Risk Tolerance to Multiple Sclerosis Therapies: Results from the Narcoms Survey

Background: Multiple disease modifying therapies (DMT) with different risk/benefit ratios are currently available for MS treatment. Little is known about tolerance to the different risks of these therapies among people with MS.

Objectives: To determine and compare risk tolerance (RT) to various risks and identify responder characteristics associated with RT.

Methods: Following four focus groups involving people with MS and subsequent field testing, we conducted a survey   among participants of the North American Research Committee on MS (NARCOMS) Registry and visitors to the National MS Society (NMSS) website who indicated having MS. Responders were first presented with a hypothetical therapy that reduced clinical relapses by 50% and slowed disability progression by 30%. Using standard gamble paradigms, we then assessed their RT to six different risks: 1) skin rash, 2) infection, 3) kidney injury, 4) thyroid injury, 5) liver injury, and 6) progressive multifocal leukoencephalopathy (PML). Starting from a risk of 1:1000, the risk was iteratively adjusted to identify the highest risk tolerated, ranging from “would take regardless of the risk of death” to “no acceptable risk.”

Results: 3371 people with MS completed the survey (2258 NARCOMS, 1113 NMSS): 79.1% female, mean (SD) age 55.1 (11.1) years, disease duration 16.6 (9.8) years, median (IQR) Patient Determined Disease Steps 3-Early Gait Disability (1-Mild Disability, 5-Late Cane Use)and 53.3% reporting current DMT use. Overall, participants reported higher tolerance to infection (median RT 1:1000), thyroid injury (1:1000) and skin rash (1:2000); and lower tolerance to liver injury (1:10,000), kidney injury (1:1,000,000) and PML (1:1,000,000). Participants that were male, younger, more disabled, and currently taking DMT reported ≥2-fold higher RT to all risk scenarios. The RT of females to skin rash (1:1,000,000) was as high as RT to kidney injury or PML. When compared to non-smokers RT among smokers was 2.5-5.0-fold higher for skin rash, infection and thyroid risks but remained unchanged for liver, kidney or PML risks. Participants currently taking injectable DMTs reported ≤2.5-fold lower tolerance to all risks than those not on injectable DMTs. 

Conclusions: People with MS report different levels of tolerance to various risks. We have identified participant characteristics associated with higher or lower risk tolerance. This information can help understand individual preferences regarding treatment choices and assist in medical decision making.