Department of Medical and Surgical Sciences and Advanced Technologies, GF Ingrassia, Catania

Author Of 1 Presentation

Pediatric MS Oral Presentation

YI02.05 - Cognition and socio-professional attainment in paediatric onset multiple sclerosis: a reappraisal after 10 years

Abstract

Background

Cognitive impairment (CI) affects nearly 30% of paediatric patients with Multiple Sclerosis (MS) and has a negative impact on school performance and participation in social activities. This study is a re-appraisal of cognitive functioning and socio-professional attainment in adulthood in an Italian cohort of paediatric MS patients after 10 years from baseline neuropsychological assessment.

Objectives

To re-assess cognitive performance and its impact on socio-professional attainment in our cohort of paediatric MS patients after 10 years from baseline evaluation and to determine predictors of the individual outcomes.

Methods

Sixty-three paediatric patients were assessed at baseline and 48 followed-up after five years. To date, 31 out of these 48 patients (17 females, mean age 27.9±2.5 years, mean EDSS 1.7±1.6) were reassessed on an extensive neuropsychological battery and compared with a matched group of 31 healthy controls. CI was defined as the failure of > 2 tests. Socio-professional attainment was evaluated on the Work and Social Assessment Scale (WSAS). Predictors of CI and WSAS score were assessed through multivariable logistic and linear models.

Results

After a mean follow-up of 12.5±2.3 years, 15 (54%) subjects were classified as cognitively impaired. Patients with CI compared with those cognitively preserved at follow-up had higher Expanded Disability Status Scale (EDSS) score (1.9±1.4 vs 1.0±0.7; p = 0.046), lower baseline intelligence quotient (IQ) (86.2±23.8 vs 103.6±14.7; p = 0.025) and were less frequently treated with disease modifying therapy (DMT) at baseline [6 (35.3%) vs 11 (78.6%); p = 0.016]. In the regression model, CI after 10 years was related to lower IQ (OR 0.93, 95% CI 0.87-0.99, p = 0. 027) and absence of DMT at baseline assessment (OR 17.78 95%; 1.72-183.65, p = 0.017).

Baseline predictors of worse socio-professional attainment on the WSAS in adulthood were CI (B=6.3, p=0.016), higher EDSS (B=2.2, p=0.023) and higher age at onset (B=0.6, p=0.041). As for 10-year correlates, only CI was associated to poor functional outcome (B=5.2, p=0.006).

Conclusions

Complete data collection is ongoing; available findings to date show that in paediatric onset subjects CI remains significant in adulthood, is related to lower cognitive reserve, higher levels of neurological impairment and delay in DMT initiation. Moreover, CI plays a key role in predicting the subject social performance and professional outcome. Early treatment and promotion of strategies aimed at enhancing cognitive reserve are recommended in paediatric patients with MS.

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Author Of 2 Presentations

Clinical Outcome Measures Poster Presentation

P0100 - Italian prospective multicentric observational real-life study of aggressive Relapsing Remitting Multiple Sclerosis treated with alemtuzumab (ID 1730)

Abstract

Background

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.

Objectives

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.

Methods

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.

Results

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%).

Conclusions

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.

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Epidemiology Poster Presentation

P0506 - Towards a validated Secondary Progressive Multiple Sclerosis definition: A study from the Italian MS Register (ID 1432)

Abstract

Background

No clear metrics for sensitive and reliable identification of the transition from relapsing-remitting multiple sclerosis (RRMS) to secondary progressive (SP)MS are available.

Objectives

To compare diagnostic performances of two different data-driven Secondary Progressive Multiple Sclerosis definitions.

Methods

patient with RRMS with a follow-up ≥5 years, with a current age ≥18 years, and with ≥3 EDSS scores recorded were selected from the Italian MS Registry. Annual incidence of SPMS conversion was reported as number of patients converting to SP every 100 patients/year. Three different SPMS definitions have been used. Data-driven definitions based on the Lorscheider’s algorithm (LA) and on the EXPAND trial inclusion criteria were validated, using the neurologist’s definition as gold standard, in terms of calibration, discrimination and goodness of fit by calculating: sensitivity, specificity, Positive Predictive Value (PPV), Negative Predictive Value (NPV), the Akaike information criterion (AIC), the Area Under the Curve (AUC). The overall calibration of the data-driven definitions was evaluated by the Calibration Slope test.

Results

a cohort of 10,240 RRMS patients was extracted from the Italian MS Registry. According to the neurologist judgment, 880 (8.59%) patients were classified as SPMS in the dataset. By applying the LA and the EXPAND definition, 1,806 (17.64%) and 1,134 (11.07%) patients, respectively, were classified as SPMS. The annual rate of SP conversion during the follow-up was 0.74 every 100 patients/year based on the neurologist’s definition, 1.57 every 100 patients/year using the LA and 0.94 every 100 patients/year applying the EXPAND definition. Both the data-driven definitions were well calibrated, with a p-value of the Calibration Slope test higher than 0.05 (LA=0.55; EXPAND definition=0.57). The AIC (LA=4301; EXPAND definition=5510) and the R-Square (LA=0.15 vs EXPAND definition=0.05), were in favor of the LA. The LA showed a greater discrimination power (AUC: 0.83 vs 0.65) and a higher sensitivity (77.1% vs 38.0%) in comparison to the EXPAND definition. Both definitions showed similar specificity (88.0% vs 91.5%). The PPV and the NPV were both higher using the LA than those obtained by the EXPAND definition (37.5% vs 29.5%; 97.6% vs 94.0%, respectively).

Conclusions

An accurate definition of SP transition is needed for a timely and efficacious treatment of SPMS patients. Real-world data from the Italian MS Registry suggests that data-driven definitions had a greater ability to capture SP transition than neurologist’s definition and that the global accuracy of LA seems to be higher than a definition based on the EXPAND trial inclusion criteria.

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