Predictive factors of disability progression in a large cohort of italian multiple sclerosis patients
SYNOPSIS AND RESULTS
Multiple sclerosis (MS) is one of the most common cause of neurological disability in young adults globally. It is a chronic degenerative illness and therefore carries a high economic and quality of life burden associated with it. One of the principal objectives in the care of people with MS is, therefore, to reduce the irreversible accumulation of neurological disability. The diagnosis of progressive MS is clinical and retrospective because based on the patient’s history and the neurological exam. In everyday clinical practice, the identification of the change in disease course is often late and there are no applicable predictors of disability progression. While group data exist that are prognostic for patients with MS, there are no individually applicable predictors of disease course or severity. This produces considerable anxiety and concern for patients, difficulty for clinicians in providing accurate information to patients and a lack of clear guidance on when and how to treat progressive MS. Therefore, the objective of the study is to identify the predictive factors of disability progression in RR-MS patients with high disability and patients with progressive course of MS included in the datasets of the Italian MS registry. The early identification of patients with unfavorable predictive variables will allow treating patients with the new therapies for MS (ocrelizumab and siponimod). The population of the Italian MS registry is representative of MS population of our Country and includes a large number of patients.
Data start
Data end
2018-09-20
2020-09-15
PARTICIPATING CENTERS
Prof.ssa Letizia Leocani – Neurologo, Responsabile Centro Stimolazione Magnetica Trascranica, INSPE, Ospedale San Raffaele, Milano
Dott. Martinelli Vittorio – Neurologo, Responsabile Unità di Neurologia e Centro Sclerosi Multipla dell’Ospedale San Raffaele di Milano.
Dott.ssa Moiola Lucia – Neurologo, Coordinatore Attività Area Centro Sclerosi Multipla-MAC-Ambulatori dell’Ospedale San Raffaele di Milano.
OUTCOME
Introduction and aims Multiple sclerosis (MS) is one of the most common cause of neurological disability in young adults globally. It is a chronic degenerative illness and therefore carries a high economic and quality of life burden associated with it. One of the principal objectives in the care of people with MS is, therefore, to reduce the irreversible accumulation of neurological disability. The diagnosis of progressive MS is clinical and retrospective because based on the patient’s history and the neurological exam. In everyday clinical practice, the identification of the change in disease course is often late and there are no applicable predictors of disability progression. While group data exist that are prognostic for patients with MS, there are no individually applicable predictors of disease course or severity. This produces considerable anxiety and concern for patients, difficulty for clinicians in providing accurate information to patients and a lack of clear guidance on when and how to treat progressive MS. Therefore, the objective of the study is to identify the predictive factors of disability progression in RR-MS patients with high disability and patients with progressive course of MS included in the datasets of the Italian MS registry. The early identification of patients with unfavorable predictive variables will allow treating patients with the new therapies for MS (ocrelizumab and siponimod). The population of the Italian MS registry is representative of MS population of our Country and includes a large number of patients.
Results This is a retrospective, longitudinal study that enrolling a large cohort of MS patients of the Italian MS registry with secondary progressive MS (SP-MS), primary progressive MS (PP-MS) and relapsing-remitting MS (RR-MS) with Expanded Disability Disability Status Scale (EDSS) > 4.0 and with an observation period at the centers of at least 6 months. The first visit to the centers is the reference point (baseline) for the beginning of observation. We included patients who performed the first visit in the centers before June 2016. Primary end-point is the disability progression (increase of EDSS score >1.0 point if baseline EDSS < 5.5 and 0.5 if baseline EDSS was > 6.0) sustained and confirmed at the end of follow-up. The 3 groups of patients have been compared during 2-year follow-up to determine predictive factors of disability progression. We included 5031 patients (3169 female and 1862 male), 1887 with SP-MS, 1096 with PP-MS and 2048 with RR-MS. Of the 5031, 1587 (32 %) had a disability progression after a mean of 15.4 months. The mean of follow-up was 22 months. At baseline we compared in the three MS groups patients with disability progression vs stable patients. The patients with disability worsening were older at disease onset compared with stable patients in all three groups [SP-MS group: 32 vs 30 years (p:0.001); PP-MS group: 41 vs 39 years (p:0.05); RR-MS group 34 vs 32 years (p:0.005)]. In progressive MS groups patients with disability progression had a shorter disease duration compared with stable patients [SP-MS group: 191 vs 219 months (p<0.0001); PP-MS group: 110 vs 128 months (p:0.004)]. Finally, patients with disability progression had a lower EDSS compared with stable patients in all three groups [SP-MS group: mean EDSS 5.6 vs 5.8 points (p<0.0001); PP-MS group: 5.4 vs 5.7 points (p<0.0001); RR-MS group 4.9 vs 5.0 points (p:0.06)]. In the RR-MS group the patients with disability worsening had also a lower numbers of relapses 1 year before baseline (p:0.018). However, the multivariable analysis not confirmed these data in SP-MS and PP-MS groups. In the RR-MS group the multivariable analysis confirmed the association between disability progression and older age at onset.
Conclusions The study not found strong clinical predictive factors of disability progression. It is necessary to identify fluid biomarkers probably more predictive of disability.
Fondazione Italiana Sclerosi Multipla – FISM – Ente del Terzo Settore/ETS e, in forma abbreviata, FISM ETS. Iscrizione al RUNTS Rep. N° 89695 - Fondazione con Riconoscimento di Personalità Giuridica - C.F. 95051730109
Predictive factors of disability progression in a large cohort of italian multiple sclerosis patients
Multiple sclerosis (MS) is one of the most common cause of neurological disability in young adults globally. It is a chronic degenerative illness and therefore carries a high economic and quality of life burden associated with it. One of the principal objectives in the care of people with MS is, therefore, to reduce the irreversible accumulation of neurological disability.
The diagnosis of progressive MS is clinical and retrospective because based on the patient’s history and the neurological exam. In everyday clinical practice, the identification of the change in disease course is often late and there are no applicable predictors of disability progression.
While group data exist that are prognostic for patients with MS, there are no individually applicable predictors of disease course or severity. This produces considerable anxiety and concern for patients, difficulty for clinicians in providing accurate information to patients and a lack of clear guidance on when and how to treat progressive MS.
Therefore, the objective of the study is to identify the predictive factors of disability progression in RR-MS patients with high disability and patients with progressive course of MS included in the datasets of the Italian MS registry. The early identification of patients with unfavorable predictive variables will allow treating patients with the new therapies for MS (ocrelizumab and siponimod).
The population of the Italian MS registry is representative of MS population of our Country and includes a large number of patients.
Prof.ssa Letizia Leocani – Neurologo, Responsabile Centro Stimolazione Magnetica Trascranica, INSPE, Ospedale San Raffaele, Milano
Dott. Martinelli Vittorio – Neurologo, Responsabile Unità di Neurologia e Centro Sclerosi Multipla dell’Ospedale San Raffaele di Milano.
Dott.ssa Moiola Lucia – Neurologo, Coordinatore Attività Area Centro Sclerosi Multipla-MAC-Ambulatori dell’Ospedale San Raffaele di Milano.
Introduction and aims
Multiple sclerosis (MS) is one of the most common cause of neurological disability in young adults globally. It is a chronic degenerative illness and therefore carries a high economic and quality of life burden associated with it. One of the principal objectives in the care of people with MS is, therefore, to reduce the irreversible accumulation of neurological disability.
The diagnosis of progressive MS is clinical and retrospective because based on the patient’s history and the neurological exam. In everyday clinical practice, the identification of the change in disease course is often late and there are no applicable predictors of disability progression.
While group data exist that are prognostic for patients with MS, there are no individually applicable predictors of disease course or severity. This produces considerable anxiety and concern for patients, difficulty for clinicians in providing accurate information to patients and a lack of clear guidance on when and how to treat progressive MS.
Therefore, the objective of the study is to identify the predictive factors of disability progression in RR-MS patients with high disability and patients with progressive course of MS included in the datasets of the Italian MS registry. The early identification of patients with unfavorable predictive variables will allow treating patients with the new therapies for MS (ocrelizumab and siponimod).
The population of the Italian MS registry is representative of MS population of our Country and includes a large number of patients.
Results
This is a retrospective, longitudinal study that enrolling a large cohort of MS patients of the Italian MS registry with secondary progressive MS (SP-MS), primary progressive MS (PP-MS) and relapsing-remitting MS (RR-MS) with Expanded Disability Disability Status Scale (EDSS) > 4.0 and with an observation period at the centers of at least 6 months. The first visit to the centers is the reference point (baseline) for the beginning of observation. We included patients who performed the first visit in the centers before June 2016. Primary end-point is the disability progression (increase of EDSS score >1.0 point if baseline EDSS < 5.5 and 0.5 if baseline EDSS was > 6.0) sustained and confirmed at the end of follow-up. The 3 groups of patients have been compared during 2-year follow-up to determine predictive factors of disability progression.
We included 5031 patients (3169 female and 1862 male), 1887 with SP-MS, 1096 with PP-MS and 2048 with RR-MS. Of the 5031, 1587 (32 %) had a disability progression after a mean of 15.4 months. The mean of follow-up was 22 months.
At baseline we compared in the three MS groups patients with disability progression vs stable patients. The patients with disability worsening were older at disease onset compared with stable patients in all three groups [SP-MS group: 32 vs 30 years (p:0.001); PP-MS group: 41 vs 39 years (p:0.05); RR-MS group 34 vs 32 years (p:0.005)]. In progressive MS groups patients with disability progression had a shorter disease duration compared with stable patients [SP-MS group: 191 vs 219 months (p<0.0001); PP-MS group: 110 vs 128 months (p:0.004)]. Finally, patients with disability progression had a lower EDSS compared with stable patients in all three groups [SP-MS group: mean EDSS 5.6 vs 5.8 points (p<0.0001); PP-MS group: 5.4 vs 5.7 points (p<0.0001); RR-MS group 4.9 vs 5.0 points (p:0.06)]. In the RR-MS group the patients with disability worsening had also a lower numbers of relapses 1 year before baseline (p:0.018). However, the multivariable analysis not confirmed these data in SP-MS and PP-MS groups. In the RR-MS group the multivariable analysis confirmed the association between disability progression and older age at onset.
Conclusions
The study not found strong clinical predictive factors of disability progression. It is necessary to identify fluid biomarkers probably more predictive of disability.
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