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

ObjectiveTo 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).MethodsPatients 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.ResultsOf 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).ConclusionPatients 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.