Clinical characteristics and disease outcomes of late onset Multiple Sclerosis: a retrospective multicenter study.

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Introduction and aims
Late onset of MS (LOMS), classically defined by the occurrence of the first symptoms after age 50, it is relatively infrequent and it occurs in less than 10% of patients. Few studies have compared the clinical and demographic characteristics of these patients with young-adult onset MS cases (YOMS), more frequently reporting a progressive course, notoriously associated with more severe disability. However, there is still uncertain information about the clinical outcomes of LOMS, the response to disease modifying treatments (DMTs), and the implication for disease prognosis.
The present project is a multicentre retrospective study that aims to describe the early and late clinical characteristics of LOMS in a large cohort of Italian MS patients, using YOMS as a comparator, in order to evaluate whether the late onset is associated with a more severe disease evolution, also in the relapsing remitting forms.
By using the "Group Based Trajectory Modeling" models, this study describes the disability trajectories of MS patients, also evaluating the characteristics associated to groups with different disability trends over time and the association with LOMS. The data used to define the disability trajectories were obtained from the Italian Multiple Sclerosis Registry. The EDSS scale was used to obtain the disability trajectories in the first 20 visits after diagnosis. The profiles of the patients’ groups identified in a specific trajectory were described using a multinomial model by the relative risk ratios (RRRs) and their 95% confidence intervals. The level of statistical significance was set at 5% and the analyses were performed with Stata® 16.

Results
Of the 20,826 patients identified in the registry, 16,159 were eligible for the study. Four groups with different disability trajectories were identified by using the "Group Based Trajectory Modeling". The group with the most severe EDSS trend (A), was made up of 12.3% of the subjects with mean EDSS > 4 points, which increased over time exceeding EDSS 6; the group with medium severity EDSS trend (B) comprised 21.9% of the sample and showed a change in EDSS score of more than 3 points over time; the larger group (C) with 50.9% of patients reported a constant 2 points in EDSS trend up to 10 visits, with an increase in EDSS in the latest evaluations; finally, the benign group (D) was made up of 14.9% of patients with a low and constant EDSS score over time. The multinomial model shows that the probability of belonging to the groups with the highest severity (A, B, C) is up to 7.0 times higher for the LOMS (p <0.001). In addition, the probability of belonging to groups with greater severity is more associated with male sex and clinical onset with brain stem, spinal cord or multifunctional symptoms.

Conclusions
Notoriously, MS is a highly heterogeneous disease for clinical, pathogenetic, and neuroradiological features; it is characterized by a high management complexity. From the onset of the disease, it is important to define its clinical characteristics, and in particular to evaluate the predictors of worse long-term clinical outcome. This project defines how LOMS conditions the disease evolution, by analyzing the disability trajectories. This is also important for the purpose of a tailored choice of DMTs that considers aging, the lower resilience of the nervous system to damage and the frequent concomitance of age-related comorbidities, in addition to the prognostic factors most strictly associated with the disease.





Pubblicazioni e Comunicazioni A Congressi/Publications end Congress Presentations

EDSS trajectories in multiple sclerosis patients from the Italian MS Register. XXV° World Congress of Neurology, 3-7 October 2021. This study has been selected as oral presentation

Le traiettorie di EDSS in pazienti con differente esordio di sclerosi multipla. Congress of medical statistics and clinical epidemiology (SISMEC). Dati, modelli, decisioni: metodi a servizio dell’organizzazione sanitaria, Bari, Italy 15-17 September 2021

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