Long-term neuroprotective effects of natalizumab and fingolimod in multiple sclerosis: Evidence from real-world clinical data.

BACKGROUND: The long-term effect of high efficacy disease modifying therapy (DMT) on neurodegeneration in people with multiple sclerosis (pwMS) is largely unknown. The aim of this study was to evaluate the long-term effect of natalizumab (NTZ) or fingolimod (FTY) therapy on the evolution of brain atrophy compared to moderate efficacy DMT in a real-world clinical setting. METHODS: A total of 438 pwMS with 2,439 MRI exams during treatment were analyzed: 252 pwMS treated with moderate efficacy DMT, 130 with NTZ and 56 with FTY. Evolution of brain atrophy was analyzed over an average follow-up of 6.6 years after treatment initiation. Brain segmentation was performed on clinical 3D-FLAIRs using SynthSeg and regional brain volume changes over time were compared between the treatment groups. RESULTS: Total brain, white matter and deep gray matter atrophy rates did not differ between moderate efficacy DMTs, NTZ and FTY. Annualized ventricle growth rates were lower in pwMS treated with NTZ (1.1 %/year) compared with moderate efficacy DMT (2.4 %/year, p < 0.001) and similar to FTY (2.0 %/year, p = 0.051). Cortical atrophy rates were lower in NTZ (-0.08 %/year) compared with moderate efficacy DMT (-0.16 %/year, p = 0.048). CONCLUSION: In a real-world clinical setting, pwMS treated with NTZ had slower ventricular expansion and cortical atrophy compared to those treated with moderate efficacy DMT.

Discontinuation of first-line disease-modifying therapy in relapse onset multiple sclerosis.

BACKGROUND: It is not known if and when first-line disease modifying therapy (DMT) can safely be discontinued in relapse onset multiple sclerosis (MS) patients. OBJECTIVES: To investigate the characteristics of patients who discontinued first-line DMT, and the occurrence of clinical and radiological inflammatory disease activity after discontinuation. METHODS: We collected clinical and MRI parameters from patients with relapse onset MS in the MS Center Amsterdam and Rijnstate Hospital Arnhem who discontinued first-line DMT with no intention of restarting or switching treatment. RESULTS: In total, 130 patients were included in the analyses. After discontinuation, 78 patients (60%) experienced disease activity. Sixty-three patients (48.5%) showed MRI activity after DMT discontinuation, 40 patients (30.8%) experienced relapse(s), and 29 patients (22.3%) restarted DMT. Higher age at DMT discontinuation was associated with a lower risk of MRI activity (45 -55 vs. <45 years: OR 0.301, p = 0.007, >55 vs. <45 years, OR: 0.296, p = 0.044), and with a lower risk of relapse(s) after discontinuation (45-55 vs. <45 years: OR=0.495, p = 0.106, >55 vs. <45 years: OR=0.081, p = 0.020). CONCLUSION: Higher age at first-line DMT discontinuation is associated with lower risk and severity of radiological disease activity in MS, and a lower risk of relapse(s) after discontinuation.

The use of multi-domain patient reported outcome measures for detecting clinical disease progression in multiple sclerosis.

OBJECTIVE: Patient reported outcome measures (PROMs) are especially relevant in times of increased interest in telehealth but little is known about their relation to functional disability measures. METHODS: We assessed 248 people with MS at baseline and at > = 5-years follow-up. We investigated cross-sectional and longitudinal correlations between changes in the Guy's Neurological disability scale (GNDS), and the physical part of the Multiple Sclerosis Impact Scale (MSIS-29) and the Expanded Disability Status Scale (EDSS), 9-hole peg test (9-HPT) and timed 25-foot walk (T25FW). RESULTS: The strongest cross-sectional correlations were found between the GNDS and EDSS in the complete cohort (r = 0.66, p <.001, n = 248) as well as in progressive patients (r = 0.72, p <.001, n = 35), and the GNDS and T25FW in progressive MS (r = 0.64, p <.001, n = 34). Longitudinal correlations were poor except for changes on the leg domain of the GNDS in relation to T25FW changes in progressive MS (r = 0.68, p <.001, n = 26). In the majority of cases a clinically significant deterioration on the EDSS also resulted in a clinically significant worsening of the GDNS and MSIS. CONCLUSION: Both PROMs correlate well with physical disability outcomes, and seem suitable for detecting changes in lower limb function in progressive MS. The GNDS has a higher agreement with EDSS progression than the MSIS-physical.

Natalizumab discontinuation in a Dutch real-world cohort.

OBJECTIVE: To determine characteristics of multiple sclerosis patients that discontinued natalizumab treatment in a real-world cohort. METHODS: Data was collected from an ongoing observational cohort study of all natalizumab treated patients at the Amsterdam UMC. RESULTS: Of 253 patients who ever received natalizumab treatment, 147 have discontinued treatment. The most frequent reason for treatment discontinuation was JC-virus (JCV) positivity. CONCLUSIONS: JCV positivity seems the most frequent reason for natalizumab discontinuation. The heterogeneity in treatment switches reflects the advances made in treatment options, and underlines the need for adequate patient counselling.