Stopping Tysabri Early Tied to Active PPMS, Smoking and Depression in Patients, Study Finds

The likelihood of discontinuing treatment with Tysabri (natalizumab) is higher among patients with progressive relapsing multiple sclerosis, and those who smoke and are depressed, a study reported.

Progressive relapsing MS (PRMS) is now largely considered a subset of primary progressive MS, or PPMS marked by periods of activity (at the time of relapses or new MRI lesions).

The study “Duration of natalizumab therapy and reasons for discontinuation in a multiple sclerosis population” was published in the Multiple Sclerosis Journal – Experimental, Translational and Clinical.

Tysabri, marketed by Biogen, is one of several disease-modifying MS therapies (DMTs), medications that work by modulating and toning down the immune system to keep inflammation in check. Tysabri is an antibody-based treatment designed to reduce inflammation in people with relapsing-remitting multiple sclerosis (RRMS) by preventing immune cells from entering the brain.

Despite their reported benefits, responses to DMTs vary significantly among patients. This has fueled interest in “predicting an individual’s response to particular DMTs before they are started, often referred to as personalized treatment,” the study noted.

Researchers at the Cleveland Clinic aimed to identify characteristics of MS patients that might predict a shorter treatment with Tysabri. They reviewed data from The Tysabri Outreach: Unified Commitment to Health (TOUCH) database.

Specifically, the team searched the TOUCH database to identify all patients followed at the Cleveland Clinic Mellen Center and Lou Ruvo Center for Brain Health between December 2005 and January 2018, who began and eventually stopped using Tysabri.

This search identified 554 MS patients (mean age, 41.1) at the two centers meeting the study’s criteria. Most (75.6%) had RRMS, and had been given an average of 30 Tysabri infusions (range from one to 140).

Slightly more than half —  305 patients (55.1%), with a mean number of 41.1 infusions — discontinued Tysabri due to its known higher risk of progressive multifocal leukoencephalopathy (PML). This rare and often fatal viral disease, caused by the John Cunningham virus (JCV), is characterized by progressive damage and/or inflammation at multiple sites in the brain.

Another 98 patients (17.7%, average number of infusions 11.5) discontinued the treatment due to intolerance, 36 (6.5%, average number of infusions 18.7) due to disability progression, and 28 (5.0%, average number of infusions 17.1) due to inflammatory disease.

The remaining 87 patients (15.7%, average number of infusions 21.2) stopped Tysabri for reasons that included payer denials or the inconvenience of monthly infusions.

Analyses showed that the 21 people with progressive relapsing MS were more than twice as likely to choose to stop Tysabri early than did those with RRMS.

Smokers and people with higher depression scores also had an increased risk of early Tysabri discontinuation.

When looking only at RRMS patients in the study group, researchers found that older age at the start of Tysabri treatment was a predictor of early discontinuation.

Analyses looking at specific reasons for treatment discontinuation — namely, inflammatory disease, disability progression, PML risk, and intolerance — revealed that progressive relapsing MS patients had more than a 14-fold increased risk of discontinuing Tysabri due to inflammatory disease than did those with RRMS.

Patients with secondary progressive MS (SPMS) were four times more likely to discontinue Tysabri due to disability progression than those with RRMS. People with progressive relapsing MS and PPMS were also more likely to discontinue Tysabri due to disability progression, but these results were not statistically significant.

Those using an assistive device for one side of the body were more likely to stop Tysabri due to disability progression than were patients not needing assistive devices. People in wheelchairs had a more than four times greater likelihood of stopping treatment due to intolerance.

As expected, patients positive for JCV antibodies (meaning that they had contact with the JC virus) were 40% more likely to stop due to the risk of PML.

In turn, smokers had an 80% increased risk of discontinuation due to intolerance.

Greater disability and a greater number of lesions seen on magnetic resonance imaging (MRI) scans at the start of treatment with Tysabri, in contrast, were significantly associated with longer use of this DMT.

“Our results suggest that smoking, depression, and a progressive relapsing multiple sclerosis phenotype are associated with shorter natalizumab [Tysabri] treatment durations,” the researchers wrote.

However, “there were only 21 patients with PRMS in our study, so our results need to be interpreted with caution,” they added.

“Based on our study, careful consideration should be given when prescribing natalizumab to patients with comorbidities such as smoking and depression, as well as to patients with PRMS, but these results require further verification in a larger, multicenter cohort,” the researchers concluded.