Brandi Vollmer, MPH
A Retrospective Chart Review
Ms. Vollmer and colleagues conducted a retrospective study to compare the discontinuation rates and efficacy of fingolimod and dimethyl fumarate to those of natalizumab. In a retrospective chart review, they identified patients with multiple sclerosis (MS) who presented to the Rocky Mountain MS Center in Aurora, Colorado. Eligible participants initiated drug therapy between January 2010 and October 2013. Patients who initiated natalizumab had to be negative for the John Cunningham virus (JCV) at baseline. Ms. Vollmer and colleagues retrospectively collected clinician-recorded data.
The study’s primary outcome was discontinuation at 24 months. Secondary outcomes included reasons for discontinuation, relapse activity, MRI activity, and a composite disease activity measure that comprised clinical relapse, contrast enhancement, and new T2 lesions on follow-up MRI. Ms. Vollmer and colleagues identified 1,302 patients who initiated insurance paperwork for natalizumab. To reduce the size of this sample, they randomly selected 800 patients, of whom 270 met the inclusion criteria. In all, 440 participants initiated paperwork for fingolimod, of whom 271 met the inclusion criteria. For dimethyl fumarate, the researchers found 592 participants who initiated the paperwork, and 342 met the inclusion criteria.
Patients receiving natalizumab were significantly younger (mean age, 39.8) than patients receiving fingolimod (42.5) or dimethyl fumarate (45.8). Furthermore, patients treated with natalizumab were more likely to be female (77.8%) than patients treated with fingolimod (72.0%) or dimethyl fumarate (69.6%). Patients receiving natalizumab also were more likely to have contrast enhancement on baseline MRI (31.2%) than were participants receiving fingolimod (24.6%) or dimethyl fumarate (14.6%). Mean disease duration was approximately 12 years for all groups.
Discontinuation and Disease Activity
The rate of discontinuation was similar for natalizumab (33.3%) and fingolimod (34.3%), but the researchers observed a significant difference between natalizumab and dimethyl fumarate (47.1%). Disease activity and adverse events were the most common reasons for discontinuation of fingolimod and dimethyl fumarate, and JCV positivity was the most common reason for discontinuation of natalizumab. Of the seven participants who discontinued natalizumab because of disease activity, five had neutralizing antibodies. Of the 20 patients who discontinued natalizumab because of adverse events, nine had rashes during infusion, eight of whom tested positive for neutralizing antibodies.
Ms. Vollmer and colleagues found no significant difference between natalizumab and fingolimod in the rate of patients with a clinical relapse (5.6% and 8.9%, respectively), but they observed a significant difference between dimethyl fumarate (12.9%) and natalizumab for this outcome. Contrast enhancement was less common among patients receiving natalizumab (6.6%), compared with fingolimod (13.1%), but there was no significant difference between natalizumab and dimethyl fumarate (10.0%).
The rate of new T2 lesions was lower with natalizumab (21.4%), compared with fingolimod (35.0%) and dimethyl fumarate (31.5%). Similarly, the composite disease activity measure was less common with natalizumab (20.7%), compared with fingolimod (34.7%) and dimethyl fumarate (33.6%). Data adjustments indicated that discontinuation was equally likely among patients receiving fingolimod and those receiving natalizumab. Patients receiving dimethyl fumarate, however, were approximately twice as likely to discontinue treatment, compared with patients receiving natalizumab.
Furthermore, patients receiving fingolimod were approximately twice as likely to discontinue treatment because of adverse events, compared with patients receiving natalizumab. Patients treated with dimethyl fumarate were approximately four times as likely to discontinue because of adverse events, compared with patients treated with natalizumab. In addition, patients were approximately twice as likely to have disease activity on fingolimod or dimethyl fumarate, compared with natalizumab.
—Erik Greb
Suggested Reading
Barbin L, Rousseau C, Jousset N, et al. Comparative efficacy of fingolimod vs natalizumab: A French multicenter observational study. Neurology. 2016;86(8):771-778.