, 1.63 times the baseline clearance for oxcarbazepine, and 1.39 the baseline clearance for topiramate. In 15 women on AED monotherapy, increased seizure frequency in the first, second, and all trimesters was associated with a lower ratio to target concentration.
Voinescu PE, Park S, Chen LQ, et al. Antiepileptic drug clearances during pregnancy and clinical implications for women with epilepsy. Neurology. 2018;91(13):e1228-e1236.
Do Dextroamphetamine and Physical Therapy Improve Function After Stroke?
Compared with placebo, dextroamphetamine combined with physical therapy does not improve recovery of motor function after stroke, according to a study published online ahead of print August 27 in JAMA Neurology. This pilot, double-blind, block-randomized clinical trial included patients with cortical or subcortical ischemic stroke and moderate or severe motor deficits. A total of 64 participants were randomized to receive 10 mg of dextroamphetamine or placebo one hour before a one-hour physical therapy session every four days for six sessions, in addition to standard rehabilitation. The primary outcome was the difference between groups in change in Fugl-Meyer motor scores from baseline to three months after stroke. Treatment was not associated with differences in the primary outcome, secondary measures, or subgroups based on stroke location or baseline severity.
Goldstein LB, Lennihan L, Rabadi MJ, et al. Effect of dextroamphetamine on poststroke motor recovery: a randomized clinical trial. JAMA Neurol. 2018 Aug 27 [Epub ahead of print].
FDA Approves Tegsedi for hATTR in Adults
The FDA has approved Tegsedi (inotersen) for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis (hATTR) in adults. The approval is based on data from the phase III randomized, double-blind, placebo-controlled, 15-month, international NEURO-TTR study in 172 patients with hATTR amyloidosis with symptoms of polyneuropathy. In NEURO-TTR, Tegsedi demonstrated significant benefit, compared with placebo, in neuropathy and quality of life, as measured by the modified Neuropathy Impairment Score +7 and the Norfolk Quality of Life Questionnaire-Diabetic Neuropathy total score. Patients treated with Tegsedi experienced similar benefit regardless of subgroup, such as age, sex, race, region, Neuropathy Impairment Score, Val30Met mutation status, and disease stage. Akcea Therapeutics, an affiliate of Ionis Pharmaceuticals that is headquartered in Boston, markets Tegsedi.
Data Review Evaluates Nusinersen’s Efficacy in SMA
A panel has reviewed the evidence for nusinersen treatment of spinal muscular atrophy (SMA). The results were published online ahead of print October 12 in Neurology. The authors systematically reviewed clinical trials of nusinersen in patients with SMA and assigned level of evidence statements. Among four published clinical trials identified, three were rated above Class IV. There is Class I evidence that in term infants with SMA and two copies of SMN2, treatment with nusinersen started in children younger than 7 months results in a better motor milestone response and higher rates of event-free survival than sham control. There is Class I evidence that in children aged 2 to 12 with SMA symptom onset after age 6 months, nusinersen yields greater improvement in motor function at 15 months than sham control.