According to new data from STRIVE, 75.4% of those treated with natalizumab achieved overall No Evidence of Disease Activity status by year 4, and no patients had incidence of progressive multifocal leukoencephalopathy.
Jai Perumal, MD
Over the course of a 4-year period in the STRIVE study, natalizumab (Tysabri, Biogen) was associated with patients with multiple sclerosis (MS) achieving overall clinical no evidence of disease activity (NEDA) status at a high rate, as well as a number of other clinical benefits.1
In total, in year 4, 75.4% of 134 patients (n = 101) had overall NEDA status. By the study’s end, 59.2% of 169 patients (n = 100) had achieved cumulative clinical NEDA status, while 50.4% of 143 (n = 72) and 27.6% of 163 (n = 45) had magnetic resonance imaging (MRI) activity free status and overall NEDA status, respectively. The data were presented in a poster session by Jai Perumal, MD, assistant professor of neurology, Weill Cornell Medicine, at ECTRIMS 2019, September 11-13 in Stockholm, Sweden.
“These results support natalizumab's long-term effectiveness in early relapsing-remitting MS patients,” Perumal and colleagues wrote. “Taken together, the results of STRIVE support the effectiveness of natalizumab over long-term treatment and provide useful information regarding the benefits and risks of initiating natalizumab early in the disease course in ant-JC virus antibody-negative patients.”
The analysis included 222 patients with active disease and a mean of 1.4 (standard deviation [SD], 1.2) relapses in the previous year and an Expanded Disability Status Scale (EDSS) score of 2.04 (SD, 1.13). At study end, the mean EDSS score was 1.77 (SD, 1.55). In the year prior to natalizumab initiation, annualized relapse rates (ARR) were 1.43, which ultimately decreased by 90.2% to 0.14 (P <.0001). The cumulative probability of EDSS worsening was 19.3%, and of EDSS improvement was 43.9% over the course of the 4-year study period.
In year 4, a baseline EDSS score ≤2.0 was predictive of NEDA status (odds ratio [OR]. 3.58; 95% CI, 1.40-9.15; P <.0008) compared to a score >2.0, while having T2 lesion volume ≤4 cc at baseline was associated with an OR of 0.36 for NEDA by year 4 (95% CI, 0.14—0.94; P <.037) than T2 lesion volume >4 cc. Those were the only statistically significant predictive covariates. Additionally, Symbol Digit Modalities Test scores improved for 174 patients by 4.6 points from baseline to year 4 (95% CI, 2.9—6.2; P <.0001).
All told, by year 4, 72.7% (56 of 77) of those with NEDA in year 1 achieved NEDA will 80.7% (46 of 57) of those without NEDA in year 1 achieved NEDA in year 4 (OR, 0.64; 95% CI, 0.28-1.46; P = .287).
Disease activity for those who did not achieve NEDA during each year of STRIVE (year 1, n = 82; year 2, n = 43; year 3, n = 42; year 4, n = 35) was measured in relapses, clinical disease worsening, new Gd+ lesions, and new or newly enlarging T2 lesions. In year 1, most patients without NEDA had new or newly enlarging T2 lesions (64.6%), while a smaller percentage had relapses (28%) or clinical disease worsening (23.2%). In year 2, most patients without NEDA experienced relapses (46.5%) or new T2 lesions (41.9%). In years 3 and 4, the majority of patients also had new T2 lesions (47.6% and 62.9%, respectively), or relapses (35.7% and 31.4%, respectively). In year 3, 23.8% of patients without NEDA had disease worsening, while in year 4, 25.7% without NEDA had new Gd+ lesions.
As for safety, the rate of serious adverse events (AEs) was 11.3%, with 25 of 222 patients reporting ≥1. Five patients (2.3%) reported MS relapse, while 2 patients each (0.9%) experienced intervertebral disc protrusion and suicide attempt. The only incidence of treatment-related serious AE was 1 patient (0.5%) with an anaphylactic reaction. There was 1 serious AE which led to death, a traumatic brain injury, subdural hematoma, though it was not deemed related to treatment. No cases of progressive multifocal leukoencephalopathy (PML) were reported.
Previously, in the phase 3 AFFIRM trial, natalizumab was shown to be associated with a higher rate of NEDA status for patients compared to placebo, with 37% of the treated cohort achieving NEDA compared to 7% of the placebo group (P <.0001).2
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1. Perumal J, Fox RJ, Balabanov R, et al. Natalizumab is associated with no evidence of disease activity and with improvement in disability and cognitive performance in anti-JC virus seronegative patients with early relapsing-remitting multiple sclerosis: STRIVE 4-year results. Presented at: ECTRIMS 2019. September 11-13, 2019; Stockholm, Sweden. Poster P1348.
2. Polman CH, O’Connor PW, Havrdova E, et al. A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N J Engl Med. 2006; 354:899-910. doi: 10.1056/NEJMoa044397.