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Updated: Jun 25, 2025
A Method of Trigonometric Modelling of Seasonal Variation Demonstrated with Multiple Sclerosis Relapse Data
Published on: December 9, 2015
Progression independent of relapse activity in relapsing multiple sclerosis: impact and relationship with secondary
Emilio Portaccio1, Matteo Betti2, Ermelinda De Meo2,3
1Department of NEUROFARBA, University of Florence, Careggi University Hospital, Florence, Italy. emilio.portaccio@unifi.it.
Objectives:
We investigated the occurrence and relative contribution of relapse-associated worsening (RAW) and progression independent of relapse activity (PIRA) to confirmed disability accrual (CDA) and transition to secondary progression (SP) in relapsing multiple sclerosis (MS).
Methods:
Relapsing-onset MS patients with follow-up > / = 5 years (16,130) were extracted from the Italian MS Registry. CDA was a 6-month confirmed increase in Expanded Disability Status Scale (EDSS) score. Sustained disability accumulation (SDA) was a CDA with no EDSS improvement in all subsequent visits. Predictors of PIRA and RAW and the association between final EDSS score and type of CDA were assessed using logistic multivariable regression and multivariable ordinal regression models, respectively.
Results:
Over 11.8 ± 5.4 years, 16,731 CDA events occurred in 8998 (55.8%) patients. PIRA (12,175) accounted for 72.3% of CDA. SDA occurred in 8912 (73.2%) PIRA and 2583 (56.7%) RAW (p < 0.001). 4453 (27.6%) patients transitioned to SPMS, 4010 (73.2%) out of 5476 patients with sustained PIRA and 443 (24.8%) out of 1790 patients with non-sustained PIRA. In the multivariable ordinal regression analysis, higher final EDSS score was associated with PIRA (estimated coefficient 0.349, 95% CI 0.120-0.577, p = 0.003).
Discussion:
In this real-world relapsing-onset MS cohort, PIRA was the main driver of disability accumulation and was associated with higher disability in the long term. Sustained PIRA was linked to transition to SP and could represent a more accurate PIRA definition and a criterion to mark the putative onset of the progressive phase.
Insights
Progression independent of relapse activity (PIRA) drives disability accumulation in relapsing multiple sclerosis (MS). Sustained PIRA is linked to long-term disability and transition to secondary progressive MS (SPMS).
Area of Science:
- Neurology
- Immunology
- Clinical Research
Background:
- Relapsing multiple sclerosis (MS) is characterized by unpredictable relapses and progressive disability.
- Understanding the distinct pathways of disability accrual, relapse-associated worsening (RAW) and progression independent of relapse activity (PIRA), is crucial for effective MS management.
- Identifying predictors and long-term consequences of these pathways can inform treatment strategies and patient outcomes.
Purpose of the Study:
- To investigate the occurrence and relative contribution of RAW and PIRA to confirmed disability accrual (CDA) in relapsing-onset MS.
- To determine the association between PIRA and RAW with the transition to secondary progressive MS (SPMS).
- To analyze the long-term impact of PIRA and RAW on disability status.
Main Methods:
- Analysis of a large cohort of relapsing-onset MS patients (n=16,130) from the Italian MS Registry with over 5 years of follow-up.
- CDA defined as a 6-month confirmed increase in Expanded Disability Status Scale (EDSS) score.
- Logistic and multivariable ordinal regression models used to assess predictors of PIRA/RAW and association with final EDSS and SPMS transition.
Main Results:
- PIRA accounted for 72.3% of all CDA events over 11.8 years.
- Sustained disability accumulation (SDA) was more frequent in PIRA (73.2%) than RAW (56.7%).
- Patients with sustained PIRA had a significantly higher transition rate to SPMS (73.2%) compared to non-sustained PIRA (24.8%). Higher final EDSS scores were associated with PIRA.
Conclusions:
- PIRA is the primary driver of disability accumulation in relapsing-onset MS.
- Sustained PIRA is strongly linked to the transition to SPMS, suggesting it may represent a more accurate definition of the progressive phase.
- These findings highlight the importance of addressing PIRA in MS management to mitigate long-term disability.
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