Anakinra is a recombinant biological agent used primarily to treat rheumatoid arthritis. Recently it has been shown to be useful in the treatment of several skin diseases.
What is anakinra?
Anakinra is an interleukin-l receptor antagonist (IL-1Ra) produced by recombinant DNA technology using an E. coli bacterial expression system. It differs from native human IL-1Ra in that it has the addition of a single methionine residue at its amino terminus.
Anakinra is not registered or subsidised in New Zealand (June 2011). In other countries such as the USA and Europe, its registered indication is rheumatoid arthritis. Kineret® is the name used for the Amgen product available in USA and elsewhere.
How does anakinra work?
In people with rheumatoid arthritis, the body produces too much of certain proteins that lead to joint damage. One of these proteins is called interleukin-1 (IL-l) which mediates various physiologic responses including inflammatory and immunological responses. Too much IL-1 contributes to the pain, swelling, and stiffness associated with rheumatoid arthritis.
Anakinra blocks the biological activity of IL-1 by competitively inhibiting IL-1 from binding to the interleukin-1 type I receptor (IL-1RI), which is expressed in a wide variety of tissues and organs.
The levels of the naturally occurring IL-1 receptor antagonist, IL-1Ra, in synovium and synovial fluid from rheumatoid arthritis patients are not sufficient to compete with the elevated amount of locally produced IL-1. Increasing the levels of IL-1Ra by artificial means reduces the negative effects (cartilage degradation, bone resorption) of IL-1.
What is anakinra used for?
Anakinra is mainly used to treat rheumatoid arthritis. While not Food and Drug Administration (FDA)-approved indications, anakinra is sometimes used for the treatment of other inflammatory conditions such as gout attacks, ankylosing spondylitis and uveitis.
Anakinra has also been found to be useful in a variety of immune-mediated and autoimmune skin disorders in which traditional therapy has failed or resulted in side effects. However, the efficacy, tolerability and dosing of anakinra in the treatment of dermatologic disease is not yet clear.
Off-label indications of anakinra in dermatology
Anecdotal reports have shown anakinra to be a promising medication in the treatment of some rare inflammatory conditions that give rise to skin rashes. These include:
- Adult-onset Stills disease
- Deficiency of the interleukin-1 receptor antagonist (DIRA)
- Schnitzler syndrome
- Cryopyrin-associated periodic syndrome (CAPS) i.e., NOMID/CINCA syndrome, Muckle-Wells syndrome and familial cold autoinflammatory syndrome
- Tumour necrosis factor receptor-associated periodic syndrome (TRAPS)
- Pyogenic arthritis, pyoderma gangrenosum and acne (PAPA) syndrome
- Some cases of familial Mediterranean fever
- Some cases of acute neutrophilic dermatosis (Sweet syndrome)
Anakinra may dramatically improve clinical and laboratory signs and symptoms in patients with the autoinflammatory syndromes described above.
Anakinra is also under investigation for the treatment of atopic dermatitis.
Dosing of anakinra
Anakinra is given as a daily subcutaneous injection, dose range 1-10mg/kg/d in children and usually 100mg daily in adults. Very young children appear to require a much higher dose per kg (6-10mg/kg/d) to control symptoms and inflammatory markers than older children or adults (1-3 mg/kg/d).
Anakinra should be started as early in life as possible for cryopyrin-associated periodic syndrome (CAPS) to minimise irreversible neurological complications. It is likely treatment will be continued for life.
Precautions in children
Very young children are at risk of developing pneumococcal infection due to the very high doses of anakinra required and their poor immune response to encapsulated bacteria. All patients should be immunised against Streptococcus pneumoniae and Haemophilus influenzae before starting therapy and it is suggested that very young children should be prescribed prophylactic antibiotics.
Adverse events from anakinra
The most serious adverse reactions to anakinra are:
- serious infection primarily bacterial events such as cellulitis, pneumonia, and bone and joint infections
- injection-site reactions (ISRs) characterized by 1 or more of the following: erythema, ecchymosis, inflammation, and pain
- malignancies – various types have been observed in rheumatoid arthritis patients treated in clinical trials with anakinra for up to 50 months
- leukopenia – in placebo-controlled studies with anakinra, treatment was associated with small reductions in the mean values for total white blood count, platelets, and absolute neutrophil blood count and a small increase in the mean eosinophil differential percentage
- other adverse events reported at a frequency of >5% versus placebo in clinical trials have included headache, nausea, diarrhoea, sinusitis, influenza-like symptoms and abdominal pain.
The use of anakinra in children and in patients with kidney or liver failure has not been studied extensively. Anakinra should be avoided during pregnancy unless the potential benefit justifies the potential risk to the fetus (Pregnancy Risk Category C). Breast-feeding mothers should be advised to discontinue nursing until circulating blood levels are no longer detectable.
Current safety information is based on treatment for rheumatoid arthritis and may not be applicable when anakinra is used for other disorders.
Overdosage with anakinra
There has been no experience with overdosage in human clinical trials.
Contraindications to anakinra
Anakinra is not recommended for treatment of patients with severe active infections.
The safety of anakinra in immunosuppressed patients or in patients with chronic infections has not been evaluated.
Anakinra is contraindicated in patients with known hypersensitivity to E coli-derived proteins. If a severe hypersensitivity reaction occurs, administration of anakinra should be discontinued and appropriate therapy initiated.
Drug interactions with anakinra
Though there have been no formal drug interaction studies performed with anakinra, concomitant use is not recommended with TNF-antagonists such as infliximab, adalimumab and etanercept, as an increased incidence of adverse effects (neutropaenia, serious infections) have been reported.
Live virus vaccines should not be administered to patients receiving anakinra even though information is not available regarding whether anakinra would affect the rate of secondary transmission of vaccine virus following administration of a live virus.