Effect of switching from natalizumab to moderate- vs high-efficacy DMT in clinical practice

Neurol Clin Pract. 2020 Dec;10(6):e53-e65. doi: 10.1212/CPJ.0000000000000809.

Abstract

Objective: To assess the real-world comparative effectiveness of switching from natalizumab (NTZ) to a moderate-efficacy (Mod) disease-modifying therapy (DMT) vs high-efficacy therapy (HET) in patients with multiple sclerosis (MS).

Methods: Patients discontinuing NTZ at two MS centers (n = 556) who switched to Mod DMT (n = 270) vs HET (n = 130) were assessed using propensity score (PS) weighting. PS model covariates included demographics and baseline clinical and MRI characteristics. All outcomes were reported as Mod DMT vs HET.

Results: Of the patients included in the study, 48.6% switched to Mod DMT (dimethyl fumarate, n = 130; fingolimod, n = 140) vs 23.4% who switched to HET (ocrelizumab, n = 106; rituximab, n = 17; alemtuzumab, n = 7). Within the first 6 months post-NTZ, switchers to Mod DMT experienced comparable relapses (odds ratio [OR] = 1.36, 95% confidence interval [CI] [0.72-1.66], p = 0.724), although they had increased MRI activity on treatment (OR = 2.59, 95% CI [1.09-3.57], p = 0.037). By 24 months post-NTZ, there was no difference in the annualized relapse rate (OR = 1.44, 95% CI [0.69-1.59], p = 0.334) or time to first clinical relapse (HR = 2.12, 95% CI [0.87-5.17], p = 0.090), although switchers to Mod DMT had higher gadolinium-enhancing (GdE) lesions (OR = 3.62, 95% CI [1.56-5.21], p = 0.005), earlier time to first GdE lesion (HR = 6.67, 95% CI [2.06-9.16], p = 0.002), lower proportion with the absence of disease activity (OR = 0.41, 95% CI [0.21-0.71], p = 0.004), and higher risk of disability progression on T25FW (OR = 1.83, 95% CI [1.06-3.02], p = 0.043) and 9-HPT (OR = 1.81, 95% CI [1.05-3.56], p = 0.044).

Conclusion: Patients switching from NTZ to Mod DMT vs HET were at relatively increased risk of disease activity within the first 6 months of NTZ withdrawal that was sustained at 24 months, yielding greater disability progression.