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.

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)