Early use of high-efficacy DMTs may keep patients on therapy longer

Study cites lack of efficacy as common reason doctors give for a switch

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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A patient holds up both hands like a scale while considering two treatment options, one a pill and the other an injection.

Starting treatment with a high-efficacy disease-modifying therapy (DMT), rather than one with lesser efficacy, may reduce the number of times people with multiple sclerosis (MS) switch therapies due to a lack of effectiveness, a study of survey responses from doctors suggests.

High-efficacy DMTs often are perceived to have a higher risk of side effects, including a risk of progressive multifocal leukoencephalopathy (PML), a rare brain infection that can be deadly or lead to severe disability. The most common reason for switching an MS treatment, however, was concern with its lack of efficacy in a patient.

“Risk perception [by doctors] was not a leading factor for [a] treatment switch,” although PML was a “key” concern among doctors whose patients were using a highly effective therapy, the researchers wrote. Rather, “the overall leading cause of treatment switch from any previous DMT was relapse frequency.”

Study findings support doctors considering a high-efficacy DMT as an initial, first-line MS treatment, they noted.

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Doctors treating over 4,000 MS patients gave reasons for DMT switch

The study, “Influence of physicians’ risk perception on switching treatments between high-efficacy and non–high-efficacy disease‑modifying therapies in multiple sclerosis,” was published in the journal Multiple Sclerosis and Related Disorders.

Not everyone experiences MS in the same way, and disease symptoms can range from problems with vision, sensation, and balance to fatigue and slowed thinking.

Various MS treatments can help change the course of the disease and ease its symptoms, particularly for people with relapsing-remitting MS. When doctors decide which treatment to give a patient, they usually consider both its proven effectiveness and potential side effects.

There are two main approaches in treating MS. One is the early use of intensive treatment, where high-efficacy DMTs — which are better at slowing disease progression but can have more side effects — are initiated shortly after a diagnosis of MS.

The other, called an escalation approach, consists of initiating treatment with a DMT with low-to-moderate efficacy. A switch to a more effective DMT is made when the disease shows signs of activity, such as the presence of relapses, new lesions, or disability progression.

Because “treatment decisions in MS have become increasingly complex,” a team of scientists, mostly in Europe, looked at what makes doctors switch from one treatment to another, and how their perception of risk affects their decision.

They drew on data from the Adelphi Real World Disease-Specific Program for MS, which offers a view of the treatment landscape from the perspective of doctors and patients. As part of the program, doctors actively involved in treating and managing MS were asked to fill in a survey regarding their treatment approaches, including switch decisions, for the next 10 to 15 patients they saw.

Reasons for a therapy switch were available for 4,129 of the 4,361 patients — mostly women, with a mean age 42.1 — whose treatment was noted in the surveys. Most (84.2%) had relapsing-remitting MS, whereas the others had secondary progressive MS. Patients had been on their previous treatment for an average of 3.3 years, and for a majority (86.4%), that treatment was not a high-efficacy DMT.

Among those on lower efficacy DMTs, nearly half (45.4%) switched to a high-efficacy DMT. Among patients in the high-efficacy group, 28.7% switched to a lesser efficacy DMT.

High-efficacy DMTs in the Adelphi database included Gilenya (fingolimod), Kesimpta (ofatumumab), Tysabri (natalizumab) and  Ocrevus (ocrelizumab). Noted lower-to-moderate efficacy DMTs included Aubagio (teriflunomide), Avonex (interferon beta-1a), glatiramer acetate (sold as Copaxone, among other names) and Rebif (interferon beta-1a).

While doctors were well aware of the risks associated with the use of DMTs, treatment changes in only 4.7% of patients were due to concerns for cancer or infection. A specific risk of PML, however, was a reason given for switching treatment in 23.9% of patients on a high-efficacy DMT and for 0.5% of those on lower efficacy therapies.

“The perceived risk of PML, when counted, played a significant role for switching in the HE [high-efficacy] DMT group,” the researchers noted.

‘Escalation approach’ still dominates early DMT use in MS, researchers say

The top reasons for switching treatment among lower efficacy DMT group were relapse frequency (26.8%), a lack of treatment efficacy (20.9%), and patient request (20.6%). In turn, the most common reasons for stopping a high-efficacy DMT were risk of PML (23.9%), new or actively inflamed lesions (17.9%), and disability progression (15.1%).

“The common reason for treatment switch in both groups was lack of efficacy, perhaps related to the fact that the escalation approach continues to be the dominant approach in MS,” the researchers wrote.

“Initiating the treatment with [high-efficacy] DMTs may potentially reduce the number of switches due to sub-optimal efficacy,” they concluded. “These findings might help physicians to engage more in discussions with patients about the benefit/risk profile of DMTs.”

Four of this study’s nine scientists are Novartis employees, or they were employed there at the time of the study. The company markets several disease-modifying treatments for MS, including the oral therapies Gilenya and Mayzent (siponimod), and the injection therapy Kesimpta.