Selection of first-line therapy in multiple sclerosis using risk-benefit decision analysis

Area of Science:

• Neurology
• Pharmacoeconomics
• Clinical Decision Making

Background:

• Multiple sclerosis (MS) treatment selection requires balancing drug efficacy with long-term risks.
• Disease-modifying therapies (DMTs) like natalizumab (NTZ), fingolimod (FGL), and glatiramer acetate (GA) have varying benefit-risk profiles.
• Quantifying long-term outcomes is crucial for guiding first-line MS treatment decisions.

Purpose of the Study:

• To integrate long-term efficacy and risk data for DMTs in multiple sclerosis.
• To guide the selection of first-line treatment for MS patients.
• To compare the net benefit of NTZ, FGL, and GA over a 30-year period.

Main Methods:

• A Markov decision model was developed to assess disability worsening and progressive multifocal leukoencephalopathy (PML) risk.
• Quality-adjusted life-years (QALYs) were calculated by integrating treatment utility, disability progression, and PML risk.
• Sensitivity analyses were conducted on PML risk, mortality, morbidity, and disease worsening rates.

Main Results:

• Natalizumab (NTZ) predicted the highest net benefit (15.06 QALYs) over 30 years compared to FGL (13.99 QALYs) and GA (12.71 QALYs), across the range of PML risks.
• NTZ treatment demonstrated delayed worsening to an Expanded Disability Status Scale score ≥6.0 (22.7 years) versus FGL (17.0 years) and GA (12.4 years).
• A higher early relative risk of death was observed with NTZ, varying with PML risk profile.

Conclusions:

• First-line treatment with NTZ offers the highest net benefit, considering PML risk, mortality, and morbidity, compared to FGL and GA.
• Integrated modeling of long-term risks and benefits supports stratified clinical decision-making for MS.
• This approach aids in patient counseling for selecting optimal first-line MS treatment options.