In the 2-year AFFIRM pivotal trial:

Relapsing MS patients received 300 mg TYSABRI every 28 days (n=627) or placebo (n=315). Patients with PPMS, SPMS, and PRMS were excluded.

83% of patients taking TYSABRI had no sustained disability progression for 12 weeks vs 71% with placebo (primary endpoint: 17% vs 29%; p<0.001)1,2

97% of patients taking TYSABRI had no Gd-enhancing lesions vs 72% with placebo

57% of patients taking TYSABRI had no new or newly enlarging T2-hyperintense lesions vs 15% with placebo

DISEASE ACTIVITY EVALUATED IN JCV− PATIENTS STARTING TYSABRI SHORTLY AFTER DIAGNOSIS

Four-year NEDA (no evidence of disease activity) status and safety evaluated in the STRIVE study3

Study description: STRIVE (Study of TYSABRI in Early Relapsing-RemItting Multiple Sclerosis in Anti-JCV Antibody NegatiVE Patients) was a 4-year, multicenter, observational, open-label, single-arm study conducted in the United States. Patients were anti-JCV antibody negative ≤6 months prior to screening or at baseline and were prescribed natalizumab 300 mg IV ≤3 years after RRMS diagnosis; 47% of patients (n=105) completed all 4 years on TYSABRI, while 41% (n=91) discontinued TYSABRI and 30% (n=67) withdrew prior to Year 4.

  • The primary endpoints were the proportion of patients achieving NEDA in Years 1 and 2 and Clinical NEDA in Years 3 and 4
    • NEDA encompassed both clinical and MRI NEDA
    • MRI NEDA was defined as no Gd+ or new/newly enlarging T2 lesions
    • NEDA was analyzed yearly. To account for potential disease activity shortly after starting therapy, an exploratory analysis assessed NEDA over Years 2–4 after MRI rebaselining at Year 1
    • NEDA analyses used observed data only. Patients with missing data who did not exhibit disease activity on available measurements were excluded, whereas patients missing data who had evidence of disease activity on ≥1 measurement were considered not to have achieved NEDA

Study limitations:

  • Because STRIVE was an open-label, single-arm study, it lacked an internal comparator group; therefore, placebo effects on the clinical outcomes cannot formally be ruled out. The open-label nature of STRIVE could introduce selection bias in the study population
  • Sample sizes were reduced by attrition and missing data, particularly with respect to the NEDA analyses

NEDA was achieved by >50% of patients in Year 1,a and >70% of patients in each of Years 2, 3, and 43

PATIENTS WITH NEDA

  • More than half of patients (58.0%) achieved NEDA in Years 2-4 after MRI rebaselining at Year 1

PATIENTS WITH CLINICAL NEDA

  • Yearly rates of clinical NEDA ranged from 81.0% to 91.9%, and yearly rates of MRI NEDA ranged from 69.9% to 88.0%

PATIENTS WITH MRI NEDA

  • When rebaselined after the first year, 70.1% of patients exhibited clinical NEDA and 83.7% exhibited MRI NEDA in Years 2 through 4

aNEDA rates in the first year were lower than those in later years and may reflect disease activity occurring shortly after treatment initiation.

Likelihood of achieving NEDA in Year 4 was similar whether or not NEDA was achieved in Year 13

NEDA STATUS IN YEAR 4 BY STATUS OF CLINICAL NEDA, MRI NEDA, OR NEDA IN YEAR 1b

bp values are based on unadjusted logistic regression models. Patients with NEDA status available during both the first and fourth years are included.

  • In the 4-year STRIVE study, annual NEDA rates ranged from 71.4% to 74.8% in Years 2 through 4
  • Annual rates of clinical NEDA (primary endpoint) were consistently >80%
  • Safety over 4 years was consistent with the well-established safety profile of natalizumab. No cases of progressive multifocal leukoencephalopathy occurred

STRIVE results support the effectiveness of TYSABRI over 4 years and provide useful information regarding the benefits and risks of initiating natalizumab early in the disease course in JCV− patients

The STRIVE study was funded by Biogen.