Peginterferon β-1a every 2 weeks increased achievement of no evidence of disease activity over 4 years in the ADVANCE and ATTAIN studies in patients with relapsing-remitting multiple sclerosis.

Background: No evidence of disease activity (NEDA) is a composite measurement, incorporating clinical and magnetic resonance imaging (MRI) elements of disease activity to sensitively evaluate the therapeutic efficacy of treatments for relapsing-remitting multiple sclerosis (RRMS). Objective: To assess the NEDA status of patients treated with peginterferon -1a in the ADVANCE and ATTAIN studies and explore its predictive value on longer-term clinical outcomes. Methods: ATTAIN was a 2-year extension of the pivotal 2-year ADVANCE study of peginterferon -1a for RRMS. Achievement of clinical NEDA, MRI NEDA, or overall NEDA was calculated cumulatively and by year over 4years. Clinical outcomes during ATTAIN were analyzed based on NEDA status at the end of ADVANCE. Results: Significantly more patients treated with peginterferon -1a every 2weeks than every 4weeks achieved clinical NEDA (60.6% versus 50.6%, p=0.0063) and MRI NEDA (28.3% versus 15.8%, p=0.0005) through year 4 and overall NEDA through year 3 (20.9% versus 13.9%, p=0.0160). Over 4years, 15.8% of patients in the every 2 weeks group and 10.7% of patients in the every 4 weeks group maintained overall NEDA (p=0.0584). Achievement of clinical NEDA, MRI NEDA, or overall NEDA in ADVANCE was predictive of annualized relapse rate in ATTAIN; achievement of clinical NEDA in ADVANCE was also predictive of NEDA achievement and confirmed disability worsening in ATTAIN. Conclusions: Peginterferon -1a every 2weeks is associated with higher levels of NEDA compared with placebo in year 1 or peginterferon -1a every 4weeks in years 2-4. Overall NEDA within the first 2years of treatment may be prognostic of long-term clinical outcomes. Clinicaltrials.gov: NCT01332019