Introduction: Limited comparative effectiveness data for rituximab (RTX) versus natalizumab (NTZ), fingolimod (FTY), and dimethyl fumarate (DMF) for the treatment of multiple sclerosis (MS) exist.
Methods: Clinician-reported data on patients prescribed RTX, NTZ, FTY, or DMF for the treatment of MS at the Rocky Mountain MS Center at the University of Colorado were retrospectively collected. Outcomes included a composite effectiveness measure consisting of clinical relapse, contrast-enhancing lesions, and/or new T2 lesions, individual effectiveness outcomes, and discontinuation. Logistic regression was used on patients matched by propensity scores and using average treatment effect on treated doubly robust weighting estimator.
Results: A total of 182, 451, 271, and 342 patients initiated RTX, NTZ, FTY, and DMF and were followed for 2 years. Before and after adjustment, the odds of experiencing disease activity was significantly higher for FTY [adjusted OR (aOR) = 3.17 (95% CI: 1.81-5.55), P < 0.001].and DMF [aOR = 2.68 (95% CI:1.67-4.29), P < 0.001], and similar for NTZ [aOR = 1.36 (95% CI:0.83-2.23), P = 0.216] versus RTX. When examining months 6-24, NTZ demonstrated higher odds of disease activity compared to RTX [aOR = 2.21 (95% CI: 1.20-4.06), P = 0.007]. Similar odds of discontinuation were seen between NTZ and RTX [aOR = 1.39 (95% CI: 0.88-2.20), P = 0.157]; however, FTY [aOR = 2.02 (95% CI: 1.24-3.30), P = 0.005] and DMF [aOR = 3.27 (95% CI: 2.15-4.97), P < 0.001] had greater odds of discontinuation than RTX.
Interpretation: RTX demonstrated superior effectiveness and discontinuation outcomes compared to FTY and DMF. Although RTX demonstrated similar effectiveness and discontinuation compared to NTZ, RTX had superior effectiveness during months 6-24 and fewer discontinuations when excluding discontinuations due to insurance issues. Results suggest superiority of RTX in reducing disease activity and maintaining long-term treatment in a real-world MS cohort.
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http://dx.doi.org/10.1002/acn3.51111 | DOI Listing |
Front Immunol
January 2025
Polpharma Biologics S.A., Gdansk, Poland.
Background: Biosimilar natalizumab (biosim-NTZ) is the first biosimilar monoclonal antibody of reference natalizumab (ref-NTZ) for treatment of relapsing forms of multiple sclerosis (MS). Within the totality of evidence for demonstration of biosimilarity, immunogenicity assessments were performed in healthy subjects and patients with relapsing-remitting MS (RRMS) to confirm a matching immunogenicity profile between biosim-NTZ and ref-NTZ.
Methods: Immunogenicity of biosim-NTZ versus ref-NTZ was evaluated in two pivotal clinical studies.
Mult Scler Relat Disord
December 2024
IRCCS Neuromedicine, Pozzilli, IS 86077, Italy; Department of Human Neurosciences, Sapienza University of Rome, Rome 00185, Italy. Electronic address:
Background: Fatigue, depression and slow processing speed are debilitating symptoms in people with Relapsing-Remitting Multiple Sclerosis (RRMS) that significantly impacts on the quality of life. Natalizumab, a disease-modifying treatment, improves clinical symptoms but questions remain about the comparative efficacy between its standard interval dosing (SID) and extended interval dosing (EID) schedules.
Objective: To examine the impact of short term natalizumab dosing schedules-SID versus EID-on the so called "invisible symptoms", specifically focusing on symptom exacerbation during the 'wearing-off' phase before infusion and the subsequent relief post-infusion.
Background: Brain volume loss (BVL) has been identified as a predictor of disability progression in relapsing multiple sclerosis (RMS). As many available disease-modifying treatments (DMTs) have shown an effect on slowing BVL, this is becoming an emerging clinical endpoint in RMS clinical trials.
Methods: In this study, a systematic literature review was conducted to identify BVL results from randomized controlled trials of DMTs in RMS.
Mult Scler Relat Disord
November 2024
Danish Multiple Sclerosis Center, Department of Neurology, Copenhagen University Hospital, Rigshospitalet, Glostrup, Denmark.
We investigated if differentially expressed mRNA targets could be used as surrogate markers for circulating B cells and subsets. In paired blood samples from patients with untreated, anti-CD20-treated, fingolimod-treated, and natalizumab-treated multiple sclerosis, whole blood expression of CD19 correlated with B cell counts determined by flow cytometry, ROR1 with transitional B cells, TCL1A and ZNF727 with naïve B cells, NEXMIF with memory B cells and BCMA with plasmablasts. CD19 expression distinguished patients with B cell repletion and may be used as an alternative to flow cytometry, but NEXMIF was unsuitable for memory B cell monitoring in rituximab-treated patients.
View Article and Find Full Text PDFMult Scler Relat Disord
November 2024
Biogen, Cambridge, MA, United States.
Background: Two-stage models of heterogenous treatment effects (HTE) may advance personalized medicine in multiple sclerosis (MS). Brain atrophy is a relatively objective outcome measure that has strong relationships to MS prognosis and treatment effects and is enabled by standardized MRI.
Objectives: To predict brain atrophy outcomes for patients initiating disease-modifying therapies (DMT) with different efficacies, considering the patients' baseline brain atrophy risk measured via brain parenchymal fraction (BPF).
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