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Introduction: Balance impairments are common in multiple sclerosis (MS). Pilates is a popular alternative method for balance performance maintenance and improvement that may reduce the rapid symptoms worsening frequently associated with physical inactivity. An Italian network of fifteen experts in MS rehabilitation developed through a User-Centered Design approach the MS-FIT exergame, a Kinect-based tool, to autonomously train balance through Pilates exercises. The MS-FIT user executes the exercises shown by a teacher's avatar and improves the performances through the feedbacks on the execution correctness. Aim(s): This study (Clinical.Trials.gov, NCT04011579) aims at evaluating the feasibility of an at-home intervention with MS-FIT. Method(s): Feasibility was investigated in terms of adherence (sessions number), usability (usability items of Tele-healthcare Satisfaction Questionnaire, u-TSQ, satisfaction (Client Satisfaction Questionnaire, CSQ-8), safety (adverse events), and physical effectiveness (Timed UP-&-GO, TUG;Timed 25-Foot Walk, T25FW;2-Minutes Walking Test, 2MWT). Result(s): Forty-five people with MS (PwMS) were enrolled and randomized into the experimental (EXP, n=23) and control (CTRL, n=22) groups. During the 6 weeks of the study, only the usual physical activities were admitted (rehabilitation excluded) and, in addition, EXP had to practice MS-FIT at least three times a week. Due to organizational consequences of COVID pandemic, 8 subjects dropped-out (EXP, n=17;CTRL, n=20). The sample analysed showed the following characteristics: gender (EXP: 6M;CTRL: 7M), age (EXP: 41.9+/-9.6y;CTRL: 43.3+/-10.5y), course (EXP: 94.4% and CTRL: 95.0% relapsing-remitting), disease duration (EXP: 9.9+/-7.2y;CTRL: 12.5+/-9.8y) and EDSS (EXP: 2.6+/-0.8;CTRL: 2.6+/-0.8). EXP highly adhered to the MS-FIT training (23.6+/-6.1 sessions);the tool was usable (u-TSQ: 3.01/4);satisfaction was medium-tohigh (CSQ-8: 25.1/32);the training with MS-FIT was safe (no adverse events). The groups did not differ in TUG, T25FW and 2MWT. An analysis separate for each group showed a significant improvement only in EXP (TUG: pre 7.5+/-1.2s, post 7.0+/-1.2s, p<0.05;T25FW: pre 6.1+/-1.5s, post 5.0+/-1.2s, p<0.01;2MWT: pre 175.4+/-51.0m, post 194.1+/-56.9m, p<0.01). Conclusion(s): MS-FIT is well-accepted and effective and could be a complement of traditional MS interventions. Based on the results and participants' feedbacks MS-FIT has been refined and is used in an ongoing randomized controlled trial.
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Introduction: Concerns have emerged during Covid-19 pandemic about management of Disease Modifying Therapies (DMTs) in patients with Multiple Sclerosis (pwMS). In particular, Ocrelizumab (OCR)-treated pwMS faced possible delays of scheduled infusions due to disruption of MS Centers activities as well as safety worries during lockdown periods. Objective(s): To assess changes of OCR infusion schedule in Italian pwMS during the first wave of COVID-19 pandemic (observation period: February-June 2020) and to investigate predictive factors determining delaying of OCR infusions. Material(s) and Method(s): Data were extracted from the Italian MS Register database. pwMS with an OCR infusion scheduled during the observation period and at least two previous OCR infusions were selected. Demographics (age, gender), disease characteristics (MS phenotype, disease duration, Expanded Disability Status Scale score, number of previous OCR infusions) and location of MS Centers among three Italian macro-regions (North, Center, South) were tested as potential predictors for treatment delay using univariable and multivariable linear model analyses. Result(s): Five-hundred ninety-nine pwMS (343 F/256 M;411 Relapsing MS/188 Progressive MS) from 65 MS centers were included in the analysis. Mean interval between two OCR infusions was 28.1 weeks (SD 2.72) before the observation period compared to 30.8 weeks (SD 5.45) during the observation period, with a mean delay of 2.7 weeks (p <0.001). No clinico-demographic factors emerged as predictors of infusion postponement, except for location of MS centers in the North of Italy (4.7 weeks vs 1.5 in the Center and 1.6 in the South). Such a difference was confirmed in multivariate analysis (p < 0.001) adjusting for prelockdown mean OCR infusion schedule. Conclusion(s): This large registry-based study shows that OCR infusions were significantly delayed during the first wave of COVID-19 pandemic in Italy. The location of the MS Centers in Northern Italy was the only predictor of OCR infusion postponement. This geographical area corresponds to the region in Italy that was hit first and more strongly by Covid-19 pandemic. The observed delay in OCR infusions disruptions of MS centers activities due to a drastic reduction of healthcare workers availability (because of infection/quarantine and/or reallocation in Covid Units) and concerns about using an immunosuppressive DMT like OCR during a new virus pandemic with many uncertainties.
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Background: Attenuated antibody and robust T-cell responses following SARS-CoV-2 vaccines have been reported in people with multiple sclerosis (PwMS) treated with ocrelizumab (OCR). Factors influencing humoral and cellular responses and how these relate to clinical protection are not well understood. Aim(s): To investigate the effect of OCR on antibody and T-cell responses to SARS-CoV-2 vaccines, and characterise clinical outcomes of breakthrough COVID-19 infections in PwMS. Method(s): Patients participating in three ongoing Phase IIIb studies evaluating the effectiveness and safety of OCR, who decided to receive a SARS-CoV-2 vaccine as part of national immunisation programmes, were invited to undergo optional exploratory assessment. Antibody responses to SARS-CoV-2 spike and nucleocapsid proteins were assessed using the Elecsys electrochemiluminescence assay. Interferon-gamma ELISpot (ImmunoSpot) was used to detect SARS-CoV-2-specific T cells against 4 different peptide pools of the spike protein. Vaccine breakthrough cases were defined as suspected or laboratory-confirmed COVID-19 infections occurring >=14 days after completion of the recommended primary immunisation schedule. Result(s): Up to Sept 2021, 111 patients provided samples for assessment of response to SARS-CoV-2 vaccination. Mean (SD) age was 41.7 (11.8) years;63.1% were female;72.1% had relapsing- remitting MS, 15.3% secondary progressive MS and 12.6% primary progressive MS.Most patients had been on treatment with OCR for at least 2 years. Mean (SD) of 78.5 (41.4) days elapsed between the first vaccine dose and last OCR infusion. 94/111 patients received an mRNA vaccine and 15 patients an adenoviral vaccine. Most samples were collected within 80 days following completion of the primary vaccine schedule. Antibody response was detected in 22/103 (21%) patients and T-cell responses to >=1 of the 4 different peptide pools in 83/95 (87%) patients. Four breakthrough infections were reported. Conclusion(s): In preliminary analysis, frequency of patients with an antibody and T-cell response were in line with published data for PwMS on OCR. Expanded analyses with a larger set of patients (approximately 450 patients, up to March 2022), including longitudinal responses, booster data, differences between vaccine platforms and assessment of factors that may affect immune responses will be presented. Correlations between level of immune responses and breakthrough infection diagnosis and severity will be explored.
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Introduction: MS centers (MSc) activities related to OCR management were strongly and diffusely hit during the first wave of COVID-19 pandemic. Concerns were mainly related to its immunosuppressive effects and the need for in-hospital administration. Objective(s): To investigate changes in OCR schedule among Italian MS centers participating to the Italian MS Register during the first wave of COVID-19 pandemic and to identify factors determining such changes. Material(s) and Method(s): A quick online survey was sent to 65 Italian MSc in order to collect from them the following data: macro-region (North, Center, South) location, number of OCRtreated patients, modifications of OCR schedule and a list of factors potentially influencing the postponement of OCR infusions (i.e. age, co-morbidity, MS phenotype, number of previous OCR cycles, disease severity/activity, CD-20 lymphocytes count, distance to MS center, fear of infection, inclusion in a research trial, infections trend, shortage of medical/paramedical staff for reallocation/ infection). Result(s): Among 55 MSc who answered the survey, 50 (91%) declared to have suspended or extended OCR interval dosing for at least one patient. The MSc that didn't modify OCR schedule were all from the South of Italy (33% of all South MSc). Main factors influencing OCR schedule delay were advanced age/comorbidity (70%) and pandemic trend in the area (72%), while recent MS-disease activity hindered OCR schedule modifications (65%). Conclusion(s): This study shows that most Italian MSc decided either to delay or suspend OCR treatment during the first wave of COVID-19 pandemic. Advanced age and co-morbidity and no evidence of recent MS-disease activity were the most relevant patient-dependent predictors of OCR postponement. Among patient-independent factors the most relevant factor was the local trend of infections. Contrary to what expected, the shortage of medical and/or paramedical staff in MSc did not come out as relevant. The disruption of OCR schedule during the first COVID-19 pandemic wave in Italy mostly reflected the geographical distribution and the impact on the National Health System of COVID- 19 pandemic.
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Background: Multiple sclerosis (MS) is a chronic disabling disease associated with negative effects on quality of life (QoL), including physical and mental health. The objective of this investigation was to evaluate the change in QoL for patients with highly active relapsing MS at 1 year after initiating treatment with cladribine tablets (CladT), by assessing changes in the physical and mental health composite scores of Multiple Sclerosis Quality of Life-54 (MSQoL-54). Material(s) and Method(s): In CLARIFY-MS (NCT03369665), patients with highly active relapsing MS were assigned to receive CladT 3.5 mg/kg cumulative dose over 2 years. Patients were recruited as per the EU label. Results in this interim analysis, conducted prior to the second year of treatment, were assessed using a mixed-effects linear model. Analyses were also conducted for cohorts separated by treatment naïve/prior disease-modifying therapy (DMT), and MSQoL reporting performed before/after the start of the COVID-19 pandemic, as defined as the first reported fatality within each country. Result(s): Of the 482 patients treated with CladT, 70.1% were female and the mean age was 37.4 years. Of the 426 patients who provided MSQoL-54 data, statistically significant (p<0.0001) improvements from Baseline to Month 12 were observed for physical and mental health composite scores with estimated changes of 4.51 (95% confidence interval [CI] 3.24–5.77) and 4.53 (95% CI 3.00–6.05), respectively. Similar trends were apparent for treatment naïve (n=121) and prior DMT (n=305) cohorts. There was no indication that the start of the COVID-19 pandemic had an impact on MSQoL-54 reporting. Regarding safety, 322 patients (66.8%) experienced at least one treatment-emergent adverse event, most commonly headache (16%), nasopharyngitis (9%), and lymphopenia (9%). The majority of observed post-baseline lymphopenia events were grade 1–2;fewer patients reported grade 3 lymphopenia, no grade 4 lymphopenia was observed. Conclusion(s): With only half a therapeutic dose of CladT, this interim analysis demonstrates a statistically significant improvement in the physical and mental health composite scores of MSQoL-54 at 1 year. No new safety concerns were found in this 1-year interim analysis, with no new severe or opportunistic infections that could have an impact on the established benefit:risk profile of CladT in MS.
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Introduction: MS patients affected by SARS-CoV-2 disease may present with a wide pattern of symptoms, not always suggestive of the severity of infection. A recent study has shown that main symptoms of Covid-19 can be grouped in seven different clusters. Risk and protective factors for their occurrence in MS patients has never been investigated. Objectives: To identify the most common symptoms of Covid-19 that are part of specific clusters in MS patients and evaluate all factors associated with their manifestation. Methods: As part of the MuSC-19 Italian project, all data were extracted from a dedicated web-based platform that allows researchers to evaluate the impact of Covid-19 on people affected by MS. After having tested the degree of agreement between different types of symptoms (Cohen's k), univariate and multivariate logistic regression models were applied to identify predicting factors for each group. Results: 1554 MS patients with confirmed Covid-19 and presenting at least one symptom referred to a specific cluster were analyzed. Patients presented nearly three groups of symptoms (mean: 2.8). The most common include fever/chills/rigor/fatigue/ cough (87%), followed by ageusia/anosmia (46%). Smoking habit was the most confirmed risk factor for developing a wide range of symptoms: common cold-like symptoms (OR:1.6, 95%CI:1.3- 2.1;p<0.001), joint and muscle pain (OR:1.3, 95%CI:1.1-1.7;p=0.037), gastrointestinal problems (OR:1.3, 95%CI: 1.1-1.7;p = 0.029), and loss of smell/taste (OR:1.4, 95%CI: 1.07-1.72;p=0.013). Smoking was confirmed also as risk factor for increasing the number of symptoms (OR:1.5, 95%CI:1.2-1.8;p<0.001), together with alcohol use (OR:1.25, 95%CI:1.1-1.5;p=0.021) and with assumption of anti-CD20 therapies (OR:1.7, 95%CI:1.2-2.5;p=0.004). Males have a lower risk for developing a major number of symptoms (OR:0.8, 95%CI:0.6 - 0.9;p=0.006). Finally, a lower EDSS was associated to a slight increment of symptoms, probably due to an already underlying presence of some common symptoms in most critical MS patients, which consequently were not reported (OR:0.9, 95%CI:0.8-0.9;p=0.005). Conclusions: Knowing possible risk factors and modifying some lifestyle behaviors might minimize the occurrence of Covid-19 symptoms. Anyway, further studies are needed for confirming these findings, and an additional follow up study on the presence of persistent symptoms after apparent Covid-19 resolution may help to better understand all possible risk factors.
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Introduction: Studies have pointed out that air pollution longterm exposure may play a role in the severity and prognosis of SARS-CoV-2 infections. Additionally, air pollution has been associated to MS prevalence and course. However, the role of air pollution in COVID-19 severity has never been explored specifically among MS patients. Aims: To explore the association between air pollution assessed by PM2.5 levels and COVID-19 severity among MS patients. Methods: Demographic and clinical characteristics as well as data about Covid-19 severity were extracted from an Italian webbased platform (Musc-19 project) containing clinician-reported data from 118 Italian MS centers. PM2.5 ground-level concentrations were derived from air quality model results, as provided by the 'Copernicus Atmospheric Monitoring Service' (CAMS). Ordered logistic regression models were used to assess the association between PM2.5 (continuous and in tertiles) and Covid-19 prognosis (defined on three levels as mild course, hospitalization, and intensive care unit (ICU) admission or death) while controlling for possible confounders. Results: PM2.5 concentrations were available for 1517 MS patients, of whom 1321(87%) were classified as mild Covid-19 cases, 172(11%) were hospitalized and 24(2%) were admitted to ICU or died. Higher concentrations of PM2.5 were associated with increased odds of developing a worst Covid-19 prognosis (10-unit increase in PM2.5: OR(95% CI)=1.76(1.16-2.67) p-value=0.008;3rd vs 1st tertile: OR(95% CI)=1.74(1.17-2.59) p-value=0.006). Results remained consistent when we included only the Covid-19 cases confirmed by a nasopharyngeal swab (N=1087). Conclusions: Higher concentrations of PM2.5 are associated with Covid-19 severity among MS patients. Further studies are needed to evaluate the impact of other air pollutants, but urgent measures to reduce air pollution must be surely adopted.
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Background: Data collected from several international platforms provided important information about risk factors, including treatment exposure, impacting COVID-19 severity in people with multiple sclerosis (PwMS). However, up to now, factors increasing the risk of getting SARS-CoV2 infection in PwMS are not known. MS registers represent a suitable tool to provide denominators for risks assessment. Objectives: To assess risk factors for SARS-CoV2 infection in PwMS by using data collected in the Italian MS Register (IMSR). Methods: A case-control (1-2) study was set-up. PwMS with (cases) and without (controls) COVID-19 were identified within the IMRS and propensity-score matched by the date of COVID-19 diagnosis (cases) and the date of last visit (controls) and for the region of residence. COVID-19 risk was estimated by multivariable logistic regression models including demographic and clinical covariates. The role of DMTs exposure was assessed in 3 different models including: last recorded DMT or DMT sequences (induction strategy/escalation strategy/only first line DMT exposure/ never treated) or last DMTs grouped according to the place of administration (at hospital or self-administered at home). A minimal treatment exposure for each DMT was defined on the basis of the recognized minimal time required to be potentially effective. Results: A total of 779 [median (IQR) age: 42.40 years (33.00- 50.80);30.17% male] confirmed COVID-19 cases were matched to 1558 controls [46.90 years (37.50-55.70);35.82% male]. In all models, comorbidities, female sex and age were significantly associated (p<0.02) to a higher risk of getting COVID-19. Patients receiving Natalizumab as last DMT (OR (95% CI): 2.38(1.66-3.42), p<0.0001) and those who underwent an escalation treatment strategy (1.57 (1.16-2.13), p=0.003) were at significant higher COVID-19 risk. Moreover, the group of PwMS receiving last DMTs requiring hospital access (1.65(1.34-2.04), p<0.0001) showed a significant higher risk than those taking selfadministered DMTs at home. Conclusions: This case-control study embedded in the IMSR showed that PwMS at higher COVID-19 risk are younger, more frequently female and with comorbidities. Long-lasting escalation approach and last therapies that expose patients to the hospital environment seem to increase significantly the risk SARS-CoV2 infection in PwMS.
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Objective: To describe the effect of disease modifying therapies (DMT) on Covid-19 severity in a large cohort of Italian patients with Covid-19 and multiple sclerosis (MS). Background: We previously presented data from a nationwide study of persons with MS with suspected or confirmed Covid-19, collected from March 2020. In June we started collecting also asymptomatic patients, when serological tests started to be routinely done. Design/Methods: This was a retrospective multi-center observational study. We defined Covid-19 severity as a 4-level variable: Level 1=asymptomatic, level 2=symptomatic without signs of pneumonia, level 3=radiologically defined pneumonia or hospitalization, level 4=intensive care unit (ICU) or death. We analysed the impact of baseline variables on this outcome by a multivariable ordinal logistic model quantifying the association by Odds Ratio (OR). Results: On October 12, we enrolled 902 MS patients, 298 (33%) with confirmed and 604 (67%) with suspected Covid-19;37 (4%) were asymptomatic. The number of ICU/deaths were 8/95 (8%) among those treated with anti-CD20 therapies (mean age=41 years), 0/84 (0%) among those treated with Interferon (mean age=47 years) and 37/723 (5%) among those treated with other drugs (mean age=43 years). Among the 37 asymptomatic patients, 7/84 (8.3%) were in Interferon, 1/95 (1.1%) was on anti-CD20 and 29/723 (4%) were on other drugs. At multivariable analysis, independent risk factors for a severe Covid-19 were age (OR=1.05, p<0.001), EDSS(OR=1.13, p=0.02), Male sex(OR=1.44, p=0.057) and DMT used: Treatment with anti-CD20 (Ocrelizumab or Rituximab) increased the risk (OR=1.99, p=0.035) and treatment with Interferon reduced the risk (OR=0.48, p=0.05) of severe Covid-19 as compared to treatment with DMF, used as the reference DMT. Conclusions: This analysis confirms on a larger population the increase of risk of severe Covid-19 of anti-CD20 therapies and highlights the protective role of Interferon. Data on asymptomatic patients are rapidly accumulating and will provide useful information about this.