Effect of switching from natalizumab to moderate- vs high-efficacy DMT in clinical practice
Carrie M. Hersh, Haleigh Harris, Devon Conway, Le H. Hua
Abstract
<h3>Objective</h3> 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). <h3>Methods</h3> 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. <h3>Results</h3> 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], <i>p</i> = 0.724), although they had increased MRI activity on treatment (OR = 2.59, 95% CI [1.09–3.57], <i>p</i> = 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], <i>p</i> = 0.334) or time to first clinical relapse (HR = 2.12, 95% CI [0.87–5.17], <i>p</i> = 0.090), although switchers to Mod DMT had higher gadolinium-enhancing (GdE) lesions (OR = 3.62, 95% CI [1.56–5.21], <i>p</i> = 0.005), earlier time to first GdE lesion (HR = 6.67, 95% CI [2.06–9.16], <i>p</i> = 0.002), lower proportion with the absence of disease activity (OR = 0.41, 95% CI [0.21–0.71], <i>p</i> = 0.004), and higher risk of disability progression on T25FW (OR = 1.83, 95% CI [1.06–3.02], <i>p</i> = 0.043) and 9-HPT (OR = 1.81, 95% CI [1.05–3.56], <i>p</i> = 0.044). <h3>Conclusion</h3> 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.