The study, “Reducing return of disease activity in patients with relapsing multiple sclerosis transitioned from natalizumab to teriflunomide: 12-month interim results of teriflunomide therapy,” was published in the journal Multiple Sclerosis Journal – Experimental, Translation and Clinical.
Inflammation is a hallmark of MS, and it contributes to the neurological impairment associated with the disease. Disease-modifying therapies have been developed to destroy, suppress, or alter the pro-inflammatory behavior of cells.
Tysabri, marketed by Biogen, is an effective therapy for relapsing MS, as it inhibits the migration of inflammatory cells into the central nervous system (CNS).
However, the use of Tysabri has been associated with an increased risk of developing progressive multifocal leukoencephalopathy (PML), a rare infection of the brain caused by the John Cunningham virus (JCV).
This PML risk has prompted physicians to discontinue Tysabri treatment in a large percentage of patients. However, studies have reported that patients often develop heightened MS disease activity, higher rates of relapse of increased severity, and relapse-related fatalities, after Tysabri withdrawal.
To date, there is limited data on successful therapeutic strategies that can help patients transition off Tysabri, while reducing the risk of disease reactivation.
So, researchers conducted a Phase 4 clinical trial (NCT01970410) to assess the use of Aubagio (marketed by Sanofi Genzyme) as a replacement therapy for clinically stable patients with relapsing MS being taken off Tysabri due to prior JCV exposure.
Aubagio is an approved MS treatment that was selected for its acceptable safety profile.
Researchers enrolled 55 clinically stable patients with relapsing MS (mean age of 47.2 years), who had completed 12 or more consecutive months of Tysabri treatment, and tested positive for JCV. Subjects started Aubagio treatment at 14 mg/day, at an average of 28 days after their final Tysabri infusion.
Researchers conducted physical examination, laboratory assessments, brain magnetic resonance imaging (MRI), and assessed the level of disability at baseline and multiple follow-up visits in all participants.
Results showed that during the 12-month study period, 52 of the 55 patients remained relapse-free. Two patients experienced one clinical relapse, and one patient had two clinical relapses, resulting in a relapse-free proportion of 0.94.
Furthermore, the average time to the first MRI lesion was 10.9 months; and the average time to three-month sustained disability worsening (which measures disability progression) was 11.8 months.
Further analysis revealed that the average number of relapses in one year was 0.08 (8%), and the proportion of patients with no evidence of disease activity was 0.68 (68%).
Regarding the treatment’s safety, 47 of the 55 MS patients (85.5%) reported adverse side effects, 95% of which were mild to moderate. According to the team, the most reported side effects “included hair thinning or loss (36.4%), diarrhea or loose stool (30.9%), headache (21.8%), nausea/vomiting (20.0%), and vertigo/balance difficulties/dizziness (20.0%),” they wrote.
There were no cases of PML, other opportunistic infections, or deaths.
Tysabri retains its therapeutic activity in the body for three or more months after the last dose, leading some clinicians to apply a post-Tysabri “washout period” in which patients don’t receive treatment due to potential risks of using a new medicine while Tysabri is still therapeutically active.
However, the risk of MS disease activity may correlate with longer post-Tysabri washout periods. That is why researchers in this Phase 4 trial did not employ a washout period. In fact, they found that Aubagio treatment without a Tysabri-washout period was beneficial for patients.
Overall, based on the results, the team concluded that “teriflunomide [Aubagio] use without washout is a potentially effective therapy for stable patients being taken off natalizumab [Tysabri], with a low risk of post-natalizumab relapses and an acceptable safety profile.”
“Clinicians may consider this a worthwhile strategy when transitioning clinically stable patients off natalizumab to another therapy,” they added.