Reduction in magnetic resonance imaging T2 burden of disease in patients with relapsing-remitting multiple sclerosis: analysis of 48-week data from the EVIDENCE (EVidence of Interferon Dose-response: European North American Comparative Efficacy) study

Background: The EVIDENCE (EVidence of Interferon Dose-response: European North American Comparative Efficacy) study was an international, randomized, open-label, assessor-blinded, parallel-group study assessing the efficacy and tolerability of interferon (IFN) beta-1a, 44 mcg subcutaneously (sc) three times weekly (tiw), and IFN beta-1a, 30 mcg intramuscularly (im) once weekly (qw), in patients with relapsing-remitting multiple sclerosis (RRMS). The aim of this analysis was to assess whether reductions in T2 burden of disease (BOD) were greater for patients receiving IFN beta-1a, 44 mcg sc tiw, than for those treated with IFN beta-1a, 30 mcg im qw, and to assess the impact of neutralizing antibodies (NAbs). Methods: A post-hoc analysis was performed on magnetic resonance imaging (MRI) data collected prospectively from the EVIDENCE study. The analysis included all patients with evaluable T2 MRI scans at the start of dosing and at week 48, and those who received at least one drug dose (n = 553). Lesions were identified by a radiologist blinded to treatment codes and the total volume of T2 lesions (BOD) was reported in mm3. Results: Both median percentage decreases and absolute reduction in BOD were greater in the IFN beta-1a, 44 mcg sc tiw, treatment group. The adjusted mean treatment difference in percentage change in BOD from baseline to week 48 showed a significant treatment benefit for patients treated with IFN beta-1a, 44 mcg sc tiw, over those treated with IFN beta-1a, 30 mcg im qw (-4.6%; standard error: 2.6%; p = 0.002). The presence of NAbs reduced the effect of IFN beta-1a 44, mcg sc tiw, on BOD, but BOD changes were still similar to those seen with IFN beta-1a, 30 mcg im qw. Conclusion: Patients with RRMS treated with IFN beta-1a, 44 mcg sc tiw, had greater reduction in T2 BOD after 48 weeks than those treated with IFN beta-1a, 30 mcg im qw, which is consistent with other clinical and MRI outcome measures in the EVIDENCE study. In patients testing positive for NAbs (NAb+) to IFN beta-1a 44 mcg sc tiw, changes in BOD were smaller than in NAb negative (NAb-) patients, but similar to those receiving IFN beta-1a, 30 mcg im qw.