Dataset Information

Improvements in Cognitive Processing Speed, Disability, and Patient-Reported Outcomes in Patients with Early Relapsing-Remitting Multiple Sclerosis Treated with Natalizumab: Results of a 4-year, Real-World, Open-Label Study.

ABSTRACT:

Background

STRIVE was a prospective, 4-year, multicenter, observational, open-label, single-arm study of natalizumab treatment in anti-JC virus antibody-negative patients with early relapsing-remitting multiple sclerosis (RRMS).

Objective

Study objectives examined the effects of natalizumab on cognitive processing speed, confirmed disability improvement (CDI), and patient-reported outcomes (PROs).

Methods

Clinical and PRO secondary endpoints were assessed annually over 4 years in STRIVE. The Symbol Digit Modalities Test (SDMT) was used as a measure of cognitive processing speed. PROs were assessed using the Multiple Sclerosis Impact Score (MSIS-29) and the Work Productivity and Activity Impairment Questionnaire (WPAI).

Results

At all four annual assessments, the proportion of patients in the intent-to-treat (ITT) population (N = 222) who exhibited clinically meaningful improvement in their SDMT score from baseline (i.e., change ≥ 4 points) ranged from 41.9 to 54.0%. The cumulative probability of CDI at 4 years in patients in the ITT population with a baseline Expanded Disability Status Scale score ≥ 2 (N = 133) was 43.9%. Statistically significant reductions in the mean change from screening in the MSIS-29 physical and psychological scores, indicating improved quality of life, were observed over all 4 years (P ≤ 0.0012 for all). A statistically significant decrease from screening in the impact of MS on regular activities, signifying an improvement in this WPAI measure, was also observed over all 4 years of the study.

Conclusion

These results further extend our knowledge of the effectiveness, specifically regarding improvements in cognitive processing speed, disability and PROs, of long-term natalizumab treatment in early RRMS patients.

Clinicaltrials

GOV: NCT01485003 (5 December 2011).

SUBMITTER: Perumal J

PROVIDER: S-EPMC9797458 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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Publications

Improvements in Cognitive Processing Speed, Disability, and Patient-Reported Outcomes in Patients with Early Relapsing-Remitting Multiple Sclerosis Treated with Natalizumab: Results of a 4-year, Real-World, Open-Label Study.

Perumal Jai J Balabanov Roumen R Su Ray R Chang Roger R Balcer Laura J LJ Galetta Steven L SL Avila Robin L RL Rutledge Danette D Fox Robert J RJ

CNS drugs 20220905 9

<h4>Background</h4>STRIVE was a prospective, 4-year, multicenter, observational, open-label, single-arm study of natalizumab treatment in anti-JC virus antibody-negative patients with early relapsing-remitting multiple sclerosis (RRMS).<h4>Objective</h4>Study objectives examined the effects of natalizumab on cognitive processing speed, confirmed disability improvement (CDI), and patient-reported outcomes (PROs).<h4>Methods</h4>Clinical and PRO secondary endpoints were assessed annually over 4 ye ...[more]

PMID: 36064841

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Project description:Background and purposeThe considerable clinical effect of natalizumab in patients with relapsing-remitting multiple sclerosis might be explained by its possible beneficial effect on axonal functioning. In this longitudinal study, the effect of natalizumab on absolute concentrations of total N-acetylaspartate, a marker for neuronal integrity, and other brain metabolites is investigated in patients with relapsing-remitting multiple sclerosis by using MR spectroscopic imaging.Materials and methodsIn this explorative observational study, 25 patients with relapsing-remitting multiple sclerosis initiating natalizumab treatment were included and scanned every 6 months for 18 months. Additionally 18 matched patients with relapsing-remitting multiple sclerosis continuing treatment with interferon-β or glatiramer acetate were included along with 12 healthy controls. Imaging included short TE 2D-MR spectroscopic imaging with absolute metabolite quantification of total N-acetylaspartate, creatine and phosphocreatine, choline-containing compounds, myo-inositol, and glutamate. Concentrations were determined for lesional white matter, normal-appearing white matter, and gray matter.ResultsAt baseline in both patient groups, lower concentrations of total N-acetylaspartate and creatine and phosphocreatine were found in lesional white matter compared with normal-appearing white matter and additionally lower glutamate in lesional white matter of patients receiving natalizumab. In those patients, a significant yearly metabolite increase was found for lesional white matter total N-acetylaspartate (7%, P < .001), creatine and phosphocreatine (6%, P = .042), and glutamate (10%, P = .028), while lesion volumes did not change. In patients receiving interferon-β/glatiramer acetate, no significant change was measured in lesional white matter for any metabolite, while whole-brain normalized lesion volumes increased.ConclusionsPatients treated with natalizumab showed an increase in total N-acetylaspartate, creatine and phosphocreatine, and glutamate in lesional white matter. These increasing metabolite concentrations might be a sign of enhanced axonal metabolism.

Project description:ImportanceMultiple sclerosis (MS) is characterized by progressive gray matter (GM) atrophy that strongly correlates with clinical disability. However, whether localized GM atrophy correlates with specific disabilities in patients with MS remains unknown.ObjectiveTo understand the association between localized GM atrophy and clinical disability in a biology-driven analysis of MS.Design, setting, and participantsIn this cross-sectional study, magnetic resonance images were acquired from 133 women with relapsing-remitting MS and analyzed using voxel-based morphometry and volumetry. A regression analysis was used to determine whether voxelwise GM atrophy was associated with specific clinical deficits. Data were collected from June 28, 2007, to January 9, 2014.Main outcomes and measuresVoxelwise correlation of GM change with clinical outcome measures (Expanded Disability Status Scale and Multiple Sclerosis Functional Composite scores).ResultsAmong the 133 female patients (mean [SD] age, 37.4 [7.5] years), worse performance on the Multiple Sclerosis Functional Composite correlated with voxelwise GM volume loss in the middle cingulate cortex (P < .001) and a cluster in the precentral gyrus bilaterally (P = .004). In addition, worse performance on the Paced Auditory Serial Addition Test correlated with volume loss in the auditory and premotor cortices (P < .001), whereas worse performance on the 9-Hole Peg Test correlated with GM volume loss in Brodmann area 44 (Broca area; P = .02). Finally, voxelwise GM loss in the right paracentral lobulus correlated with bowel and bladder disability (P = .03). Thus, deficits in specific clinical test results were directly associated with localized GM loss in clinically eloquent locations.Conclusions and relevanceThese biology-driven data indicate that specific disabilities in MS are associated with voxelwise GM loss in distinct locations. This approach may be used to develop disability-specific biomarkers for use in future clinical trials of neuroprotective treatments in MS.

Project description:Background: Natalizumab (NTZ) and fingolimod (FTY) are second-line disease modifying treatments (DMTs) approved for Relapsing - Remitting Multiple Sclerosis (RRMS). Few studies are available on a direct comparison between NTZ and FTY, based on post-marketing experience, with conflicting results and reporting relatively short follow-up period. Aim: We hereby report real-world experience of a MS Center with respect to NTZ vs. FTY comparison in terms of efficacy and safety, referencing long-term follow-up. Methods: We used retrospective data for all patients that received 2nd-line treatment NTZ (since May 2007) or FTY (since September 2011). Primary endpoints were, among others, annual EDSS score (mean change from baseline), time to disability worsening or improvement, Annualized Relapse Rate (ARR) after 12 and 24 months and upon total treatment duration, time to first relapse and time to radiological progression. Results: A total of 138 unmatched patients, 84 treated with NTZ and 54 treated with FTY were included. Following Propensity Score (PS) matching, 31 patients in each group were retained. Mean follow-up period for NTZ- and FTY-treated patients was 4.43 ± 0.29 and 3.59 ± 0.32 years (p = 0.057), respectively. In the matched analysis, time to disability improvement and time to disability worsening was comparable between groups. A higher proportion of patients remained free of relapse under NTZ, compared to FTY (Log Rank test p = 0.021, HR: 0.25, 95% CI: 0.08-0.8), as well as free of MRI activity (Log Rank test p = 0.006, HR: 0.26, 95% CI: 0.08-0.6). Treatment discontinuation due to MRI activity was significantly higher for FTY-treated patients compared to NTZ (Log Rank test p = 0.019, HR: 0.12, 95% CI: 0.05-0.76). Conclusion: Our results indicate toward NTZ superiority with respect to relapse and MRI activity outcomes. The fact that NTZ-treated patients may achieve long-standing clinical and radiological remission points toward the need for long follow-up data.

Dataset Information

Improvements in Cognitive Processing Speed, Disability, and Patient-Reported Outcomes in Patients with Early Relapsing-Remitting Multiple Sclerosis Treated with Natalizumab: Results of a 4-year, Real-World, Open-Label Study.

Background

Objective

Methods

Results

Conclusion

Clinicaltrials

Publications

Improvements in Cognitive Processing Speed, Disability, and Patient-Reported Outcomes in Patients with Early Relapsing-Remitting Multiple Sclerosis Treated with Natalizumab: Results of a 4-year, Real-World, Open-Label Study.

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