Relapse-independent multiple sclerosis progression under natalizumab

Area of Science:

• Neurology
• Immunology
• Clinical Research

Background:

• Relapsing-remitting multiple sclerosis (RRMS) is characterized by unpredictable relapses and progression.
• Long-term treatment with natalizumab is used to manage RRMS, but its effect on progression independent of relapse activity (PIRA) requires further investigation.

Purpose of the Study:

• To investigate the occurrence and influencing factors of confirmed progression independent of relapse activity (PIRA) in RRMS patients receiving long-term natalizumab therapy.
• To determine if PIRA is associated with Expanded Disability Status Scale (EDSS) score at treatment onset, disease duration, or therapy duration.

Main Methods:

• Retrospective, cross-sectional study of 184 RRMS patients treated with natalizumab for ≥24 months at two German centers.
• PIRA defined as ≥12-week confirmed disability progression (1-point EDSS increase for EDSS ≤3, 0.5-point for EDSS ≥3.5) without a relapse.
• Cox proportional hazard models and stepwise forward regression analysis were used to identify risk factors.

Main Results:

• 24% (44/184) of patients developed PIRA during natalizumab treatment, irrespective of baseline EDSS.
• Time to PIRA was not significantly affected by baseline EDSS, disease duration, or natalizumab therapy duration.
• Earlier natalizumab initiation relative to disease duration was associated with earlier PIRA onset.
• Disease duration was identified as the main factor for PIRA development (P = 0.005).

Conclusions:

• PIRA occurs in a substantial proportion of RRMS patients on long-term natalizumab.
• Disease duration, not baseline disability or treatment duration, is the primary predictor of PIRA.
• Initiating natalizumab early in the disease course, often for aggressive phenotypes, may increase the risk of early PIRA.