No evidence of disease activity status in patients treated with early vs. delayed subcutaneous interferon ß-1a.

ABSTRACT

BACKGROUND: Clinically isolated syndrome (CIS) is defined as a monophasic clinical episode highly suggestive of multiple sclerosis (MS). Regardless, studies have shown that treatment at this early stage of MS can delay a second event and prolong the transition to clinically diagnosed MS. The objective of this post-hoc analysis was to determine the effect of early CIS treatment with once weekly (qw) or three times weekly (tiw) subcutaneous interferon (scIFN) ß-1a vs. delayed treatment (DT) on the composite endpoint of no evidence of disease activity (NEDA)-3. METHODS: In REFLEX, patients with CIS were randomized to double-blind scIFN ß-1a 44 µg tiw, qw, or placebo for 24 months. Upon clinically-definite MS, patients switched to open-label scIFN ß-1a tiw. Patients who completed REFLEX entered an extension (REFLEXION). Patients initially randomized to placebo switched to tiw (DT); scIFN ß-1a patients continued their initial qw/tiw regimen for up to 60-months post-randomization. This post-hoc analysis was conducted in the integrated intent-to-treat REFLEX plus REFLEXION population (tiw, n = =171; qw, n = =175; DT, n = =171). All p values are nominal. CIS was defined using the McDonald 2010 criteria. RESULTS: Patients receiving early treatment (ET) with scIFN ß-1a tiw and qw were more likely to achieve NEDA-3 than DT at year 2 (tiw vs. DT OR 4.26, 95% CI 2.02-8.98, p = =0.0001; qw vs. DT OR 2.99, 95% CI 1.39-6.43, p = =0.005). Compared with DT, ET with scIFN ß-1a tiw was more likely to achieve NEDA-3 at year 3 (OR 3.73, 95% CI 1.63-8.55, p = =0.002) and year 5 (OR 12.96, 95% CI 1.66-101.04, p = =0.015). Between ET regimens, the odds of achieving NEDA-3 were not significantly improved by scIFN ß-1a 44 µg tiw at year 2 (OR 1.42, 95% CI 0.81-2.50, p = =0.22) but were at year 3 (OR 2.26, 95% CI 1.11-4.60, p = =0.024) and year 5 (OR 3.22, 95% CI 1.01-10.22, p = =0.048), indicating that the beneficial effects of more frequent scIFN ß-1a dosing become more apparent over time in patients with CIS. In the subgroup of patients with Gd+ lesions at baseline the odds for achieving NEDA-3 were higher for ET up to year 2 compared with DT (tiw OR 10.21, 95% CI 1.23-84.82, p = =0.03; qw OR 8.97, 95% CI 1.08-74.28, p = =0.04). In patients without Gd+ lesions at baseline, those receiving ET were more likely to achieve NEDA-3 at year 2 (OR 3.56, 95% CI 1.56-8.10, p = =0.003), year 3 (OR 2.54, 95% CI 1.05-6.18, p = =0.04) and year 5 (OR 9.63, 95% CI 1.19-77.79, p = =0.034) than patients who received DT. CONCLUSIONS: ET with scIFN ß-1a tiw was associated with a higher likelihood of achieving NEDA-3 not only at 2 but also at 3 and 5 years.