Evaluating Age-Dependent Efficacy of Multiple Sclerosis Treatments in a Real-Life Cohort
SYNOPSIS AND RESULTS
The role of age and ageing in Multiple Sclerosis (MS) is becoming increasingly important since epidemiological studies worldwide showed an ever-growing prevalence of MS in older age, which nowadays in many countries has been demonstrated to peak between 55-59 years, altogether with a relatively stable incidence of the disease. Many possible causes have been hypothesized: a better quality of care, prolonged life-expectancy, greater case ascertainment… These changes are rising multiple issues in patient management, specifically about safety and efficacy of disease modifying drugs (DMDs) (1). A recent meta-analysis of all blinded, randomized, clinical trials of immunomodulatory DMDs showed that there is no predicted benefit of receiving DMDs after age 53 and that higher efficacy treatments exert their benefit over lower efficacy treatments only for patients younger than 40.5 years (2). In this meta-analysis up to 42% of the variance in drug-based inhibition of disability progression was attributed to age (2). Moreover, the comparative DMT effectiveness between younger and older pwMS has been investigated through subgroup analysis within each phase 3 trial demonstrating a fail to significantly reduce the risk of disability progression in pwMS older than 40 years old for natalizumab, fingolimod, dimethyl fumarate, teriflunomide, ocrelizumab (3). Another intrinsic limitation of these meta-analysis of RCTs is the lack of trials with mean age under 30 and over 55 years. On the other hand, data from large national registries showed that DMDs continue to be commonly prescribed in the elderly pwMS (5). Such discrepancy poses a major clinical challenge as neurologists seek to utilize trial-based knowledge on older patient. With this background, the aim of the present project is to evaluate the age-related efficacy of DMDs on real-world patients, not included in randomized controlled trials, through a multicentric, retrospective cohort study based on prospectively acquired data. Patients will be divided into 4 arms according with the received DMDs as follows: 1) Patients taking low-efficacy DMDs (interpherons and glatiramer acetate); 2) Patients taking high efficacy DMDs (fingolimod, natalizumab, cladribine, anti CD20 antibodies, alemtuzumab); 3) Patients switching to high efficacy drgus; 4) Patients taking no DMD (identified as reference or control group). Age-related efficacy of DMDs will be evaluated through calculation of percent inhibition of disability progression (%IDP), ie a relative risk reduction of confirmed disability progression (CDP) between DMD treated patients (with first or second line agents) and not treated patients across all age groups; CDP will be considered a worsening of EDSS status 6 months-confirmed. Secondary evaluation will consider disease activity through the annualized relapse rate (ARR) and MRI variables as presence/absence of new Gd+ lesions and/or presence/absence of new /enlarging T2 lesions.
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
Evaluating Age-Dependent Efficacy of Multiple Sclerosis Treatments in a Real-Life Cohort
The role of age and ageing in Multiple Sclerosis (MS) is becoming increasingly important since epidemiological studies worldwide showed an ever-growing prevalence of MS in older age, which nowadays in many countries has been demonstrated to peak between 55-59 years, altogether with a relatively stable incidence of the disease. Many possible causes have been hypothesized: a better quality of care, prolonged life-expectancy, greater case ascertainment… These changes are rising multiple issues in patient management, specifically about safety and efficacy of disease modifying drugs (DMDs) (1).
A recent meta-analysis of all blinded, randomized, clinical trials of immunomodulatory DMDs showed that there is no predicted benefit of receiving DMDs after age 53 and that higher efficacy treatments exert their benefit over lower efficacy treatments only for patients younger than 40.5 years (2). In this meta-analysis up to 42% of the variance in drug-based inhibition of disability progression was attributed to age (2). Moreover, the comparative DMT effectiveness between younger and older pwMS has been investigated through subgroup analysis within each phase 3 trial demonstrating a fail to significantly reduce the risk of disability progression in pwMS older than 40 years old for natalizumab, fingolimod, dimethyl fumarate, teriflunomide, ocrelizumab (3). Another intrinsic limitation of these meta-analysis of RCTs is the lack of trials with mean age under 30 and over 55 years. On the other hand, data from large national registries showed that DMDs continue to be commonly prescribed in the elderly pwMS (5). Such discrepancy poses a major clinical challenge as neurologists seek to utilize trial-based knowledge on older patient.
With this background, the aim of the present project is to evaluate the age-related efficacy of DMDs on real-world patients, not included in randomized controlled trials, through a multicentric, retrospective cohort study based on prospectively acquired data. Patients will be divided into 4 arms according with the received DMDs as follows: 1) Patients taking low-efficacy DMDs (interpherons and glatiramer acetate); 2) Patients taking high efficacy DMDs (fingolimod, natalizumab, cladribine, anti CD20 antibodies, alemtuzumab); 3) Patients switching to high efficacy drgus; 4) Patients taking no DMD (identified as reference or control group).
Age-related efficacy of DMDs will be evaluated through calculation of percent inhibition of disability progression (%IDP), ie a relative risk reduction of confirmed disability progression (CDP) between DMD treated patients (with first or second line agents) and not treated patients across all age groups; CDP will be considered a worsening of EDSS status 6 months-confirmed.
Secondary evaluation will consider disease activity through the annualized relapse rate (ARR) and MRI variables as presence/absence of new Gd+ lesions and/or presence/absence of new /enlarging T2 lesions.
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