Natalizumab Emerges on Top in Network Meta-Analysis
There have been few head-to-head studies of disease-modifying drugs for MS. This study used a statistical technique called “network meta-analysis” to address that deficiency.
How do the various drugs approved for treating relapsing multiple sclerosis (MS) compare with one another in terms of safety and efficacy? Little is known about that, since no definitive randomized controlled comparisons exist.
However, a new network meta-analysis of 48 studies, involving more than 20,000 patients, has shed at least some light on that issue (Hadjigeorgiou et al., 2013).
The result? Natalizumab (Tysabri, Biogen Idec) emerged on top on two measures: patients free of relapse and patients without MRI progression. The study authors urged caution in interpreting their results.
The meta-analysis was conducted by G. M. Hadjigeorgiou, M.D., of the University of Thessaly School of Medicine in Larissa, Greece, along with colleagues. The results were published online August 20, 2013, in the Journal of Clinical Pharmacy and Therapeutics.
"The relative effectiveness and safety profile of the treatments with marketing authorization for relapsing multiple sclerosis (MS) are not well known because randomized controlled trials with head-to-head comparisons between these treatments do not exist," the authors wrote.
Aiming to make better use of the experience that has been accumulated with drugs for relapsing MS, these investigators conducted a network multiple-treatments meta-analysis that focused on four clinical outcomes: patients free of relapse, patients without disease progression, patients without MRI progression, and patients with adverse events.
With those criteria as a base, they searched both PubMed and the Cochrane Central Register of Controlled Trials for randomized, controlled trials (RCT) involving patients with MS who had been treated with the following regimens: Betaferon, Avonex, Rebif, Aubagio, Copaxone, Tysabri, Gilenya, and Novantrone. They included patients with all forms of relapsing MS, namely patients solely with relapsing-remitting MS, secondary progressive MS with relapses, primary relapsing MS, or combinations of those disease types.
Those searches yielded 48 trials and encompassed a total of 20,455 patients. To assess the safety and efficacy of the drugs, the investigators used pairwise comparisons that employed both direct and indirect analyses.
Direct analysis indicated that fingolimod (Gilenya, Novartis) demonstrated better results than interferon beta-1a (Avonex, Biogen Idec; Rebif, EMD Serono; CinnoVex, CinnaGen) in regard to two outcomes: patients free of relapse and patients without MRI progression. Interferon beta-1b (Betaferon, Betaseron, Bayer), too, appeared to outperform interferon beta-1a, but in two different outcomes: patients without disease progression and patients without MRI progression, the researchers said.
Results of the indirect analysis showed that Tysabri may be more effective than other treatment options for two outcomes: patients free of relapse and patients without MRI progression.
The researchers said data were insufficient to come to any definitive conclusions about adverse events associated with the drugs.
In conclusion, they wrote, "Although some treatments have shown better response, the results of the network analysis should be interpreted with caution because of the lack of RCTs with head-to-head comparisons between treatments.”
Key open questions
- Would the results derived from this network meta-analysis be borne out in actual head-to-head randomized controlled trials of the drugs approved for treatment of relapsing MS?
- How do the various drugs approved for treatment of relapsing MS compare in terms of adverse events?
The authors have disclosed no relevant financial conflicts of interest.