Abstract
The presence of chronic black holes, i.e., chronic lesions that are hypointense on T1-weighted images and are indicative of more severe tissue injury, has been increasingly utilized as a surrogate marker of therapeutic outcome in multiple sclerosis. The ADVANCE study was a 2-year, double-blind, pivotal trial evaluating the safety and efficacy of subcutaneous peginterferon beta-1a 125 mcg in 1512 patients with relapsing–remitting multiple sclerosis (RRMS). This report describes the correlation of clinical outcomes with the evolution of acute lesions into chronic black holes in ADVANCE, and the efficacy of peginterferon beta-1a in reducing this evolution. Treatment with peginterferon beta-1a significantly reduced the mean number of new/enlarging T2-weighted (NET2) lesions (0.76 vs. 1.03 from week 24, p = 0.0037; 0.44 vs. 0.99 from week 48, p < 0.0001) and new gadolinium-enhancing (Gd+) lesions (0.15 vs. 0.32 from week 24, p < 0.0001; 0.09 vs. 0.19 from week 48) that evolved into chronic black holes by 2 years. Patients with NET2 or Gd+ lesions at 24 weeks that evolved into chronic black holes showed significantly worse clinical outcomes, including a greater proportion with 12-week (14.9 vs. 8.4%; p = 0.0167) and 24-week (12.3 vs. 7.0%; p = 0.0333) confirmed disability worsening and higher mean annualized relapse rate (0.62 vs. 0.43; p = 0.0118), compared with patients with lesions that did not evolve into black holes. The correlation was independent of treatment. Reduced risk of evolution of new lesions into chronic black holes with peginterferon beta-1a treatment suggests potential to reduce long-term disability in RRMS by preventing irreversible tissue damage.
Highlights
The objective of these post hoc evaluations of the ADVANCE study was (1) to examine the correlation of clinical outcomes with new/enlarging T2-weighted (NET2) or Gd+ lesions that evolve into chronic black holes (BHs), and (2) to investigate the efficacy of peginterferon beta-1a in reducing the evolution of NET2 lesions and Gd+ lesions to chronic BHs at 2 years in patients with RRMS
Continuous treatment with SC peginterferon beta-1a every 2 weeks for 2 years significantly reduced the number of NET2 lesions and new Gd+ lesions that evolved into chronic BHs versus delayed treatment, as well as the proportion of patients with such lesions
Patients with NET2 or Gd+ lesions detected at week 24 that evolved into chronic BHs 2 years later showed significantly worse clinical outcomes compared with patients with lesions at week
Summary
Subcutaneous (SC) peginterferon beta-1a 125 mcg administered every 2 weeks is a treatment for relapsing–remitting multiple sclerosis (RRMS) with the advantage of a more convenient, low-frequency dosing regimen compared with other interferon betas [1, 2]. In multiple sclerosis (MS), chronic lesions that appear hypointense on T1-weighted images are often referred to as T1 black holes (BHs). Measuring the proportion of Gd+ or new/enlarging T2-weighted (NET2) hyperintense lesions that develop into chronic BHs is one approach to quantifying neuroprotective effects of therapy. The objective of these post hoc evaluations of the ADVANCE study was (1) to examine the correlation of clinical outcomes with NET2 or Gd+ lesions that evolve into chronic BHs, and (2) to investigate the efficacy of peginterferon beta-1a in reducing the evolution of NET2 lesions and Gd+ lesions to chronic BHs at 2 years in patients with RRMS. False-positive lesions identified by this software were corrected as necessary by expert readers
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