Predictive Value of MRI Measures in Patients with Relapsing Multiple Sclerosis Receiving IFN ß-1a SC tiw or IFN ß-1a IM qw: Post Hoc Analyses of EVIDENCE Data

Background: In EVIDENCE, patients with relapsing multiple sclerosis were randomly assigned to interferon beta-1a (IFN β-1a) 44 µg subcutaneously (SC) three times weekly (tiw; n=339) or IFN β-1a 30 µg intramuscularly (IM) once weekly (qw; n=338).

Objectives: Examine predictive value of early magnetic resonance imaging lesions for achieving no evidence of disease activity (NEDA) at Week 48 (no relapses or confirmed 12-week disability worsening [≥1 point Expanded Disability Status Scale increase] by Week 48, and no T2 lesions newly occurring or enlarging from Weeks 24 to 48) in patients treated with IFN β-1a.

Methods: T2 and pre-/post-contrast T1 scans were performed at screening, Study Day 1, and every 4 weeks through Week 24, with another T2 scan at Week 48. Post hoc analysis assessed predictive values of early lesions for future NEDA status.

Results: By Week 8, mean gadolinium-enhancing (Gd+) lesions/patient/scan (including all scans up to that point) were 0.79 with IFN β-1a SC tiw vs 1.34 with IFN β-1a IM qw (p=0.002); mean new/enlarging T2 lesions/patient/scan were 0.42 vs 0.55, respectively, by Week 12 (p=0.008). Differences remained significant at subsequent monthly time points up to the final monthly scan at Week 24.

At Week 48, more patients receiving IFN β-1a SC tiw vs IFN β-1a IM qw met NEDA status (44% vs 32% respectively; p=0.003). Of those without baseline (BL) Gd+ lesions, 81/150 and 61/143 IFN β-1a SC tiw and IFN β-1a IM qw patients, respectively, achieved Week 48 NEDA (negative predictive value [NPV] 54.0% and 42.7%); 41/129 and 31/134 with BL Gd+ lesions in these groups achieved Week 48 NEDA (31.8% and 23.1%).

Of those without Week 8 Gd+ lesions, 109/220 and 74/192 IFN β-1a SC tiw and IFN β-1a IM qw patients, respectively, achieved Week 48 NEDA (NPV 49.5% and 38.5%); 16/71 and 19/100 with Week 8 Gd+ lesions in these groups achieved Week 48 NEDA (22.5% and 19.0%). Similar predictive value was seen for Week 8 T2 lesions.

56.8% and 44.5% of IFN β-1a SC tiw and IFN β-1a IM qw groups, respectively, with no BL or Week 8 Gd+ lesions had Week 48 NEDA, as did 37.0% and 29.1% with Gd+ lesions at BL but not Week 8.

Conclusions: IFN β-1a 44 µg SC tiw patients had significantly fewer lesions vs IFN β-1a 30 µg IM qw by early in treatment and higher likelihood of Week 48 NEDA status. BL/Week 8 lesions predicted future disease activity, but patients receiving IFN β-1a 44 µg SC tiw were more likely to achieve Week 48 NEDA status with or without early lesions.