Extending the natalizumab interval after the 24th administration could reduce the risk of progressive multifocal leukoencephalopathy (PML). The objective is to evaluate the noninferiority of the ...efficacy of an extended interval dosing (EID) compared with the standard interval dosing (SID) of natalizumab. It is an observational, multicenter (14 Italian centers), retrospective cohort study, starting from the 24th natalizumab infusion to the loss of follow-up or 2 years after baseline. Patients were grouped in 2 categories according to the mean number of weeks between doses: < 5 weeks, SID; ≥ 5 weeks, EID. Three hundred and sixty patients were enrolled. Median dose interval (MDI) following 24th infusion was 4.7 weeks, with a bimodal distribution (modes at 4 and 6 weeks). Two hundred and sixteen patients were in the SID group (MDI = 4.3 weeks) and 144 in the EID group (MDI 6.2 weeks). Annualized relapse rate was 0.060 (95% CI = 0.033–0.087) in the SID group and 0.039 (95% CI = 0.017–0.063) in the EID group. The non-inferiority of EID
versus
SID was satisfied. In conclusion, there is no evidence of a reduced efficacy of natalizumab in an EID setting. This observation confirms previous results and together with the emerging evidence of a reduced risk of PML associated to an EID, supports the need of a randomized study to assess the need to change the standard of the natalizumab dosing schedule.
Background:
Rituximab, an anti-CD20 monoclonal antibody leading to B lymphocyte depletion, is increasingly used as an off-label treatment option for multiple sclerosis (MS).
Objective:
To investigate ...the effectiveness and safety of rituximab in relapsing–remitting (RR) and progressive MS.
Methods:
This is a multicenter, retrospective study on consecutive MS patients treated off-label with rituximab in 22 Italian and 1 Swiss MS centers. Relapse rate, time to first relapse, Expanded Disability Status Scale (EDSS) progression, incidence of adverse events, and radiological outcomes from 2009 to 2019 were analyzed.
Results:
A total of 355/451 enrolled subjects had at least one follow-up visit and were included in the outcome analysis. Annualized relapse rate significantly decreases after rituximab initiation versus the pre-rituximab start year in RRMS (from 0.86 to 0.09, p < .0001) and in secondary-progressive (SP) MS (from 0.34 to 0.06, p < .0001) and had a slight decrease in primary-progressive (PP) MS patients (from 0.12 to 0.07, p = 0.45). After 3 years from rituximab start, the proportion of patients with a confirmed EDSS progression was 14.6% in the RRMS group, 24.7% in the SPMS group, and 41.5% in the PPMS group. No major safety concerns arose.
Conclusion:
Consistently with other observational studies, our data show effectiveness of rituximab in reducing disease activity in patients with MS.
Background:
Little is known about COVID-19 course and outcomes after a third booster dose of mRNA vaccine against SARS-CoV-2 (mRNA-Vax) in patients with multiple sclerosis (pwMS) treated with ...ocrelizumab (OCR) and fingolimod (FNG), which showed a weakened immune response to mRNA-vax.
Objectives:
The aim of this study was to evaluate COVID-19 course and outcomes in pwMS on OCR and FNG after receiving the third dose of mRNA-Vax and to compare it with pwMS on natalizumab (NTZ).
Methods:
Inclusion criteria: >18 years of age, being treated with OCR/FNG/NTZ since the first mRNA-Vax dose; COVID-19 after a third booster dose of mRNA-Vax; no steroids use.
Results:
Overall, 290 pwMS (79 NTZ, 126 OCR, and 85 FNG) from 17 Italian MS centers were included. Age, Expanded Disability Status Scale (EDSS) score, MS phenotype, disease, and treatment duration were significantly different across groups. PwMS who had COVID-19 on OCR and FNG compared with those on NTZ were slightly more symptomatic with higher hospitalization rates (11.1% vs 7.1% vs 1.3%, respectively). Regression models showed that the majority of the differences observed were not related to the disease-modifying treatments (DMTs) used. No fatal cases were observed.
Conclusion:
Our results support the effectiveness of the third booster dose of mRNA-Vax against severe forms of COVID-19 in pwMS treated with OCR and FNG.
Background:
In the general population, maternal COVID-19 is associated with worse maternal and fetal outcomes. Two previous studies have assessed COVID-19 clinical outcomes in pregnant women with ...multiple sclerosis (MS), but there are no data about maternal and fetal outcomes.
Objectives:
In this multicenter study, we aimed to assess maternal and fetal outcomes in pregnant women with MS and COVID-19 infection.
Methods:
We recruited pregnant patients with MS who contracted COVID-19 and were followed up in Italian and Turkish Centers, during 2020–2022. A control group was extracted from a previous Italian cohort. Associations between group (COVID-19 or healthy patients) and clinical outcomes (maternal complications, fetal malformations, and spontaneous abortion) were investigated with a weighted logistic regression where propensity score–based inverse probability of treatment weighting (IPTW) approach was applied for adjusting for difference in baseline confounders.
Results:
In the multivariable analysis, COVID-19 during pregnancy was associated with a higher risk of maternal complications (odd ratio (OR) = 2.12; 95% confidence interval (CI) = 1.32–3.48; p = 0.002), while it was not associated with higher risk of spontaneous abortion and fetal malformations.
Conclusion:
Our data indicate that COVID-19 during pregnancy increases the risk of maternal complications, while it seems to have no significant impact on fetal outcomes.
Objectives:
To assess the impact of timing of natalizumab cessation/redosing on long-term maternal and infant outcomes in 72 out of the original 74 pregnancies of the Italian Pregnancy Dataset in ...multiple sclerosis (MS).
Methods:
Maternal outcomes in patients who received natalizumab until conception and restarted the drug within 1 month after delivery (“treatment approach,” (TA)) and patients who stopped natalizumab before conception and/or restarted the drug later than 1 month after delivery (“conservative approach,” (CA)) were compared through multivariable Cox regression analyses. Pediatric outcomes were assessed through a semi-structured questionnaire.
Results:
After a mean follow-up of 6.1 years, CA (hazard ratio (HR) = 4.1, 95% CI 1.6–10.6, p = 0.003) was the only predictor of relapse occurrence. Worsening on the Expanded Disability Status Scale (EDSS) was associated with higher annualized relapse-rate during the follow-up (HR = 3.3, 95% CI 1.4–7.9 p = 0.007). We found no major development abnormalities in children.
Discussion:
Our data confirm that TA reduces the risk of disease activity; we did not observe an increase in major development abnormalities in the child.
Evidence underlines the importance of microRNAs (miRNAs) in the pathogenesis of multiple sclerosis (MS). Based on the fact that miRNAs are present in human biological fluids, we previously showed ...that miR-223, miR-23a and miR-15b levels were downregulated in the sera of MS patients versus controls. Here, the expression levels of these candidate miRNAs were determined in peripheral blood mononuclear cells (PBMCs) and the serum of MS patients, in addition to three genotyped single nucleotide polymorphisms (SNPs). Mapping in the genomic regions of miR-223, miR-23a and miR-15b genes, 399 cases and 420 controls were tested. Expression levels of miR-223 and miR-23a were altered in PBMCs from MS patients versus controls. Conversely, there were no differences in the expression levels of miR-15b. A significantly decreased genotypic frequency of miR-223 rs1044165 T/T genotype was observed in MS patients. Moreover, the allelic frequency of miR-23a rs3745453 C allele was significantly increased in patients versus controls. In contrast, there were no differences in the distribution of miR-15b SNP. In conclusion, our results suggest that miR-223 and miR-23a could play a role in the pathogenesis of MS. Moreover, miR-223 rs1044165 polymorphism likely acts as a protective factor, while miR-23a rs3745453 variant seems to act as a risk factor for MS.
Introduction:
Limited data are available on the course of Coronavirus disease 2019 (COVID-19) in people with Multiple Sclerosis (MS). More real-world data are needed to help the MS community to ...manage MS treatment properly. In particular, it is important to understand the impact of immunosuppressive therapies used to treat MS on the outcome of COVID-19.
Methods:
We retrospectively collected data on all confirmed cases of COVID-19 in MS patients treated with ocrelizumab, followed in two MS Centers based in University Hospitals in Northern Italy from February 2020 to June 2021.
Results:
We identified 15 MS patients treated with ocrelizumab with confirmed COVID-19 (mean age, 50.47 ± 9.1 years; median EDSS, 3.0; range 1.0–7.0). Of these, 14 were confirmed by nasal swab and 1 was confirmed by a serological test. COVID-19 severity was mild to moderate in the majority of patients (
n
= 11, 73.3%; mean age, 49.73; median EDSS 3.0). Four patients (26.7%; mean age, 52.5 years; median EDSS, 6) had severe disease and were hospitalized; one of them died (age 50, EDSS 6.0, no other comorbidities). None of them had underlying respiratory comorbidities.
Conclusion:
This case series highlights the large variability of the course of COVID-19 in ocrelizumab-treated MS patients. The challenges encountered by the healthcare system in the early phase of the COVID-19 pandemic might have contributed to the case fatality ratio observed in this series. Higher MS-related disability was associated with a more severe COVID-19 course.
Kappa free light chains (κ-FLC) in the cerebrospinal fluid (CSF) are an emerging biomarker in multiple sclerosis (MS).
To investigate whether κ-FLC index has similar diagnostic value in patients with ...primary progressive multiple sclerosis (PPMS) compared to oligoclonal bands (OCB).
Patients with PPMS were recruited through 11 MS centres across 7 countries. κ-FLC were measured by immunonephelometry/-turbidimetry. OCB were determined by isoelectric focusing and immunofixation.
A total of 174 patients (mean age of 52±11 years, 51% males) were included. κ-FLC index using a cut-off of 6.1 was positive in 161 (93%) and OCB in 153 (88%) patients.
κ-FLC index shows similar diagnostic sensitivity than OCB in PPMS.
PDF
