Background

Natalizumab extended interval dosing (EID) is associated with lower risk of progressive multifocal leukoencephalopathy than every-4-week standard interval dosing (SID). Independent real-world (RW) studies suggest that natalizumab effectiveness is maintained in patients who switch from SID to EID. MS PATHS (Multiple Sclerosis Partners Advancing Technology and Health Solutions) is a learning health system comprised of a collaborative network of healthcare institutions that provides access to RW clinical and MRI data collected using standardized acquisition protocols.

Objectives

Compare the effectiveness of natalizumab EID and SID using quantitative MRI metrics from highly standardized RW images in MS PATHS.

Methods

An MRI segment was defined as 2 MRI acquisitions and associated interval duration. MS PATHS patients with ≥1 MRI segment, ≥2 infusion cycles (infusion interval >21 days and ≤84 days), and complete covariate information were eligible. MRI segments with average infusion cycle (AIC) ≤35 days and >35 days were defined as SID and EID, respectively. For each MRI segment, new T2 lesions and changes in T2 lesion volume (T2LV) and brain parenchymal fraction (BPF) were compared for SID and EID using inverse probability weighting (IPW) with logistic regression and robust linear regression.

Results

IPW analysis included 327 SID patients (596 MRI segments) and 67 EID patients (85 MRI segments). The mean AIC for SID was 29.5 (standard deviation [SD] 1.8) days and 40.8 (4.9) days for EID. Mean MRI segment duration for SID and EID was 9.7 (SD 5.5) and 9.6 (5.3) months, respectively. Proportions of patients with no new T2 lesions were similar for the SID and EID groups (75.6% vs 75.3%; adjusted odds ratio for 0 vs ≥1 lesion=0.967 [95% CI 0.500, 1.871]; P=0.921). SID and EID patients did not differ significantly in adjusted T2LV change (−0.070 [95% CI −0.129, 0.111] mL vs 0.022 [−0.132, 0.180] mL; P=0.233) or BPF change (−0.1222% [95% CI −0.1524%, −0.0921%] vs −0.1442% [−0.2234%, −0.0649%]; P=0.617).

Conclusions

MRI activity was low in SID and EID MS PATHS patients, and there were no significant differences in MRI outcomes between the 2 groups. These results confirm and extend previous RW studies of natalizumab EID effectiveness. Study limitations include modest EID sample size and potential channeling bias. The ongoing phase 3b randomized trial NOVA (clinicaltrials.gov NCT03689972) will further evaluate the effectiveness of natalizumab EID versus SID.

MS PATHS is supported by Biogen.