Highly Effective Therapies Used in Only a Minority of Relapsing MS Cases, Study Finds

Despite growth in the use of highly effective disease-modifying therapies (DMTs) for relapsing-remitting multiple sclerosis (RRMS) in recent years, these agents account for a minority of all DMT for the condition and only about one-third of first-line therapy. So finds a large observational study examining DMT for RRMS at 10 MS centers in the U.S. and Europe over the past 25 years.

“There is currently no universally accepted treatment paradigm for relapsing MS, and this has resulted in significant practice variability,” says Marisa McGinley, DO, a neurologist in Cleveland Clinic’s Mellen Center for Multiple Sclerosis Treatment and Research, who reported the findings at the 2019 annual meeting of the American Academy of Neurology on May 7. “Many neurologists start treatment with low- and then moderate- and then high-efficacy drugs, probably in large part because that’s the order in which these DMTs came onto the market. But that actually might not be the best order for use, and we need more guidance on this issue.”

Evidence on optimal sequencing may be on the way

The question of which type of DMTs should be used for specific patients with RRMS — and at what point in the disease process — is a pressing one. In fact, it spurred two ongoing clinical trials that have attracted major funding by the congressionally authorized Patient-Centered Outcomes Research Institute (PCORI): TREAT-MS, which is examining whether early aggressive therapy can prevent or delay disability, and the Cleveland Clinic-led DELIVER-MS study, which is comparing the benefits and risks of starting treatment with an escalation approach versus an early highly effective treatment approach for RRMS.

“These large ongoing studies should help clarify the relative merits of an escalation approach — which begins with safer, older DMTs that have low to moderate efficacy — versus early, aggressive treatment with highly effective drugs that have the potential for rare but significant adverse effects,” says Dr. McGinley.

A snapshot of DMT use over time

In the meantime, she and a team of Cleveland Clinic researchers decided to evaluate how widely the newer highly effective DMT agents have been adopted in practice to date. They used the MS PATHS database (profiled in this earlier Consult QD post) to compile data on the entire RRMS population at 10 academic MS centers in the U.S. and Europe from 1993 through 2018.

The analysis specifically assessed the use of highly effective therapy (HET) — i.e., the monoclonal antibodies natalizumab, alemtuzumab, ocrelizumab and rituximab — compared with low- to moderate-efficacy therapies, classified as any other FDA-approved medication for RRMS, including beta interferons, glatiramer acetate and oral medications.

“The older drugs have a known safety profile,” Dr. McGinley explains, “while the HET agents are well-tolerated but stronger medications that affect the immune system to a greater degree, with the potential for more serious side effects. Clinicians have to balance the risks of these medications with the risk of MS worsening when deciding which medication to use.”

Key cohort findings

A total of 5,520 treated patients with RRMS were identified in the database, with the following collective profile:

• Mean age, 46 + 11.5 years
• Mean disease duration, 11 + 8 years
• 75% female
• 63.5% white
• 37.6% treatment-naïve when added to the database

Among the overall cohort, HET was first used at a rate of 27.3% in 2006, which rose to 43.8% by 2018. Among those who were treatment-naïve, the first use of HET was in 2009, at a rate of 9.5%, which increased to 32.3% by 2018.

“We weren’t surprised by these findings,” observes Dr. McGinley, “given that no HET agents were available until around 2006.” (Natalizumab, the first agent, was initially approved in the U.S. in 2004 but removed from the market in 2005 due to safety concerns; it was reintroduced in the U.S. in 2006. It has been available in Europe since 2007.)

She adds that use of HET varied significantly across the study’s 10 treatment sites.

“We’re in a great position with MS treatment today in that we have many drugs to use with a range of efficacy and different mechanisms of action,” Dr. McGinley concludes. “Now we need to figure out how to sequence them. We’re hopeful that the two ongoing PCORI-funded trials will add much-needed data to our knowledge base on this question.”