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EUROPEAN MEDICINES AGENCY

SCIENCE MEDICINES HEALTH

EMA/106442/2016

EMEA/H/C/363

EPAR summary for the public

Kineret

anakinra

This is a summary of the European public assessment report (EPAR) for Kineret. It explains how the Committee for Medicinal Products for Human Use (CHMP) assessed the medicine to reach its opinion in favour of granting a marketing authorisation and its recommendations on the conditions of use for Kineret.

What is Kineret?

Kineret is a medicine that contains the active substance anakinra. It is available as a solution for

injection.

What is Kineret used for?

Kineret is used to treat:

•    signs and symptoms of rheumatoid arthritis (an immune system disease causing inflammation of the joints) in adults. It is used in combination with methotrexate (a medicine used to reduce inflammation) in patients who have not responded adequately to methotrexate alone;

•    cryopyrin-associated periodic syndromes (CAPS) in patients from 8 months of age and weighing at least 10 kg. CAPS are a group of diseases where patients have a defect in the gene that produces a protein called cryopyrin. This leads to inflammation in many parts of the body, with symptoms such as fever, rash, joint pain and tiredness. Severe disabilities such as deafness and loss of vision may also occur.

How is Kineret used?

Kineret can only be obtained with a prescription and treatment should be started and supervised by a doctor who has experience in the treatment of rheumatoid arthritis or CAPS as appropriate.

The recommended dose of Kineret for rheumatoid arthritis is 100 mg once a day, given by injection under the skin at around the same time each day. For CAPS, the dose depends on body weight and the

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severity of the condition; the recommended starting dose is 1 to 2 mg per kg of body weight daily, given by injection under the skin. The injection site should be varied with each dose to avoid discomfort. Kineret should be used with caution in patients who have severely reduced liver function or moderately reduced kidney function, and should not be used in patients with severely reduced kidney function.

How does Kineret work?

The active substance in Kineret, anakinra, is an immunosuppressive medicine (a medicine that reduces the activity of the immune system). It blocks the receptors for a chemical messenger in the body called interleukin 1. This messenger is produced in high levels in patients with rheumatoid arthritis, causing inflammation of the joints and joint damage, and is also involved in the inflammation associated with CAPS. By attaching to the receptors that interleukin 1 would normally attach itself to, anakinra blocks the activity of interleukin 1, helping to relieve the symptoms of these diseases.

The active substance in Kineret, anakinra, is a copy of a natural human protein called 'human interleukin 1 receptor antagonist'. It is produced by a method known as 'recombinant DNA technology': it is made by a bacterium into which a gene (DNA) has been introduced, which makes it able to produce anakinra. The replacement anakinra acts in same way as the natural protein.

How has Kineret been studied?

Kineret has been studied in three main studies involving a total of 1,388 patients with rheumatoid arthritis. All three studies compared the effectiveness of Kineret with that of placebo (a dummy treatment). The first study included 468 patients, some of whom had taken other medicines for their disease in the past, and who were given either Kineret on its own or placebo. In the other two studies, the medicines were used as an add-on to existing treatment including methotrexate: one study, which involved 419 patients, used a range of doses of Kineret that depended on the patient's weight, and the other study, which involved 501 patients, used Kineret at a fixed dose of 100 mg once a day. In all three studies, the main measure of effectiveness was the number of patients with an improvement in symptoms of at least 20% after six months. Symptoms were measured by the doctor and the patient using the 'American College of Rheumatology' score, which includes measurements of the number of painful or tender joints, disease activity, pain, disability and levels of C reactive protein in the blood (a marker of inflammation).

For CAPS, Kineret has been studied in one main study involving 43 patients with neonatal-onset multisystem inflammatory disease (NOMID/CINCA syndrome, a form of CAPS). Patients were given Kineret at a starting dose of 1 to 2 mg per kg body-weight daily, increased after a month if necessary. The main measures of effectiveness were improvement in symptom scores and in the level of amyloid A in the blood (another marker of inflammation).

What benefit has Kineret shown during the studies?

The first study in rheumatoid arthritis showed that certain doses of Kineret were more effective than placebo in reducing the symptoms of the disease. However, because of the way the study was designed, the results were considered insufficient to support the use of the medicine on its own.

The other two studies in rheumatoid arthritis showed that Kineret was more effective than placebo when used as an add-on to methotrexate. In the study using a fixed dose of Kineret, 38% of the

Kineret

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patients adding Kineret had at least a 20% reduction in symptoms after six months, compared with 22% of those adding placebo.

The study in CAPS showed a significant and rapid improvement in symptoms, with a fall in average symptom score from 4.5 to 0.8 within 3 days of starting treatment. The improvement was maintained over a follow-up period of up to 60 months. Levels of amyloid A were also reduced.

What is the risk associated with Kineret?

The most common side effects with Kineret (seen in more than 1 patient in 10) are headache, injection site reactions (redness, bruising, pain and inflammation), and increase in blood cholesterol. For the full list of all side effects reported with Kineret, see the package leaflet.

Kineret must not be used in people who are hypersensitive (allergic) to anakinra, to any of the other ingredients, or to proteins produced by Escherichia coli (a type of bacterium). Kineret must not be used in patients who have severely reduced kidney function and must not be started in patients who have neutropenia (low levels neutrophils, a type of white blood cell that fights infection). The use of Kineret with tumour necrosis factor (TNF) antagonists (other medicines used in rheumatoid arthritis) is not recommended.

Why has Kineret been approved?

The CHMP decided that Kineret's benefits are greater than its risks for the treatment of the signs and symptoms of rheumatoid arthritis in combination with methotrexate, in patients with an inadequate response to methotrexate alone. The Committee recommended that Kineret be given marketing authorisation. Given the rapid effect and the fact that there were no new safety concerns, the Committee also considered that the benefits outweighed the risks in patients with CAPS.

What measures are being taken to ensure the safe use of Kineret?

A risk management plan has been developed to ensure that Kineret is used as safely as possible.

Based on this plan, safety information has been included in the summary of product characteristics and the package leaflet for Kineret, including the appropriate precautions to be followed by healthcare professionals and patients.

In addition, the company that makes Kineret will provide educational material for healthcare providers and for patients or their caregivers. These will focus on the details of how Kineret doses should be measured and injected, and how to manage injection site reactions.

Other information about Kineret

The European Commission granted a marketing authorisation valid throughout the European Union for Kineret on 8 March 2002.

The full EPAR for Kineret can be found on the Agency's website: ema.europa.eu/Find medicine/Human medicines/European public assessment reports. For more information about treatment with Kineret, read the package leaflet (also part of the EPAR) or contact your doctor or pharmacist..

This summary was last updated in 02-2016.

Kineret

EMA/106442/2016