Evaluating natalizumab first-line and later-line use in multiple sclerosis: a US claims database analysis.

Background: Limited information exists on the healthcare resource utilization (HCRU) associated with real-world natalizumab used as a first-line (1L) versus later-line (2L+) treatment in multiple sclerosis (MS).

Objectives: To describe natalizumab use in newly diagnosed MS patients treated as 1L or 2L+ and evaluate unadjusted annualized relapse rates (ARR) and MS-related HCRU before and after treatment initiation.

Design: This retrospective observational study utilized Komodo Health Sentinel claims data from October 2015 to August 2022. The study included adults diagnosed with incident MS who initiated natalizumab treatment, with insurance coverage for at least 12 months before diagnosis and 24 months after. The index date was the first natalizumab claim on or after the diagnosis. Baseline was defined as the 365 days prior to the index date, truncated at the time of diagnosis. Follow-up ended at the earliest occurrence of death, insurance disenrollment, treatment discontinuation (gap ⩾45 days), switch to another disease-modifying therapy before natalizumab discontinuation, or study end.

Methods: Relapses and HCRU were assessed using person-time methods to account for varying follow-up times. Relapses were identified using a validated claims-based algorithm, and time to first relapse was analyzed using Kaplan-Meier methods. Hazard ratios for relapse were estimated using univariate Cox models. Mean differences (MD) in HCRU between baseline and follow-up and between 1L and 2L+ treatment groups were calculated.

Results: A total of 1174 patients in the 1L group (mean age 39.0, 72.0% female) and 394 in the 2L+ group (mean age 39.7, 79.4% female) were included. Patients in the 1L group had a significantly higher baseline ARR (1.48 vs 0.92,  < 0.001) and lower on-treatment ARR (0.28 vs 0.41 for 2L+,  < 0.001). HCRU decreased significantly in the 1L group from baseline to follow-up: hospitalizations (MD 17.01 visits/year), length of stay (LOS; MD 20.96 days/year), emergency room visits (MD 9.83 visits/year), non-natalizumab outpatient visits (MD 12.11 visits/year) and long-term care facility stays (MD 22.18 days/year,  = 0.002). The 1L group showed greater reductions in inpatient visits (MD 10.01 visits//year), LOS (MD 16.73 days/year) and non-natalizumab outpatient visits (MD 11.64 visits/year) compared to the 2L+ group.

Conclusion: Natalizumab as a first-line treatment was associated with greater reductions in ARR and MS-related HCRU compared to later-line use.