Interferon-beta
Summary: Interferon-beta preparations have been the workhorse of MS treatment for decades. They are moderately effective; only a minority of MSers achieve long-term NEDA. Their impact on end-organ damage (brain volume loss and reduced neurofilament levels) is very modest. In general IFN-beta formulations are poorly tolerated in the short-term due to injection site reactions and flu-like side effects. Both the injection site reaction and flu-like side effects can be effectively managed in the majority of MSers. Monitoring requirements are not too onerous. Adherence has been a problem long-term due to injection fatigue. As IFN-beta is a biological it can induce neutralising antibodies (NABs), the rate of which varies according to the different formulations. I have always had concerns about the potential of anti-IFN-beta NABs to neutralise one's own IFNbeta and to potentially cross the placenta and affect the role of IFN-beta in foetal development. Because of this I have tended to favour the formulations with the lowest NAB rates. With more effective DMTs to choose from, that have more favourable attributes, most MSers tend to choose non-injectable treatments. Despite this there is still a role for IFN-beta in the treatment of MS.
Trade Names: Betaseron, Betaferon, Extavia (IFN-beta-1b) and Avonex, Rebif, Plegridy (IFN-beta-1a)
Mode of action: Immunomodulatory; with many different effects on the immune system. In general IFN-beta is not immunosuppressive.
Efficacy: Moderate
Class: Maintenance, immunomodulatory
Immunosuppression: No
Posology:
- IFN-beta-1b (Betaseron, Betaferon, Extavia; continuous type 1 interferon receptor stimulation and downregulation), freeze-dried, 250ug s.c. alt. day
- IFN-beta-1a (Avonex; pulsatile, type 1 interferon stimulation), prefilled syringe, 30ug IM weekly
- IFN-beta-1a (Rebif; continuous type 1 interferon receptor stimulation and downregulation), prefilled syringe or cartridge, 22/44ug sc TIW
- Peg-IFN-beta-1a (Plegridy; pegylated hence long-circulating half-life with continuous type 1 interferon receptor stimulation, prefilled syringe 125ug sc 2-weekly)
Main adverse events: Injection site reactions, flu-like symptoms, abnormal liver function tests (LFTs), low lymphocyte counts (lymphopaenia), low white cell counts (leukopaenia)
Rare adverse events of special interest:
- Thrombotic microangiopathy, manifested as thrombotic thrombocytopenic purpura (TTP) or haemolytic uraemic syndrome (HUS)
- Liver failure or autoimmune hepatitis
- Pulmonary oedema, or capillary leak syndrome, in MSers with a monoclonal gammopathy
- Severe bone marrow suppression
Neutralizing Antibodies (NAbs): Yes; ~30% IFN-beta-1b (Betaseron, Betaferon, Extavia), <5% IFN-beta-1a (Avonex), 12-25% IFN-beta-1a (Rebif) and <2% Peg-IFN-beta-1a (Plegridy)
Monitoring requirements:
- Baseline: FBC, U&E, LFTs, TFTs, serum protein electrophoresis, renal protein.
- Follow-up: 1-month, 3-month, 6-month and 6-monthly FBC, U&E and LFTs. TFTs 12 monthly. NAbs 12 & 24 months
Rebaselining: A rebaseline MRI needs to be done after IFN-beta has had sufficient time to work. I would recommend 6 months after starting treatment and to include Gd-enhancement as part of the MRI. The presence of Gd-enhancing lesions on the rebaseline scan is suffient evidence at this stage to switch/escalate treatment to another DMT.
Pregnancy: Increased risk of spontaneous abortion. Initiation of treatment is not recommended during pregnancy. In case of unplanned pregnancy on IFN-beta termination is not necessary and many neurologists are recommending continuing IFN-beta treatment throughout pregnancy.
Breastfeeding: Safe, not contraindicated.
Male Fertility: Safe
Vaccination: Safe
Summary of Product Characteristics (SmPC): Betaseron, Betaferon, Extavia (IFN-beta-1b) and Avonex, Rebif, Plegridy (IFN-beta-1a)
Interferon-beta
