NATIONAL HARBOR, MD. – Consider his 40-year-old female patient who’s averse to vaccines, often misses appointments, and seems to be unable to take blood pressure drugs as prescribed. In this case, the best strategy may not be the drug with the highest efficacy.
“There’s no pharmaceutical insert that’s going to tell you what to do with all of this information,” John R. Rinker II, MD, of the University of Alabama at Birmingham, said in a presentation at the annual meeting of the Consortium of Multiple Sclerosis Centers. “It’s important to not only know about the disease and the specifics of the pharmaceuticals, but also about the patient’s personal circumstances, their comorbidities, their social situation, and how it all ties together.”
Fortunately, he said, there are about two dozen medication options now available for RRMS. Noting that his scale is at best “a crude approximation of reality,” he said their efficacy runs the gamut from low (glatiramer acetate and beta-interferons) to high (cladribine, alemtuzumab). He places sphingosine-1 phosphate (SIP1) modulators in the mid-range in terms of efficacy and B cell-depleting agents and natalizumab toward the high side.
Why go low?
Why put someone on a low-efficacy drug? One reason is because they’re the safest options, he said, while the two highest-efficacy drugs – cladribine and alemtuzumab – are the least safe. But even the older, safer drugs can cause problems: Beta interferons can cause flu-like symptoms early on along with depression and miscarriage, and glatiramer acetate can spur injection site reactions and acute post injection syndrome “that can feel like a panic attack or even a heart attack.”
Dimethyl fumarate “is probably the easiest of the oral agents to initiate because there’s no extra doctor’s appointments. And there’s no concerns really about hair loss, liver failure, or birth defects,” he said. “But it’s one of the oral agents that has the most side effects associated with it.” Flushing is almost universal but “rarely a cause of discontinuation,” while gastrointestinal symptoms can lead to discontinuation.
Alemtuzumab, a high-efficacy drug that’s administered in two annual cycles, he said, is especially convenient but monthly labs are required for years to check for problems due to its dampening of the immune system. Patients on ocrelizumab must be closely monitored for the same reason.
There are other factors to consider. Lower-efficacy drugs tend to be better options in younger patients – “they’re more resilient, and they tend to recover a little bit better after their early relapses,” Dr. Rinker said.
The drugs are especially helpful in patients who recover well after their initial episodes and who have sensory instead of motor symptoms, he said.
The case for high efficacy
Higher-efficacy drugs are best for older patients and those with heavy disease burden.
What about the 40-year-old patient? She’s female (women get less sick from MS) and has low disease burden, suggesting that a lower-efficacy drug may be appropriate, he said. “On the other hand, she has an incomplete recovery, and she’s got spinal cord disease and motor symptoms, so the tendency is going to be more towards the higher-efficacy end of the [drug] spectrum.”
But which drug? S1P modulators aren’t a good option since they require redosing or titration if doses are missed: “It’s important that you don’t prescribe them to patients where you have concerns about compliance.”
Also, he said, “we don’t think we’re to the point that we’re willing to put her at risk of severe medical complications by putting her on medicines with a high monitoring burden like cladribine or alemtuzumab.”
The best option may be teriflunomide, a once-daily pill, he said. It’s forgiving if a patient misses a dose since the medication stays in the body for a long time.
“There’s no single right answer,” Dr. Rinker said. “But there are ways to eliminate a lot of the choices based upon what we know about the medications and what we know about the patient. Then we can tailor a specific range of medications for a specific patient.”
Dr. Rinker disclosed research support from GW Pharmaceuticals.