Development of interferon beta-neutralising antibodies in multiple sclerosis--a systematic review and meta-analysis

Interferon beta (IFN-β) is the drug of choice for treatment of relapsing forms of multiple sclerosis and is known to reduce the frequency and severity of relapses. This systematic review determines the occurrence of neutralising antibodies (NAbs) against different formulations of IFN-β: IFN-β-1a Avonex™, IFN-β-1a Rebif™ and IFN-β-1b Betaferon/Betaseron™. The databases used in the review included MEDLINE Ovid (from 1950 to March 2015), Embase Ovid (from 1980 to March 2015), CENTRAL on The Cochrane Library (2011, Issue 4) and ClinicalTrials.gov (from 1997 to March 2015). All studies that compared the efficacy of the different formulations of IFN-β in patients with relapsing forms of multiple sclerosis including IFN-β-1a Avonex™, IFN-β-1a Rebif™, IFN-β-1b Betaferon/Betaseron™ and IFN-β-1b Extavia™ were included. Assessment of randomised controlled trials demonstrated that Avonex™ was 76 % less likely than Rebif™ to lead to the formation of NAbs. Avonex™ was 88 % less likely than Betaferon/Betaseron™ to lead to the formation of NAbs. Similar findings were also observed in the non-randomised controlled studies, with Avonex™ having the lowest risk. The formation of NAbs was dose dependent: Avonex™ at 30 μg was 64 % less risky than Avonex™ at 60 μg. Our data show that 2.0–18.9 % of patients developed NAbs to Avonex™, 16.5–35.4 % of patients developed NAbs to Rebif™ and 27.3–53.3 % of patients developed NAbs to Betaferon/Betaseron™.