Recent developments in interferon-based therapies for multiple sclerosis

ABSTRACT

Introduction: Multiple sclerosis (MS) is a chronic and disabling immune-mediated disease of the central nervous system. Beta-interferons are the first approved and still the most widely used first-line disease-modifying treatment in MS.

Areas covered: Here we focus on recent developments in pharmacology and delivery systems of beta-interferons, and discuss their place within current state of the art therapeutic approaches. We briefly review the clinical trials for classical and PEGylated formulations, emphasizing effectiveness, safety concerns, and tolerability. The mechanisms of action of IFN-β in view of MS pathogenesis are also debated.

Expert opinion: Though only modestly efficient in reducing the annualized relapse rate, beta-interferons remain a valid first-line option due to their good long-term safety profile and cost-efficacy. Moreover, they are endogenous class II cytokines essential for mounting an effective antiviral response, and they may interact with putative MS triggering factors such as Epstein-Barr virus infection and human endogenous retroviruses. Recent improvements in formulations, delivery devices and drug regimens tackle the tolerability and adherence issues frequently seen with these drugs, and scientific advances may offer means for a better selection of patients. Although a well-established immunomodulatory treatment, beta-interferons have not said their last word in the management of MS.

KEYWORDS:

• Interferon beta
• multiple sclerosis
• immunomodulation
• PEGylated

Article highlights

• Beta IFNs are the first approved DMTs for MS; they remain a valid first-line option due to their good long-term safety profile and cost-efficacy.

• IFN-β-regulated pathways are a central pathogenic feature of MS.

• Standard formulations decrease the annualized relapse rate by about 30% and possibly the long-term disability accrual in people with relapsing MS.

• PEG-IFN-β-1a is an improved formulation with similar safety profile, and better cost-effectiveness, tolerance, and adherence.

• The use of ‘smart’ autoinjector devices improves tolerance and adherence.

• The response to IFN-β-based therapies may not be uniform over time or among people with MS.

• There is a need of better defining the early predictors for treatment failure and factors that may confer responsiveness or refractoriness to IFN-β therapies over the course of MS.

This box summarizes key points contained in the article.

Declaration of interest

L Dumitrescu has received support for attending scientific meetings from AbbVie, Biogen Idec and Teva and consultancy fees from AbbVie. C Constantinescu has received research grant support, support for attending scientific meetings, and consultancy fees from Biogen Idec, Bayer Schering, Genzyme, Merck Serono, MorphoSys, Novartis, Roche, Sanofi Pasteur and Merck Sharp and Dohme. C Constantinescu was investigator in the ADVANCE trial. R Tanasescu received support for attending scientific meetings from AbbVie, Biogen Idec, Teva and Genzyme and was sub-investigator in several DMTs trials. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. One peer reviewer has done trials and research for all of the IFN companies.

Additional information

Funding

This paper is not funded.