Natalizumab, Rituximab More Effective for MS Patients Who Switch from Interferon, Glatiramer Acetate

Patients with relapsing-remitting multiple sclerosis (RRMS) on interferon or glatiramer acetate (IFN/GA) with breakthrough disease who switch to natalizumab (Tysabri, Biogen) or rituximab (Rituxan, Biogen) experienced less disease activity than those who switched to fingolimod (Gilenya, Novartis).

In total, 241 patients with RRMS were included in the study, of which 105 switched to natalizumab, 48 to rituximab, and 88 to fingolimod. The adjusted hazard ratios (HR) for relapse were 1.0 (95% CI, 0.2 to 5.6) for rituximab and 3.4 (95% CI, 1.3 to 9.2) for fingolimod compared to natalizumab.

The annualized relapse rates (AAR) were 0.02 for natalizumab, 0.03 for rituximab, and 0.07 for fingolimod, with the percentage of patients having a relapse being 5.7% (n = 6), 8.3% (n = 4), and 18.2% (n = 16), respectively.

“This study suggests a superior effect of [natalizumab] and [rituximab] compared with [fingolimod] in suppressing further disease activity in RRMS patients switching from IFN/GA due to breakthrough disease. Overall medication persistence was better with RTX, mainly because of switches due to positive JC virus serology in [natalizumab] treated patients, and lack of efficacy in [fingolimod] treated patients,” the authors, led by Malin Boremalm, from the Department of Pharmacology and Clinical Neuroscience at Umeå University, wrote.

Additionally, rituximab showed displayed better medication persistence than both natalizumab and fingolimod. Of 83 patients who discontinued therapy, 2.1% (n = 1) discontinued rituximab compared to 44.8% (n = 47) with natalizumab and 39.8% (n = 35) in the fingolimod group. The annualized drug discontinuation rates were 0.15, 0.01, and 0.15 for natalizumab, rituximab, and fingolimod, respectively.

The leading reason for drug discontinuation was positive JC virus serology in natalizumab-treated patients, which occurred in 70.2% (33 of 47 patients) of patients; disease breakthrough in fingolimod-treated patients, which occurred in 65.7% (23 of 35 patients) of patients; and pregnancy in the single patient who discontinued rituximab.

“Information on the comparative effectiveness and safety of disease modulatory treatments available for RRMS in different clinical situations is limited. Continued disease activity during first-line injectables indicates a suboptimal treatment response and should prompt a switch to a more effective therapy,” Boremalm and colleagues wrote.

Contrast enhancing lesions (CELs) which numbered ≥1 were present in 13 patients—1 patient on natalizumab (1%), 1 patient on rituximab (2.1%), and 11 patients on fingolimod (12.5%). Magnetic resonance imaging (MRI) was conducted at a rate of 0.83, 0.70, and 0.78 times per year per patient in the natalizumab, rituximab, and fingolimod groups, respectively.

After 1 year, 99 patients on natalizumab, 46 patients on rituximab, and 74 patients on fingolimod were at-risk for relapse, with those numbers dropping to 14, 2, and 4, respectively, by year 5. The crude and adjusted HRs for time to first relapse compared with natalizumab in rituximab-treated patients were 1.6 (95% CI, 0.5 to 5.8) and 1.0 (95% CI, 0.2 to 5.6); and in fingolimod-treated patients were 3.8 (95% CI, 1.5 -9.8), and 3.4 (95% CI, 1.3 to 9.2), respectively. During the extended observation period, there was 1 relapse in the fingolimod group 80 days after the final dose and 1 relapse in the natalizumab group 8 days aftethe r final dose.

As for safety outcomes, Boremalm and colleagues reported that 19 patients experienced an adverse events (AE). In total, they occurred in 8 (7.6%), 5 (10.4%) and 6 (6.8%) patients in the natalizumab, rituximab, and fingolimod treated groups, respectively, for AE per year rates of 0.03, 0.04, and 0.03, respectively.

“The results of this study, implying similar efficacy for suppression of disease activity for [natalizumab] and [rituximab], are in line with a previous study on treatment-naïve RRMS patients initiating a first DMT,” the investigators wrote. “Also, our results are in line with a previous study suggesting superior efficacy of [rituximab] compared with [fingolimod] after switch from [natalizumab]due to JC virus positivity.”

REFERENCES

1. Boremalm M, Juto A, Axelsson M. Natalizumab, rituximab and fingolimod as escalation therapy in multiple sclerosis. Eur J Neurol. Published online February 14, 2019. doi: 10.1111/ene.13936.