Lower rates of relapse and discontinuation with ocrelizumab after natalizumab vs dimethyl fumarate and fingolimod in MS

A retrospective observational cohort study finds that patients with relapsing-remitting multiple sclerosis (RRMS) who switched from natalizumab to ocrelizumab had lower annual relapse and discontinuation rates and longer time to first relapse than those who switched to dimethyl fumarate or fingolimod.

Natalizumab is monoclonal antibody with established efficacy in RRMS. [N Engl J Med 2003;348:15-23; N Engl J Med 2006;354:899-910] However, its long-term use is associated with an increased risk of progressive multifocal leukoencephalopathy caused by JC virus (JCV). [N Engl J Med 2012;366:1870-1880] Therefore, in patients who become positive for anti-JCV antibody, natalizumab is often discontinued to mitigate PML risk and their disease-modifying therapy (DMT) is usually switched to either fingolimod, dimethyl fumarate, or ocrelizumab. [JAMA Neurol 2014;71:436-441; J Neurol Neurosurg Psychiatry 2017;88:1073-1078; Mult Scler 2021;27:790-794]

“Evidence has been inconsistent regarding the comparative efficacy of these three common DMTs after switching from natalizumab, and a direct comparison between them is lacking,” wrote the researchers. “Therefore, conducted a retrospective study to directly compare the treatment outcomes in participants treated with dimethyl fumarate, fingolimod, or ocrelizumab after natalizumab cessation using the MSBase registry data set.” [JAMA Neurol 2023;doi:10.1001/jamaneurol.2023.1542]

In the data set, a total of 1,386 patients (mean age, 41.3 years; female, 71 percent) switched to dimethyl fumarate (9.9 percent), fingolimod (59.4 percent), or ocrelizumab (30.7 percent) after ≥6 months on natalizumab and within 3 months of its discontinuation.

The annualized relapse rates (ARR) were follows: ocrelizumab, 0.06 (95 percent confidence interval [CI], 0.04–0.08); fingolimod, 0.26 (95 percent CI, 0.12–0.48); and dimethyl fumarate, 0.27 (95 percent CI, 0.12–0.56). The ARR ratio of fingolimod to ocrelizumab was 4.33 (95 percent CI, 3.12–6.01) and of dimethyl fumarate to ocrelizumab was 4.50 (95 percent CI, 2.89–7.03). Compared with ocrelizumab, the hazard ratio (HR) of time to first relapse was 4.02 (95 percent CI, 2.83–5.70) for fingolimod and 3.70 (95 percent CI, 2.35–5.84) for dimethyl fumarate. “No significant difference in ARR and time to first relapse was found between fingolimod and dimethyl fumarate use,” added the researchers.

Compared with ocrelizumab, fingolimod (HR, 2.57; 95 percent CI, 1.74–3.80) and dimethyl fumarate (HR, 4.26; 95 percent CI, 2.65–6.84) were associated with a significant increase in treatment discontinuation rates over time. The most commonly reported reason for treatment discontinuation with fingolimod and dimethyl fumarate was lack of efficacy (48 percent and 31 percent, respectively) and adverse events for ocrelizumab (35 percent).

“Of note, a switch to fingolimod was associated with a 49 percent higher risk [HR, 1.49; 95 percent CI, 1.07–2.07] for disability accumulation vs ocrelizumab,” highlighted the researchers. “However, there was no significant difference in disability improvement between the two agents.”