Emerging evidence suggests that PIRA is not restricted to progressive MS forms, starting early in the disease and contributing to disability accrual in MS. However, how PIRA starts and the factors accelerating its onset remain uncertain.

178 SPMS patients were included out of which 108 were females. The median follow-up duration was 11.83 years (4.83-18.58), 139 patients were classified as active. Median time since the first evidence of PIRA was 7.58 years (5-35), and in 43 patients this occurred within 5 years (early PIRA, EP).

Patients with EP were older compared to late PIRA (LP) (EP 38, 32-46.5 vs. LP 32, 25-42.75, p=0.02) with female predominance (62% vs. LP 32%, 25- 42.7, p=0.02). No increased risk of EP was observed at age 60 or older.

Myelitis was the first clinical symptom presented in EP more frequently (70% vs. 36%, p<0.005). EP patients transitioned to SPMS faster (74 vs 162 months, p<0.01). 

Frequency of EP decreased with age; those initiating treatment between 30-39 years presented OR=6.2 (95%CI=1.8-21.4, p=0.004), at 40-49 years OR=6.1 (95%CI=1.6-23, p=0.007), and at 50-59 years OR=5.77 (95%CI=1.1-28, p=0.03). 

Early PIRA occurrence is influenced by age, initial symptoms, and treatment onset,

highlighting the complexity of MS progression.