Author Of 5 Presentations
LB1154 - COVID-19 in cladribine-treated patients with relapsing-remitting multiple sclerosis: a monocentric experience (ID 1085)
Abstract
Background
Cladribine significantly reduces disease activity and disability progression in relapsing-remitting multiple sclerosis (RRMS) through a selective but transient depletion of lymphocyte subsets. The SARS-COV-2 outbreak has raised several concerns regarding cladribine use for RRMS patients.
Objectives
To evaluate the prevalence and clinical features of COVID-19 disease among cladribine-treated relapsing-remitting MS patients.
Methods
Fifty-six RRMS patients treated with cladribine in our centre (female=39; mean age=33.8 years [y]; median Expanded Disability Status Scale [EDSS]=1.5, disease duration [DD]=5.2 y, treatment duration=1.15 y) were asked if they had developed manifestations suggestive of SARS-COV-2 infection up to June 30th 2020. Their detailed characteristics were collected.
Results
At June 30th 2020, nasal/pharyngeal swabs have been found positive in 0.94% of the Lombardy population. Since the pandemic start, 2/56 (3.6%) cladribine-treated RRMS complained a symptomatology suggestive of COVID-19 disease, with a prevalence similar to that of the whole MS population of our centre (84/2950, 2.8%). The first patient was a 30-year-old male with RRMS (DD=1.2 y, EDSS=1.5) and no comorbidities. He started cladribine on January 10th 2020. One week later, he developed fever (<37.5°), ageusia, cough, fatigue, sputum production, sore throat, nasal congestion, shortness of breath without desaturation and conjunctivitis.
The second patient is a 39-year-old female with RRMS (DD=13.2 y, EDSS=3.5), and no comorbidities. She started cladribine on February 13th 2020 and underwent the second week of the first treatment course from March 5th 2020. On March 30th, she developed fever (<37.8°), anosmia, ageusia, cough, fatigue, and bone/joint pain. Serology for SARS-COV-2 was positive in May 2020. For both patients, blood examinations performed before and after COVID-19 disease were within normal limits. Both patients were telephone-monitored at home and completely recovered within 15 days.
Conclusions
Only a minority of cladribine-treated RRMS patients developed a mild and self-limiting COVID-19 disease. In our cohort, this occurred in two RRMS patients within a few weeks from treatment course and the possible nadir of selective immunosuppression. Both patients recovered completely. Cladribine administration seems to be safe also in the setting of the COVID-19 pandemic.
LB1158 - COVID-19 pandemic and mental distress in Multiple Sclerosis: implications for clinical management (ID 1300)
Abstract
Background
in multiple sclerosis (MS), disease-related factors and dysfunctional coping might favour the development of mental distress induced by COVID-19 containment measures.
Objectives
to explore the relationship between mental distress, disability and coping strategies in the Italian MS population under lockdown.
Methods
Structural equation modeling (SEM) was applied to information collected via web-survey to identify modifiable factors that could account for mental distress. Information about the following domains was collected: (1) socio-demographic features; (2) general and MS related health status; (3) changes in lifestyle; (4) COVID-19 infection and risk perception; (5) physical disability assessed via the Patient-Determined Disease Steps (PDDS) scale and the Upper Extremity Function – Short Form (UEF) from the Quality of Life in Neurological Disorders (Neuro-QoL) measurement system; (6) cognitive function investigated using the Cognition Function– Short Form from the Neuro-QoL. Abstract reasoning, logical thinking and, in part, sustained attention, were measured using six Raven-like matrices; (7) mental distress: four domains from the Neuro-QoL were explored. Specifically, sleep disturbances, anxiety feelings, depressive symptoms, emotional dyscontrol; (8) coping strategies: individual response to lockdown was assessed using 18 items from the COPE-NVI-25, evaluating five independent coping strategies: avoidance (AV), social support (SS), positive attitude (PA), problem solving (PS) and turning to religion (TR).
Results
845 subjects (497 MS and 348 controls) were included in the study. MS patients showed higher scores than controls for depression (p=0.005), but not for anxiety, emotional dyscontrol or sleep disturbances. The SEM explained 74% of the variance observed in depression score. Within the model, three latent factors were characterized from measured variables: motor disability and cognitive dysfunction contributed to disability (β=0.509 and β=0.836, p<0.001); positive attitude and exercise contributed to active attitude (β=0.386 and β=0.297, p<0.001); avoidance, social support and watching TV contributed to passive attitude (β=0.301, β=0.243 and β=0.212, p<0.001). As per the relationship between latent factors and their influence on depression, disability contributed to passive attitude (β=0.855, p<0.001) while both passive and active attitude significantly influenced depression (β=0.729 and β=-0.456, p<0.001).
Conclusions
As practical implication of our model, favoring exercise would enhance active attitude and its positive impact on mental well-being while, at the same time, reducing the negative impact of disability on depression, representing a valuable tool for the long term management of COVID-19 related mental distress in MS.
P0273 - A multicentre, real-life study on the risk of lymphopenia and infections discloses a favourable safety profile of cladribine in MS patients. (ID 1086)
Abstract
Background
Background. Lymphopenia monitoring during treatment with disease modifying drugs for MS is relevant because of the potential increased risk of infections. Lymphopenia is an anticipated effect of cladribine (CLD) treatment, given its mechanism of action.
Objectives
Objectives. We aimed to i) characterize the absolute lymphocyte count (ALC) changes, and ii) evaluate the risk of infections in CLD-treated RRMS patients. ALCs were graded according to the Common Terminology Criteria for Adverse Events (CTCAE v5.0).
Methods
Materials and methods. In this observational multicentre study, demographic, clinical and MRI data of the patients included in the Free Of Charge CLD program were collected. ALC was also collected at baseline (before therapy initiation) and at month 3, 7, 12, 15, 19 and 24.
Results
Results. 236 patients were enrolled in 56 Italian MS Centres (71% F; mean age: 39+11.5 years; mean disease duration: 10+8.5 years). The median baseline EDSS was 3.0 (quartiles 1.5-3.5; range 0-6.5). 53 patients (22.5%) were treatment naïve, 107 (45.3%) switched to CLD from first line DMDs (for inefficacy), 76 (32.2%) switched to CLD after a second line therapy (33/76 for safety reason, 43/76 for inefficacy). Mean follow up was 12.2+5 months. At baseline, median ALC was 1615.0 cell/mm3 (quartiles, 1300.0-2200.0). At month 3, ALC was available in 190/236 and 101/190 had lymphopenia: 12 (6.3%) grade 3, 47 (24.7%) grade 2 and 42 (22.1%) grade 1. Among patients presenting grade 3 at month 3, only one had persistent ALC <500 cell/mm3 at month 7. At month 7, ALC was available in 180/236 and 77/180 had lymphopenia: 1 (0.6%) grade 4, 1 (0.6%) grade 3, 43 (23.9%) grade 2 and 32 (17.8%) grade 1. Up to date, 159/236 patients were re-treated. No retreatment was delayed because of grade 4 lymphopenia. No patient presented grade 4 lymphopenia at month 15, 6/89 (6.6%) experienced grade 3, 37/89 (40.7%) grade 2, 17/89 (18.7%) grade 1. At month 19, 1/38 (2.6%) presented grade 3 lymphopenia, 11/38 (29.0%) grade 2 and 9/38 (23.7%) grade 1. At month 24, 1/9 (11.1%) patient presented grade 3 and 1/9 (11.1%) presented grade 4 lymphopenia. During treatment course, 15 patients experienced infections (1 VZV, 3 HSV), none occurring in grade 3 or 4 lymphopenia.
Conclusions
Conclusions. In our study, the risk of grade 3 and 4 lymphopenia was lower compared to that observed in RCT. Moreover, grade 3 lymphopenia was transient in the majority of the patients. Compared to RTC, a more favourable CLD safety profile emerged in our study.
P0666 - Telemedicine in/outside the pandemic: a survey about satisfaction of this tool in a cohort of multiple sclerosis patients and their neurologists (ID 1810)
Abstract
Background
Telemedicine is a live communication between patients and physicians through different technological tools. It became fundamental during COVID-19 pandemic to keep on taking care of patients in more medical fields than before. Given the chance for telemedicine to become a pivotal part of neurological routine practice, we investigated patients and neurologists satisfaction about this tool.
Objectives
This survey aimed to understand satisfactionabout telemedicine during pandemic and its possible use in the future outside pandemic
Methods
We administered a brief survey to a cohort of Multiple Sclerosis (MS) patients and their neurologists at MS center of San Raffaele Hospital, Milan. Demographic and clinical data (EDSS, treatment) were collected.
Results
151 patients filled out the survey: 75% females; mean age 42.2yy (18-73); median EDSS 1.5 (0-7). Treatments were almost equally distributed across first and second-line drugs (10% interferon, 10% glatiramer acetate, 14% teriflunomide, 22% dimethylfumarate, 23% fingolimod, 3% cladribine, 8% alemtuzumab, 10% ocrelizumab).
87% of patients appreciated telemedicine during pandemic; 10% had a positive opinion but with a need for traditional evaluations, while 3% were not satisfied.
Considering the possible routine use of telemedicine outside the pandemic, 82% firmly stated the importance of traditional evaluations. In particular, 44% would alternate in person and remote visits, while 38% strongly preferred traditional ones. Among the latters, the main reasons were the need for human empathy with the neurologist and the feeling that traditional evaluations may lead to better clinical outcomes. The remaining 18% would always use telemedicine except in the case of acute events. Neurologists and residents (n=18) were inquired about telemedicine: no one would use it as the only tool, 33% would alternate it with traditional practice and 67% would use it only in special contexts.
Conclusions
In our survey, both patients and neurologists recognized the importance of telemedicine during a pandemic. Patients more than physicians seemed ready to use it in everyday clinical practice. These data may be biased by a still ongoing patients fear and physicians lack of confidence in this multifaceted tool. The pandemic spurred the development of institutional telematic platforms capable of providing legal protection and traceability of visits and communication between patients and physicians. So far, we can conclude that telemedicine is a useful tool to overcome space-time limits, giving the best care to all patients in any condition. However, it cannot replace but only integrate traditional medicine.
P0910 - Relapse-free and NEDA status with Cladribine in a real life population: a multicentre study (ID 1484)
Abstract
Background
Trials leading to Cladribine (CLD) approval for the treatment of Multiple Sclerosis (MS) were conducted over a decade ago: there is a need of proof of CLD efficacy and safety profile in the present MS therapeutic landscape.
Objectives
To evaluate CLD efficacy and safety profile in the current MS population, and to identify early predictors of response.
Methods
Before the drug was marketed under the national healthcare system, in Italy CLD was available through a Free Of Charge (FOC) program. We asked all participating MS centres to contribute to the present study, collecting demographic, clinical and MRI data of the patients who received CLD in the FOC program.
Results
56 MS centres participated to the study, for a total of 236 patients (71% F) (mean age: 39 + 11,5 years; mean disease duration: 10 + 8,5 years). Mean Annualized Relapse Rate (ARR) in the two years before CLD was 0,7 + 0,6; median baseline EDSS was 3 (quartiles 1,5-3,5; range 0-6,5). 53 patients (22,5%) were treatment naïve, 107 (45,3%) switched to CLD from first-line DMDs (for inefficacy), 76 (32,2%) switched to CLD from a second line therapy (33/76 for safety or loss of tolerability, 43/76 for inefficacy). Mean follow up was 12,2 + 5 months. 84,7% of the patients were relapse-free at follow-up. Mean ARR at follow-up was 0,2 + 0,6. Patients taking CLD as first therapy were less likely to experience a relapse (HR 0,6; 95% CI: 0,2-0,8; p = 0,04) while a higher baseline ARR was a predictor of clinical activity (HR 2,7, 95% CI: 1,4-5,6; p = 0,004). Median EDSS at follow up was 2 (quartiles 1-3,5). EDSS was stable in 73.7%, improved of at least 1 point in 21,6% and worsened of at least 1 point in 4,7% of the patients. 157/236 patients completed one year of follow up. Of these 92 (59,7%) reached No Evidence of Disease Activity (NEDA-3); NEDA-3 was achieved more frequently by naive patients (70%) than switchers from a first (57%) or a second line (50%) (HR 2,3; 95% CI: 1,01-5,3; p = 0,04). 33/236 patients reported at least one adverse event (AE), most frequently infections (15 cases); other AEs included gastrointestinal side effects, cutaneous rash, aphthous stomatitis and headache. Two severe AEs were reported (one pneumonia, one melanoma).
Conclusions
Even with the limitations of a retrospective study, our data confirm CLD safety and efficacy profile. Consistently with previous studies on patients with a first demyelinating event, CLD efficacy is maximized when used early in the course of MS.