Predictive Value of Early MRI Measures in Patients with RRMS Receiving Interferon ß-1a SC tiw or Placebo: Post Hoc Analyses of PRISMS Data

Background: In the PRISMS-2 study, interferon beta-1a (IFN β-1a) subcutaneous (SC) three times weekly (tiw), 22 and 44 µg (Rx22 and Rx44), demonstrated clinical and MRI benefits vs placebo in patients with relapsing–remitting multiple sclerosis. In the 2-yr extension, outcomes were consistently better for patients who continued on Rx44 vs patients who switched from placebo to IFN β-1a SC after 2 yr (delayed treatment; DTx).

Objectives: To examine the predictive value of early MRI results on future clinical outcomes of patients receiving DTx or continuous IFN β-1a SC tiw treatment.

Methods: In PRISMS-2, all patients had T2-weighted scans 2x/yr; a frequent-MRI cohort (n=205) had monthly T2 and T1 gadolinium-enhancing (Gd+) scans before and during the first 9 mo. Post hoc analysis examined cumulative mean numbers of Gd+ and active (new/enlarging) T2 lesions/patient/scan; analysis of the entire cohort by presence or absence of T2 lesions at 6 mo assessed the predictive value of early MRI response for EDSS worsening (increase ≥1 point if baseline ≤5.5, or increase of 0.5 point if baseline ≥6), EDSS progression (worsening confirmed 3 mo later) and relapses over 2 or 4 yr.

Results: IFN β-1a SC tiw was associated with significantly (p<0.05) fewer Gd+ (from 2 mo) and active T2 (from 3 mo) lesions/patient/scan vs placebo in analysis of frequent-MRI cohort data. In the overall PRISMS cohort, 147/187 (78.6%) patients in the DTx group had ≥1 active T2 lesion at 6 mo vs 100/189 (52.9%) and 87/184 (47.3%) patients in Rx22 and Rx44 groups. In the DTx group, 42.9% with 6-mo T2 lesions vs 25.6% without had confirmed EDSS progression, 74.1% vs 53.8% had any EDSS worsening, and 89.1% vs 66.7% had relapses over 2 yr; presence of 6-mo T2 lesions had positive predictive values of 74.1% and 89.1% for EDSS worsening and relapse over 2 yr. In the Rx22 group, 37.0% vs 25.9% of patients with or without 6-mo T2 lesions had confirmed EDSS progression, 59.0% vs 51.8% had any EDSS worsening, and 79.0% vs 68.2% had relapses over 2 yr. In the Rx44 group, 23.0% vs 31.6% of patients with or without 6-mo T2 lesions had confirmed EDSS progression, 50.6% vs 53.7% had any EDSS worsening, and 65.5% vs 70.5% had relapses over 2 yr. 4-yr results were similar.

Conclusions: Presence of T2 lesions after 6 mo of placebo administration was predictive of poorer long-term clinical outcomes; T2 lesions at 6 mo in patients receiving IFN β-1a 44 µg SC tiw were not associated with poorer clinical outcomes.