Interferon beta (IFN-β) is now established as an effective maintenance therapy for multiple sclerosis (MS) that can both slow disease progression and reduce clinical exacerbations.^1–6 Studies have demonstrated that the three widely used IFN-βa formulations – IFN-β1b 250μg (8MIU) by subcutaneous (SC) injection every other day (EOD; Betaferon®, Bayer Schering Pharma); IFN-β1a 44μg (12MIU) by SC injection three times per week (Rebif®, Merck Serono); and IFN-β1a30μg (6MIU) by intramuscular (IM) injection once per week (Avonex®, Biogen Idec) – all offer acceptable tolerability and safety profiles.^7,8 Data suggest that the two higher-dose, more frequent formulations (Betaferon and Rebif) offer better efficacy than the lower-dose, less frequent Avonex.^7–9 Adverse events (AEs) are reported to be similar across all three formulations.^7,8 However, according to one comparative study there may be an increase in headaches and injection-site reactions (ISRs) with higher-dose SC formulations compared with lower-dose IM IFN-β.⁷ However, this study pre-dated the development of new SC injector technology that is likely to influence ISRs. Injection-site pain (ISP) and ISRs are a common concern with injectable therapies and can impair adherence to treatment and potentially contribute to discontinuation of therapy.^7,8,10 This article reviews evidence on factors influencing ISRs, ISP and adherence, and presents the results of patient and nurse surveys on a new IFN-β auto-injector.

Impact of Injection-site Pain and Reactions
The growing recognition of the importance of ISP and ISRs has fuelled research into drug formulations and mechanisms of administration. Although a number of orally administered drugs are in development for the treatment of MS, none is currently approved, thus continued research into minimising the ISP and ISRs associated with IFN-β could improve adherence to the therapies that are widely used today. The use of auto-injectors has been shown to be one approach that can reduce ISRs. Auto-injectors were linked with significantly lower rates of ISRs in over 1,800 patients with relapsing–remitting MS (RRMS) receiving IFN-β over three weeks (79% versus 85% with physician-assessed ISRs and 66% versus 72% with patient-reported ISRs; p<0.001 for bothcomparisons).¹¹ An earlier report suggested that auto-injectors could reduce ISRs by close to 60% compared with manual injection.¹² Interestingly, in the pivotal IFN-β1b trial, which utilised manual injections, 69% of patients in the active treatment group reported at least one ISR compared with 6% of those receiving placebo.¹³ By contrast, the more recent BENEFIT trial, in which IFN-β1b was predominantly administered by auto-injector, the reported ISR rate was 48% versus 8.5% with placebo.¹⁴

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