Multiple sclerosis (MS) patients switching from Tysabri (natalizumab) to other disease-modifying therapies may have an increased risk of disease activity, though the risk is lower if the switch is limited to three months, a study found.
The results were published in an article, “Effect of switching from natalizumab to moderate- vs high-efficacy DMT in clinical practice,” in the journal Neurology Clinical Practice.
Tysabri, marketed by Biogen, is an antibody treatment that blocks immune system cells from moving into the brain and spinal cord. It was approved by the U.S. Food and Drug Administration (FDA) as a treatment for MS in 2004, but was pulled from the market after being linked to a rare neurological disorder called progressive multifocal leukoencephalopathy (PML).
The FDA in 2006 determined that the benefits of Tysabri outweighed the risks, although it is only available through a risk minimization plan called Tysabri Outreach Unified Commitment to Health (the TOUCH Prescribing Program).
Nevertheless, due to the risk of PML, as well as issues of non-responsiveness or disease relapse in some patients, several doctors chose to switch their patients to alternative treatments.
Researchers at the Lou Ruvo Center for Brain Health at the Cleveland Clinic sought to determine the effects of taking MS patients off Tysabri treatment and switching them to moderate- or high-efficacy therapies.
In total, researchers analyzed data from 556 MS patients who discontinued treatment with Tysabri between December 2005 and January 2018, at two Cleveland Clinic MS centers. Some 305 patients, or 54.9%, discontinued treatment due to the increased risk of PML.
Patients were split into two main groups: those who switched to a moderate-efficacy treatment (270 patients), and those who switched to a high-efficacy treatment (130 patients). Other patients not considered in the analysis were either switched to a lower-efficacy treatment, switched to another type of treatment, were not given any other treatment, or resumed Tysabri treatment.
The moderate-efficacy treatments considered included Gilenya (fingolimod) and Tecfidera (dimethyl fumarate); whereas the high-efficacy treatments included Ocrevus (ocrelizumab), rituximab (used off-label in MS), and Lemtrada (alemtuzumab).
Results showed that 48.6% of the patients analyzed switched to moderate-efficacy treatments (140 to Gilenya, and 130 to Tecfidera), while 23.4% switched to high-efficacy treatments (106 to Ocrevus, 17 to rituximab, and seven to Lemtrada).
Researchers analyzed patients based on the likelihood of disease relapse and disease activity. Data were collected at six months and two years after Tysabri treatment was discontinued, and compared with data collected 12 months prior to the switch. When analyzing the data, the team took into account a number of variables — such as demographics, disease history, additional illnesses, lab test results, and previous treatments — to determine the true effect of the treatment switch.
They found that patients who switched to other treatments (moderate- or high-efficacy) had comparable relapse rates (no significant difference was found) at both six months and two years.
Prior studies have indicated that switching treatments can increase the risk of relapse. The researchers said they didn’t observe an increased risk in their study, which had a shorter washout period ( the time between discontinuation of one treatment to the start of the next one). The mean washout periods in the study were 1.4 months for those who switched to a moderate-efficacy treatment and 1.8 months for those on high-efficacy treatment, compared with 4.3 months in a 2014 study.
The researchers said they believe the shorter washout period lowered “the risk of disease reactivation.”
However, the data showed an increased disease activity risk after switching treatments, as measured by the presence of lesions on magnetic resonance imaging (MRI) scans.
Six months after the switch, patients receiving moderate-efficacy treatments showed a statistically significant increase in the risk of disease activity by MRI — higher MRI disease activity and number of MRI lesions — than those who switched to a high-efficacy therapy.
Two years after switching, both groups showed a statistically significant increased risk of disease activity, representing a greater disability progression.
There were no cases of PML or other serious opportunistic infections reported in either group.
The “sensitivity analysis on treatment at six-month follow-up and cumulative MRI disease activity over 24 months demonstrated lower effectiveness in NTZ [Tysabri] switchers to Mod [moderate] DMT [disease-modifying therapy] compared with HET [high-efficacy therapy],” the researchers wrote.
The most effective strategy when switching patients from Tysabri is to chose a high-efficacy disease-modifying therapy, and to make the transition within a period of less than three months, they said.
“Switching to a DMT of at least moderate efficacy following NTZ discontinuation is effective in reducing the risk of rebound disease when restricting the washout period to [less than] three months, particularly in those switching to HET,” they said. “Thus, these data suggest that an HET should be considered in the appropriate clinical setting when transitioning a patient off of NTZ.”
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