Serious adverse events, excluding MS relapses, occurred in 5% of the placebo group, 6% of the low-dose group, and 8% of the high-dose group. One daclizumab-treated patient died due to a complication of a psoas abscess. Serious adverse events in the daclizumab-treated patients included an increase in serious infections (2%), serious cutaneous events (1%), and elevations in liver function tests (4%).
Clinical and MRI Outcomes in Patients With MS Treated With Fingolimod
Fingolimod at an oral dose of 0.5 mg consistently improved relapse rates, disability, and MRI outcomes compared with placebo or IM interferon beta-1a in all patient subgroups with active relapsing-remitting MS, investigators reported.
Eva Havrdová, PhD, from the Department of Neurology, First Faculty of Medicine, Charles University, Prague, and colleagues reported the results of post hoc analyses from FREEDOMS and TRANSFORMS in three patient subgroups: 1) patients who received interferon beta in the year before study entry and had equal or more relapses in the year immediately before the study than in the year two years before the study; 2) patients who received interferon beta in the year before study entry and had at least one relapse in the previous year plus at least one gadolinium-enhancing T1 lesion or nine T2 lesions at baseline; or 3) treatment-naïve patients with rapidly evolving severe relapsing-remitting MS.
In FREEDOMS, fingolimod 0.5 mg significantly reduced annualized relapse rates compared with placebo in all three subgroups. In TRANSFORMS, fingolimod 0.5 mg significantly reduced annualized relapse rates compared with IM interferon beta-1a in groups 1 and 2. Results in group 3 (n = 27) did not reach statistical significance. In both studies fingolimod reduced the risk of disability progression versus placebo and interferon beta-1a in all subgroups.
The researchers concluded that fingolimod (0.5 mg) improved clinical outcomes compared with placebo or IM interferon beta-1a in patients with relapsing-remitting MS with high disease activity despite previous treatment and in treatment-naïve patients with rapidly evolving severe relapsing-remitting MS.
Laquinimod: A Potential Novel Oral Agent for Relapsing-Remitting MS
Both preclinical and clinical data suggest that the oral immunomodulator laquinimod holds promise for patients with relapsing-remitting MS, according to investigators.
Giancarlo Comi, MD, Professor and Chairman of the Department of Neurology and Director of the Institute of Experimental Neurology at Vita-Salute San Raffaele University, Scientific Institute San Raffaele Milan, reported that a phase 2 study demonstrated reductions of MRI-active lesions, a trend for slowing the rate of MRI-measured brain volume loss, and a favorable safety and tolerability profile. Dr. Comi also summarized findings from the multicenter, randomized, double-blind, placebo-controlled Allegro trial. In the phase 3 trial, patients received a once-daily oral dose of 0.6 mg laquinimod or placebo for 24 months.
The study met the primary end point, with laquinimod achieving a decrease in relapse rate (23% reduction). The risk for EDSS disability progression was significantly reduced (36%) compared with placebo. Rate of brain atrophy progression was reduced by 33% at month 24.
Laquinimod was well-tolerated. Adverse events were similar in both groups, with the exception of transient, reversible elevations of liver enzymes without concomitant signs of liver dysfunction in the laquinimod group.
Dr. Comi also provided an advance glimpse of findings from the BRAVO (Benefit-Risk Assessment of Avonex and Laquinimod) study. The profile of reduced annualized relapse rate, MRI-active lesions, brain-volume loss, and EDSS was similar to that seen in the Allegro study.
Teriflunomide: A Promising New Oral Therapy for Patients With Relapsing-Remitting MS
Data from TEMSO, the first pivotal phase 3 trial of teriflunomide, were reported by Paul O’Connor, FRCPC, MSc.
The two-year, double-blind study found a significant reduction in annualized relapse rates with both the 7-mg and 14-mg doses of teriflunomide compared with placebo, as well as a significant reduction in the risk of sustained disability progression in the higher dose group. Both doses showed good safety and tolerability in patients with relapsing-remitting MS. Both doses were superior to placebo on a range of MRI end points in a dose-dependent fashion.
A long-term extension of TEMSO showed that teriflunomide was well tolerated with a favorable safety profile up to six years following randomization, with no unexpected adverse events related to long-term treatment.
Dr. O’Connor, Professor of Medicine at the University of Toronto and Director of the MS Clinic at St. Michael’s Hospital in Toronto, also discussed results from an extension of the phase 2 study of teriflunomide, which has provided information on up to nine years of teriflunomide treatment. Clinical and MRI disease activity remained low during the course of this extension and treatment-related adverse events were similar to those in the initial 36-week double-blind trial.