Evaluation of the efficacy of the SARS-CoV-2 vaccine additional and booster doses in immunocompromised patients with multiple sclerosis: the COVACiMS studyLadeira, Nobrega, Cerqueira
et alJ Neurol (2025) 272 (4), 288
Abstract: Studies evaluating COVID-19 primary vaccination with two vaccines reported a blunt response in Multiple Sclerosis (MS) patients under anti-CD20 and sphingosine-1-phosphate (S1P) modulators. An extended primary vaccination (EPV) was recommended in immunosuppressed MS patients. Data on the effectiveness of the EPV and subsequent booster dose are limited. A prospective cohort study (n = 270) was conducted to evaluate the humoral and cellular immunogenicity of the EPV scheme in immunocompromised MS patients (i.e., treated with anti-CD20, S1P modulators, natalizumab, teriflunomide, or dimethyl fumarate) vs. regular primary vaccination in non-treated patients - primary course (PC) cohort. The effect of a subsequent booster dose was also assessed - first booster (FB) cohort . The seroconversion rates were 55% and 56% in anti-CD20 and 75% and 67% in S1P modulators group in PC and FB cohort, respectively, and 100% in the remaining groups. A positive SARS-CoV-2 Spike T-spot was observed in 22% of patients under S1P modulators in PC cohort and 67% in FB cohort; the remaining groups had 75% or more. Similar rates of breakthrough infection were observed in both groups vs. controls. Compared to non-treated MS patients, immunosuppressed patients under anti-CD20 and S1P modulators drugs receiving EPV scheme or booster dose still present lower protection rates to SARS-CoV-2.© 2025. The Author(s).
Neurodegeneration correlates of iron-related lesions and leptomeningeal inflammation in multiple sclerosis clinical subtypesVakrakou, Papadopoulos, Brinia
et alNeuroradiology (2025)
Abstract: The aim of this study was to investigate the significant implications of different types of lesions as assessed by QSM (quantitative-susceptibility-mapping) as well as leptomeningeal contrast-enhancement in a cohort of Relapsing-Remitting (RR) and Primary Progressive (PP) MS patients and to assess their association with clinical disability and MRI-measures of brain structural damage.Different types of white-matter lesions were identified and quantified using QSM in 24 RRMS and 15 PPMS (11 patients with follow-up MRI). Leptomeningeal contrast-enhancement (LMCE; foci) was assessed on 3D-FLAIR post-gadolinium.Both RRMS and PPMS presented PRL (paramagnetic-rim lesions) and LMCE, with PPMS showing a trend towards more LMCE (RRMS 37%, PPMS 53%). In QSM RRMS patients showed more hyperintense white-matter lesions with greater lesion volume. In RRMS PRL correlated with disease duration and lesion burden especially the volume of juxtacortical Flair-hyperintense lesions. Besides, the presence of PRL lesions in PPMS was associated with subcortical atrophy mainly thalamus and pallidum volumetry. In all MS-cohort, patients with more than 3-PRLs exhibited reduced regional cortical thickness in specific temporal areas and post/para central gyrus. Forest-analysis selected age, increased NAWM (normal appearing white-matter) QSM intensity, total lesion volume and the presence of LMCE as informative predictors of cortical thickness. After anti-CD20 treatment, no significant change was observed regarding the number of PRL and LMCE, but the percentage of PRL lesions over the total lesion types and the QSM rim intensity increased.Our findings suggest that QSM-lesion types and leptomeningeal inflammation capture different aspects of progressive disease biology in both RRMS and PPMS.© 2025. The Author(s).
Cost-Effectiveness Analysis of Ofatumumab versus Teriflunomide for Relapsing-Remitting Multiple Sclerosis: A 10-Year Markov ModelAlmalki, Alshammari, Almazrou
et alClinicoecon Outcomes Res (2025) 17, 217-232
Abstract: Ofatumumab, a fully human anti-CD20 monoclonal antibody, is a promising disease-modifying therapy (DMT) for relapsing-remitting multiple sclerosis (RRMS). This study investigates its cost-effectiveness compared to teriflunomide from the perspective of Saudi healthcare payers. This comparison is crucial for informing treatment strategies and resource allocation in Saudi Arabia, where RRMS poses a significant healthcare burden and access to newer DMTs is evolving.A Markov model was constructed to evaluate the long-term cost-effectiveness of ofatumumab compared to teriflunomide for treating RRMS in Saudi Arabia. This model simulates disease progression over 10 years, a timeframe chosen for its clinical relevance and consistency with similar studies. To reflect the Saudi patient population, the model uses a hypothetical cohort with characteristics mirroring those in the ASCLEPIOS I/II clinical trials. The model incorporates transition probabilities between disease states, primarily derived from the British Columbia MS (BCMS) database and further refined using data from the ASCLEPIOS trials. To ensure relevance to the Saudi context, local data sources were utilized, including drug costs from the Saudi Food and Drug Authority (SFDA) and health state costs from published local studies. Clinical expert input was incorporated to validate model assumptions.The primary outcome measure was the incremental cost per quality-adjusted life-year (QALY) gained. Sensitivity analyses were conducted to assess the robustness of the model findings.Compared to teriflunomide, ofatumumab yielded incremental cost-effectiveness ratios (ICERs) of $46,188 per QALY over the 10-year period. Ofatumumab demonstrated a greater impact on reducing disability progression, particularly in the early stages of the disease. At a willingness-to-pay (WTP) threshold of $99,120 per QALY, ofatumumab demonstrated a 99.14% probability of cost-effectiveness in probabilistic sensitivity analyses.This cost-effectiveness analysis demonstrates that ofatumumab is a cost-effective treatment for RRMS in Saudi Arabia, with an ICER below the WTP. Policymakers should consider including ofatumumab in national formularies and prioritize its use in early-stage RRMS to maximize patient benefit and cost-effectiveness.© 2025 Almalki et al.
Effective long-term treatment with moss-produced factor H by overcoming the antibody response in a mouse model of C3GTschongov, Konwar, Kleindienst
et alFront Immunol (2025) 16, 1535547
Abstract: Complement-associated disorders are caused by the dysregulation and disbalance of the complement system, especially excessive activation. Most drugs that target the complement system are designed to inhibit the complement pathway at either the proximal or terminal levels. The use of a natural complement regulator such as factor H (FH) could provide a superior treatment option by restoring balance to an overactive complement system. We recently reported the moss-based production of an analog of human FH with an optimized glycan profile (CPV-104), which showed in vitro and in vivo characteristics comparable to its human counterpart. Here, we follow up our previous work, focusing in more detail on the time course and long-term efficacy of CPV-104 treatment in FH-deficient (FH -/-) mice. The analysis of long-term treatment effects following multiple injections of human FH into mice was previously hindered by the immune response, so we developed a protocol for the sustained depletion of CD20+ B-cells and CD4+ T-cells, preventing antibody formation without influencing the C3G phenotype. Using this dual-depletion method, we were able to complete dosing interval experiments in FH -/- mice, administering up to three injections of CPV-104 at different intervals. Repeated CPV-104 administration was able to lastingly resolve C3 deposits, offering additional rationale for the clinical testing of CPV-104 in human C3G patients. Moreover, our novel dual-depletion method has the potential for adaptation to different mouse models, allowing the testing of multiple doses of other therapeutic proteins.Copyright © 2025 Tschongov, Konwar, Kleindienst, Dabrowska-Schlepp, Busch, Schaaf, Schell, Rogg and Häffner.
膜杰作
Star Staining
