Immunomodulators and immunosuppressants for multiple sclerosis: a network meta-analysis

Abstract

Background Different therapeutic strategies are available for treatment of multiple sclerosis (MS) including immunosuppressants, immunomodulators, and monoclonal antibodies. Their relative effectiveness in the prevention of relapse or disability progression is unclear due to the limited number of direct comparison trials. A summary of the results, including both direct and indirect comparisons of treatment effects, may help to clarify the above uncertainty. Objectives To estimate the relative efficacy and acceptability of interferon ß-1b (IFNß-1b) (Betaseron), interferon ß-1a (IFNß-1a) (Rebif and Avonex), glatiramer acetate, natalizumab, mitoxantrone, methotrexate, cyclophosphamide, azathioprine, intravenous immunoglobulins, and long-term corticosteroids versus placebo or another active agent in participants with MS and to provide a ranking of the treatments according to their effectiveness and risk-benefit balance. Search methods We searched the Cochrane Database of Systematic Reviews, the Cochrane MS Group Trials Register, and the Food and Drug Administration (FDA) reports. The most recent search was run in February 2012. Selection criteria Randomized controlled trials (RCTs) that studied one of the 11 treatments for use in adults with MS and that reported our pre-speci ed efficacy outcomes were considered for inclusion.

Comparative effectiveness of glatiramer acetate and interferon beta formulations in relapsing–remitting multiple sclerosis

“…29 This suggests that any differences in relapse activity between the injectable immunomodulators are minimal and detectable only on sufficient follow-up duration. In their network meta-analysis, Filippini and colleagues used a combination of direct and indirect comparisons to estimate relative treatment efficacy among the commonly used disease-modifying therapies, including IFNβ and GA. 30 In agreement with our findings, the meta-analysis showed superiority of IFNβ-1a SC over the other IFNβ preparations in their effect on relapse outcomes. In addition, unlike our analysis, it reported superiority of IFNβ-1a SC over GA.…”

“…30 Therefore, the outcomes of network meta-analyses may be susceptible to confounding introduced by the heterogeneity of indirectly compared trial populations. Our analysis used matched head-to-head comparisons with uniform inclusion criteria and follow-up protocol, and was therefore relatively resistant to population heterogeneity.…”

Therapeutic approaches to disease modifying therapy for multiple sclerosis in adults: An Australian and New Zealand perspective Part 2 New and emerging therapies and their efficacy

“…These compare favourably, to within a 10% range, which is adequate for approximate comparisons. More formal attempts to compare trials using network meta-analysis and similar approaches have shown conflicting results [65][66][67][68]. What is striking in the comparison shown in Table 1 is the high degree of concordance between the observed effect on Gad-enhancing lesions and relapse rates and between measures of brain atrophy and disability progression in what is a very consistent pattern across therapies.…”

Oral drugs in multiple sclerosis therapy: an overview and a critical appraisal

“…It was largely abandoned as a first-line therapy in many countries in the mid-1990s when the b-interferons ushered in a new generation of MS therapeutics [165]. However, recently, new findings showed the possibility to consider azathioprine as an inexpensive treatment option for RRMS.…”