Summary
Interferon-beta (IFN-beta) preparations have been the workhorse of MS treatment for decades. They are moderately effective; only a minority of people with MS receiving IFN-beta achieve long-term NEIDA (no evident inflammatory disease activity). Their impact on preventing end-organ damage (brain volume loss) and reducing neurofilament levels (an indicator of damaged nerve fibres) is modest. In general, IFN-beta formulations are poorly tolerated in the short term owing to injection site reactions and flu-like side effects, but both these side effects can be effectively managed in most people with MS. Monitoring requirements are not too onerous. Adherence has been a problem long-term owing to injection fatigue. IFN-beta is a biological so it can induce neutralising antibodies (NAbs), the rate of which varies according to the different formulations.
IFN-beta belongs to the class of cytokines and is produced by the body to help fight infections, particularly viral infections and possibly cancers. IFN-beta also plays a role in foetal bone development. I have long had concerns about the potential of anti-IFN-beta NAbs to neutralise one’s own IFN-beta and to cross the placenta and affect the role of IFN-beta in foetal development. Therefore, I have favoured the formulations with the lowest NAb levels. Given that more effective DMTs are now available, with more favourable attributes, most people with MS tend to choose other, non-injectable treatments. Despite this, there is still a role for IFN-beta preparations in the treatment of MS, particularly as they have now been shown to be safe in pregnancy.
Trade names
Avonex (IFN-beta-1a), Betaferon (IFN-beta-1b), Betaseron (IFN-beta-1b), Extavia (IFN-beta-1b), Plegridy (Peg-IFN-beta-1a), Rebif (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.
Dosing
- Betaseron, Betaferon, Extavia; 250 micrograms (µg) subcutaneous (SC) alternate days.
- Avonex; 30 µg IM weekly.
- Rebif; 22/44 µg SC three times a week.
- Plegridy; 125 µg SC or IM 2-weekly.
Main adverse events and monitoring requirements
- Injection site reactions, flu-like symptoms, abnormal liver function tests (LFTs), low lymphocyte counts (lymphopaenia), low white cell counts (leukopaenia).
- Increased risk of spontaneous abortion. Initiation of treatment is not recommended during pregnancy, but termination of pregnancy is not necessary in case of unplanned pregnancy; established IFN-beta treatment can generally be continued throughout pregnancy.
Rare adverse events of special interest
- Thrombotic microangiopathy, which manifests as so-called thrombotic thrombocytopenic purpura or haemolytic ̶ uraemic syndrome, i.e. low platelet levels, blood clots, brusing and renal failure.
- Liver failure or autoimmune hepatitis.
- Pulmonary oedema, or capillary leak syndrome, in patients with a monoclonal gammopathy.
- Severe bone marrow suppression.