To describe the real-world effectiveness of natalizumab in patients with early RRMS who were treatment-naive versus those who had prior DMT use at natalizumab initiation.

STRIVE was a 4-year observational study of natalizumab-treated anti–JC virus antibody negative patients with early RRMS (disease duration ≤3 years).

No evidence of disease activity (NEDA) included attainment of both Clinical NEDA (no relapses and no 24-week CDW) and MRI NEDA (no gadolinium-enhancing lesions and no new or newly enlarging T2 lesions). Confirmed disability worsening (CDW) was defined as an Expanded Disability Status Scale score increase ≥0.5 from a baseline score ≥6.0, an increase ≥1.0 from a baseline score of 1.0 to <6.0, or an increase ≥1.5 from a baseline score of 0.0, confirmed after 24 weeks.

The STRIVE intent-to-treat population included 222 patients (treatment-naive, n=119; prior-DMT, n=103). Baseline characteristics were similar in treatment-naive and prior-DMT patients except for mean time since MS diagnosis (1.2 vs 2.1 years; P<0.0001) and mean number of relapses in the prior year (1.2 vs 1.7; P=0.0002). Similar proportions of treatment-naive and prior-DMT patients achieved NEDA except at year 2 (80.9% vs 63.8%; P=0.0192). Significantly more treatment-naive patients achieved Clinical NEDA compared to prior-DMT patients in years 1 (89.1% vs 71.1%; P=0.0018) and 2 (92.0% vs 75.7%; P=0.0045); however, similar proportions were seen between groups in years 3 and 4. MRI NEDA achievement did not differ by group. While both groups demonstrated significant on-natalizumab reductions in annualized relapse rate (ARR), treatment-naive patients had significantly lower on-natalizumab ARR (P<0.05 for all years). At 4 years, the cumulative probability of CDW was lower in treatment-naive than prior-DMT patients (11.5% vs 29.0%; P=0.0015).

Results confirm natalizumab’s effectiveness regardless of prior DMT use. However, treatment-naïve patients receiving natalizumab early in their disease course had improved clinical outcomes over the long term.