The effectiveness of natalizumab vs fingolimod-A comparison of international registry studies.

BACKGROUND: Natalizumab and fingolimod were the first preparations recommended for disease breakthrough in priorly treated relapsing-remitting multiple sclerosis. Of three published head-to-head studies two showed that natalizumab is the more effective to prevent relapses and EDSS worsening. METHODS: By re-analyzing original published results from MSBase, France, and Denmark using uniform methodologies, we aimed at identifying the effects of differences in methodology, in the MS-populations, and at re-evaluating the differences in effectiveness between the two drugs. We gained access to copies of the individual amended databases and pooled all data. We used uniform inclusion/exclusion criteria and statistical methods with Inverse Probability Treatment Weighting. RESULTS: The pooled analyses comprised 968 natalizumab- and 1479 fingolimod treated patients. The on-treatment natalizumab/fingolimod relapse rate ratio was 0.77 (p=0.004). The hazard ratio (HR) for a first relapse was 0.82 (p=0.030), and the HR for sustained EDSS improvement was 1.4 (p=0.009). There were modest differences between each of the original published studies and the replication study, but the conclusions of the three original studies remained unchanged: in two of them natalizumab was more effective, but in the third there was no difference between natalizumab and fingolimod. CONCLUSION: The results were largely invariant to the epidemiological and statistical methods but differed between the MS populations. Generally, the advantage of natalizumab was confirmed.

Brief international cognitive assessment for multiple sclerosis (BICAMS): A danish validation study of sensitivity in early stages of MS.

BACKGROUND: Cognitive impairment is highly prevalent in multiple sclerosis (MS). Due to the lack of specialized neuropsychological resources in many MS clinics, a brief cognitive monitoring tool that can be administered by other MS clinic staff is needed. BICAMS (Brief International Cognitive As-sessment for Multiple Sclerosis) has been developed and recommended by MS experts to monitor MS-related cognitive impairment. International validations of the tool are warranted. OBJECTIVE: The primary aim of the study was to establish a Danish translation of BICAMS as a feasible cognitive monitoring tool and to provide a Danish contribution to the international validation of BI-CAMS. A secondary aim was to determine if BICAMS correlated with self-reported cognition. The study population comprised people with MS (pwMS) with relatively early MS and newly diagnosed. METHODS: 65 pwMS were compared to healthy controls (HCs) matched on age, sex and education. PwMS and controls completed the BICAMS test battery which includes the Symbol Digit Modalities Test (SDMT, oral version), California Verbal Learning Test-II (CVLT-II) and the Brief Visuospatial Memory Test-Revised (BVMT-R). In addition, self-reported cognition, fatigue, depression and quality of life were assessed. To evaluate the reliability of the BICAMS test, all participants were retested 2-3 weeks later with alternate versions of the tests. RESULTS: Mean age of the MS group was 37.2 years; 63% were female and all pwMS had a relapsing-remitting disease course. MS disease duration was relatively short; mean disease duration was 3.9 years and 32 of 65 pwMS (49%) were newly diagnosed with MS, i.e. diagnosed within the last 2 years. Mean EDSS was 1.8 with a span from 0-4. Comparison of the groups showed that the MS group performed significantly below the control group on the 3 BICAMS measures: SDMT (p<0.005), CVLT-II (p<0.05) and BVMT-R (p<0.05). When the results were controlled for influence from depression and fatigue by regression analysis, group differences were limited to the SDMT (p<0.05) and the BVMT-R (p<0.05) and these group differences were only found at the retest session. The BICAMS measures were reliable over time (r = 0.90 for SDMT, r = 0.82 for CVLT-II and r = 0.68 for BVMT-R). 32.3% of the MS population was cognitively impaired on at least one of the 3 BICAMS tests (defined as -1.5 SD compared to HCs). In the MS group 20% were impaired on the SDMT; 16.9% were impaired on the BVMT-R and 10.7% were impaired on the CVLT-II. There was no relationship between BICAMS test-scores and subjectively reported cognition, fatigue or depression. CONCLUSION: The Danish translation of BICAMS was a reliable and feasible cognitive assessment tool. This finding was confirmed even in an MS population characterized by relatively early MS and high cognitive reserve. Frequency of cognitive dysfunction detected by BICAMS in this study was relatively low due to population characteristics.