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. Supplementary Information The online version contains supplementary material available at 10.1007/s12325-021-01722-w.

Improvements in Cognitive Processing Speed, Disability, and Patient-Reported Outcomes in Patients with Early Relapsing-Remitting Multiple Sclerosis Treated with Natalizumab: Results of a 4-year, Real-World, Open-Label Study

“…The median number of gadolinium-enhancing (Gd+) lesions and new or newly enlarging T2 lesions at each annual assessment was 0, indicating that over half of the patients did not exhibit new radiological activity. Safety outcomes in STRIVE were consistent with the established safety profile of natalizumab [ 6 ].…”

“…STRIVE (Study of Tysabri in Early Relapsing-Remitting Multiple Sclerosis in Anti-JC Virus Antibody Negative Patients; clinicaltrials.gov NCT01485003) was a prospective, 4-year, multicenter, observational, open-label, single-arm study conducted at 45 sites in the USA from February 2012 to November 2018 [ 6 ]. Patients in STRIVE received 300 mg of natalizumab intravenously every 4 weeks.…”

“…Details of the study design, inclusion and exclusion criteria, patient disposition, and baseline characteristics of the ITT and 4-year natalizumab completer populations, as well as the study’s primary and related secondary endpoint results, have been published [ 6 ]. Briefly, eligible patients were aged 18–65 years with a documented diagnosis of RRMS (McDonald 2010 criteria) [ 8 ], a disease duration ≤ 3 years, and an Expanded Disability Status Scale (EDSS) score ≤ 4.0, as well as a negative test for anti-JCV antibodies within 6 months prior to screening or at the baseline visit.…”

“…Data from the 10-year interim analysis of the TYSABRI Observational Program (TOP), the largest ongoing prospective real-world study of natalizumab-treated RRMS patients, support these clinical trial findings and demonstrate long-term safety and clinical disease control with respect to relapses and disability [ 5 ]. Outside of TOP, the only other long-term prospective observational study examining the safety and effectiveness of natalizumab in RRMS patients is the 4-year STRIVE study [ 6 ]. STRIVE complements and extends the results of TOP by capturing radiological outcomes as well as additional clinical and patient-reported outcomes (PROs) not collected in TOP.…”

“…The results of STRIVE’s primary endpoint (i.e., the proportion of patients achieving No Evidence of Disease Activity (NEDA) in years 1 and 2 and clinical NEDA in years 3 and 4) as well as some of its secondary endpoints (i.e., annualized relapse rate (ARR), MRI, 24-week confirmed disability worsening (CDW)) and safety were recently published [ 6 ]. In the intent-to-treat (ITT) population 56.1% and 73.6% of patients achieved NEDA in years 1 and 2, respectively, and 84.6% and 91.9% of patients achieved clinical NEDA in years 3 and 4, respectively.…”