A Window into Patients’ Perceptions of the Risks of Multiple Sclerosis Therapies

Individuals with multiple sclerosis (MS) show wide variability in their levels of risk tolerance to MS therapies, concludes the most comprehensive study of the issue reported to date.

The Cleveland Clinic-led study, recently published in Neurology (2019 Mar 19 [Epub ahead of print]), carries implications for how MS clinicians may better guide patients toward individualized treatment choices, says lead author Robert Fox, MD, a neurologist with Cleveland Clinic’s Mellen Center for Multiple Sclerosis Treatment and Research. “Understanding variations in risk perception and tolerance can ultimately lead to greater patient satisfaction with therapy choices — and perhaps better treatment adherence,” he explains.

A survey on real-world risks of a hypothetical MS med

Dr. Fox and colleagues invited people with MS from the North American Research Committee on Multiple Sclerosis Registry (NARCOMS) and the National Multiple Sclerosis Society website to complete an online survey on their tolerance to real-world risks associated with a hypothetical disease-modifying therapy (DMT) for MS.

After being told the DMT would yield a fixed benefit — i.e., a 50 percent reduction in relapses and 30 percent slowing of disability — survey participants were asked if they would take the therapy if it were associated with a specific risk that occurs at a rate of 1 in 1,000 people. If they responded yes, they were asked if they would take it if the risk level were higher — say, 1 in 100 people. If they responded no, they were asked if they’d take the medication if the risk were lower — say, 1 in 10,000 people. Multiple risk levels were presented to pinpoint respondents’ maximum tolerance for each of six adverse effects associated with actual commercially available DMTs:

• Skin rash
• Infection
• Kidney injury
• Thyroid injury
• Liver injury
• Progressive multifocal leukoencephalopathy (PML)

Key results from over 3,000 respondents

The survey was completed by 3,171 people with MS (mean age, 55.1 years) over a one-month period in 2016. Key findings included the following:

• Risk tolerance was lowest for PML and kidney injury (1:1,000,000 for each) and highest for thyroid injury and infection (1:1,000 for each).
• Men, younger patients (< 41 years) and those with greater levels of disability (Patient Determined Disease Steps score ≥ 6) had the highest risk tolerance under all scenarios.
• About 53 percent of participants reported current use of a DMT, and these individuals showed greater risk tolerance in all scenarios. Across the board, those taking oral and infusion DMTs were more risk-tolerant than those taking injectables.
• Despite variable risk tolerance throughout the sample, a large share of participants were risk-averse: 17 to 39 percent were unwilling to assume any risk for a beneficial therapy, depending on the specific adverse effect.
• In contrast, fewer than 2 percent of respondents were willing to accept any risk for the benefit of the hypothetical DMT.

A need for more conversation around acceptable risk

Dr. Fox acknowledges that the survey was limited by a single fixed benefit (50-percent relapse reduction plus 30-percent disability slowing) and its focus on just six potential — albeit commonly reported — risks of DMTs.

“Nevertheless,” he observes, “identifying the best therapy for a patient involves not only assessing a medication’s benefits and risks but also an awareness of the patient’s perception of acceptable risk. These findings outline some general trends around those perceptions and underscore the importance of initiating conversations about acceptable risks, given the large heterogeneity we found in patient perceptions and comfort levels.”

An accompanying editorial in Neurology echoes that view: “Fox et al. provide cause for serious reflection on the issue of MS patient perception of, and response to, the risks involved in DMTs,” write editorialists Gavin V. McDonnell, MD, from Northern Ireland, and James J. Marriott, MD, from Canada. Noting concern “that so many patients are apparently averse to any level of risk for what many would perceive to be a reasonable level of benefit,” the editorialists conclude that “it is incumbent on us to develop strategies for communicating both treatment risks and benefits effectively and succinctly.”