In The Literature - April 2016

VBCN - April 2016 Volume 3, No 1

In This Article




Natalizumab Shows Efficacy versus Fingolimod in Relapsing-Remitting Multiple Sclerosis

Recent observational studies have reported inconsistent results on multiple sclerosis (MS) clinical activity at 1 year with natalizumab (Tysabri) and fingolimod (Gilenya) for the treatment of patients with relapsing-remitting MS (RRMS), but none have compared the clinical efficacy or magnetic resonance imaging (MRI) disease activity at 2 years in a large cohort. To address this gap and provide additional information on the relative efficacy of natalizumab and fingolimod, researchers conducted an observational study to compare the clinical and MRI outcomes in patients with RRMS (Barbin L, et al. Neurology. 2016;86:771-778).

For the study, the researchers performed a retrospective analysis of data from 27 MS centers participating in the French follow-up cohort Observatoire of Multiple Sclerosis. The study included patients aged 18 to 65 years who received treatment with natalizumab (N = 326) or fingolimod (N = 303), with an Expanded Disability Status Scale score of 0 to 5.5, and an available brain MRI performed within the year before the initiation of treatment. The primary end point was the proportion of patients with ≥1 relapses within the first year of treatment. The secondary end points included the proportion of patients with ≥1 relapses at 2 years of treatment, and the proportion of patients with ≥1 gadolinium-enhancing lesions and ≥1 new T2 lesions on MRI at 1 and 2 years.

The investigators found that nataliz­umab was more effective than fingolimod on disease activity as assessed by relapse rate, new gadolinium-enhancing lesions, and new T2 lesions on MRI after 1 and 2 years of treatment. The proportion of patients with ≥1 relapses within the first and second years of treatment was significantly lower in the natalizumab group than in the fingolimod group (21.1% vs 30.4% at 1 year, respectively; and 30.9% vs 41.7% at 2 years, respectively). Statistically significant associations were also observed in the natalizumab arm compared with in the fingolimod arm in gadolinium-enhancing lesions and new T2 lesions at 1 year (gadolinium-enhancing lesions, 9.3% vs 29.8%, respectively; new T2 lesions, 10.6% vs 29.6%, respectively) and at 2 years (gadolinium-enhancing lesions, 9.1% vs 22.1%, respectively; new T2 lesions, 16.9% vs 34.1%, respectively) after the initiation of treatment.

The results suggest that natalizumab is more effective than fingolimod in reducing MS activity at 1 and 2 years in patients with RRMS. Furthermore, the findings may help to guide clinicians in choosing second-line treatment options for this patient population.

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Accuracy of Parkinson’s Disease Clinical Diagnosis Is Suboptimal

An accurate diagnosis of Parkinson’s disease relies on the clinician’s ability to recognize its signs and symptoms from a patient’s history and neurologic examination. Although studies have evaluated the accuracy of clinical diagnosis of Parkinson’s disease, a meta-analysis of their results is lacking. This led researchers to conduct a systematic review and meta-analysis to evaluate the validity of the clinical diagnosis of Parkinson’s disease as reported in the past 25 years (Rizzo G, et al. Neurology. 2016;86:566-576).

Using the MEDLINE and Embase databases, the researchers identified 20 studies of Parkinson’s disease, including 11 that used pathologic examination as the gold standard, that were published between 1988 and August 2014. The studies reported the diagnostic parameters regarding the clinical diagnosis of Parkinson’s disease or crude data, and were further subclassified based on their setting (ie, clinic-based and community-based), the type of test diagnosis, and the type of gold standard diagnosis used.

Only approximately 8 of 10 patients with Parkinsonism were diagnosed correctly. The most frequent misdiagnoses among clinic-based studies were multiple system atrophy (range, 0%-9.8%), Lewy body dementia (range, 0%-8%), vascular encephalopathy (range, 0%-7.7%), and progressive supranuclear palsy (0%-6.5%). Considering only the 11 studies that used pathologic examination as the gold standard, the researchers reported a pooled diagnostic accuracy of 80.6%. The pooled accuracy for diagnosis by nonexperts was 73.8%. The diagnostic accuracy was a little higher when the test diagnosis was provided by experts in movement disorders, which rose from 79.6% of the initial assessment to 83.9% of the refined diagnosis after follow-up. The refined diagnosis by experts was also slightly better than the diagnosis performed using the UK Parkinson’s Disease Society Brain Bank Research Center criteria, which had a pooled diagnostic accuracy of 82.7%.

In the past 25 years, the accuracy of the clinical diagnosis of Parkinson’s disease did not significantly improve. The diagnosis of early-stage Parkinson’s disease is challenging, which the researchers attribute to the dopaminergic treatment response being less defined, and the hallmarks of alterative diagnoses, such as atypical Parkinsonism, not having emerged as considerations for low diagnostic accuracy in the early phase of the disease. The misdiagnosis rate should be taken into account when calculating sample sizes for clinical trials in patients who are diagnosed with Parkinson’s disease. The findings also underscore the needs for imaging and biomarkers to improve the accuracy of clinical diagnosis in vivo.

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Study Examines Serious Adverse Events with Long-Term Sumatriptan in Patients with Chronic Cluster Headache

Chronic cluster headache is a rare, debilitating condition in which some patients continue to have daily attacks even with medication. Individuals with drug-resistant chronic cluster headache use abortive agents, mainly subcutaneous sumatriptan injection, multiple times daily and for long periods; however, the recommended maximum dose is 2 injections (12 mg) daily. Little is known about the risk for serious adverse events (AEs) when the drug is used ≥2 times daily long-term. In a new study, researchers investigated the occurrence of serious AEs in 52 patients with chronic cluster headache using sumatriptan ≥2 times daily for at least 2 years (Leone M, Proietti Cecchini A. Neurology. 2016;86:194-195).

During the study, all patients were carefully followed with regular visits, and the frequency of headaches and sumatriptan use were recorded in diaries. All patients needed the full 6-mg dose of sumatriptan. Electrocardiogram was obtained at least twice at 6-month to 18-month intervals. Serious AEs, including angina and any vascular event, were recorded. Patients had no history of vascular disorders.

The researchers did not observe any serious AEs, and no patients required the discontinuation of sumatriptan in the 2-year study period. No electrocardiogram abnormalities were detected. The patients in the study took more than their prescribed dose of sumatriptan, despite their physician fully explaining the additional risks of smoking while taking the medication; the majority of patients reported smoking more than 10 cigarettes daily. At the end of the study, 42% of patients noticed a subjective certain reduction of sumatriptan efficacy in terms of latency to efficacy and on pain intensity; however, they still considered the agent their first choice to treat their chronic cluster headaches.

This study provides evidence that in well-selected patients with chronic cluster headache, long-term daily sumatriptan injection for ≥2 years did not cause serious AEs; the findings are in line with observations from previous studies with shorter time periods. Additional data are needed to investigate serious AEs attributable to the long-term daily use of sumatriptan, with a main focus on prophylaxis, because sumatriptan overdose can increase the frequency of chronic cluster headaches.

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