Cladribine tablets (CLAD) for adult patients with highly active relapsing multiple sclerosis (RMS) have been available in Italy since 2018. We aimed to assess predictors of ...no-evidence-of-disease-activity-3 (NEDA-3) status after 24 months of the last dose of CLAD.
We included 88 patients (70.5% female, mean age at CLAD start 35.4 ± 11.4). Eighteen patients were treatment naïve, 48 switched to CLAD from a First line Disease Modifying Drug (DMD), and 22 from Second line DMDs. All patients were observed for a median follow-up time of 2.4 (1–4) years after the last dose of CLAD. Forty-nine patients (55.7%) showed NEDA at the last available follow-up. Naïve patients (p = 0.001), those with a lower number of previous DMDs (p < 0.001) and, even though not significantly, those switching from first line DMDs (p = 0.069) were more likely NEDA3 at the last available follow-up. In a subgroup of 30 patients (34%), Serum Light Neurofilaments (sNFL) levels showed a decrease from baseline to the 24 months of follow-up, statistically significant from baseline to the sixth month, and from the first to the second year detection. sNFL levels at 12th month showed a strong inverse correlation with the time to NEDA3 loss.
Our experience provides information for the 2-years after the last dose of CLAD, confirming a higher effectiveness of CLAD when placed early in the treatment algorithm. Given the ongoing expansion of the therapeutic landscape in MS, sNfL could support individualized decision-making, used as blood-based biomarker for CLAD responses in clinical practice.
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•Immune reconstitution therapies might be challenging for their right positioning.•Results obtained from “unselected cohorts” are crucial, as this single centre experience about the 2-years after the last dose of CLAD.•sNfL could support individualized decision-making, used as blood-based biomarker for CLAD responses in clinical practice.
To assess the relationship between breastfeeding and risk of puerperal relapses in a large cohort of patients with multiple sclerosis (MS).
We prospectively followed-up pregnancies occurring between ...2002 and 2008 in women with MS, recruited from 21 Italian MS centers, and gathered data on breastfeeding through a standardized interview. The risk of relapses after delivery was assessed using the Cox regression analysis.
A total of 302 out of 423 pregnancies in 298 women resulted in full-term deliveries. Patients were followed up for at least 1 year after delivery. The time-dependent profile of the relapse rate before, during, and after pregnancy did not differ between patients who breastfed and patients who did not. In the multivariate analysis, adjusting for age at onset, age at pregnancy, disease duration, disability level, and relapses in the year prior to pregnancy and during pregnancy, treatment with disease-modifying drugs (DMDs), and exposure to toxics, the only significant predictors of postpartum relapses were relapses in the year before pregnancy (hazard ratio HR = 1.5; 95%confidence interval CI 1.3-1.9; p < 0.001) and during pregnancy (HR = 2.2; 95% CI 1.5-3.3; p < 0.001).
In our sample, postpartum relapses were predicted only by relapses before and during pregnancy. Therefore, the reported association between breastfeeding and a lower risk of postpartum relapses may simply reflect different patient behavior, biased by the disease activity. Our results can assist neurologists facing the breastfeeding issue in mother counseling and shared decision-making. Especially, among patients with high risk of postpartum relapses, breastfeeding may not be feasible and early postpartum treatment should be an option.
The impact of neutralizing antibodies (NAbs) on interferon β (IFNβ) efficacy in MS patients is still an object of controversy. To evaluate the clinical response to IFNβ during NAb-positive (NAb+) and ...NAb-negative (NAb−) statuses on a large population of relapsing remitting (RR) MS patients were followed up to 5 years. Sera from 567 RR MS patients treated with IFNβ for 2–5 years were collected every 6–12 months and evaluated for NAb presence by a cytopathic effect assay. The relapse rate and expanded disability status scale (EDSS) score were assessed at baseline and every 6 months for each patient. A NAb+ status was defined after two consecutive positive titers of NAbs >/= 20 neutralizing units (NU)/mL. Multivariate models were used to analyze the relapse rate, the time to first relapse, the time to confirmed EDSS score 4 during NAb+ and NAb− statuses. A propensity score (PS) matching analysis was performed to assess the robustness of the multivariate models. Fourteen percent of patients became NAb+ during the follow-up. A significant increase of the relapse rate (IRR = 1.38;
p
= 0.0247) and decrease of the time to 1st relapse (IRR = 1.51;
p
= 0.0111) were found during NAb+ periods. The PS matching analysis, in a selected cohort of patients, demonstrated a negative trend of NAbs on the time to reach the milestone EDSS 4 (IRR = 2.94;
p
= 0.0879). This long-term post-marketing observational study further confirms that the occurrence of NAbs significantly affects the risk of disease worsening in IFNβ- treated RRMS.
To assess pregnancy and fetal outcomes after in utero exposure to interferon-β (IFNβ) in all pregnancies occurring in women with multiple sclerosis (MS) during the study period, with a specific focus ...on the risk of spontaneous abortion.
In this cohort study, data were gathered through a standardized, semi-structured interview. Patients who discontinued IFNβ less than 4 weeks from conception (exposed) were compared with those who had discontinued the drug at least 4 weeks from conception or who were never treated (not exposed). Possible confounders were handled through multivariate analyses adjusted for propensity score (PS).
We collected data on 396 pregnancies in 388 women, 88 classified as exposed (mean exposure 4.6 ± 5.8 weeks). IFNβ exposure was not associated with an increased risk of spontaneous abortion (PS-adjusted odds ratio OR 1.08, 95% confidence interval CI 0.4 to 2.9, p = 0.88), although it was associated with both lower baby weight (PS-adjusted β -113.8, p < 0.0001) and length (PS-adjusted β -1.102, p < 0.0001). Proportion of spontaneous abortion in exposed patients fell within the range expected for the Italian population in the same period. IFNβ exposure (PS-adjusted OR 2.11, 95% CI 1.18 to 3.78, p = 0.012) and cesarean delivery were the only predictors of preterm delivery. In the exposed group, we did not observe any significant fetal complications, malformations, or developmental abnormalities over a median follow-up of 2.1 years.
Our findings point to the relative safety of IFNβ exposure times of up to 4 weeks and can assist neurologists facing therapeutic decisions in women with MS with a pregnancy plan.
Abstract We investigated, lymphocyte count (LC) and lymphocyte subpopulations (LS) in a real life setting of Fingolimod (FTY) treated Relapsing MS (RMS) patients. Peripheral blood counts with LS, ...relapses and MRI scans were recorded in a cohort of 119 FTY patients, during one year of treatment. Simple and multivariate logistic regression models, were performed. ROC analysis identified cut-off values of LS predicting a higher risk of relapses and of Gd + lesions. We demonstrated a FTY-induced re-modulation of the immune system, suggesting that LS in RMS FTY treated patients can predict the clinical response to the drug.
The prevalence of trigeminal neuralgia (TN) in patients with Multiple Sclerosis (MS) is higher than in the general population and its management can be particularly challenging due to a number of ...reasons including high recurrence rates, lack of MS-specific treatment guidelines and uncertainties about pain pathophysiology.
Aim of this cross-sectional, multicentre survey was to gather information on the current treatment modalities and options of MS-related TN across 23 Italian MS centres.
Initial medical management (carbamazepine or oxcarbazepine) of MS-related TN was fairly homogeneous throughout Italian centres. The most commonly available surgical procedure was microvascular decompression, but the frequency and types of surgical procedures available locally differed considerably throughout MS centers, and were unavailable in one quarter of them.
This survey reveals some of the issues that could hamper an optimal patient management and underlines the need for a consensus on MS-related TN to support health-care professionals in their approach to this challenging condition and to facilitate the development of local guidelines aimed at ensuring equity in access to care and treatment optimization.
•Multiple Sclerosis (MS)-related trigeminal neuralgia (TN) management is challenging.•MS-related TN treatment guidelines are lacking.•There are considerable differences amongst Italian centres in the surgical options available locally.
Objective
Recent findings support greater efficacy of early vs. delayed interferon beta (IFNβ) treatment in patients with a first clinical event suggestive of multiple sclerosis (MS). We aimed to ...evaluate the effectiveness of early IFNβ treatment in definite relapsing‐remitting MS (RRMS) and to assess the optimal time to initiate IFNβ treatment with regard to the greatest benefits on disability progression.
Methods
A cohort of 2,570 IFNβ‐treated RRMS patients was prospectively followed for up to 7 years in 15 Italian MS Centers. A Cox proportional hazards regression model adjusted for propensity score (PS) quintiles was used to assess differences between groups of patients with early vs. delayed IFNβ treatment on risk of reaching a 1‐point progression in the Expanded Disability Status Scale (EDSS) score, and the EDSS 4.0 and 6.0 milestones. A set of PS‐adjusted Cox hazards regression models were calculated according to different times of treatment initiation (within 1 year up to within 5 years from disease onset). A sensitivity analysis was performed to assess the robustness of findings.
Results
The lowest hazard ratios (HRs) for the three PS quintiles–adjusted models were obtained by a cutoff of treatment initiation within 1 year from disease onset. Early treatment significantly reduced the risk of reaching a 1‐point progression in EDSS score (HR = 0.63; 95% CI = 0.48–0.85; p < 0.002), and the EDSS 4.0 milestone (HR = 0.56; 95% CI = 0.36–0.90; p = 0.015). Sensitivity analysis showed the bound of significance for unmeasured confounders.
Interpretation
Greater benefits on disability progression may be obtained by an early IFNβ treatment in RRMS. Ann Neurol 2009;66:513–520
Besides the impact of disease per se, the use of immunomodulatory therapies in adolescents with relapsing-remitting multiple sclerosis (RRMS) may have an effect on quality of life (QL). The FUTURE ...(Quality of liFe in adolescent sUbjecTs affected by mUltiple sclerosis treated with immunomodulatoRy agEnt using self-injecting device) study was designed to evaluate the changes in QL of Italian adolescents with RRMS receiving treatment with IFN-β1a (Rebif; 22 μg), administered subcutaneously three times weekly using the RebiSmart™ electronic autoinjection device over a 52-week period. Fifty adolescents with RRMS were enrolled and 40 completed the study. Changes from baseline to end of treatment (EoT) in adolescent self-reported and parent-reported QL were assessed using the Pediatric Quality of Life Inventory Multidimensional Fatigue Scale (PedsQL), which has been validated for use in pediatric MS and for which an Italian version is available. The adolescent self-reported total PedsQL4.0 score and all of its subscales tended to increase from baseline to EoT, the only exception being “Emotional functioning.” In parent-reported measures, the total PedsQL4.0 score increased significantly from baseline to EoT (+ 5.27 points,
p
= 0.041). Significant increases were also evident for parent-reported “Psychosocial health summary score” (+ 5.90 points;
p
= 0.015) and “School functioning” (+ 7.84 points;
p
= 0.029). Our results indicate that adolescents with RRMS using the electronic injection device RebiSmart™ for self-administration of Rebif® can experience long-term improvements in QL.
Objective:
The objective of this paper is to identify clinical or magnetic resonance imaging (MRI) predictors of long-term clinical progression in a large cohort of multiple sclerosis (MS) patients.
...Methods:
A total of 241 relapsing–remitting (RR) MS patients were included in a nine-year follow-up (FU) study. The reference MRIs were acquired at baseline (BL) as part of a multicenter, cross-sectional, clinical-MRI study. Volumetric MRI metrics were measured by a fully automated, operator-independent, multi-parametric segmentation method. Clinical progression was evaluated as defined by: conversion from RR to secondary progressive (SP) disease course; progression of Expanded Disability Status Scale (EDSS); achievement and time to reach EDSS 4.
Results:
We concluded that conversion from RR to SP (OR 0.79; CI 0.7–0.9), progression of EDSS (OR 0.85; CI 0.77–0.93), achievement of EDSS 4 (OR 0.8; CI 0.7–0.9), and time to reach EDSS 4 (HR 0.88; CI 0.82–0.94) were all predicted by BL gray matter (GM) volume and, except for progression of EDSS, by BL EDSS (respectively: (OR 2.88; CI 1.9–4.36), (OR 2.7; CI 1.7–4.2), (HR 3.86; CI 1.94–7.70)).
Conclusions:
BL GM volume and EDSS are the best long-term predictors of disease progression in RRMS patients with a relatively long and mild disease.
In the last years, change in multiple sclerosis (MS) therapeutic scenario has highlighted the need for an improved doctor-patient communication in advance of treatment initiation in order to allow ...patient’s empowerment in the decision-making process.
Aims
The aims of our project were to review the strategies used by Italian MS specialists to inform patients about treatment options and to design a multicentre shared document that homogenizes the information about disease-modifying treatment (DMTs) and the procedure of taking informed consent in clinical practice.
Results
The new resource, obtained by consensus among 31 neurologists from 27 MS Centres in Italy with the supervision of a medico-legal advisor, received the aegis of Italian Neurological Society (SIN) and constitutes a step toward a standardized decision process around DMTs in MS.
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