≥4 Active T2 Lesions at 6 Months Predicts Future Relapse/Disability in Patients with RMS on Placebo but Not IFN ß-1a SC tiw: Post Hoc PRISMS Analyses

Background: In PRISMS-2, interferon beta-1a (IFN β-1a) given subcutaneously (SC) three times weekly (tiw) reduced T2 lesions, relapses, and disability progression versus placebo in patients with relapsing multiple sclerosis (RMS).

Objectives: To examine relationships between active T2 lesion numbers and subsequent clinical events in patients receiving IFN β-1a SC tiw or placebo.

Methods: Patients were randomized to IFN β-1a 44 μg SC tiw, IFN β-1a 22 µg SC tiw (not examined here) or placebo for 2 years, undergoing magnetic resonance imaging (MRI) scans biannually. In a 2-year extension, patients switched from placebo to IFN β-1a SC or continued IFN β-1a SC. Post hoc between-treatment comparisons of annualized relapse rate (ARR), according to the number of active T2 lesions on MRI scans at Month 6 (0, ≥1, 0–1, ≥2 or ≥4 lesions), were performed using a negative binomial model; relapses (yes/no) and disability progression were compared using logistic regression.

Results: Among placebo patients (n=187), ARR over 2 years was higher for those with ≥4 versus 0–1 (rate ratio 1.54; p=0.0013), ≥2 versus 0–1 (1.28; p=0.0394), and ≥4 versus 0 (1.58; p=0.0045) active T2 lesions at Month 6; no significant effect was seen in IFN β-1a 44 µg SC tiw patients (n=184). Similar results were seen over 4 years: active T2 lesions (≥4 vs 0–1, ≥2 vs 0–1, ≥4 vs 0) were associated with higher ARR in the placebo/delayed treatment group only. Placebo/delayed treatment patients were significantly more likely to have had a relapse by Year (Y) 2 and Y4 with ≥2 versus 0–1, ≥1 versus 0, and ≥4 versus 0 active 6-month T2 lesions, and to have relapses at Y4 with ≥4 versus 0–1 active 6-month T2 lesions. For patients in the placebo/delayed treatment group, the presence of ≥2 versus 0–1 active 6-month T2 lesions predicted disability progression at Y2 and Y4, and the presence of ≥4 versus 0–1 active 6-month T2 lesions predicted progression at Y2. No comparisons predicted relapse or disability in IFN β-1a 44 µg SC tiw patients at Y2 or Y4.

Conclusions: Greater T2 lesion activity predicted worsened clinical results in patients with RMS receiving placebo/delayed treatment but not in those receiving IFN β-1a 44 µg SC tiw. Patients with multiple T2 lesions after 6 months on treatment might be expected to be treatment non-responders; however, this analysis suggests that the presence of multiple T2 lesions after 6 months does not predict poorer outcomes in patients treated with IFN β-1a 44 µg SC tiw.