Primum Non Nocere. In practice, “First do no harm” might be more accurately stated “First do no relative harm.” Medications have side effects and surgeries have complications, but an ethical physician counsels a patient on a course of treatment in which the benefits outweigh the risks.
Neurologists who prescribe disease-modifying therapies (DMT) for multiple sclerosis (MS) know this all too well. While DMT can slow disease progression, these medications can produce significant and sometimes dangerous side effects. Here balancing risks and benefits to “do no harm” is not a simple or straightforward task.
For this reason, the American Academy of Neurology released guidelines for the use of DMT in MS in 2002, with updates to the guidelines released in April of 2018. They offer significant guidance on starting, switching, and stopping patients, with a heavy emphasis on counseling patients. The guidelines recommend stopping DMT in patients who do not have ongoing relapses (or gadolinium-enhanced lesions on MRI) and have not been ambulatory for at least 2 years. The guidelines also acknowledge that there are no randomized-controlled trials to address this question.
In spite of these recommendations, DMT use in patients with secondary progressive MS (SPMS) actually increased between 2000 and 2009. A study presented as a poster at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2019 found that DMT use in SPMS increased from 47.2 percent to 51.5 percent during the period, even after the AAN guidelines were released. This means that many patients are shouldering a high cost of treatment and at risk for adverse events while the benefit side of the risk-benefit scale grows lighter.
Study author Revere Kinkel, MD, acknowledges that a clinician may have good reason to deviate from guidelines in individual patients. But, according to the study, “prescribers were not aware of or were not following evidence-based guidelines for individuals with non-relapsing courses, over age 54, and severe disability.” So physicians must consider, and patients must be educated about, the risks and potential benefits of DMT. They must also consider its cost, which the study found averaged around $16,000 to $19,000. All the options must be fully discussed so a shared decision about treatment can be reached by patient and physician.
Physicians must remember that these are guidelines to consider along with all the other factors used to make treatment decisions. In the end, more evidence is needed, as no randomized clinical trials address the issue. Until that time, more education is needed to ensure patients receive the most appropriate treatment for their circumstances. Strong evidence and consistent education are the best route for helping the sick when it’s tricky to “do no harm.”