Patients with multiple sclerosis (MS) switching from Tysabri (natalizumab) to moderate-efficacy disease-modifying therapies (DMTs) are at a higher risk of showing signs of MS activity and experiencing disability progression than those switching to high-efficacy DMTs, a real-world study found.
Based on these findings, the researchers are arguing that, when possible, MS patients should be started on high-efficacy DMTs when switching from Tysabri.
The study, “Effect of switching from natalizumab to moderate- vs high-efficacy DMT in clinical practice,” was published in the journal Neurology Clinical Practice.
Marketed by Biogen, Tysabri is a high-efficacy DMT often used to treat people with relapsing forms of MS. This antibody-based therapy is thought to work by preventing immune cells from entering the brain and attacking neurons.
Clinical trials have shown that Tysabri can reduce the number of relapses as well as the number of new or enlarging MS lesions. But in clinical practice, its long-term use has been associated with a series of complications, including the development of a serious brain infection known as progressive multifocal leukoencephalopathy, or PML.
These known safety risks can be reduced by having patients switch from Tysabri to another DMT.
“However, the transition between NTZ [natalizumab] and alternative therapies poses additional risks because disease reactivation can occur upon NTZ discontinuation in the form of relapses and/or … lesions,” the researchers wrote.
Some studies have investigated the effects of therapy switching in groups of patients who were at a high risk of experiencing Tysabri side effects. However, no consensus has yet been achieved on what type of DMT they should be started on after discontinuing Tysabri.
“Real-world studies are therefore needed to investigate the effects of various post-NTZ sequencing strategies on both early and longer-term MS disease activity and disability progression,” the team wrote.
Now, researchers at the Cleveland Clinic, in Ohio, are reporting the findings of a real-world study that sought to compare the effectiveness of different types of DMTs in MS patients discontinuing Tysabri treatment.
Data was reviewed for 556 MS patients who were being followed at two MS clinical centers, the Cleveland Clinic Lou Ruvo Center for Brain Health and the Cleveland Clinic Mellen Center.
More than half of the patients (54.9%) included in the analysis had discontinued treatment with Tysabri because they were at a higher risk of developing PML.
From the 400 patients who had two-year follow-up data available, 270 switched from Tysabri to a moderate-efficacy DMT, and 130 to a high-efficacy DMT.
In the first six months following the treatment switch, the percentage of patients who experienced MS relapses was similar among those who were started on a moderate-efficacy DMT (11.7%) and a high-efficacy DMT (8.7%).
However, analyses showed that those individuals who were started on a moderate-efficacy DMT were at a 2.59 times higher risk of showing signs of disease activity in MRI scans — including new or enlarging active MS lesions — compared with those who switched to a high-efficacy DMT.
No significant differences in the annual number of MS relapses, or in the time to first relapse, were observed in the two groups of patients at two years after stopping treatment with Tysabri.
Yet, patients who switched to a moderate-efficacy DMT were more likely to develop gadolinium-enhancing MRI lesions (active lesions) at two years, compared with those who switched to a high-efficacy DMT.
Using surrogate markers of disability progression, those switching from Tysabri to a moderate-efficacy DMT experienced 20% higher odds of worsening of the T25FW (OR = 1.83, 95% CI [1.06–3.02], p = 0.043) and 20% worsening of the 9-HPT (OR = 1.81, 95% CI [1.05–3.56], p = 0.044). There were no cases of PML or other serious opportunistic infections reported in either group.
Moreover, those who switched to a moderate-efficacy DMT were nearly seven times more likely to have their first lesion sooner than those who switched to a high-efficacy DMT.
Researchers also found that patients who switched to a moderate-efficacy DMT had around a 20% higher risk of experiencing disability progression than those who were on a high-efficacy DMT.
None of the patients analyzed developed PML, or any other type of opportunistic infection, during follow-up.
“Patients switching from NTZ to Mod [moderate-efficacy] DMT vs HET [high-efficacy treatment] are at relatively increased risk of disease activity within the first 6 months of NTZ withdrawal, which is sustained at 24 months, yielding greater disability progression,” the researchers wrote.
“Thus, these data suggest that an HET should be considered in the appropriate clinical setting when transitioning a patient off of NTZ, especially when due to breakthrough disease,” they added.
The team is planning to conduct a larger study to confirm their findings and to assess the short- and long-term effects of DMT switching.
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