The main aim of the study is to evaluate the efficacy and safety profile of ocrelizumab (OCR), rituximab (RTX), and cladribine (CLA), employed as natalizumab (NTZ) exit strategies in ...relapsing–remitting multiple sclerosis (RRMS) patients at high-risk for progressive multifocal leukoencephalopathy (PML). This is a multicentre, retrospective, real-world study on consecutive RRMS patients from eleven tertiary Italian MS centres, who switched from NTZ to OCR, RTX, and CLA from January 1st, 2019, to December 31st, 2019. The primary study outcomes were the annualized relapse rate (ARR) and magnetic resonance imaging (MRI) outcome. Treatment effects were estimated by the inverse probability treatment weighting (IPTW), based on propensity-score (PS) approach. Additional endpoint included confirmed disability progression (CDP) as measured by Expanded Disability Status Scale and adverse events (AEs). Patients satisfying predefined inclusion and exclusion criteria were 120; 64 switched to OCR, 36 to RTX, and 20 to CLA. Patients from the 3 groups did not show differences for baseline characteristics, also after post hoc analysis. The IPTW PS-adjusted models revealed that patients on OCR had a lower risk for ARR than patients on CLA (ExpB
OCR
0.485, CI 95% 0.264–0.893,
p
= 0.020). This result was confirmed also for 12-month MRI activity (ExpB
OCR
0.248 CI 95% 0.065–0.948,
p
= 0.042). No differences were found in other pairwise comparisons (OCR vs RTX and RTX vs CLA) for the investigated outcomes. AEs were similar among the 3 groups. Anti-CD20 drugs were revealed to be effective and safe options as NTZ exit strategies. All investigated DMTs showed a good safety profile.
Background and aim
Peginterferon beta-1a (Plegridy) offers the advantage of a prolonged half-life with less-frequent administration and a higher patient adherence. However, the use of an interferon ...may lead to flu-like symptoms (FLS) and injection-site reactions (ISR) that results in drug discontinuation. The objective of this Delphi analysis was to obtain consensus on the characteristics and management of FLS/ISR of peginterferon beta-1a in patients with relapsing-remitting MS based on real-world clinical experiences.4
Methods
A steering committee of MS neurologists and nurses identified issues regarding the features and management of adverse events and generated a questionnaire used to conduct three rounds of the Delphi web survey with an Italian expert panel (54 neurologists and nurses).
Results
Fifty-three (100%), fifty-one (96.22%), and forty-two (79.24%) responders completed questionnaires 1, 2, and 3 respectively. Responders reported that, during the first 6 months of treatment, FLS generally occurred 6–12 h after injection; the fever tended to resolve after 12–24 h; otherwise, FLS lasted up to 48 h. FLS improved or disappeared after 6 months of treatment in most cases. Paracetamol was recommended as the first choice for managing FLS. Erythema was the most common ISR and usually resolved within 1 week after injection. Responders reported that the adherence to treatment increases after adequate patient education on the drug’s tolerability profile.
Conclusions
Patient education and counseling play a key role in promoting adherence to treatment especially in the first months also in patients switching from nonpegylated IFNs to peginterferon beta-1a.
Background:
The aim of the study was to evaluate the achievement of ‘no evidence of disease activity’ (NEDA) over a 12-month period in a large multicenter population with relapsing remitting multiple ...sclerosis (RRMS) treated with delayed-release dimethyl fumarate (DMF) and teriflunomide (TRF) using a propensity-score adjustment.
Methods:
A time-to-event method was used to determine the percentages of patients with RRMS (pwRRMS) in both groups achieving NEDA 3 (no relapses, no 12-week confirmed disability progression, and no new T2/gadolinium-enhancing brain lesions). We described the safety profile of the investigated drugs.
Results:
Of the 587 pwRRMS treated with DMF and the 316 pwRRMS treated with TRF, 468 pwRRMS were successfully paired by propensity score: 234 on DMF and 234 on TRF. The percentages of pwRRMS who achieved NEDA 3 were 80.3% in the DMF group and 77.2% in the TRF group. Serious adverse events occurred in four (1.9%) pwRRMS on DMF and in three (1.3%) pwRRMS on TRF.
Conclusions:
DMF and TRF significantly impacted RRMS disease activity in our study. Serious safety concerns were recorded in less than 2% of the studied population.
Background: The intervals between two courses of anti CD20 therapies in the COVID19 pandemic era provided the opportunity to individually delay therapy, known as extended interval dosing (EID). ...Methods: We collect real-world data on patients with primary progressive MS (PPMS) treated with Ocrelizumab (OCR) during the COVID’19 pandemic. The observation period in which the standard interval dosing (SID) or EID occurred (always a maintenance cycle, 600 mg) was from January 2020 to June 2021. All patients had two infusions during the observation period. Our first aim was to compare confirmed disability progression (CDP) between SID and EID patients. Results: From a total cohort of 410 patients treated with OCR, 96 patients fulfilled the inclusion criteria. All patients received two infusions during the index window, 71 received only SID infusions whilst 25 received at least one EID infusion throughout the entire follow-up. During the entire available follow-up (median 10 months, IQR 7-11), CDP was recorded in 5 patients (3/71, 4.2% SID and 2/25, 8% EID, V-Cramer = 0.141, p-value = 0.167). EID regimen did not influence the risk of CDP during the investigated follow up. Conclusion: In our multicentre real-world cohort, the EID regimen in PPMS patients did not result in increased CDP during the available follow-up.
Trends of disease activity during pregnancy, the postpartum period, and until 24 months from the delivery in the era of new drugs for the treatment of relapsing-remitting multiple sclerosis (RRMS) ...need to be investigated.
In this cross-sectional Italian multicenter study, women with RRMS were included; the disease-modifying treatment (DMT) at the time of conception included were: interferons, glatiramer acetate, teriflunomide, dimethyl fumarate, fingolimod, and natalizumab. The main outcome of the study was to determine the rate of relapse occurrence during pregnancy and the postpartum period in all women grouped for each DMT. The secondary outcome was to determine the overall disease activity assessed by NEDA 3 (relapse, disability level, and radiological activity) at 24 months from the date of delivery.
Completed data were available for 81 pregnancies (in 74 women). Women on interferons and glatiramer had longer disease duration than women on dimethyl fumarate, fingolimod, and natalizumab (
< 0.05). Overall, we recorded 25 relapses during pregnancy (11 in 11 women) and the postpartum period (14 in 14 women). Natalizumab was the most commonly DMT in women (3) who experienced relapses during pregnancy. IFNs were the most commonly prescribed DMT in women (8) who experienced relapses during the postpartum period. At logistic regression analysis, specific treatment
was not associated with relapse occurrence. No differences among the DMTs groups were recorded about NEDA 3 status at 24 months of follow-up.
In our population, there was no difference in terms of relapses occurrence, disability status, and the overall disease activity during a follow up of 24 months.
Abstract Objective Thiamine or vitamin B1 deficiency diminishes thiamine-dependent enzymatic activity, alters mitochondrial function, impairs oxidative metabolism, and causes selective neuronal ...death. We analyzed for the first time, the role of all known mutations within three specific thiamine carrier genes, SLC19 A2, SLC19 A3 , and SLC25 A19 , in a patient with atrophic beriberi, a multiorgan nutritional disease caused by thiamine deficiency. Methods A 44-year-old male alcoholic patient from Morocco developed massive bilateral leg edema, a subacute sensorimotor neuropathy, and incontinence. Despite normal vitamin B1 serum levels, his clinical picture was rapidly reverted by high-dose intramuscular thiamine treatment, suggesting a possible genetic resistance. We used polymerase chain reaction followed by amplicon sequencing to study all the known thiamine-related gene mutations identified within the Human Gene Mutation Database. Results Thirty-seven mutations were tested: 29 in SLC19 A2, 6 in SLC19 A3, and 2 in SLC25 A19 . Mutational analyses showed a wild-type genotype for all sequences investigated. Conclusion This is the first genetic study in beriberi disease. We did not detect any known mutation in any of the three genes in a sporadic dry beriberi patient. We cannot exclude a role for other known or unknown mutations, in the same genes or in other thiamine-associated genes, in the occurrence of this nutritional neuropathy.
Abstract Objective To assess the association between diabetes preceding Parkinson's disease (PD) and PD. Methods PD individuals were matched to PD free individuals randomly selected from people in ...the same municipality as the cases. Occurrence of diabetes preceding PD onset among cases and controls was assessed through a structured questionnaire. Information regarding current and past medical treatment and other variables was also collected. We used univariate and multivariate logistic models to calculate crude and adjusted odds ratios (OR). Covariates are adjusted for included education, smoking habit, alcohol and coffee consumption. Results 318 PD individuals (165 women, 153 men) and 318 matched controls were included in the study. PD patients had a mean age at interview of 66.7 years. Mean age at PD onset was 60.8 years and mean PD duration 5.9 years. We found an inverse association between PD and diabetes preceding PD onset in all groups stratified by gender, age at PD onset, body mass index (BMI), smoking habit, alcohol and coffee consumption. Multivariate analysis yielded the same findings after controlling for the variables (adjusted OR 0.4; 95% CI, 0.2–0.8). Conclusions Our findings provide additional support for a potential link between diabetes and PD.
In patients with Multiple Sclerosis (pwMS) disease-modifying therapies (DMTs) affects immune response to antigens. Therefore, post-vaccination serological assessments are needed to evaluate the ...effect of the vaccine on SARS-CoV-2 antibody response.
We designed a prospective multicenter cohort study enrolling pwMS who were scheduled for SARS-Cov-2 vaccination with mRNA vaccines (BNT162b2, Pfizer/BioNTech,Inc or mRNA-1273, Moderna Tx,Inc). A blood collection before the first vaccine dose and 4 weeks after the second dose was planned, with a centralized serological assessment (electrochemiluminescence immunoassay, ECLIA, Roche-Diagnostics). The log-transform of the antibody levels was analyzed by multivariable linear regression.
780 pwMS (76% BNT162b2 and 24% mRNA-1273) had pre- and 4-week post-vaccination blood assessments. 87 (11·2%) were untreated, 154 (19·7%) on ocrelizumab, 25 (3·2%) on rituximab, 85 (10·9%) on fingolimod, 25 (3·2%) on cladribine and 404 (51·7%) on other DMTs. 677 patients (86·8%) had detectable post-vaccination SARS-CoV-2 antibodies. At multivariable analysis, the antibody levels of patients on ocrelizumab (201-fold decrease (95%CI=128–317), p < 0·001), fingolimod (26-fold decrease (95%CI=16–42), p < 0·001) and rituximab (20-fold decrease (95%CI=10–43), p < 0·001) were significantly reduced as compared to untreated patients. Vaccination with mRNA-1273 resulted in a systematically 3·25-fold higher antibody level (95%CI=2·46–4·27) than with the BNT162b2 vaccine (p < 0·001). The antibody levels on anti-CD20 therapies correlated to the time since last infusion, and rituximab had longer intervals (mean=386 days) than ocrelizumab patients (mean=129 days).
In pwMS, anti-CD20 treatment and fingolimod led to a reduced humoral response to mRNA-based SARS-CoV-2 vaccines. As mRNA-1273 elicits 3·25-higher antibody levels than BNT162b2, this vaccine may be preferentially considered for patients under anti-CD20 treatment or fingolimod. Combining our data with those on the cellular immune response to vaccines, and including clinical follow-up, will contribute to better define the most appropriate SARS-CoV-2 vaccine strategies in the context of DMTs and MS.
FISM2021/Special-Multi/001; Italian Ministry of Health‘Progetto Z844A 5 × 1000′.
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