AAN Issues New Guidelines on Disease-Modifying Therapies in MS, Including Switching, Stopping and Pregnancy

The new guideline aims to help clinicians choose among as many as two dozen potential therapies which, it is hoped, will delay disease progression, and help more patients avoid fearsome consequences like severe disability and reduce life expectancy. But doctors also face the challenge of limited follow-up for many of these drugs, one of which was recently voluntarily removed from the market due to side effects.

A new practice guideline published by the American Academy of Neurology on April 23 attempted to sort out recommendations among an explosion of drugs for multiple sclerosis which are considered to be disease-modifying therapies (DMTs) which have been approved in recent years. The guideline, which discussed clinical questions such as choice of therapies, as well as strategies including switching or stopping DMTs, was published during the Academy’s annual meeting in Los Angeles.

The guideline discussed 17 FDA-approved medications, and also made a weak recommendation regarding off-label use of six other drugs. (Patients may also have to take other drugs to treat their symptoms, which DMTs are not intended to address).

The cornucopia of new medications, at least seven of which have only been approved since 2010, has its origin in immune strategies.

“If you trace it back to the very first FDA-approved medicine, interferon in 1993, the scientists knew MS had something to do with the immune system,” said Alexander Rae-Grant, MD, professor of medicine at the Cleveland Clinic Lerner College of Medicine, and lead author on the article.

Another older drug, glatiramer acetate, was approved in 1996. “It is like a molecular mimic; it confuses the immune system into attacking the medicine, because it looks like myelin,” the substance that surrounds nerve cells, said Rae-Grant. “We know everything there is to know about that medicine.

“Since then, we’ve become much more targeted in our approach, and we’ve adapted some medications used in cancer populations, as well as rheumatology,” he added.

Head-to-Head Clinical Trials Urgently Needed

But much less is known about some of the newer medications, leading the members of the guideline committee to make recommendations about the need for clinical trials in areas like comparative effectiveness and pregnancy-related issues. And prior to just last year, with the approval of ocrelizumab, there was no DMT for the primary progressive form of MS. (A classification system for several varieties of MS was revised in 2016).

The uncertainty some clinicians may experience is illustrated by the voluntary withdrawal from the market of one drug, daclizumab, which was initially referred to in the guideline, according to Rae-Grant (daclizumab was first approved in 1997 for transplant patients).

Neurologists are hopeful that the new therapies will be life-changing for some patients. Perhaps the most feared consequences of MS are severe disability and a somewhat reduced life expectancy.

“It used to be that about half of the patients would not be able to walk independently after about 25 years. But we don’t have a lot of long-term data on the MS population,” noted Rae-Grant.

“If we go back to earliest therapies, some cohorts have been followed for 20 years. But some of the new DMTs have only been available for two-to-five years, and disease progression is typically measured by relapses which occur over two to three years,” explained Ruth Ann Marrie, MD, PhD, professor at the University of Manitoba in Winnipeg, and co-author on the article. “So it’s difficult to say what a new therapy is going to do for somebody 20 years from now.”

But neurologists are hopeful that patients will experience some long-term benefits, including a delay of progression. In determining how to do that, the experts debated questions like whether to prescribe the strongest therapies first, or to switch to them if less potent drugs stop working.

Continue Reading