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.
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).


CONCLUSIONS
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.


BACKGROUND
ClinicalTrials.gov: NCT00906399 ; Registered on: May 20, 2009.
Montreal Neurological Institute, McGill University, Montreal, QC, Canada.|NeuroRx Research, Montreal, QC, Canada.
Douglas L
DL
Arnold
Department of Neurology, Johns Hopkins University, Baltimore, MD, USA.
Peter A
PA
Calabresi
Department of Neurology, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany.|Biogen, 225 Binney St, Cambridge, MA, USA.
Bernd C
BC
Kieseier
Biogen, 225 Binney St, Cambridge, MA, USA.
Shifang
S
Liu
Biogen, 225 Binney St, Cambridge, MA, USA.
Xiaojun
X
You
Biogen, 225 Binney St, Cambridge, MA, USA.
Damian
D
Fiore
Biogen, 225 Binney St, Cambridge, MA, USA. serena.hung@biogen.com.
Serena
S
Hung
D000328:Adult; D001921:Brain / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D016899:Interferon-beta / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000473:pathology*; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D016896:Treatment Outcome
D007155:Immunologic Factors; D011092:Polyethylene Glycols; D016899:Interferon-beta; C428112:peginterferon beta-1a
Clinical trial; Interferon; Magnetic resonance imaging; Multiple sclerosis; NEDA; No evidence of disease activity; Peginterferon beta-1a; Pegylation; Phase 3; Relapse-remitting multiple sclerosis