Outcomes of natalizumab treatment within 3 years of relapsing-remitting multiple sclerosis diagnosis: a prespecified 2-year interim analysis of STRIVE

Abstract

Background: STRIVE is a multicenter, observational, open-label, single-arm study of natalizumab in anti-JC virus (JCV) seronegative patients with early relapsing-remitting multiple sclerosis (RRMS). The objective of this prespecified 2-year interim analysis was to determine the effectiveness of natalizumab in establishing and maintaining no evidence of disease activity (NEDA) in early RRMS.

Methods: Patients aged 18-65 years had an RRMS diagnosis < 3 years prior to screening, an Expanded Disability Status Scale (EDSS) score ≤ 4.0, and anti-JCV antibody negative status. Magnetic resonance imaging was performed at baseline and yearly thereafter. Cumulative probabilities of 24-week-confirmed EDSS worsening and improvement were evaluated at 2 years. NEDA (no 24-week-confirmed EDSS worsening, no relapses, no gadolinium-enhancing lesions, and no new/newly enlarging T2-hyperintense lesions) was evaluated over 2 years. The Symbol Digit Modalities Test (SDMT) and Multiple Sclerosis Impact Score (MSIS-29) were assessed at baseline and 1 and 2 years. Statistical analysis used summary statistics and frequency distributions.

Results: The study population (N = 222) had early RRMS, with mean (standard deviation [SD]) time since diagnosis of 1.6 (0.77) years and mean (SD) baseline EDSS score of 2.0 (1.13). NEDA was achieved in 105 of 187 patients (56.1%) during year 1 and 120 of 163 (73.6%) during year 2. Over 2 years, 76 of 171 patients (44.4%) attained overall NEDA. Probabilities of 24-week-confirmed EDSS worsening and improvement were 14.1% and 28.4%, respectively. After 2 years, patients exhibited significant improvements from baseline in SDMT (n = 158; mean [SD]: 4.3 [11.8]; p < 0.001) and MSIS-29 physical (n = 153; mean [SD]: - 3.9 [14.7]; p = 0.001), psychological (n = 152; mean [SD]: - 2.0 [7.9]; p < 0.001), and quality-of-life (n = 153; mean [SD]: - 6.0 [21.3]; p < 0.001) scores.

Conclusions: These results support natalizumab's effectiveness over 2 years, during which nearly half of early RRMS patients achieved NEDA. During year 2, nearly 75% of patients exhibited NEDA. Over 2 years, patients continued to experience significant cognitive and quality-of-life benefits. These results are limited by the lack of a comparator group to determine the extent of a placebo effect.

Trial registration: clinicaltrials.gov, NCT01485003 , registered 5 December 2011.

Keywords: Anti-JCV antibody; Brain atrophy; Natalizumab; No evidence of disease activity; Optical coherence tomography; Patient-reported outcomes; Relapsing-remitting multiple sclerosis.

Conflict of interest statement

JP has received fees from Acorda, Biogen, Genzyme, and Teva. RJF has received consulting fees from Actelion, Biogen, Genentech, Mallinckrodt, MedDay, Novartis, Teva, and XenoPort, advisory board fees from Biogen and Novartis, and grant/research support from Novartis. RB has received consulting fees from Biogen, Sanofi, and Teva and grant/research support from Biogen. LB has received consulting fees from Biogen and Genzyme. SG has received consulting fees from Biogen. SM, CH, and LL are employees of and hold stock and/or stock options in Biogen. SS is an employee of Cytel.

Figures

Fig. 1

Patient disposition up to 2 years. ITT = intent to treat

Fig. 2

Proportions of patients with (a) overall, clinical, and MRI NEDA maintained over 2 years, and (b) no relapses, no confirmed disability worsening, and no MRI lesions over 2 years. Patients missing measurements who achieved NEDA on all available measurements were excluded, whereas patients missing measurements who had evidence of disease activity on ≥1 measurement were considered as not achieving NEDA. CI = confidence interval; EDSS = Expanded Disability Status Scale; MRI = magnetic resonance imaging; NEDA = no evidence of disease activity

Fig. 3

Overall NEDA over 2 years stratified by baseline characteristics. Patients who did not achieve NEDA at year 1 and who had missing data at year 2 were included in the analysis population. Statistically significant outcomes are shown in bold. CI = confidence interval; EDSS = Expanded Disability Status Scale; Gd + = gadolinium enhancing; MS = multiple sclerosis; NEDA = no evidence of disease activity; OR = odds ratio

Fig. 4

Proportion of patients with overall NEDA during the first or second year of natalizumab treatment. Only patients with no missing data at the time of the assessment were included. NEDA = no evidence of disease activity

Fig. 5

Cumulative probability of (a) relapse, (b) 24-week–confirmed disability worsening, and (c) 24-week–confirmed disability improvement over 2 years. Cumulative probabilities are based on Kaplan-Meier analysis or the Cox proportional-hazards model. Solid line shows the estimated cumulative probability; dashed lines show the 95% CI. Relapses in the year prior to starting natalizumab were reported by the patient. On-treatment relapses were reported by the physician. For disability outcomes, time point listed is for onset of EDSS increase or decrease, which was then confirmed 24 weeks later. CI = confidence interval; EDSS = Expanded Disability Status Scale

Fig. 6

a Change from baseline to 1 and 2 years in SDMT score, b percentage of patients with clinically significant improvement in SDMT score (defined as an increase ≥4 points) at 1 and 2 years, c change in SDMT score from baseline to 2 years by baseline characteristics, and d change from baseline to 1 and 2 years in MSIS-29 physical, psychological, and quality-of-life scores. p-values are based on a paired t-test. CI = confidence interval; MSIS-29 = Multiple Sclerosis Impact Scale; SDMT = Symbol Digits Modality Test

Fig. 7

Proportions of patients with worsened VA (defined as a loss of ≥7 letters) or improved VA (defined as an increase of ≥7 letters) in both eyes over 2 years in the STRIVE OCT subgroup per protocol population (n = 50)