Publications by authors named "Maria Trojano"

254 Publications

Dengue fever in a multiple sclerosis patient taking Ocrelizumab.

Mult Scler 2021 Aug 27:13524585211030214. Epub 2021 Aug 27.

Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari "Aldo Moro," Bari, Italy.

Dengue fever (DF) is an endemic infectious disease in tropical and subtropical regions. Ocrelizumab is a humanized monoclonal antibody that targets the CD20 antigen on B cells, which is approved for the treatment of both relapsing-remitting multiple sclerosis (RRMS) and primary-progressive multiple sclerosis (PPMS). We describe the favorable clinical outcome of DF in an RRMS patient treated with Ocrelizumab, who neither presented hemorrhagic or systemic shock symptoms nor reported neurological worsening.
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http://dx.doi.org/10.1177/13524585211030214DOI Listing
August 2021

Guillain-Barré syndrome after AstraZeneca COVID-19-vaccination: A causal or casual association?

Clin Neurol Neurosurg 2021 Sep 13;208:106887. Epub 2021 Aug 13.

Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari "Aldo Moro", piazza Giulio Cesare 11, 70100 Bari, Italy.

We report a case of Guillain-Barré syndrome (GBS) following the first dose of Oxford/AstraZeneca COVID-19 vaccine with papilledema as atypical onset. As the COVID-19 vaccination campaign progresses worldwide, GBSs vaccine-related have been increasingly reported. After reviewing the available literature, considering the annual incidence of GBS, in this historical moment, the public health systems cannot afford an unjustified distrust in vaccines, caused by misinterpretation of epidemiological data. Nonetheless, it is important for clinicians to promptly recognize neurological complications potentially associated with COVID-19 vaccinations and report them to pharmacovigilance agencies.
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http://dx.doi.org/10.1016/j.clineuro.2021.106887DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8360997PMC
September 2021

Job satisfaction among physicians and nurses involved in the management of multiple sclerosis: the role of happiness and meaning at work.

Neurol Sci 2021 Aug 7. Epub 2021 Aug 7.

Department of Biomedical and Clinical Sciences L. Sacco, Università degli Studi di Milano, Milan, Italy.

Objective: Health professionals caring for persons with multiple sclerosis (MS) are faced with increasingly complex working conditions that can undermine their job satisfaction and the quality of their healthcare services. The aim of this study was to delve into health professionals' job satisfaction by assessing the predictive role of happiness and meaning at work. Specifically, it was hypothesized that job meaning would moderate the relationship between job happiness and satisfaction.

Methods: The study hypothesis was tested among 108 healthcare professionals (53 physicians and 55 nurses) working in eight MS centers in Italy. Participants were administered the Eudaimonic and Hedonic Happiness Investigation and the Job Satisfaction Questionnaire. Hierarchical regression analysis was performed to test the moderating role of job meaning between job happiness and satisfaction.

Results: A significant interaction effect of job happiness and meaning on job satisfaction was identified for both physicians and nurses. When work was attributed low meaning, participants experiencing high job happiness were more satisfied with their work than those reporting low happiness; by contrast, when work was perceived as highly meaningful, participants' levels of job happiness did not significantly contribute to job satisfaction.

Conclusions: Focusing on the interplay between job happiness and meaning, findings bring forward practical suggestions for the preservation and promotion of job satisfaction among health professionals working with MS patients. Particularly, they suggest the need to strengthen those job-related aspects that may enhance job meaning, thus providing health professionals with significant reasons to persevere in their work in the face of daily challenges.
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http://dx.doi.org/10.1007/s10072-021-05520-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8346783PMC
August 2021

SARS-CoV-2 serology after COVID-19 in multiple sclerosis: An international cohort study.

Mult Scler 2021 Jul 30:13524585211035318. Epub 2021 Jul 30.

Department of Neuroscience, Mental Health and Sensory Organs, Sapienza University of Rome, Rome, Italy/Unit of Neurology, IRCCS Neuromed, Isernia, Italy.

Background: The MuSC-19 project is an Italian cohort study open to international partners that collects data on multiple sclerosis (MS) patients with COVID-19. During the second wave of the pandemic, serological tests became routinely available.

Objective: To evaluate the seroprevalence of anti-SARS-CoV-2 antibodies according to the use of disease-modifying therapy (DMT) in a subset of patients included in the MuSC-19 data set who had undergone a serological test.

Methods: We evaluated the association between positive serological test results and time elapsed since infection onset, age, sex, Expanded Disability Status Scale score, comorbidities and DMT exposure using a multivariable logistic model.

Results: Data were collected from 423 patients (345 from Italy, 61 from Turkey and 17 from Brazil) with a serological test performed during follow-up. Overall, 325 out of 423 tested patients (76.8%) had a positive serological test. At multivariate analysis, therapy with anti-CD20 was significantly associated with a reduced probability of developing antibodies after COVID-19 (odds ratio (OR) = 0.20,  = 0.002).

Conclusion: Patients with MS maintain the capacity to develop humoral immune response against SARS-COV-2, although to a lesser extent when treated with anti-CD20 drugs. Overall, our results are reassuring with respect to the possibility to achieve sufficient immunization with vaccination.
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http://dx.doi.org/10.1177/13524585211035318DOI Listing
July 2021

DMTs and Covid-19 severity in MS: a pooled analysis from Italy and France.

Ann Clin Transl Neurol 2021 08 7;8(8):1738-1744. Epub 2021 Jul 7.

Department of Neurology, CIC INSERM 1434, CHU de Strasbourg, Strasbourg, France.

We evaluated the effect of DMTs on Covid-19 severity in patients with MS, with a pooled-analysis of two large cohorts from Italy and France. The association of baseline characteristics and DMTs with Covid-19 severity was assessed by multivariate ordinal-logistic models and pooled by a fixed-effect meta-analysis. 1066 patients with MS from Italy and 721 from France were included. In the multivariate model, anti-CD20 therapies were significantly associated (OR = 2.05, 95%CI = 1.39-3.02, p < 0.001) with Covid-19 severity, whereas interferon indicated a decreased risk (OR = 0.42, 95%CI = 0.18-0.99, p = 0.047). This pooled-analysis confirms an increased risk of severe Covid-19 in patients on anti-CD20 therapies and supports the protective role of interferon.
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http://dx.doi.org/10.1002/acn3.51408DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8351392PMC
August 2021

First-line therapies in late-onset multiple sclerosis: An Italian registry study.

Eur J Neurol 2021 Jul 3. Epub 2021 Jul 3.

Department "G.F. Ingrassia,", MS Center University of Catania, Catania, Italy.

Background And Purpose: The diagnosis of late-onset (age ≥50 years old) relapsing remitting multiple sclerosis (LORRMS) has been increasingly described in clinical practice, whereas data focusing on the specific therapeutic management of LORRMS are scarce. Our objective was to compare the effectiveness of injectable and oral first-line disease-modifying therapies (DMTs) in a cohort of LORRMS patients with time to first relapse, time to confirmed disability progression (CDP), and time to discontinuation.

Methods: This is a multicenter, observational, retrospectively acquired cohort study on LORRMS-naïve patients from the Italian MS Register who started either injectable or oral first-line DMTs between January 1, 2013 and December 31, 2017. LORRMS patients were divided into two groups, namely the injectable group (IG) and oral group (OG). Cox models adjusted with inverse probability-weighted propensity score were built for the investigated outcomes.

Results: Of a cohort of 3989 patients, 302 were enrolled (203 in the IG and 99 in the OG). The two cohorts did not differ in baseline characteristics. Time to first relapse did not show any difference between the two groups (hazard ratio [HR]: 1.10; 95% confidence interval [CI]: 0.50-2.46, p = 0.797). Furthermore, no differences were found between the two groups with respect to the risk of CDP (HR: 1.04; 95% CI: 0.35-3.06, p = 0.939), nor for the risk of DMT discontinuation (HR: 0.90; 95% CI: 0.17-2.08, p = 0.425).

Conclusions: Real-world data from the Italian MS Register suggested that both injectables and oral first-line DMTs similarly controlled the investigated outcomes in LORRMS.
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http://dx.doi.org/10.1111/ene.15006DOI Listing
July 2021

Longitudinal machine learning modeling of MS patient trajectories improves predictions of disability progression.

Comput Methods Programs Biomed 2021 Sep 18;208:106180. Epub 2021 May 18.

19 Mayis University, Samsun, Turkey.

Background And Objectives: Research in Multiple Sclerosis (MS) has recently focused on extracting knowledge from real-world clinical data sources. This type of data is more abundant than data produced during clinical trials and potentially more informative about real-world clinical practice. However, this comes at the cost of less curated and controlled data sets. In this work we aim to predict disability progression by optimally extracting information from longitudinal patient data in the real-world setting, with a special focus on the sporadic sampling problem.

Methods: We use machine learning methods suited for patient trajectories modeling, such as recurrent neural networks and tensor factorization. A subset of 6682 patients from the MSBase registry is used.

Results: We can predict disability progression of patients in a two-year horizon with an ROC-AUC of 0.85, which represents a 32% decrease in the ranking pair error (1-AUC) compared to reference methods using static clinical features.

Conclusions: Compared to the models available in the literature, this work uses the most complete patient history for MS disease progression prediction and represents a step forward towards AI-assisted precision medicine in MS.
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http://dx.doi.org/10.1016/j.cmpb.2021.106180DOI Listing
September 2021

Pregnancy in multiple sclerosis women with relapses in the year before conception increases the risk of long-term disability worsening.

Mult Scler 2021 Jun 16:13524585211023365. Epub 2021 Jun 16.

Division Neurological Rehabilitation, Department of NEUROFARBA, University of Florence, Florence, Italy/IRCCS Fondazione Don Carlo Gnocchi, Florence, Italy.

Background: The influence of pregnancy on long-term disability in multiple sclerosis (MS) is still controversial.

Objective: To assess the risk of long-term disability worsening after pregnancy in MS women as compared with a propensity-score (PS) matched group of MS women without pregnancy.

Methods: In the setting of the Italian Pregnancy Dataset, MS patients with (pregnancy group (PG)) and without pregnancy (control group (CG)) were recruited. Time to disability worsening on the Expanded Disability Status Scale (EDSS) was assessed through a multivariable Cox regression model.

Results: The PS-matching retained 230 PG and 102 CG patients. After a follow-up of 6.5 +/- 3.1 years, disability worsening occurred in 87 (26.2%) women. In the multivariable analysis, disability worsening was associated with pregnancy in women with relapses in the year before conception (adjusted hazard ratio (aHR) = 1.74; 95% confidence interval (CI) 1.06-2.84; = 0.027), higher EDSS (aHR = 1.39; 95% CI 1.12-1.74; = 0.003), younger age (aHR = 0.95; 95% CI 0.91-0.99; = 0.022) and shorter DMD exposure over the follow-up ( < 0.008).

Conclusion: Pregnancy in MS women with relapses in the year before conception increases the risk of long-term disability worsening. Our findings underscore the importance of counselling in MS women facing a pregnancy that should be planned after a period of clinical stability, favouring treatment optimization in patients with recent disease activity.
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http://dx.doi.org/10.1177/13524585211023365DOI Listing
June 2021

The effectiveness of natalizumab vs fingolimod-A comparison of international registry studies.

Mult Scler Relat Disord 2021 Aug 8;53:103012. Epub 2021 May 8.

KTU Medical Faculty Farabi Hospital, Trabzon, Turkey.

Background: Natalizumab and fingolimod were the first preparations recommended for disease breakthrough in priorly treated relapsing-remitting multiple sclerosis. Of three published head-to-head studies two showed that natalizumab is the more effective to prevent relapses and EDSS worsening.

Methods: By re-analyzing original published results from MSBase, France, and Denmark using uniform methodologies, we aimed at identifying the effects of differences in methodology, in the MS-populations, and at re-evaluating the differences in effectiveness between the two drugs. We gained access to copies of the individual amended databases and pooled all data. We used uniform inclusion/exclusion criteria and statistical methods with Inverse Probability Treatment Weighting.

Results: The pooled analyses comprised 968 natalizumab- and 1479 fingolimod treated patients. The on-treatment natalizumab/fingolimod relapse rate ratio was 0.77 (p=0.004). The hazard ratio (HR) for a first relapse was 0.82 (p=0.030), and the HR for sustained EDSS improvement was 1.4 (p=0.009). There were modest differences between each of the original published studies and the replication study, but the conclusions of the three original studies remained unchanged: in two of them natalizumab was more effective, but in the third there was no difference between natalizumab and fingolimod.

Conclusion: The results were largely invariant to the epidemiological and statistical methods but differed between the MS populations. Generally, the advantage of natalizumab was confirmed.
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http://dx.doi.org/10.1016/j.msard.2021.103012DOI Listing
August 2021

Long-term disability trajectories in relapsing multiple sclerosis patients treated with early intensive or escalation treatment strategies.

Ther Adv Neurol Disord 2021 31;14:17562864211019574. Epub 2021 May 31.

Dipartimento di Neurologia, Neurofisiologia e Neuroriabilitazione, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.

Background And Aims: No consensus exists on how aggressively to treat relapsing-remitting multiple sclerosis (RRMS) nor on the timing of the treatment. The objective of this study was to evaluate disability trajectories in RRMS patients treated with an early intensive treatment (EIT) or with a moderate-efficacy treatment followed by escalation to higher-efficacy disease modifying therapy (ESC).

Methods: RRMS patients with ⩾5-year follow-up and ⩾3 visits after disease modifying therapy (DMT) start were selected from the Italian MS Registry. EIT group included patients who received as first DMT fingolimod, natalizumab, mitoxantrone, alemtuzumab, ocrelizumab, cladribine. ESC group patients received the high efficacy DMT after ⩾1 year of glatiramer acetate, interferons, azathioprine, teriflunomide or dimethylfumarate treatment. Patients were 1:1 propensity score (PS) matched for characteristics at the first DMT. The disability trajectories were evaluated by applying a longitudinal model for repeated measures. The effect of early late start of high-efficacy DMT was assessed by the mean annual Expanded Disability Status Scale (EDSS) changes compared with baseline values (delta-EDSS) in EIT and ESC groups.

Results: The study cohort included 2702 RRMS patients. The PS matching procedure produced 363 pairs, followed for a median (interquartile range) of 8.5 (6.5-11.7) years. Mean annual delta-EDSS values were all significantly ( < 0.02) higher in the ESC group compared with the EIT group. In particular, the mean delta-EDSS differences between the two groups tended to increase from 0.1 (0.01-0.19,  = 0.03) at 1 year to 0.30 (0.07-0.53,  = 0.009) at 5 years and to 0.67 (0.31-1.03,  = 0.0003) at 10 years.

Conclusion: Our results indicate that EIT strategy is more effective than ESC strategy in controlling disability progression over time.
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http://dx.doi.org/10.1177/17562864211019574DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170278PMC
May 2021

Multicenter Interventional Phase IV Study for the Assessment of the Effects on Patient's Satisfaction of Peg IFN Beta-1a (Pre-filled Pen) in Subjects With Relapsing-Remitting Multiple Sclerosis Unsatisfied With Other Injectable Subcutaneous Interferons (PLATINUM Study).

Front Neurol 2021 22;12:637615. Epub 2021 Apr 22.

Biogen Italia, Milan, Italy.

Subcutaneous (SC) interferons beta (IFN-beta) are effective therapies for the treatment of relapsing-remitting multiple sclerosis (RRMS). Factors such as dosing schedule, needle intolerance/fatigue, and side effects may impact patient satisfaction with treatment. Improvement of patient satisfaction may increase the adherence to treatment and the patient quality of life. This study was aimed at evaluating the impact of switching to "Peginterferon beta-1a (Peg-IFN beta-1a)" in patients with RRMS unsatisfied with other SC interferons. The multicenter, open-label, phase IV PLATINUM study was conducted in 32 Italian centers. The primary endpoint was changes from baseline in the score of a convenience satisfaction domain of the TSQM-9 questionnaire at 12 weeks. The secondary endpoints were patients' global satisfaction, short-term adherence to treatment, satisfaction with the injection system, effect on fatigue, disease activity, and patient inability score. A total of 193 patients were enrolled and 166 (86%) completed the study, receiving Peg-IFN beta-1a for 24 weeks. Patients switching to Peg-IFN beta-1a from other SC interferons reported a significant improvement ( < 0.001) of Convenience Score and all other scores of the TSQM-9 questionnaire at 12 and 24 weeks ( < 0.001). Peg IFN beta-1a attained very high adherence to the treatment (92 and 86% at 12 and 24 weeks, respectively) with a stable annualized relapse rate (ARR). At 24 weeks, 94% of the participants were relapse free. Adverse events (AEs), recorded on 82 patients (42%), were mild or moderate. The most common AE was flu-like syndrome (29.2%). Patients switching from SC IFN beta therapy to Peg IFN beta-1a showed high treatment satisfaction with a positive safety profile, comparable with that of other currently approved first-line injectable SC interferons. This study suggests that Peg IFN beta-1a might represent a treatment choice to improve adherence in RRMS patients unsatisfied with other SC interferons.
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http://dx.doi.org/10.3389/fneur.2021.637615DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8101263PMC
April 2021

Migraine during COVID-19: Data from Second Wave Pandemic in an Italian Cohort.

Brain Sci 2021 Apr 10;11(4). Epub 2021 Apr 10.

Applied Neurophysiology and Pain Unit, SMBNOS Department, Bari Aldo Moro University, 70121 Bari, Italy.

Objectives: The study aims to assess the impact of the second COVID-19 pandemic wave on migraine characteristics.

Methods: This is an observational cross-sectional study conducted on migraine patients previously interviewed during the first Italian pandemic outbreak. A second structured telephone interview was conducted between 20 November 2020 and 18 January 2021. We compared migraine characteristics among T0 (before pandemic), T1 (during the first pandemic phase), and T2 (during the second pandemic phase).

Results: Among the 433 patients interviewed during the first pandemic phase, 304 cases were finally considered. One hundred forty-eight patients had a control visit between March 2020 and December 2020, 120 had an in-person visit, 14 by phone, the remainder used telemedicine software provided by the hospital. Frequency of headache, number of symptomatic drugs and headache intensity worsened during T2, compared to T0 and T1, especially in episodic migraine. Headache intensity increased relating to the negative emotional impact of the pandemic. Migraine management during the pandemic did not influence the clinical outcome.

Conclusion: The prolongation of the pandemic seems to have a negative impact on migraine evolution. The arousal and negative psychological behavior toward the COVID-19 outbreak seem to worsen migraine.
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http://dx.doi.org/10.3390/brainsci11040482DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8070557PMC
April 2021

Magnetoencephalography and High-Density Electroencephalography Study of Acoustic Event Related Potentials in Early Stage of Multiple Sclerosis: A Pilot Study on Cognitive Impairment and Fatigue.

Brain Sci 2021 Apr 9;11(4). Epub 2021 Apr 9.

Department of Basic Medical Sciences, Neurosciences, and Sense Organs, University of Bari "Aldo Moro", 70121 Bari, Italy.

Cognitive impairment (CI) is a common and disabling symptom of Multiple Sclerosis (MS) with a negative impact on daily living. In this pilot study, we applied magnetoencephalography (MEG) and high density (hd) electroencephalography (EEG) study to evaluate acoustic P300 features in a cohort of early MS. Sixteen MS patients (pwMS) and 19 healthy controls (HCs) matched for age and gender underwent an MEG-/(hd)-EEG-co-recording, using 306-channel Vectorview and 64 scalp electrodes. CI was assessed using Rao's Brief Repeatable Battery (BRB). Moreover, we performed psychometric tests to assess depression and fatigue. In pwMS, we observed a slight latency prolongation of P300 peak compared to HCs, while P300 amplitude and scalp distribution were similar in the two groups. pwMS did not show an amplitude reduction and different scalp distribution of Event-Related Potentials (ERPs) and Event Related Fields (ERFs) related to an acoustic oddball paradigm. We found an inverse correlation between P300 amplitude and fatigue (r Spearman = -0.4; = 0.019). In pwMS, phenomena of cortical adaptation to early dysfunction could preserve the cognitive performance of the P300 acoustic task, while the development of fatigue could prospectively lead to amplitude decline of P300, suggesting its possible role as a biomarker.
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http://dx.doi.org/10.3390/brainsci11040481DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8069556PMC
April 2021

Early treatment delays long-term disability accrual in RRMS: Results from the BMSD network.

Mult Scler 2021 Sep 26;27(10):1543-1555. Epub 2021 Apr 26.

Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari Aldo Moro, Bari, Italy.

Background: The optimal timing of treatment starts for achieving the best control on the long-term disability accumulation in multiple sclerosis (MS) is still to be defined.

Objective: The aim of this study was to estimate the optimal time to start disease-modifying therapies (DMTs) to prevent the long-term disability accumulation in MS, using a pooled dataset from the Big Multiple Sclerosis Data (BMSD) network.

Methods: Multivariable Cox regression models adjusted for the time to first treatment start from disease onset (in quintiles) were used. To mitigate the impact of potential biases, a set of pairwise propensity score (PS)-matched analyses were performed. The first quintile, including patients treated within 1.2 years from onset, was used as reference.

Results: A cohort of 11,871 patients (median follow-up after treatment start: 13.2 years) was analyzed. A 3- and 12-month confirmed disability worsening event and irreversible Expanded Disability Status Scale (EDSS) 4.0 and 6.0 scores were reached by 7062 (59.5%), 4138 (34.9%), 3209 (31.1%), and 1909 (16.5%) patients, respectively. The risk of reaching all the disability outcomes was significantly lower ( < 0.0004) for the first quintile patients' group.

Conclusion: Real-world data from the BMSD demonstrate that DMTs should be commenced within 1.2 years from the disease onset to reduce the risk of disability accumulation over the long term.
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http://dx.doi.org/10.1177/13524585211010128DOI Listing
September 2021

Disease-modifying therapies and SARS-CoV-2 vaccination in multiple sclerosis: an expert consensus.

J Neurol 2021 Apr 12. Epub 2021 Apr 12.

MS Center and Neurology Unit, IRCCS San Raffaele Scientific Institute, Via Olgettina, 60, 20132, Milan, Italy.

Coronavirus disease (COVID-19) appeared in December 2019 in the Chinese city of Wuhan and has quickly become a global pandemic. The disease is caused by the severe acute respiratory syndrome coronavirus type-2 (SARS-CoV-2), an RNA beta coronavirus phylogenetically similar to SARS coronavirus. To date, more than 132 million cases of COVID19 have been recorded in the world, of which over 2.8 million were fatal ( https://coronavirus.jhu.edu/map.html ). A huge vaccination campaign has started around the world since the end of 2020. The availability of vaccines has raised some concerns among neurologists regarding the safety and efficacy of vaccination in patients with multiple sclerosis (MS) taking immunomodulatory or immunosuppressive therapies.
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http://dx.doi.org/10.1007/s00415-021-10545-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8038920PMC
April 2021

A randomized study of natalizumab dosing regimens for relapsing-remitting multiple sclerosis.

Mult Scler 2021 Apr 6:13524585211003020. Epub 2021 Apr 6.

Biogen, Cambridge, MA, USA.

Background: REFINE was an exploratory, dose- and frequency-blinded, prospective, randomized, dose-ranging study in relapsing-remitting multiple sclerosis (RRMS) patients.

Objective: To examine the efficacy, safety, and tolerability of natalizumab administered via various regimens in RRMS patients.

Methods: Clinically stable RRMS patients previously treated with 300 mg natalizumab intravenously for ⩾12 months were randomized to one of six natalizumab regimens over 60 weeks: 300 mg administered intravenously or subcutaneously every 4 weeks (Q4W), 300 mg intravenously or subcutaneously every 12 weeks (Q12W), or 150 mg intravenously or subcutaneously Q12W. The primary endpoint was the mean cumulative number of combined unique active magnetic resonance imaging (MRI) lesions at week 60.

Results: In total, 290 patients were enrolled. All Q12W dosing arms were associated with increased clinical and MRI disease activity and closed early; ⩾39.5% of patients in each Q12W arm met rescue criteria. In the 300 mg intravenous and subcutaneous Q4 W arms, the mean cumulative number of combined unique active MRI lesions was 0.23 and 0.02, respectively; annualized relapse rates were 0.07 and 0.08, respectively; and trough natalizumab serum levels and α4-integrin saturation were comparable.

Conclusion: Natalizumab 300 mg subcutaneous Q4W was comparable to 300 mg intravenous Q4W dosing with respect to efficacy, pharmacokinetics/pharmacodynamics, and safety.
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http://dx.doi.org/10.1177/13524585211003020DOI Listing
April 2021

Treatment Switching and Discontinuation Over 20 Years in the Big Multiple Sclerosis Data Network.

Front Neurol 2021 17;12:647811. Epub 2021 Mar 17.

Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.

Although over a dozen disease modifying treatments (DMTs) are available for relapsing forms of multiple sclerosis (MS), treatment interruption, switching and discontinuation are common challenges. The objective of this study was to describe treatment interruption and discontinuation in the Big MS data network. We merged information on 269,822 treatment episodes in 110,326 patients from 1997 to 2016 from five clinical registries in this cohort study. Treatment stop was defined as a clinician recorded DMT end for any reason and included treatment interruptions, switching to alternate DMTs and long-term or permanent discontinuations. The incidence of DMT stopping cross the full observation period was lowest in FTY (19.7 per 100 person-years (PY) of treatment; 95% CI 19.2-20.1), followed by NAT (22.6/100 PY; 95% CI 22.2-23.0), IFNβ (23.3/100 PY; 95% CI 23.2-23.5). Of the 184,013 observed DMT stops, 159,309 (86.6%) switched to an alternate DMT within 6 months. Reasons for stopping a drug were stable during the observation period with lack of efficacy being the most common reason followed by lack of tolerance and side effects. The proportion of patients continuing on most DMTs were similarly stable until 2014 and 2015 when drop from 83 to 75% was noted. DMT stopping reasons and rates were mostly stable over time with a slight increase in recent years, with the availability of more DMTs. The overall results suggest that discontinuation of MS DMTs is mostly due to DMT properties and to a lesser extent to risk management and a competitive market.
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http://dx.doi.org/10.3389/fneur.2021.647811DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010264PMC
March 2021

Longitudinal Evaluation of Serum MOG-IgG and AQP4-IgG Antibodies in NMOSD by a Semiquantitative Ratiometric Method.

Front Neurol 2021 8;12:633115. Epub 2021 Mar 8.

Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari "Aldo Moro", Bari, Italy.

Immunoadsorption (IA) is an antibody-depleting therapy used to treat neuromyelitis optica spectrum disorder (NMOSD) associated to antiaquaporin 4 (anti-AQP4-IgG) and antimyelin oligodendrocyte glycoprotein (anti-MOG-IgG) serum autoantibodies. Our aim was to evaluate longitudinal changes of serum MOG-IgG and AQP4-IgG antibody titer and to correlate it with the clinical status. Autoantibody titer and clinical features of two MOG-IgG+/AQP4-IgG- and two AQP4-IgG+/MOG-IgG- patients with NMOSD were collected at baseline (T0), after 6 IA courses (T1), and then 2 weeks (T2) and 6 months after treatment (T3). A fluorescent ratiometric assay was used for a quantitative detection of MOG and AQP4 antibodies, based on HEK-293 cells transfected with the full-length hMOG fused to GFP or h-AQP4-M23 isoform fused to m-cherry, respectively. We defined the antibody titer as MOG quantitative ratio (MOGqr) and AQP4 quantitative ratio (AQP4qr). In Case 1, the MOGqr dropped from 0.98 at T0 to 0.14 at T3, and in Case 2, it decreased from 0.96 at T0 to undetectable at T3. In Case3, the AQP4qr remained high: 0.90 at T0 and 0.92 at T3. In Case 4, the AQP4qr decreased from 0.50 at T0 to undetectable at T3. Complete recovery was found in Cases 1, 2, and 4. Semiquantitative ratiometric method accurately detects even slight variation of MOG-IgG and AQP4-IgG titer, suggesting it may be useful to monitor the antibody titer during the disease course and maintenance immunotherapy.
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http://dx.doi.org/10.3389/fneur.2021.633115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7982799PMC
March 2021

Long-term comparative analysis of no evidence of disease activity (NEDA-3) status between multiple sclerosis patients treated with natalizumab and fingolimod for up to 4 years.

Neurol Sci 2021 Mar 6. Epub 2021 Mar 6.

Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari "Aldo Moro", Piazza G. Cesare 11, 70124, Bari, Italy.

Background: Comparative effectiveness of natalizumab and fingolimod over a follow-up longer than 2 years has been not addressed yet.

Objectives: To compare the effect on no evidence of disease activity (NEDA-3) in relapsing-remitting multiple sclerosis (RRMS) patients treated with natalizumab or fingolimod for at least 4 years.

Methods: We included RRMS patients switched from first-line agents to natalizumab or fingolimod. Patients were propensity score (PS)-matched on a 1-to-1 basis. Percentages of patients reaching NEDA-3 status at 2 and 4 years of follow-up were compared using the chi-square test. The risk of not achieving NEDA-3 at 4 years was explored in matched samples by Cox regression models.

Results: We evaluated 174 PS-matched patients. Patients receiving natalizumab reached a NEDA-3 status at 2 and 4 years more frequently than those exposed to fingolimod (63% vs 44%, p=0.037; 45.7% vs 25.8%, p=0.015, respectively). Patients receiving natalizumab were at a significant lower risk of not achieving the NEDA-3 status at 4 years compared to those exposed to fingolimod (hazard ratio (95% confidence interval): 0.54 (0.36-0.80), p=0.002).

Conclusions: Although both medications were effective in patients non-responding to first-line agents, natalizumab seems to be superior to fingolimod in RRMS in obtaining NEDA-3 status at 4 years.
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http://dx.doi.org/10.1007/s10072-021-05127-zDOI Listing
March 2021

Assessing long-term effectiveness of MS treatment - a matter of debate.

Nat Rev Neurol 2021 Apr;17(4):197-198

Department of Basic Medical Sciences, Neurological Sciences and Sense Organs, University of Bari Aldo Moro, Bari, Italy.

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http://dx.doi.org/10.1038/s41582-021-00476-xDOI Listing
April 2021

Therapeutic recommendations and seasonal influenza vaccine for multiple sclerosis patients in treatment with ocrelizumab: an expert consensus.

J Neurol 2021 Apr 20;268(4):1540-1543. Epub 2021 Feb 20.

Neurology and Neurophysiopathology Unit, Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari "Aldo Moro", Bari, Italy.

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http://dx.doi.org/10.1007/s00415-021-10466-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7896178PMC
April 2021

Injectable Versus Oral First-Line Disease-Modifying Therapies: Results from the Italian MS Register.

Neurotherapeutics 2021 Apr 2;18(2):905-919. Epub 2021 Feb 2.

Department "G.F. Ingrassia", MS center, University of Catania, Policlinico G. Rodolico, V. Santa Sofia 78, 95123, Catania, Italy.

The current study aims to compare injectable and oral first-line disease-modifying therapies (DMTs) for time to first relapse, time to confirmed disability progression (CDP), and time to discontinuation using a cohort of relapsing remitting multiple sclerosis (RRMS) patients, with data extracted from the Italian MS Register. This multicenter, observational, retrospectively acquired, and propensity-adjusted cohort study utilized RRMS-naïve patients from the Italian MS Register who started either injectable or oral first-line DMTs between January 1, 2010, and December 31, 2017, to evaluate the impact on disability outcomes in patients. Enrolled patients were divided into two groups, namely the injectable group (IG) and the oral group (OG). Of a cohort of 11,416 patients, 4602 were enrolled (3919 in the IG and 683 in the OG). The IG had a higher rate of women (67.3% vs 63.4%, p < 0.05) and a lower mean age (36.1 ± 10.9 vs 38.9 ± 11.8, p < 0.001). The event time to first relapse demonstrated a lower risk in the OG (HR = 0.58; CI 95% 0.48-0.72, p < 0.001). However, no differences were found between the two groups with respect to the risk of CDP (HR = 0.94; CI 95% 0.76-1.29, p = 0.941), while a lower risk of DMT was found in the OG (HR = 0.72; CI 95% 0.58-0.88, p = 0.002) for the event time to discontinuation. Real-world data from the Italian MS Register suggests that first-line oral DMTs are associated with a lower risk of experiencing a new relapse and of therapy discontinuation compared to injectable DMTs.
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http://dx.doi.org/10.1007/s13311-020-01001-6DOI Listing
April 2021

Disease-Modifying Therapies and Coronavirus Disease 2019 Severity in Multiple Sclerosis.

Ann Neurol 2021 04 9;89(4):780-789. Epub 2021 Feb 9.

Department of Neuroscience, Mental Health, and Sensory Organs, Sapienza University of Rome, Rome, Italy.

Objective: This study was undertaken to assess the impact of immunosuppressive and immunomodulatory therapies on the severity of coronavirus disease 2019 (COVID-19) in people with multiple sclerosis (PwMS).

Methods: We retrospectively collected data of PwMS with suspected or confirmed COVID-19. All the patients had complete follow-up to death or recovery. Severe COVID-19 was defined by a 3-level variable: mild disease not requiring hospitalization versus pneumonia or hospitalization versus intensive care unit (ICU) admission or death. We evaluated baseline characteristics and MS therapies associated with severe COVID-19 by multivariate and propensity score (PS)-weighted ordinal logistic models. Sensitivity analyses were run to confirm the results.

Results: Of 844 PwMS with suspected (n = 565) or confirmed (n = 279) COVID-19, 13 (1.54%) died; 11 of them were in a progressive MS phase, and 8 were without any therapy. Thirty-eight (4.5%) were admitted to an ICU; 99 (11.7%) had radiologically documented pneumonia; 96 (11.4%) were hospitalized. After adjusting for region, age, sex, progressive MS course, Expanded Disability Status Scale, disease duration, body mass index, comorbidities, and recent methylprednisolone use, therapy with an anti-CD20 agent (ocrelizumab or rituximab) was significantly associated (odds ratio [OR] = 2.37, 95% confidence interval [CI] = 1.18-4.74, p = 0.015) with increased risk of severe COVID-19. Recent use (<1 month) of methylprednisolone was also associated with a worse outcome (OR = 5.24, 95% CI = 2.20-12.53, p = 0.001). Results were confirmed by the PS-weighted analysis and by all the sensitivity analyses.

Interpretation: This study showed an acceptable level of safety of therapies with a broad array of mechanisms of action. However, some specific elements of risk emerged. These will need to be considered while the COVID-19 pandemic persists. ANN NEUROL 2021;89:780-789.
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http://dx.doi.org/10.1002/ana.26028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8013440PMC
April 2021

Determinants of therapeutic lag in multiple sclerosis.

Mult Scler 2021 Jan 11:1352458520981300. Epub 2021 Jan 11.

CHU de Caen, MS Expert Centre, Department of Neurology, avenue de la Côte-de-Nacre, Normandy University, Caen, France.

Background: A delayed onset of treatment effect, termed therapeutic lag, may influence the assessment of treatment response in some patient subgroups.

Objectives: The objective of this study is to explore the associations of patient and disease characteristics with therapeutic lag on relapses and disability accumulation.

Methods: Data from MSBase, a multinational multiple sclerosis (MS) registry, and OFSEP, the French MS registry, were used. Patients diagnosed with MS, minimum 1 year of exposure to MS treatment and 3 years of pre-treatment follow-up, were included in the analysis. Studied outcomes were incidence of relapses and disability accumulation. Therapeutic lag was calculated using an objective, validated method in subgroups stratified by patient and disease characteristics. Therapeutic lag under specific circumstances was then estimated in subgroups defined by combinations of clinical and demographic determinants.

Results: High baseline disability scores, annualised relapse rate (ARR) ⩾ 1 and male sex were associated with longer therapeutic lag on disability progression in sufficiently populated groups: females with expanded disability status scale (EDSS) < 6 and ARR < 1 had mean lag of 26.6 weeks (95% CI = 18.2-34.9), males with EDSS < 6 and ARR < 1 31.0 weeks (95% CI = 25.3-36.8), females with EDSS < 6 and ARR ⩾ 1 44.8 weeks (95% CI = 24.5-65.1), and females with EDSS ⩾ 6 and ARR < 1 54.3 weeks (95% CI = 47.2-61.5).

Conclusions: Pre-treatment EDSS and ARR are the most important determinants of therapeutic lag.
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http://dx.doi.org/10.1177/1352458520981300DOI Listing
January 2021

Mitochondria, Oxidative Stress, cAMP Signalling and Apoptosis: A Crossroads in Lymphocytes of Multiple Sclerosis, a Possible Role of Nutraceutics.

Antioxidants (Basel) 2020 Dec 28;10(1). Epub 2020 Dec 28.

CNR-Institute of Biomembranes, Bioenergetics and Molecular Biotechnologies, 70126 Bari, Italy.

Multiple sclerosis (MS) is a complex inflammatory and neurodegenerative chronic disease that involves the immune and central nervous systems (CNS). The pathogenesis involves the loss of blood-brain barrier integrity, resulting in the invasion of lymphocytes into the CNS with consequent tissue damage. The MS etiology is probably a combination of immunological, genetic, and environmental factors. It has been proposed that T lymphocytes have a main role in the onset and propagation of MS, leading to the inflammation of white matter and myelin sheath destruction. Cyclic AMP (cAMP), mitochondrial dysfunction, and oxidative stress exert a role in the alteration of T lymphocytes homeostasis and are involved in the apoptosis resistance of immune cells with the consequent development of autoimmune diseases. The defective apoptosis of autoreactive lymphocytes in patients with MS, allows these cells to perpetuate, within the CNS, a continuous cycle of inflammation. In this review, we discuss the involvement in MS of cAMP pathway, mitochondria, reactive oxygen species (ROS), apoptosis, and their interaction in the alteration of T lymphocytes homeostasis. In addition, we discuss a series of nutraceutical compounds that could influence these aspects.
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http://dx.doi.org/10.3390/antiox10010021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7823468PMC
December 2020

Effect of Disease-Modifying Therapy on Disability in Relapsing-Remitting Multiple Sclerosis Over 15 Years.

Neurology 2021 02 28;96(5):e783-e797. Epub 2020 Dec 28.

From CORe (T.K., I.D., S.S., C.M.), Department of Medicine, University of Melbourne; MS Centre (T.K., I.D., S.S., C.M.), Department of Neurology, Royal Melbourne Hospital, Australia; Karolinska Institute (T.S.), Stockholm, Sweden; Department of Neuroscience (T.S., V.J., A.v.d.W., O.S., H.B.), Central Clinical School, Monash University, Melbourne; Burnet Institute (T.S.), Melbourne, Australia; Department of Neurology and Center of Clinical Neuroscience (D.H., E.K.H.), General University Hospital and Charles University in Prague, Czech Republic; Department of Basic Medical Sciences, Neuroscience and Sense Organs (M. Trojano), University of Bari, Italy; Hospital Universitario Virgen Macarena (G.I.), Sevilla, Spain; Department of Neuroscience, Imaging and Clinical Sciences (A.L.), University "G. d'Annunzio," Chieti; Department of Biomedical and Neuromotor Sciences (A.L.), University of Bologna, IRCCS Istituto delle Scienze Neurologiche di Bologna, Italy; Hopital Notre Dame (A.P., M.G., P.D.), Montreal; CHUM and Universite de Montreal (A.P., M.G., P.D.); CISSS Chaudière-Appalache (P.G.), Levis, Canada; Department of Neurology (V.J., A.v.d.W., O.S., H.B.), Alfred Hospital, Melbourne, Australia; Neuro Rive-Sud (F. Grand'Maison), Quebec, Canada; Department of Neuroscience (P.S., D.F.), Azienda Ospedaliera Universitaria, Modena, Italy; Isfahan University of Medical Sciences (V.S.), Isfahan, Iran; Amiri Hospital (R. Alroughani), Kuwait City, Kuwait; Zuyderland Ziekenhuis (R.H.), Sittard, the Netherlands; Medical Faculty (M. Terzi), 19 Mayis University, Samsun; KTU Medical Faculty Farabi Hospital (C.B.), Karadeniz Technical University, Trabzon, Turkey; School of Medicine and Public Health (J.L.-S.), University Newcastle; Department of Neurology (J.L.-S.), John Hunter Hospital, Newcastle, Australia; UOC Neurologia (E.P.), Azienda Sanitaria Unica Regionale Marche-AV3, Macerata, Italy; Cliniques Universitaires Saint-Luc (V.V.P.), Brussels, Belgium; University of Parma (F. Granella); C. Mondino National Neurological Institute (R.B.), Pavia; Azienda Ospedaliera di Rilievo Nazionale San Giuseppe Moscati Avellino (D.S.), Italy; Flinders University (M. Slee), Adelaide; Westmead Hospital (S.V.), Sydney, Australia; Nemocnice Jihlava (R. Ampapa), Czech Republic; University of Queensland (P.M.), Brisbane; Royal Brisbane and Women's Hospital (P.M.), Brisbane, Australia; Hospital Germans Trias i Pujol (C.R.-T.), Badalona, Spain; CSSS Saint-Jérôme (J.P.), Canada; Hospital Universitario Donostia (J.O.), Paseo de Begiristain, San Sebastián, Spain; Hospital Italiano (E.C.), Buenos Aires, Argentina; Brain and Mind Centre (M.B.), University of Sydney, Australia; INEBA-Institute of Neuroscience Buenos Aires (M.L.S.), Argentina; Hospital de Galdakao-Usansolo (J.L.S.-M.), Galdakao, Spain; Liverpool Hospital (S. Hodgkinson), Sydney, Australia; Jahn Ferenc Teaching Hospital (C.R.), Budapest, Hungary; Craigavon Area Hospital (S. Hughes), UK; Jewish General Hospital (F.M.), Montreal, Canada; Deakin University (C.S.), Geelong; Monash Medical Centre (E.B.), Melbourne, Australia; South East Trust (O.G.), Belfast, UK; Perron Institute (A.K.), University of Western Australia, Nedlands; Institute of Immunology and Infectious Diseases (A.K.), Murdoch University; Sir Charles Gairdner Hospital (A.K.), Perth, Australia; Department of Neurology (T.C.), Faculty of Medicine, University of Debrecen, Hungary; Bombay Hospital Institute of Medical Sciences (B.S.), Mumbai, India; St Vincents Hospital (N.S.), Fitzroy, Melbourne, Australia; Veszprém Megyei Csolnoky Ferenc Kórház zrt (I.P.), Veszprem, Hungary; Royal Hobart Hospital (B.T.), Australia; Semmelweis University Budapest (M. Simo), Hungary; Central Military Emergency University Hospital (C.-A.S.), Bucharest; Titu Maiorescu University (C.-A.S.), Bucharest, Romania; BAZ County Hospital (A.S.), Miskolc, Hungary; and Box Hill Hospital (H.B.), Melbourne, Australia.

Objective: To test the hypothesis that immunotherapy prevents long-term disability in relapsing-remitting multiple sclerosis (MS), we modeled disability outcomes in 14,717 patients.

Methods: We studied patients from MSBase followed for ≥1 year, with ≥3 visits, ≥1 visit per year, and exposed to MS therapy, and a subset of patients with ≥15-year follow-up. Marginal structural models were used to compare the cumulative hazards of 12-month confirmed increase and decrease in disability, Expanded Disability Status Scale (EDSS) step 6, and the incidence of relapses between treated and untreated periods. Marginal structural models were continuously readjusted for patient age, sex, pregnancy, date, disease course, time from first symptom, prior relapse history, disability, and MRI activity.

Results: A total of 14,717 patients were studied. During the treated periods, patients were less likely to experience relapses (hazard ratio 0.60, 95% confidence interval [CI] 0.43-0.82, = 0.0016), worsening of disability (0.56, 0.38-0.82, = 0.0026), and progress to EDSS step 6 (0.33, 0.19-0.59, = 0.00019). Among 1,085 patients with ≥15-year follow-up, the treated patients were less likely to experience relapses (0.59, 0.50-0.70, = 10) and worsening of disability (0.81, 0.67-0.99, = 0.043).

Conclusion: Continued treatment with MS immunotherapies reduces disability accrual by 19%-44% (95% CI 1%-62%), the risk of need of a walking aid by 67% (95% CI 41%-81%), and the frequency of relapses by 40-41% (95% CI 18%-57%) over 15 years. This study provides evidence that disease-modifying therapies are effective in improving disability outcomes in relapsing-remitting MS over the long term.

Classification Of Evidence: This study provides Class IV evidence that, for patients with relapsing-remitting MS, long-term exposure to immunotherapy prevents neurologic disability.
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http://dx.doi.org/10.1212/WNL.0000000000011242DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884998PMC
February 2021

A case report of late-onset atypical Hemolytic Uremic Syndrome during interferon beta in multiple sclerosis: Open issues in literature review.

Brain Behav 2021 01 16;11(1):e01930. Epub 2020 Dec 16.

Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari "Aldo Moro", Bari, Italy.

Background And Aims: Interferon beta (IFNβ) is a well-established first-line therapy for relapsing-remitting multiple sclerosis (RRMS) patients and remains the most widely prescribed agent. Atypical hemolytic uremic syndrome (aHUS) represents a rare but severe adverse effect (AE) that could occur even after many years from the beginning of IFNβ therapy. Eculizumab is currently approved for treatment of aHUS and recently for neuromyelitis optica spectrum disorder (NMOSD) with aquaporin-4 antibodies (AQP4-IgG). In this article, we report the case of the latest onset of IFNβ-related aHUS experienced by an MS patient and we briefly review the literature on this topic.

Methods: We performed a systematic review of the literature using PubMed, and we performed a retrospective analysis of RRMS patients that received IFNβ-1a in our center and developed thrombotic microangiopathy (TMA). From this search, we identified only one patient.

Results: In the published literature, we identified 24 MS patients who received IFNβ as disease-modifying treatment (DMT) and then developed thrombotic microangiopathy with kidney injury. The aHUS has been diagnosed in 6, all received IFNβ-1a and the latest onset was after 15 years. We report a case of a 39-year-old man affected by RRMS who assumed IFNβ-1a since 1999. In July 2018, he developed an IFNβ-related aHUS. After the failure of plasma exchange, he underwent eculizumab, with an improvement of glomerular filtration rate and without new signs of MS activity.

Conclusion: To our knowledge, this case represents the latest onset of IFNβ-related aHUS in MS patients. Up to now, there are not literary reports about the possibility to reintroduce a DMT as add-on therapy to eculizumab.
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http://dx.doi.org/10.1002/brb3.1930DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7821561PMC
January 2021

Oral nomegestrol acetate and transdermal 17-beta-estradiol for preventing post-partum relapses in multiple sclerosis: The POPARTMUS study.

Mult Scler 2021 Aug 3;27(9):1458-1463. Epub 2020 Dec 3.

INSERM U 1195, Le Kremlin-Bicêtre, France.

Background: Sex steroids could explain the course of multiple sclerosis (MS) in pregnancy.

Objective: To compare the annualized relapse rate (ARR) 12 weeks post-partum in women treated with nomegestrol acetate (NOMAc) and 17-beta-estradiol (E2) versus placebo.

Methods: POPARTMUS is a randomized, proof-of-concept trial in women with MS, receiving oral NOMAc 10 mg/day and transdermal estradiol 75 µg/week, or placebo.

Results: Recruitment was stopped prematurely due to slow inclusions ( = 202). No treatment effect was observed on ARR after 12 weeks (sex steroids = 0.90 (0.58-1.39), placebo = 0.97 (0.63-1.50) ( = 0.79)).

Conclusion: POPARTMUS failed showing efficacy of a NOMAc-E2 combination in preventing post-partum relapses.
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http://dx.doi.org/10.1177/1352458520978218DOI Listing
August 2021

Investigating the Effects of COVID-19 Quarantine in Migraine: An Observational Cross-Sectional Study From the Italian National Headache Registry (RICe).

Front Neurol 2020 10;11:597881. Epub 2020 Nov 10.

Applied Neurophysiology and Pain Unit, Scienze Mediche di Base, Neuroscienze e Organi di Senso Department, Bari Aldo Moro University, Bari, Italy.

Previous studies during SARS and Ebola pandemics have shown that quarantine is associated with several negative psychological effects, such as post-traumatic stress symptoms, confusion, and anger. These conditions may affect the course of many diseases, including migraine. Although it is possible that the quarantine measures for the current COVID-19 pandemic affect migraine burden, no information is currently available on this issue. In this study, we aimed to: (1) explore the possible changes in migraine frequency, severity, and days with acute medication intake during quarantine period; (2) evaluate possible differences in migraine outcomes in consideration of lifestyle changes, emotions, pandemic diffusion, and COVID-19 infection. We interviewed patients who were included in the observational Italian Headache Registry (Registro Italiano Cefalee, RICE), retrospectively collecting information on main headache features, lifestyle factors, emotions, individual infection status, and perception of COVID-19 for 2 months before (pre-quarantine) and after the beginning of the quarantine (quarantine). Inclusion criteria were: age > 18, diagnosis of migraine without aura, migraine with aura and chronic migraine, last in-person visit more than 3 months preceding the beginning of quarantine. A total of 433 migraine subjects agreed to be interviewed. We found an overall reduction in headache frequency (9.42 ± 0.43 days with headache vs. 8.28 ± 0.41) and intensity (6.57 ± 0.19 vs. 6.59 ± 0.21) during the quarantine, compared to pre-quarantine. There was a correlation between improvement and number of days of stay-at-home. When results were stratified for geographic area, we found a tendency toward worsening of headache frequency in northern Italy. Disgust regarding viral infection corresponded to a minor improvement in migraine. Migraine patients showed a mild improvement of migraine features, probably attributable to resilient behavior toward pandemic distress. Disgust regarding the contagion whereas potentially favoring defensive behavior, could potentially worsen migraine. The spontaneous limitation of migraine burden during quarantine could favor patient follow-up via the use of telemedicine visits, reliable diaries, and frequent remote contacts.
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http://dx.doi.org/10.3389/fneur.2020.597881DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7683429PMC
November 2020

Transition to secondary progression in relapsing-onset multiple sclerosis: Definitions and risk factors.

Mult Scler 2021 03 19;27(3):430-438. Epub 2020 Nov 19.

Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari "Aldo Moro," Bari, Italy.

Background: No uniform criteria for a sensitive identification of the transition from relapsing-remitting multiple sclerosis (MS) to secondary-progressive multiple sclerosis (SPMS) are available.

Objective: To compare risk factors of SPMS using two definitions: one based on the neurologist judgment (ND) and an objective data-driven algorithm (DDA).

Methods: Relapsing-onset MS patients ( = 19,318) were extracted from the Italian MS Registry. Risk factors for SPMS and for reaching irreversible Expanded Disability Status Scale (EDSS) 6.0, after SP transition, were estimated using multivariable Cox regression models.

Results: SPMS identified by the DDA ( = 2343, 12.1%) were older, more disabled and with a faster progression to severe disability ( < 0.0001), than those identified by the ND ( = 3868, 20.0%). In both groups, the most consistent risk factors ( < 0.05) for SPMS were a multifocal onset, an age at onset >40 years, higher baseline EDSS score and a higher number of relapses; the most consistent protective factor was the disease-modifying therapy (DMT) exposure. DMT exposure during SP did not impact the risk of reaching irreversible EDSS 6.0.

Conclusion: A DDA definition of SPMS identifies more aggressive progressive patients. DMT exposure reduces the risk of SPMS conversion, but it does not prevent the disability accumulation after the SP transition.
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http://dx.doi.org/10.1177/1352458520974366DOI Listing
March 2021
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