Association of Initial Disease-Modifying Therapy With Later Conversion to Secondary Progressive Multiple Sclerosis.

Area of Science:

• Neurology
• Clinical Therapeutics
• Epidemiology

Background:

• Relapsing-remitting multiple sclerosis (MS) often progresses to secondary progressive MS (SPMS), characterized by irreversible disability accrual.
• The impact of disease-modifying treatments (DMTs) on the conversion rate to SPMS has been understudied, particularly using validated definitions.

Purpose of the Study:

• To investigate the association between the use, type, and timing of DMTs and the risk of conversion to SPMS.
• To utilize a validated definition for SPMS diagnosis to ensure accurate assessment of treatment effects.

Main Methods:

• A prospective cohort study involving 1555 patients with relapsing-remitting MS across 68 centers in 21 countries.
• Patients initiated DMTs (interferon beta, glatiramer acetate, fingolimod, natalizumab, alemtuzumab) or clinical monitoring between 1988-2012.
• Propensity-score matching was employed to control for confounding factors, with a minimum follow-up of 4 years.

Main Results:

• Initial treatment with fingolimod, alemtuzumab, or natalizumab was associated with a significantly lower hazard of conversion to SPMS compared to glatiramer acetate or interferon beta.
• Earlier initiation of glatiramer acetate or interferon beta (within 5 years of onset) reduced the risk of conversion compared to later initiation.
• Escalating treatment from glatiramer acetate or interferon beta to fingolimod, alemtuzumab, or natalizumab within 5 years also lowered conversion risk.

Conclusions:

• The choice of initial DMT significantly influences the risk of conversion to SPMS in patients with relapsing-remitting MS.
• Treatments such as fingolimod, alemtuzumab, and natalizumab demonstrate superior efficacy in preventing SPMS conversion compared to glatiramer acetate and interferon beta.
• These findings support personalized DMT selection based on efficacy, risk profiles, and treatment timing to optimize long-term outcomes in MS management.