Safety of Oral DMTs for RRMS in Real-world Use Seen to Match Trial Findings

People with relapsing-remitting multiple sclerosis (RRMS) using approved oral disease-modifying therapies generally tolerate the treatments well, with real-world adverse event profiles similar to those seen in clinical trials, an analysis of U.S. data indicates.

Results also suggest high adherence to these therapies — meaning patients are usually taking the therapies as prescribed, including those reporting an adverse event.

The analysis was conducted by AllianceRx Walgreens Prime in conjunction with Duquesne University School of Pharmacy, and findings presented at the 2021 Academy of Managed Care Pharmacy annual conference, held virtually in April.

Researchers used pharmacy claims and clinical data covering 10,370 adults with RRMS, who had completed initial clinical assessments and at least one MS refill clinical assessment between July 1, 2019, and Dec. 31, 2020. About three-quarters of patients were female, and over half were between the ages of 40 and 59.

About one-third of the analyzed patients resided in the South, while another third resided in the Midwest.

“Our findings revealed more patients in the southern part of the U.S. compared to the north,” Scott Carson, of AllianceRx Walgreens Prime, who helped conduct the analysis, said in a press release.

The most commonly used oral therapy was Tecfidera (dimethyl fumarate), prescribed to nearly half of the patients (45.3%), while the least common was Vumerity (diroximel fumarate), prescribed to 0.6% of patients. The researchers noted that Tecfidera, by Biogen, was available for the longest time (first approved in the U.S. in 2013), while Vumerity, by Alkermes and Biogen, was a relatively new oral therapy, gaining U.S. approval in October 2019.

In total, 257 (2.5%) patients switched from one oral therapy to another over the study’s 17 months. Among them, 53.7% switched to a therapy in the same medication class — meaning a different therapy that works in much the same way — while the rest switched to a therapy in a different medication class.

Researchers assessed adherence by calculating proportion of days covered, or PDC,  a measure of how many days a patient has taken their medication as directed.

PDC is relatively straightforward to calculate from prescription data. For example, if a person is prescribed 30 days’ worth of medicine, and they refill their prescription after 35 days, then it follows that, for five days, they were not being treated appropriately. As such, the PDC is 30 out of 35 days, or about 86%.

All of the medications assessed had similar PDCs — about 80%. Notably, PDCs were similar among patients who did or did not report an adverse drug event (ADE).

“The study found no statistically significant difference in medication adherence as measured by Proportion of Days Covered (PDC) based upon the presence or absence of a patient-reported ADE. This may be an indication oral DMTs are well tolerated from an ADE perspective,” Carson said.

“However, the analysis only accounted for presence/absence of an ADE and did not account for their type, frequency or severity,” he added.

ADEs were reported by over half of the patients (61.5%) who switched from one therapy to another, whereas they were substantially less common in people who continued with a given therapy.

This suggests that ADEs often prompt people to switch therapies. But some who switched had no reported ADEs, so “patient non-adherence and switching behavior may not be solely due to ADEs,” the researchers wrote, noting a need for further research to identify factors that affect these behaviors.

In other analyses, the researchers reported the relative frequency of common ADEs associated with different types of oral MS therapies.

For nuclear factor activators, namely Vumerity and Tecfidera, the most common adverse events were flushing (54.7%), abdominal pain (8.8%), and diarrhea (4%).

Among sphingosine 1-phosphate receptor modulators — fingolimod (sold by Novartis as Gilenya, generics available) and Mayzent (siponimod, also by Novartis) — the most common ADEs were abdominal pain (17.8%), fatigue (9.7%), and headache (9.4%).

For Aubagio (teriflunomide, by Sanofi), a dihydroorotate dehydrogenase inhibitor, the most common ADEs were hair loss or thinning (22.5%), abdominal pain (12.2%), and diarrhea (11.7%).

Broadly, these reported ADEs are comparable to what has been found in clinical trials of the various medications.

“The study demonstrated that real world ADE data aligned with clinical trial ADE data — an important finding,” said Rick Miller, vice president of clinical and professional practice at AllianceRx Walgreens Prime.