Measuring disease progression in MS: do patients' and physicians' perspectives match?

Uitdehaag, B.M.J. [Promotor]Polman, C.H. [Promotor

Influence of personalized extended interval dosing on the natalizumab wearing-off effect - a sub-study of the NEXT-MS trial

Background and objectives: Wearing-off symptoms during natalizumab treatment in multiple sclerosis are characterized by an increase of MS-related symptoms prior to natalizumab administration. The influence of extended interval dosing (EID) on wearing-off symptoms are important to consider, as this might cause hesitancy in initiating or continuing EID. Methods: Participants of the NEXT-MS trial, in which treatment intervals are adjusted based on drug concentrations, were divided into two groups: an extended group containing participants with at least one week of additional interval extension, and a group with a fixed interval during the trial (range 4–7 weeks). Changes in the occurrence, frequency, onset, and severity of wearing-off symptoms were evaluated. Results: 255 participants were included (extended group n = 171, fixed group n = 84). The odds on occurrence of wearing-off symptoms in the extended group did not increase after extending the treatment interval. Additional analyses for frequency, onset, and severity of wearing-off symptoms showed no changes over time. Mean decrease in natalizumab drug concentration did not influence the frequency of wearing-off symptoms. Discussion: Wearing-off symptoms were not reinforced by further extending the natalizumab interval. Wearing-off symptoms might increase in a minority of patients after EID, although our data support the view that wearing-off symptoms appear to be unrelated to the decrease in natalizumab trough drug concentrations.</p

Clinical scales in progressive MS: predicting long-term disability

Background: To determine which short-term changes on clinical scales including the Expanded Disability Status Scale (EDSS), Timed 25-Foot Walk (T25FW), 9-Hole Peg test (9HPT) and Guy's Neurological Disability Scale (GNDS) are most predictive of long-term outcome of disability as rated by the EDSS in progressive multiple sclerosis (MS). Methods: From a longitudinal database, all progressive patients, both primary (PP) and secondary (SP), were selected on the basis of at least two complete examinations being available within a time interval of 1-2 years (short-term change). All patients who fulfilled the selection criteria were invited for a third visit after an interval of at least 3 years (long-term outcome). We used ordinal logistic regression to see which early changes were most predictive of the long-term EDSS. Results: 181 patients fulfilled the selection criteria. Early change on EDSS and T25FW were the best predictors of long-term EDSS; both were significant predictors in a 'single predictor' model. Early EDSS change was a slightly stronger single predictor (R2 0.38, Wald χ2 42.65, p < 0.001) compared with early T25FW change (R2 0.27, Wald χ2 12.35, p < 0.001). Adding early T25FW change to early EDSS change in a 'combined predictor' model improved prediction (p = 0.036). Conclusion: Both early change on EDSS and T25FW predict long-term EDSS with comparable strength. Early change on T25FW adds significant independent information and improves the prediction model with early EDSS change only. Therefore we support the use of early T25FW examinations in future clinical trials in progressive MS. © 2012 SAGE Publications

Outcome measurement in multiple sclerosis: detection of clinically relevant improvement

Item does not contain fulltextBecause the development of new treatments in multiple sclerosis as well as the awareness of the importance of patient-oriented measures have become more important in the last two decades, new outcome measures have been developed with the aim of being more responsive to change and more clinically relevant to patients. The ability to detect improvement is sparsely studied. In the present study we evaluate the responsiveness of the Expanded Disability Status Scale and two quantitative tests (the timed 25-foot walk test and the nine-hole peg test) separately and in combination, to detect improvement after intravenous methylprednisolone. The Expanded Disability Status Scale, the timed 25-foot walk test and the nine-hole peg test were assessed in 112 multiple sclerosis patients before and 6 weeks after intravenous methylprednisolone. In addition patients were asked to rate their change as an anchor to evaluate the performance of the tests. Combining the timed 25-foot walk test and the nine-hole peg test turned out to be the optimal combination of measures to predict patient perceived improvement (positive predictive value of 67% and a negative predictive value of 59%, likelihood ratio of positive test 2.31 (95% confidence interval 1.08-4.95)). In the higher Expanded Disability Status Scale range (4.5 and higher), for all measures a significant change was more often perceived as clinically relevant than in the lower disability range. The Expanded Disability Status Scale seems not to be the preferred outcome of choice to detect patient perceived improvement in multiple sclerosis, especially in the lower Expanded Disability Status Scale range. Combining the timed walk test and the nine-hole peg test can improve the sensitivity to detect clinically relevant changes without conceding with respect to specificity.1 mei 201