Natalizumab in Early Relapsing-Remitting Multiple Sclerosis: A 4-Year, Open-Label Study

Abstract

Introduction: STRIVE was a 4-year, multicenter, observational, open-label, single-arm study of natalizumab treatment in anti-JC virus antibody-negative (JCV-negative) relapsing-remitting multiple sclerosis (RRMS) patients with disease duration ≤ 3 years. The objective of STRIVE was to examine no evidence of disease activity (NEDA) status and predictors of NEDA in natalizumab-treated patients with early RRMS.

Methods: Proportions of patients with NEDA were evaluated along with baseline predictors of NEDA, annualized relapse rate, 24-week confirmed disability worsening (CDW), magnetic resonance imaging assessments (T2 and gadolinium-enhancing lesions), and serious adverse events.

Results: In years 1 and 2, 56.1% (95% confidence interval [CI] 48.7-63.4%) and 73.6% (95% CI 66.2-80.2%) of patients (intent-to-treat population [N = 222]), respectively, achieved NEDA. In years 3 and 4, 84.6% (95% CI 78.0-89.9%) and 91.9% (95% CI 86.4-95.8%) of patients, respectively, achieved Clinical NEDA (no relapses or 24-week CDW). Baseline predictors of NEDA in year 4 were Expanded Disability Status Scale score ≤ 2.0 (odds ratio [OR] = 3.85 [95% CI 1.54-9.63]; p = 0.004) and T2 lesion volume > 4 cc (OR = 0.39 [95% CI 0.15-0.98]; p = 0.046), with the latter also predicting Clinical NEDA in year 4 (OR = 0.21 [95% CI 0.05-0.92]; p = 0.038). The cumulative probability of CDW at year 4 was 19.3%. Serious adverse events were reported in 11.3% of patients.

Conclusion: These results support the long-term safety and effectiveness of natalizumab. Baseline predictors of NEDA help to inform benefit-risk assessments of natalizumab treatment in JCV-negative patients with early RRMS.

Trial registration: ClinicalTrials.gov identifier NCT01485003.

Keywords: Anti-JCV antibody negative; Magnetic resonance imaging; Natalizumab; No evidence of disease activity; Relapsing-remitting multiple sclerosis.

© 2021. The Author(s).

Figures

Fig. 1

Patient disposition. JCV JC virus ITT intent to treat

Fig. 2

Anti-JC virus antibody status in the intent-to-treat population by change from previously available test result (regardless of whether the patient remained on natalizumab treatment or not)

Fig. 3

a No evidence of disease activity (NEDA), b clinical NEDA, and c MRI NEDA in each year of STRIVE and in years 2–4 of STRIVE with rebaselining in the STRIVE intent-to-treat (ITT) and 4-year natalizumab completer populations. Clinical NEDA no relapses or 24-week confirmed disability worsening, MRI NEDA no gadolinium-enhancing lesions and no new or newly enlarging T2-hyperintense lesions

Fig. 4

Baseline characteristics that predicted a clinical NEDA and b NEDA in the intent-to-treat ITT population at year 4 of STRIVE. Odd ratios (ORs) are based on multivariate logistic regression. Statistically significant predictors (p < 0.05) are shown in bold. CI confidence interval, Clinical NEDA no relapses or 24-week confirmed disability worsening, EDSS Expanded Disability Status Scale, Gd+ gadolinium enhancing, MS multiple sclerosis, NEDA no evidence of disease activity

Fig. 5

No evidence of disease activity (NEDA) status in year 4 by clinical NEDA, MRI NEDA, or NEDA status in year 1 in the intent-to-treat (ITT) population. p values are based on unadjusted logistic regression models. Patients with NEDA status available during both years 1 and 4 are included. CI confidence interval, Clinical NEDA no relapses or 24-week confirmed disability worsening, MRI NEDA no gadolinium-enhancing lesions and no new or newly enlarging T2-hyperintense lesions, OR odds ratio

Fig. 6

Summary of the clinical outcome measures a annualized relapse rate (ARR) and b 24-week confirmed disability worsening over 4 years in STRIVE in the intent-to-treat (ITT) and 4-year natalizumab completer populations. Dashed lines indicate 95% confidence interval (CI)