BACKGROUND AND PURPOSE: Feasibility of brain atrophy measurement in patients with MS in clinical routine, without prior standardization of the MRI protocol, is unknown. Our aim was to investigate the feasibility of brain atrophy measurement in patients with MS in clinical routine.

Multiple patient-reported outcomes (PROs) are currently being used in multiple sclerosis (MS) but their application is inconsistent and guidance on the appropriateness of each tool is lacking. The objective of our study was to identify MS-specific PROs and systematically to assess the development process and the reliability and validity of various instruments. A systematic literature search was conducted on multiple data sources, including MEDLINE, Embase (using the Ovid platform) and Google Scholar, from 1996 to March 2015. Search terms included combinations of MS, PROs and quality of life. Randomized controlled trials or observational studies conducted on patients with MS and published in English were included. In addition, the PROQOLID database was explored. The MS-specific PROs were systematically assessed using the Evaluating the Measurement of Patient-Reported Outcomes tool. In total, 8094 articles were screened and 405 PROs were identified from 1102 relevant articles. PROs were classified into MS-specific (n = 82) and non-MS-specific (n = 323). The results for the eight PROs that are most commonly used in MS clinical trials are presented here. For these eight PROs, the overall summary scores ranged between 50.1 and 68.7. The Multiple Sclerosis Impact Scale-29 had the best overall mean score (68.7), followed by the Leeds Multiple Sclerosis Quality of Life (67.0). This is the first study to provide a standardized assessment of all PROs for MS. There is a lack of data on content validity for PROs used in MS research, which indicates the need for a robust instrument in MS developed according to the US Food and Drug Administration guidelines.

The included studies provide good evidence of the real-world effectiveness of fingolimod and highlight the diversity of methodologies used to assess treatment benefit in clinical practice. Future studies could address the evidence gaps found in the literature and the challenges associated with researching MS when designing real-world studies, assessing data, and comparing evidence across studies.

BackgroundA percent brain volume change (PBVC) cut-off of −0.4% per year has been proposed to distinguish between pathological and physiological changes in multiple sclerosis (MS). Unfortunately, standardized PBVC measurement is not always feasible on scans acquired outside research studies or academic centers. Percent lateral ventricular volume change (PLVVC) is a strong surrogate measure of PBVC, and may be more feasible for atrophy assessment on real-world scans. However, the PLVVC rate corresponding to the established PBVC cut-off of −0.4% is unknown.ObjectiveTo establish a pathological PLVVC expansion rate cut-off analogous to −0.4% PBVC.MethodsWe used three complementary approaches. First, the original follow-up-length-weighted receiver operating characteristic (ROC) analysis method establishing whole brain atrophy rates was adapted to a longitudinal ventricular atrophy dataset of 177 relapsing-remitting MS (RRMS) patients and 48 healthy controls. Second, in the same dataset, SIENA PBVCs were used with non-linear regression to directly predict the PLVVC value corresponding to −0.4% PBVC. Third, in an unstandardized, real world dataset of 590 RRMS patients from 33 centers, the cut-off maximizing correspondence to PBVC was found. Finally, correspondences to clinical outcomes were evaluated in both datasets.ResultsROC analysis suggested a cut-off of 3.09% (AUC = 0.83, p < 0.001). Non-linear regression R2 was 0.71 (p < 0.001) and a − 0.4% PBVC corresponded to a PLVVC of 3.51%. A peak in accuracy in the real-world dataset was found at a 3.51% PLVVC cut-off. Accuracy of a 3.5% cut-off in predicting clinical progression was 0.62 (compared to 0.68 for PBVC).ConclusionsVentricular expansion of between 3.09% and 3.51% on T2-FLAIR corresponds to the pathological whole brain atrophy rate of 0.4% for RRMS. A conservative cut-off of 3.5% performs comparably to PBVC for clinical outcomes.

BACKGROUND & PURPOSETo describe methodology, interim baseline, and longitudinal magnetic resonance imaging (MRI) acquisition parameter characteristics of the multiple sclerosis clinical outcome and MRI in the United States (MS‐MRIUS).MATERIAL & METHODSThe MS‐MRIUS is an ongoing longitudinal and retrospective study of MS patients on fingolimod. Clinical and brain MRI image scan data were collected from 600 patients across 33 MS centers in the United States. MRI brain outcomes included change in whole‐brain volume, lateral ventricle volume, T2‐ and T1‐lesion volumes, and new/enlarging T2 and gadolinium‐enhancing lesions.RESULTSInterim baseline and longitudinal MRI acquisition parameters results are presented for 252 patients. Mean age was 44 years and 81% were female. Forty percent of scans had 3‐dimensional (3D) T1 sequence in the preindex period, increasing to 50% in the postindex period. Use of 2‐dimensional (2D) T1 sequence decreased over time from 85% in the preindex period to 65% in the postindex. About 95% of the scans with FLAIR and 2D T1‐WI were considered acceptable or good quality compared to 99–100% with 3D T1‐WI. There were notable changes in MRI hardware, software, and coil (39.5% in preindex to index and 50% in index to postindex). MRI sequence parameters (orientation, thickness, or protocol) differed for 36%, 29%, and 20% of index/postindex scans for FLAIR, 2D T1‐WI, and 3D T1‐WI, respectively.CONCLUSIONSThe MS‐MRIUS study linked the clinical and brain MRI outcomes into an integrated database to create a cohort of fingolimod patients in real‐world practice. Variability was observed in MRI acquisition protocols overtime.