An analysis of first-line disease-modifying therapies in patients with relapsing-remitting multiple sclerosis using the French nationwide health claims database from 2014-2017.

BACKGROUND: Little is known about the use of first-line treatments for relapsing-remitting multiple sclerosis (RRMS), whether oral (teriflunomide and dimethyl fumarate) or injectable (interferons/glatiramer acetate [GA]) in France. We conducted an observational study to determine patient profile, persistence and compliance to first-line disease-modifying treatments (DMT), and factors related to discontinuation in naïve patients with RRMS. METHODS: This is a retrospective study using the French Nationwide Health Data System (SNDS) which collects outpatient and hospitalization data for the entire population. Naïve patients aged 18 and older, starting first-line DMT between September 1,2014 and August 31,2016, were identified and followed-up until the end of 2017. Treatment persistence identified by the first and last dispensation dates, death, DMT discontinuation ≥6 months, compliance measured by the Medication Possession Ratio (MPR), and number of relapses were estimated. RESULTS: During the inclusion period, 10,240 patients starting a first-line DMT for RRMS (mainly oral) were identified. Patients treated with teriflunomide were older, more often men with reduced relapses in the year prior to treatment initiation compared to those treated with dimethyl fumarate. Treatment compliance with teriflunomide was 81% [95% CI 80-82] at 6 months and 60% at 24 months [95% CI 58-62] compared to 79% [95% CI 78-80] at 6 months, 55% [95% CI 53-56] at 24 months with dimethyl fumarate versus 74% [95% CI 73-76] at 6 months and 39 % [95% CI 37-41] at 24 months with interferons/GA. After patient profile's adjustment, the risk of discontinuing first-line DMT was higher with interferons/GA and dimethyl fumarate than teriflunomide (HR=1.74, p <0.0001 and HR=1.12, p <0.0001; respectively). Although compliance was good with all treatments, it was significantly better with oral therapies compared to injectables. Probability to relapse at least once in the year after treatment initiation is lower for patients starting oral treatments than those treated with injectables, even after adjusting for patient profile. CONCLUSION: This real-world study demonstrated better compliance and persistence to oral therapies in naïve patients initiating first-line DMT for RRMS in France. Within oral therapies, persistence to teriflunomide was higher compared to dimethyl fumarate, with no difference observed in treatment compliance or risk on relapses' occurrence after patient profile's adjustment.

Dextromethorphan and memantine after ketamine analgesia: a randomized control trial.

PURPOSE: Intravenous ketamine is often prescribed in severe neuropathic pain. Oral N-methyl-D-aspartate receptor (NMDAR) antagonists might prolong pain relief, reducing the frequency of ketamine infusions and hospital admissions. This clinical trial aimed at assessing whether oral dextromethorphan or memantine might prolong pain relief after intravenous ketamine. PATIENTS AND METHODS: A multicenter randomized controlled clinical trial included 60 patients after ketamine infusion for refractory neuropathic pain. Dextromethorphan (90 mg/day), memantine (20 mg/day) or placebo was given for 12 weeks (n=20 each) after ketamine infusion. The primary endpoint was pain intensity at one month. Secondary endpoints included pain, sleep, anxiety, depression, cognitive function and quality of life evaluations up to 12 weeks. RESULTS: At 1 month, dextromethorphan maintained ketamine pain relief (Numeric Pain Scale: 4.01±1.87 to 4.05±2.61, p=0.53) and diminished pain paroxysms (p=0.03) while pain intensity increased significantly with memantine and placebo (p=0.04). At 3 months, pain remained lower than at inclusion (p=0.001) and was not significantly different in the three groups. Significant benefits were observed on cognitive-affective domains and quality of life for dextromethorphan and memantine (p<0.05). CONCLUSIONS: Oral dextromethorphan given after ketamine infusion extends pain relief during one month and could help patients to better cope with pain. Future studies should include larger populations stratified on pharmacogenetics screening. Optimization of an oral drug that could extend ketamine antihyperalgesia, with fewer hospital admissions, remains a prime challenge in refractory neuropathic pain.

Sturge-Weber syndrome with late onset hemiplegic migraine-like attacks and progressive unilateral cerebral atrophy.

BACKGROUND: Sturge-Weber syndrome (SWS) is an uncommon etiology of hemiplegic migraine-like (HM-like) attacks, associated with epilepsy and mental retardation. CASE: We report the case of a 40-year-old woman with SWS who has been suffering from HM-like episodes since she was 24, with no history of seizure or mental retardation. Susceptibility weighted imaging (SWI)-MRI and CT scans have shown bilateral calcifications of the choroidal plexuses, a developmental venous anomaly with dilated transmedullary veins and a left parieto-occipital leptomeningeal angioma. (18)F-Fluorodeoxyglucose (FDG)-PET/CT revealed a diffuse left-hemisphere hypometabolism. The comparison between the MRI performed at the age of 24 and the one performed at the age of 40 highlighted a progressive unilateral fronto-temporo-parietal atrophy. Surprisingly, even now, cognitive functions of this patient are relatively preserved. Lamotrigine permitted an improvement of HM-like attacks. DISCUSSION: Explanations for this minimally symptomatic form of SWS may be the absence of seizure, the importance of her deep venous drainage, the absence of cortical calcification and white matter impairment in the affected hemisphere, and, paradoxically, the severely asymmetric cortical metabolism. Furthermore, this case reinforces the hypothesis that alteration of cerebral hemodynamics could precipitate the cortical spreading depression giving rise to migraine with aura. CONCLUSION: We propose to consider SWS as a cause of apparently isolated hemiplegic migraine and lamotrigine as a preventive medication in HM-like attacks.