Cost-effectiveness analysis of escalating to natalizumab or switching among immunomodulators in relapsing-remitting multiple sclerosis in Italy.

BACKGROUND: Published literature suggests that early treatment with natalizumab ("escalation strategy") is more effective than switch within the same class of immunomodulators (interferons/glatiramer acetate, "switching strategy") in relapsing-remitting multiple sclerosis (RRMS) patients who failed first-line self-injectable disease-modifying treatment (DMT). The present analysis aims to evaluate the cost-effectiveness profile of escalation strategy vs. switching strategy, adopting the Italian societal perspective. METHODS: A lifetime horizon Markov model was developed to compare early escalation to natalizumab vs. switching among immunomodulators, followed by subsequent escalation to natalizumab. The two compared treatment algorithms were: a) early escalation until progression to Expanded Disability Status Scale (EDSS) = 7.0 vs. b) switching until EDSS = 4.0, followed by escalation until EDSS = 7.0. The model analyzed social costs, quality-adjusted survival and effects of therapies in prolonging time without disability progression and burden of relapses. Clinical data were mainly extracted from a published observational study. RESULTS: Lifetime costs of early escalation to natalizumab and switching among immunomodulators amounted to €699,700 and €718,600 per patient, respectively. Early escalation was associated with prolonged quality-adjusted survival (11.19 vs. 9.67 QALYs, + 15.8%). A slight overall survival increase was also observed (20.10 vs. 19.67 life years). Both deterministic and probabilistic sensitivity analyses confirmed the robustness of findings. CONCLUSIONS: Adopting the Italian social perspective, early escalation to natalizumab is dominant vs. switching among immunomodulators, in RRMS patients who do not respond adequately to conventional immunomodulators.

Long-term assessment of No Evidence of Disease Activity with natalizumab in relapsing multiple sclerosis.

In this study we assessed the proportion of patients with relapsing multiple sclerosis (R-MS) who had No Evidence of Disease Activity (NEDA-3), defined as absence of relapses, absence of confirmed disability worsening, and absence of radiological activity (detected by magnetic resonance imaging of the brain and spinal cord) up to 7years after starting natalizumab. Out of 152 patients considered, 58 were still on treatment and 94 discontinued treatment after a median time of 3years. According to an intention-to-treat approach, 52 (34%) patients maintained the NEDA status at the end of follow-up. The proportion of patients with NEDA increases to 41% after excluding from the analysis 64 patients who discontinued natalizumab due to concerns about progressive multifocal leukoencephalopathy. Our findings suggest that natalizumab may ensure higher proportion of patients achieving sustained long-term disease remission than that previously reported with self-injectable treatments (<10%).

The dual task-cost of standing balance affects quality of life in mildly disabled MS people.

The aim of this study was to explore the correlations between the dual-task cost (DTC) of standing balance and quality of life (QoL) in mildly disabled patients with multiple sclerosis (MS). In this cross-sectional study, patients affected by MS with an expanded disability status scale (EDSS) score of 3.0 or less and without an overt balance impairment were tested by means of static posturography under eyes-opened (single-task condition) and while performing the Stroop word-color test (dual-task condition), to estimate the DTC of standing balance. The self-reported 54-item MS quality of life questionnaire (MSQoL-54) was also administered to obtain a MS-specific assessment of health-related QoL. Among the 120 screened patients, 75 (53 women, 22 men) were tested. Although there was no impact of the DTC of standing balance on the physical and mental composite scores of MSQoL-54, patients who had a greater DTC of standing balance scored worse on role limitations due to physical problems (p = 0.007) and social function (p < 0.001), irrespective of demographic and other clinical characteristics including walking performance and cognitive status. However, the EDSS step and fatigue also contributed to reduced scores in these two QoL domains (p-values < 0.01). In conclusion, the phenomenon of cognitive-motor interference, investigated as DTC of standing balance, may affect specific QoL domains even in mildly disabled patients with MS and in the absence of an overt balance dysfunction.

We-Measure: Toward a low-cost portable posturography for patients with multiple sclerosis using the commercial Wii balance board.

This study was aimed at investigating whether postural sway measures derived from a standard force platform were similar to those generated by a custom-written software ("We-Measure") acquiring and processing data from a commercial Nintendo balance board (BB). For this purpose, 90 patients with multiple sclerosis (MS) and 50 healthy controls (HC) were tested in a single-day session with a reference standard force platform and a BB-based system. Despite its acceptable between-device agreement (tested by visual evaluation of Bland-Altman plot), the low-cost BB-based system tended to overestimate postural sway when compared to the reference standard force platform in both MS and HC groups (on average +30% and +54%, respectively). Between-device reliability was just adequate (MS: 66%, HC: 47%), while test-retest reliability was excellent (MS: 84%, HC: 88%). Concurrent validity evaluation showed similar performance between the reference standard force platform and the BB-based system in discriminating fallers and non-fallers among patients with MS. All these findings may encourage the use of this balance board-based new device in longitudinal study, rather than in cross-sectional design, thus providing a potential useful tool for multicenter settings.

A low-cost cognitive rehabilitation with a commercial video game improves sustained attention and executive functions in multiple sclerosis: a pilot study.

OBJECTIVE: To evaluate the effectiveness of a home-based cognitive rehabilitation (CR) program based on the video game Dr Kawashima's Brain Training (DKBT; Nintendo, Japan), in improving attention, processing speed, and working memory of patients with multiple sclerosis (MS). METHODS: This was a randomized, wait-list control study. Patients with MS and failure in at least one between Stroop Test (ST), Paced Auditory Serial Addition Test (PASAT), and Symbol Digit Modalities Test (SDMT) were submitted to an 8-week home-based CR program playing DKBT. Patients were evaluated at baseline and after DKBT by the aforementioned tests, by the Modified Fatigue Impact Scale (MFIS) and by the MS Quality of Life-54 questionnaire (MSQoL-54). RESULTS: Fifty-two 52 patients were screened for eligibility; 35 (mean [standard deviation] age of 43.9 [8.4] years, median Expanded Disability Status Scale score of 2.0 (range = 2.0-6.0) were randomly assigned to the intervention group (n = 18) or wait-list control group (n = 17). ANCOVA analysis showed a significant effect of DKBT on ST (F = 5.027; P = .034; F(2) = 0.210), SDMT (F = 4.240; P = .049; F(2) = 0.177), and on some subscales of MSQoL-54. The PASAT and cognitive subscale of MFIS also showed an improvement, but this was just not significant (F = 4.104, P = .054, F(2) = 0.171, and F = 4.226, P = .054, F(2) = 0.237, respectively). CONCLUSION: We suggest that a home-based DKBT program may improve cognitive functions, some aspects of QoL, and cognitive fatigue in patients with MS.