Towards an unified definition of progression independent of relapse activity in relapsing multiple sclerosis
SYNOPSIS AND RESULTS
Both controlled clinical trials and observational studies provided unequivocal evidence that steady progression independent of relapse activity (PIRA) is a frequent feature across the full spectrum of traditional multiple sclerosis (MS) phenotypes, including clinically isolated syndromes (CIS). PIRA occurs in approximately one quarter of early relapsing MS patients, and is the main driver of disability accumulation in these subjects. Moreover, PIRA is associated with more severe disability levels in the long-term and higher risk of transition to secondary progressive (SP) MS, particularly when it develops within the first five years of the disease. Disease modifying treatment (DMT) seems to be, at least partially, effective in reducing disability accumulation deriving from PIRA. However, different defintions of PIRA have been applied: PIRA has been classified on the basis of disability assessment on the Expanded Disability Status Scale (EDSS) or compound measures, with different baseline disability evaluations (fixed, re-baselined, roving measure), different worsening confirmation intervals (12 weeks, 24 weeks, 48 weeks, 96 weeks, sustained) and different time intervals between worsening and relapse activity. Moreover, it is debated whether PIRA should be defined purely clinically or taking into account magnetic resonance imaging (MRI) activity. Since a consensus defintion of PIRA events is lacking, the primary objective of the present study is to assess sensitivity, specificity and predictive accuracy of different PIRA definitions against hard outcome measures, namely the reaching of EDSS 6.0 and transition to SP MS. Secondary objectives include the assessment of sensitivity, specificity and predictive accuracy against the same outcomes of progression independent of relapse and MRI activity and of different definitions of PIRA in a subsample of patients with at least one EDSS evaluation per year.
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
Towards an unified definition of progression independent of relapse activity in relapsing multiple sclerosis
Both controlled clinical trials and observational studies provided unequivocal evidence that steady progression independent of relapse activity (PIRA) is a frequent feature across the full spectrum of traditional multiple sclerosis (MS) phenotypes, including clinically isolated syndromes (CIS). PIRA occurs in approximately one quarter of early relapsing MS patients, and is the main driver of disability accumulation in these subjects. Moreover, PIRA is associated with more severe disability levels in the long-term and higher risk of transition to secondary progressive (SP) MS, particularly when it develops within the first five years of the disease. Disease modifying treatment (DMT) seems to be, at least partially, effective in reducing disability accumulation deriving from PIRA.
However, different defintions of PIRA have been applied: PIRA has been classified on the basis of disability assessment on the Expanded Disability Status Scale (EDSS) or compound measures, with different baseline disability evaluations (fixed, re-baselined, roving measure), different worsening confirmation intervals (12 weeks, 24 weeks, 48 weeks, 96 weeks, sustained) and different time intervals between worsening and relapse activity. Moreover, it is debated whether PIRA should be defined purely clinically or taking into account magnetic resonance imaging (MRI) activity.
Since a consensus defintion of PIRA events is lacking, the primary objective of the present study is to assess sensitivity, specificity and predictive accuracy of different PIRA definitions against hard outcome measures, namely the reaching of EDSS 6.0 and transition to SP MS. Secondary objectives include the assessment of sensitivity, specificity and predictive accuracy against the same outcomes of progression independent of relapse and MRI activity and of different definitions of PIRA in a subsample of patients with at least one EDSS evaluation per year.
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