Author Of 6 Presentations
LB1169 - Psychological consequences of COVID-19 pandemic in Italian MS patients: a surprising resilience (ID 1668)
Italy was strongly hit by COVID-19 pandemic, therefore the Italian Government decreed urgent measures promoting social distancing in order to limit the spread of the virus. In fact, since March 11th, all not indispensable work, social, sporting, retail and recreational activities were suspended or, where possible, converted to the so-called smart-working. Fear of getting sick from COVID-19, government’s lockdown and the imposed social distancing might have an impact on anxiety, depression and quality of life (QoL) in people with Multiple Sclerosis (pwMS).
The aim of our study was to investigate anxiety, depression and QoL changes in pwMS during SARS-CoV-2 outbreak and lockdown in Italy.
Sixty-seven pwMS with a previous (less than 6 months) neuropsychological evaluation before SARS-CoV-2 outbreak (T0) were re-evaluated at the time of the outbreak and lockdown in Italy (T1). They underwent a clinical and neurological evaluation (at T0) and completed the State-Trait Anxiety Inventory (STAI-Y1), the Beck Depression Inventory second edition (BDI-II), and Multiple Sclerosis Quality of Life-54 (MsQoL-54) at T0 and T1. Bonferroni correction for multiple comparisons was applied.
BDI-II and STAI-Y1 scores did not change between T0 and T1, whereas the satisfaction on sexual function subscale of MsQoL-54 was significantly higher at T1 (p<0.001).
Despite the tight Italian lockdown due to the COVID-19 pandemic and the fear of getting sick, we did not observe a relevant negative impact on anxiety, depression and QoL of our sample of pwMS. Contrariwise, we were even able to detect some positive effects on specific aspects of QoL, such as sexual satisfaction.
P0085 - Harmonization of real-world studies in multiple sclerosis: retrospective analysis from the RIReMS group (ID 687)
Worldwide multiple sclerosis (MS) centers have coordinated their efforts to use data acquired in clinical practice for real-world observational studies.
In this retrospective study, we aim to harmonize outcome measures, and to evaluate their heterogeneity within the Rising Italian Researchers in MS (RIReMS) study group.
RIReMS members filled in a structured questionnaire evaluating the use of different outcome measures in clinical practice. Thereafter, thirty-four already-published papers from RIReMS centers were used for heterogeneity analyses, using the DerSimonian and Laird random-effects method to compute the between-study variance (τ2).
Based on questionnaire results, we defined basic modules for diagnosis and follow-up, consisting of outcome measures recorded by all participating centers at the time of diagnosis, and, then, at least annually; we also defined more detailed/optional modules, with outcome measures recorded less frequently and/or in the presence of specific clinical indications. Looking at heterogeneity, we found 5-year variance in age at onset (ES=27.34; 95%CI=26.18, 28.49; p<0.01; τ2=4.76), and 7% in female percent (ES=66.42; 95%CI=63.08, 69.76; p<0.01; τ2=7.15). EDSS variance was 0.2 in studies including patients with average age <36.1 years (ES=1.96; 95%CI=1.69, 2.24; p<0.01; τ2=0.19), or from 36.8 to 41.1 years (ES=2.70; 95%CI=2.39, 3.01; p<0.01; τ2=0.18), but increased to 3 in studies including patients aged >41.4 years (ES=4.37; 95%CI=3.40, 5.35; p<0.01; τ2=2.96). The lowest variance of relapse rate was found in studies with follow-up duration ≤2 years (ES=9.07; 95%CI=5.21, 12.93; p=0.02; τ2=5.53), whilst the lowest variance in EDSS progression was found in studies with follow-up duration >2 years (ES=5.41; 95%CI=3.22, 7.60; p=0.02; τ2=1.00).
We suggest common sets of biomarkers to be acquired in clinical practice, that can be used for research purposes. Also, we provide researchers with specific indications for improving inclusion criteria and data analysis, ultimately allowing data harmonization and high-quality collaborative studies.
P0100 - Italian prospective multicentric observational real-life study of aggressive Relapsing Remitting Multiple Sclerosis treated with alemtuzumab (ID 1730)
- L. Moiola
- M. Di Cristinzi
- A. Sultana
- C. Zanetta
- F. Rinaldi
- L. Brambilla
- J. Frau
- S. Malucchi
- P. Annovazzi
- G. Puorro
- A. Bianco
- G. Lus
- P. Cavalla
- F. Sangalli
- M. Romeo
- G. Marfia
- A. Gallo
- V. Barcella
- S. Bucello
- M. Ferrò
- C. Lapucci
- L. Chiveri
- C. Chisari
- E. Baldi
- R. Clerici
- P. Banfi
- C. Tortorella
- R. Totaro
- R. Cerqua
- S. Tonietti
- V. Mantero
- G. Santuccio
- M. Filippi
Alemtuzumab(ALEM) is an anti-CD52 monoclonal antibody approved for the treatment of active Multiple Sclerosis(MS) which showed an overall high efficacy in clinical trials, also in the highly active subgroup of patients.
The aim of this multicenter obervational study is to evaluate efficacy and safety of ALEM-treatment in a population of aggressive MS naïve-patients at year 2 and 3 after a complete cycle of treatment.
We conducted a multicenter prospective observational study in a cohort of ALEM-naïve MS patients. Clinical and neuroradiological parameters were collected from patients’ clinical records in 26 Italian MS Centers from October 2015 to May 2020.
133 naïve patients were treated with ALEM: 60,2% females, mean age 31,4(± 8,9) years, mean disease duration 18,5(± 22,7) months, mean follow-up(FU) 34,2(± 12,1) months, median EDSS 3(0-6,5), ARR in the year preceding treatment 1,8 (± 0,9), mean number of brain T2/FLAIR-hyperintense lesions 29,8 (± 20,8) and mean number of Gd-enhancing lesions 3,4(± 5,1). Regarding ALEM efficacy, we report data obtained after the first complete cycle of treatment (2 ALEM-courses) because the occurrence of disease activity between the first and second course is not indicative of a therapeutic failure. 99 and 61 over 133 patients have at least 24 and 36 months FU respectively: 97% and 82% were relapse-free, ARR was 0,02 and 0,1, 92.9% and 82% were MRI activity-free and 97,7% and 91,8% progression-free with median EDSS of 2,0 and 1,5 (IQR 1 – 2,5) at year 2 and 3. The mean time to first relapse was 27,6(± 6,4) months 89,2% and 69,4% of patients reached NEDA-3 at year 2 and year 3 respectively. 5,3% of patients needed a third cycle of therapy. Overall 74,4% of patients had adverse events. Infusion-reaction and infections occurred respectively in 70,1% and 9,8% of patients; regarding secondary autoimmune disease the most frequent was thyroid dysfunction (15,8%).
In our very active MS-population after ALEM-treatment a strong reduction of both relapse rate and MRI activity was achieved. These results strengthen the assumption that aggressive naïve patient is an ideal candidate for immune system resetting, likely due to young age, short disease duration and low disability. Furthermore, absence of previous immunomodulating/immunosuppressant drugs altering the immune system could play a key role in determining effectiveness of this powerful drug. However, longer FU is needed to confirm our data and evaluate whether an early induction therapy could be worthy in this specific population, balancing benefit-risk ratio.
P0544 - Atrophy of different cortical and subcortical compartments contributes to explain clinical disability in patients with MS: a multicenter study (ID 1082)
In MS, neurodegenerative processes involve several cortical and subcortical structures of the central nervous system.
To perform a multiparametric assessment of cortical, deep grey matter (DGM), cerebellar and cervical cord atrophy to characterize MS phenotypes and to explain patients’ disability.
3T brain and cervical cord T2- and 3D T1-weigthed images were acquired from 198 MS patients (139 relapsing-remitting [RR] MS, 59 progressive [P] MS) and 67 healthy controls (HC) at three European sites. Cortical thickness (CTh), DGM volumes, cerebellar volumes and cervical cord cross-sectional area (CSA) were compared between MS patients and HC and across clinical phenotypes. In patients, sex-, age-, and site-corrected stepwise linear regression models investigated the association of brain and cord lesion burden and cortical, DGM, cerebellar and cervical cord atrophy with clinical disability.
Compared to HC, MS patients had widespread atrophy in all cortical lobes, DGM nuclei and cerebellar lobules, as well as reduced cord CSA. Similar results were observed in RRMS patients vs HC, except for the left superior parietal lobule and left frontal pole (p=range from <0.001 to 0.04). In PMS patients, additional cortical atrophy vs RRMS was identified in all investigated lobes (p=range from <0.001 to 0.03), except for selected cingulate, parietal and occipital regions. At the univariate analysis, in MS patients higher disability was associated with more severe cortical, DGM, cerebellar and cervical cord atrophy (p=range<0.00-0.047). The multivariate model retained cerebellar and cervical cord atrophy as significant predictors of higher EDSS score (R2=0.45, p<0.001) as well as of pyramidal (R2=0.42, p<0.001), sensory (R2=0.28, p<0.001) and cerebellar (R2=0.50, p<0.001) functional system scores.
Abnormalities of regional CTh, DGM volume, volume of the cerebellar lobules and cervical cord CSA characterized the main MS clinical phenotypes. Atrophy within the cerebellum and cervical cord was crucial for explaining clinical disability, mainly within sensorimotor domains.
P0557 - Characterizing 1-year development of cervical cord atrophy across different MS phenotypes: a voxel-wise, multicenter analysis (ID 1115)
In multiple sclerosis (MS) the cervical spinal cord is often affected by demyelination and neuro-axonal injury, leading to irreversible tissue loss.
To use voxel-wise analysis to evaluate the distribution and changes over time of cervical cord atrophy in MS patients from a multicentre dataset acquired at 7 European sites.
Baseline and 1-year 3D T1-weighted cervical cord scans and clinical evaluation were obtained from 54 healthy controls (HC) and 110 MS patients (13 clinically isolated syndromes [CIS], 75 relapsing-remitting [RR] and 22 progressive [P]MS). A pipeline optimized for longitudinal analysis was used to co-register baseline and 1-year follow-up cervical cord scans to a cord template, obtained by averaging straightened HC images from all centers. Voxel-wise differences of cervical cord atrophy, their longitudinal changes and correlations with clinical variables were assessed using SPM12 and full factorial models (sex-, age-, center- and total cord volume-corrected).
Compared to HC, MS patients exhibited significant (p<0.05, family-wise error [FWE] corrected) baseline cervical cord atrophy, mainly located in anterior, posterior and lateral cord regions at C1/C2, as well as in posterior regions between C4 and C6. While CIS patients showed a slight cord tissue expansion vs HC at posterior C4, RRMS presented significant clusters of cord atrophy vs CIS, mostly in lateral and posterior C2-C4 regions, and PMS showed widespread cord atrophy vs RRMS patients at C4-C5 and C7 levels. During the follow-up, a significant progression (p<0.05, FWE) of cord atrophy was detected in MS patients, predominantly in the posterior and lateral cord at C2, and between C4 and C6. Such pattern of cord atrophy progression was mainly driven by RRMS patients, while CIS patients did not show cord tissue loss at follow-up vs baseline, and PMS patients showed circumscribed tissue loss in posterior regions at C2 and C6. A strong relationship (p<0.05, FWE) was found between baseline clinical disability and baseline cord atrophy in the posterior and lateral cord at C2-C4. Also, baseline atrophy in the lateral cord at C3-C4 correlated with clinical disability at 1-year follow-up.
Voxel-wise analysis of cervical atrophy allowed to detect a differential involvement of cord levels and to characterize 1-year evolution of tissue loss across phenotypes. Cord atrophy was clinically relevant and contributed to explain follow-up clinical disability.
P0910 - Relapse-free and NEDA status with Cladribine in a real life population: a multicentre study (ID 1484)
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.
To evaluate CLD efficacy and safety profile in the current MS population, and to identify early predictors of response.
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.
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).
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.