Dr Carrie HershCarrie Hersh, DO, MSc
Patients with multiple sclerosis (MS) who switched from treatment with natalizumab to a moderate efficacy disease-modifying therapy (DMT) was linked to a relatively increased risk of disease activity within 6 months compared to switching to a high-efficacy therapy.

Additionally, lead author Carrie Hersh, DO, MSc, neurologist, Cleveland Clinic Lou Ruvo Center for Brain Health, and colleagues noted that the disease activity was sustained at 24 months, yielding greater disability progression for those individuals. The data reveal important information for clinicians who may be transitioning patients off of natalizumab, particularly those who are switched due to breakthrough disease, the authors wrote.

“The current study provides real-world clinical insights into DMT switching patterns following natalizumab discontinuation,” Hersh et al. detailed. “The current study also demonstrates that switching to a DMT of at least moderate efficacy following natalizumab discontinuation is effective in reducing the risk of rebound disease when restricting the washout period to <3 months, particularly in those switching to high efficacy therapy.”
 
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The retrospective observational study included 556 patients from 2 MS centers discontinued natalizumab who switched to either moderate (n = 270) or high (n = 130) efficacy DMT. The 48.6% who switched to a moderate DMT did so to dimethyl fumarate (n = 130) and fingolimod (n = 140), while the 23.4% who switched to high DMT did so to ocrelizumab (n = 106), rituximab (n = 17), and alemtuzumab (n = 7).

Data revealed that within 6 months of discontinuation, those in the moderate group had comparable relapses to the high group (odds ratio [OR], 1.36; 95% CI, 0.72–1.66; P = .724), though MRI activity was increased upon treatment (OR, 2.59; 95% CI, 1.09–3.57; P = .037). At 24 months, annualized relapse rate (ARR; OR, 1.44; 95% CI, 0.69–1.59; P = .334) and time to first clinical relapse (hazard ratio[ HR], 2.12; 95% CI, 0.87–5.17; P = .090) were not significantly different.

Although, at 24 months, those who switched to moderate DMTs had significantly higher gadolinium-enhancing (Gd+) lesions (OR, 3.62; 95% CI, 1.56–5.21; P = .005) and earlier time to first Gd+ lesion (HR, 6.67; 95% CI, 2.06–9.16; P = .002). As well, the moderate group had a lower proportion of patients with an absence of disease activity (OR, 0.41; 95% CI, 0.21–0.71; P = .004), and higher risk of disability progression on Timed 25-Foot Walk (OR, 1.83; 95% CI, 1.06–3.02; P = .043) and 9-Hole Peg Test (OR, 1.81; 95% CI, 1.05–3.56; P = .044).

Notably, long-term use of natalizumab is limited in clinical practice due to an elevated risk of adverse events (AEs), including progressive multifocal leukoencephalopathy (ML), specifically in those with >2 years exposure to the treatment, exposure to immunosuppressive therapy, and those with high anti-JC virus antibody indices. Additionally, attempts to reduce this risk by switching therapies from natalizumab after a period of time are met with an additional risk of disease reactivation upon treatment interruption.

“Consensus is currently lacking on DMT switching strategies after natalizumab withdrawal and is primarily based on single-arm investigations with variable outcomes, a few small comparative effectiveness studies, or expert opinion,” Hersh and colleagues wrote. “Further observational studies are thus warranted to compare the effectiveness of post natalizumab sequencing strategies to guide decision making in clinical practice.”
REFERENCE
Hersh CM, Harris H, Conway D, Hua LH. Effect of switching from natalizumab to moderate- vs high-efficacy DMT in clinical practice. Neurology Clin Pract. Published online February 12, 2020, DOI: https://doi.org/10.1212/CPJ.0000000000000809.