The risk of a relapse is two to three times higher in relapsing-remitting multiple sclerosis (RRMS) patients who switch from Tysabri (natalizumab) to an oral or other injectable disease-modifying therapy after two or more years of its use, than it is in those who stay with Tysabri, a large observational study found.
A return of disease activity was not found to exceed pretreatment levels in the patient group analyzed, the researchers noted.
But these findings highlight the importance of evaluating a person’s risk factors, including treatment duration and necessary “washout” time, before choosing to move from Tysabri to a different disease-modifying therapy (DMT).
The study, “Clinical outcomes in patients who discontinue natalizumab therapy after 2 years in the Tysabri Observational Program (TOP),” was published in the Multiple Sclerosis Journal.
Tysabri, marketed by Biogen, is an antibody-based injection therapy that lowers inflammation in RRMS patients by preventing immune cells from entering the brain. Several clinical trials and real-world studies show it to be highly efficacious in treating RRMS, and it is approved in both the U.S. and EU.
“However, several factors may prompt physicians and patients to consider switching to another therapy, most notably the risk of progressive multifocal leukoencephalopathy (PML),” investigators wrote.
PML is a rare brain infection caused by the John Cunningham virus, and it is more likely to affect patients who have a weakened immune system. Long-term treatment (more than two years) with Tysabri has been associated with a higher risk of PML.
Previous studies also report that patients who stop using Tysabri are at a higher risk of experiencing a relapse, particularly in the four to eight months after their last dose.
“Determining the best therapy to switch to and establishing the optimal timing for start of the next therapy” are both crucial factors to consider when switching, the study stated.
To investigate in more detail factors that could increase a relapse risk, researchers analyzed data from the Biogen-sponsored Tysabri Observational Program (TOP; NCT00493298), the largest real-world study of the medication’s effectiveness and safety.
Researchers gathered and compared data from RRMS patients who switched to an oral or injectable DMT after being on Tysabri for at least two years with data on those who remained on Tysabri after two years of treatment.
In total 3,221 RRMS patients were included in their analyses. Of these, 2,466 people remained on Tysabri after two years of treatment, and 660 switched to an oral DMT and 95 to a different injectable DMT, all for at least one year.
People who switched to an oral DMT had a 2.18 times higher risk of relapse than those who continued with Tysabri. This risk was even higher — 3.02 times — for those who switched to an injectable therapy, analyses found.
“If a switch from natalizumab is indicated, these results from the TOP population show that oral DMTs provide better disease control than injectable DMTs,” the investigators wrote.
However, moving to an oral therapy after shorter periods on Tysabri (less than three years use, as opposed to three or more years) — and longer washout times (more than three months, as opposed to four or fewer weeks) — also posed a higher risk of relapses, statistical analyses of oral switchers only found.
“These results from TOP also indicate that minimizing the treatment gap to [less than four] weeks when switching from natalizumab may reduce the risk of return of disease activity,” the researchers wrote.
Those who had a high number of relapses before initiating treatment with Tysabri, and higher Expanded Disability Status Scale scores when they first started treatment, also had higher chances of experiencing relapses. (This scale, known as EDSS, is a measure of disability in MS patients.)
“Overall, better outcomes were observed in patients who continued natalizumab therapy than in those who switched to another DMT,” the investigators wrote.
“These results highlight the need to assess patient PML risk and the risk of return of disease activity prior to making switching decisions,” they concluded.
This study was supported by Biogen, and five of its 10 authors are or were Biogen employees at the time of these analyses.
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