Peginterferon beta-1a improves MRI measures and increases the proportion of patients with no evidence of disease activity in relapsing-remitting multiple sclerosis: 2-year results from the ADVANCE randomized controlled trial

Abstract

Background: Subcutaneous peginterferon beta-1a has previously been shown to reduce the number of T2-hyperintense and gadolinium-enhancing (Gd+) lesions over 2 years in patients with relapsing-remitting multiple sclerosis (RRMS), and to reduce T1-hypointense lesion formation and the proportion of patients showing evidence of disease activity, based on both clinical and radiological measures, compared with placebo over 1 year of treatment. The objectives of the current analyses were to evaluate T1 lesions and other magnetic resonance imaging (MRI) measures, including whole brain volume and magnetization transfer ratio (MTR) of normal appearing brain tissue (NABT), and the proportions of patients with no evidence of disease activity (NEDA), over 2 years.

Methods: Patients enrolled in the ADVANCE study received continuous peginterferon beta-1a every 2 or 4 weeks for 2 years, or delayed treatment (placebo in Year 1; peginterferon beta-1a every 2 or 4 weeks in Year 2). MRI scans were performed at baseline and Weeks 24, 48, and 96. Proportions of patients with NEDA were calculated based on radiological criteria (absence of Gd + and new/newly-enlarging T2 lesions) and clinical criteria (no relapse or confirmed disability progression) separately and overall.

Results: Peginterferon beta-1a every 2 weeks significantly reduced the number and volume of T1-hypointense lesions compared with delayed treatment over 2 years. Changes in whole brain volume and MTR of NABT were suggestive of pseudoatrophy during the first 6 months of peginterferon beta-1a treatment, which subsequently began to resolve. Significantly more patients in the peginterferon beta-1a every 2 weeks group compared with the delayed treatment group met MRI-NEDA criteria (41% vs 21%; odds ratio [OR] 2.56; p < 0.0001), clinical-NEDA criteria (71% vs 57%; OR 1.90; p < 0.0001) and achieved overall-NEDA (37% vs 16%; OR 3.09; p < 0.0001).

Conclusion: Peginterferon beta-1a provides significant improvements in MRI measures and offers patients a good chance of remaining free from evidence of MRI, clinical and overall disease activity over a sustained 2-year period.

Trial registration: ClinicalTrials.gov: NCT00906399 ; Registered on: May 20, 2009.

Keywords: Clinical trial; Interferon; Magnetic resonance imaging; Multiple sclerosis; NEDA; No evidence of disease activity; Peginterferon beta-1a; Pegylation; Phase 3; Relapse-remitting multiple sclerosis.

Figures

Fig. 1

MRI lesions at Week 96: a new T1 hypointense lesions; b new-active lesions Gd+, gadolinium-enhancing lesions. MRI analysis population (ITT population dosed in Year 2 with at least 1 MRI result). a P values based on multiple logit regression, adjusted for baseline number of T1 lesions. b P values based on negative binomial regression, adjusted for baseline number of Gd + lesions

Fig. 2

Percentage reduction in whole brain volume from baseline, and from Week 24 (inset). ITT population dosed in Year 2. *p < 0.05; †p < 0.01; ‡p < 0.001 vs delayed treatment (Wilcoxon rank-sum test)

Fig. 3

Percentage reduction in MTR of NABT. MTR, magnetization transfer ratio; NABT, normal appearing brain tissue. ITT population dosed in Year 2. *p < 0.05 vs delayed treatment (Wilcoxon rank-sum test)

Fig. 4

Proportions of patients with NEDA over 2 years (baseline to Week 96): a LOCF analysis; b observed dataa. MRI, magnetic resonance imaging; NEDA, no evidence of disease activity; OR, odds ratio. aSensitivity analysis excluding patients with missing MRI data

Fig. 5

Proportions of patients with NEDA in Year 2 (Week 48–96). MRI, magnetic resonance imaging; NEDA, no evidence of disease activity; OR, odds ratio. LOCF analysis (includes patients who did not have all measurements, but had no evidence of disease activity on any of the available measurements). ITT population dosed in Year 2