That’s because the term (sometimes spelled out as “higher-efficacy therapies”) refers to a specific group of disease-modifying drugs: the monoclonal antibodies Lemtrada (alemtuzumab), Tysabri (natalizumab), Ocrevus (ocrelizumab), and Rituxan (rituximab). (Rituxan is sometimes used off-label to treat MS.) And while studies have indeed shown these drugs to be effective at reducing relapses in RRMS, they’ve also been associated with significant side effects, including increased risk for serious infusion reactions, infection, stroke, and liver damage, depending on the particular drug. A study presented May 7 during the annual meeting of the American Academy of Neurology examined how neurologists and patients are weighing the potential benefits and risks of these drugs.
Most People With MS Tend to Gravitate Toward the Lower-Risk Options
“For many years, we started most MS patients on traditional injectable medications that were very safe but had limited efficacy, and even after the advent of HETs, we’ve seen that most people with MS tend to gravitate toward the lower-risk options, when presented with a choice, because they feel that they will be safer,” says Daniel Ontaneda, MD, a staff neurologist at the Cleveland Clinic Mellen Center for Multiple Sclerosis and a researcher and assistant professor at the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, in Ohio. The problem, according to Dr. Ontaneda, is that with no consensus within the field as to when or even if to prescribe HETs, and no published clinical trials comparing outcomes of treating with the newer monoclonal antibodies against treating with older, “lower-risk” options, physicians don’t have the data to make informed recommendations. Thus, people with RRMS can’t make informed decisions.
How Are Neurologists Currently Using HETs to Manage RRMS?
To get a sense of how neurologists are currently using HETs in the management of RRMS, Ontaneda and several colleagues reviewed the health records of those with RRMS who are enrolled in two ongoing clinical trials (DELIVER-MS, for which the Cleveland Clinic is a participating center and Ontaneda the principal investigator, and TREAT-MS, which is being sponsored by John Hopkins University in Baltimore), both of which are designed to compare outcomes following initial treatment with so-called low-moderate efficacy treatments (LMTs) to those achieved with first-line use of HETs. For the purposes of the study, HETs were defined as initial use of any of the four medications listed above, while LMTs were considered any other U.S. Food and Drug Administration (FDA)–approved therapy for RRMS. In all, the team reviewed the use of either approach on more than 5,500 people with RRMS over a 25-year period between 1993 and 2018. Notably, they discovered that in the entire RRMS population, HET was initially used in 2006, and was used in 27.3 percent of the included cases. By 2018, that percentage had increased to 43.8 percent. Among 2,060 people who had never before been treated for RRMS, HET was initially used as the first-line approach in 2009 and in 9.5 percent of cases. That figure increased to 32.3 percent last year.
‘We Still Don’t Know Which Is Better’
“If nothing else, our findings highlight the need for more [clinical] trials comparing the two approaches,” Ontaneda says, “because we still really don’t know which is better. Right now, when we sit in front of patients and say to them, ‘These are the different options we have,’ we don’t have studies that compare medication X with medication Z. As a result, we end up prescribing based on how much risk the patient is willing to take.” In the bigger picture, this also means people with RRMS may be receiving radically different treatments based on where they live and where their doctors practice — particularly given that there are currently 16 FDA-approved medications for the condition. “If I’m a patient, I don’t want my care to vary based on whether I go to center A, B, C, D, or F. I would like to think that wherever you go for your MS treatment across the country, you’re going to basically get the same treatment. And right now that’s not true,” Ontaneda says.
‘We Don’t Do a Good Enough Job at Quantifying the Risks’
Although things may change once the findings of DELIVER-MS and TREAT-MS come to light, the early analysis performed by Ontaneda and his team should provide food for thought as well as ammunition for talking with your doctor about the treatment options available and what’s best for you and your RRMS. “The main stakeholders are always the individuals with MS,” Ontaneda says. “I always encourage my patients and say, ‘This is a decision you have to think about.’ Get informed about the different treatment options and think about the risk you’re willing to take. As neurologists, we don’t do a good enough job at quantifying the real risks associated with HETs, and that means our patients don’t have an understanding of the real risks associated with them.”
