Recent studies in the uses of Natalizumab and Peginterferon Beta-1a to Treat Relapsing-Remitting Multiple Sclerosis
At a satellite symposium during the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) conference, presenters focused upon the usage of disease-modifying treatments (DMT) in relapsing-remitting multiple sclerosis (RRMS). The presentation echoed the efficacy of using DMT to delay disease progression and to improve quality-of-life in patients with RRMS. More specifically, discussion focused upon newer therapies, natalizumab and peginterferon beta-1a, and traced their respective efficacies.
Presenting at the symposium were Hans-Peter Hartung, MD, PhD, chair of neurology at Heinrich-Heine-University, Düsseldorf, Germany; Gavin Giovannoni, PhD, chair of neurology, Blizard Institute of Cell and Molecular Science, Barts and The London School of Medicine and Dentistry; and Peter Calabresi, professor of neurology, director, Division of Neuroimmunology, Director, the Johns Hopkins Multiple Sclerosis Center.
Dr Giovannoni advocated for the use of natalizumab in the treatment of RRMS. Giovannoni revealed the overall benefit of the therapy in a post-hoc analysis illustrating years of disease-free activity in patients with RRMS, concluding with a staggering 37% natalizumab versus 7% placebo at the 2-year mark. Giovannoni went on to demonstrate that natalizumab can stabilize EDSS scores, especially when used earlier in the disease course, and that it can bring improvements in fatigue, cognition, bladder function, and quality-of-life.
Natalizumab’s most serious adverse event, according to Giovannoni, is the risk of progressive multifocal leukoencephalopathy (PML). While the risk of PML is minimal (1 in 10,000) in anti-JCV antibody-negative patients, there is a considerable risk of PML in anti-JCV antibody-positive patients (≤1 in 1000). Giovannoni pointed out, however, that some patients with high PML risk did not want to switch therapies, evidence that the DMT is truly beneficial in terms of quality-of-life. Current practice recommends that the usage of natalizumab for more than 2 years be considered on a case-by-case basis.
Prof Calabresi then discussed another DMT, peginterferon beta-1a, and the recent phase-3 ADVANCE study that traced its efficacy. According to Calabresi, peginterferon beta-1a continues the benefits of other interferons including producing meaningful results in multiple measures of MS disease activity, and being well-tolerated with a known side effect profile. To demonstrate the efficacy of the therapy, Calabresi pointed to favorable results in the primary endpoint and secondary end points of the ADVANCE study.
With its focus on annualized relapse rate, ADVANCE’s primary end point showed that in year 1 of an annualized relapse rate, the use of peginterferon beta-1a (every 2 to 4 weeks) greatly reduced this rate. When compared to placebo (n = 500) 0.397, peginterferon beta-1a q4w (n = 500) brought a 28% reduction (0.288), and peginterferon beta-1a q2w (n = 512) brought a 36% reduction (0.256).
In a secondary end point looking at time to disability progression, peginterferon beta-1a showed significant reduction in the risk of disability progression. Results illustrated a 38% reduction against placebo when the DMT was administered every 2 or 4 weeks. Other observed benefits of peginterferon beta-1a included significant reduction in the number of new or newly enlarged T2 lesions and GD+ lesions (when administered every 2 weeks), low rates of neutralizing antibody formation regardless of dosing regimen.
While peginterferon beta-1a has not yet been approved, Calabresi hopes to see it included in the line of efficacious IFN beta therapies in relapsing MS.