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EUROPEAN MEDICINES AGENCY

SCIENCE MEDICINES HEALTH

EMA/462803/2016

EMEA/H/C/000955

EPAR summary for the public

RoActemra

tocilizumab

This document is a summary of the European Public Assessment Report (EPAR) for RoActemra. 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 RoActemra.

What is RoActemra and what is it used for?

RoActemra is a medicine used to treat rheumatoid arthritis (an immune system disease causing inflammation of the joints) in adults with:

•    severe disease that is getting worse and who have not been previously treated with a medicine called methotrexate;

•    moderate to severe active disease whose previous treatments (called disease modifying antirheumatic drugs or DMARDs), such as methotrexate or medicines known as tumour necrosis factor (TNF) blockers, have not worked well or were not tolerated.

RoActemra is also used in children from 2 years of age to treat two childhood arthritis conditions, active systemic juvenile idiopathic arthritis and juvenile idiopathic polyarthritis, in patients who have not responded to other treatments (NSAIDs and corticosteroids).

RoActemra is usually used in combination with methotrexate but can be used on its own in patients for whom methotrexate is inappropriate.

RoActemra contains the active substance tocilizumab.

How is RoActemra used?

RoActemra can only be obtained with a prescription and treatment should be started by a doctor who has experience in the diagnosis and treatment of rheumatoid arthritis, active systemic juvenile idiopathic arthritis or juvenile idiopathic polyarthritis.

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RoActemra is available as a concentrate that is made up into a solution for infusion (drip) into a vein, and as a solution for injection under the skin in a pre-filled syringe.

In rheumatoid arthritis, RoActemra can be given as an infusion into a vein or as an injection under the skin. When given by infusion, the recommended dose is 8 mg per kilogram body weight once every 4 weeks, but doses above 800 mg per infusion are not recommended. The infusion should last 1 hour. When injected under the skin, the recommended dose is 162 mg once every week. Patients can inject themselves with the pre-filled syringe if they have been trained appropriately. The site of injection should be changed with each injection.

In systemic juvenile idiopathic arthritis, RoActemra is given as a 1-hour infusion once every two weeks at a dose of 8 mg per kilogram body weight in children weighing 30 kg or more, or 12 mg per kilogram body weight in children weighing less than 30 kg. If no improvement is seen after 6 weeks it may be appropriate to discontinue treatment.

In juvenile idiopathic polyarthritis, RoActemra is given as a 1-hour infusion once every four weeks at a dose of 8 mg per kilogram body weight in children weighing 30 kg or more, or 10 mg per kilogram body weight in children weighing less than 30 kg. If no improvement is seen after 12 weeks it may be appropriate to discontinue treatment.

The dose of RoActemra or methotrexate may need to be adjusted or treatment interrupted in patients who develop liver or blood problems. Doctors should monitor kidney function carefully in patients with moderately or severely reduced kidney function.

How does RoActemra work?

The active substance in RoActemra, tocilizumab, is a monoclonal antibody. A monoclonal antibody is an antibody (a type of protein) that has been designed to recognise and attach to a specific structure (called an antigen) that is found in the body. Tocilizumab has been designed to attach to the receptor for a messenger molecule or 'cytokine' in the body called interleukin-6. This messenger is involved in causing inflammation and is found at high levels in patients with rheumatoid arthritis, systemic juvenile idiopathic arthritis and juvenile idiopathic polyarthritis. By preventing interleukin-6 attaching to its receptors, tocilizumab reduces the inflammation and other symptoms of these diseases.

What benefits of RoActemra have been shown in studies?

In severe rheumatoid arthritis not previously treated with methotrexate, RoActemra given by infusion has been investigated in one main study involving 1,162 patients. RoActemra, on its own or in combination with methotrexate, was compared with placebo (a dummy treatment) plus methotrexate. After six months of treatment, 45% of patients taking RoActemra in combination with methotrexate (130 out of 290) and 39% of patients taking RoActemra on its own (113 out of 292) achieved remission (did not show symptoms of the disease), compared with 15% of those taking placebo plus methotrexate (43 out of 287).

For the treatment of moderate to severe rheumatoid arthritis where other medicines have been unsuccessful, RoActemra given by infusion has been studied in five main studies involving a total of over 4,000 adults. In three of these studies, RoActemra was compared with placebo, as an add-on to failing treatment with conventional rheumatoid arthritis medicines in a total of over 3,000 patients. Results showed that patients adding RoActemra were around 4 times more likely to respond to treatment than those adding placebo. One of the studies, which involved 1,196 patients, also showed that the combination of RoActemra and methotrexate slowed down the damage to the joints and

RoActemra

improved physical function after up to 2 years, when compared with the combination of placebo and methotrexate. In the fourth study, which included 498 patients who had an inadequate response to TNF blockers, patients receiving RoActemra with methotrexate were around 9 times more likely to respond than those receiving placebo with methotrexate. The fifth study involving 673 patients showed that patients receiving RoActemra on its own were more likely to respond than those taking methotrexate on its own. Almost 4,000 patients from these 5 studies went on to enter studies looking at the long-term effects of RoActemra treatment and results showed that response to RoActemra is maintained for at least two years.

RoActemra given by injection under the skin has been investigated in two studies involving 1,918 patients with moderate to severe rheumatoid arthritis where previous treatment with DMARD had not worked well. In the first study, RoActemra was more effective than placebo in treating rheumatoid arthritis: after 6 months of treatment with RoActemra, 61% of patients responded to treatment compared with 32% on placebo. The other study, which compared RoActemra injected under the skin with RoActemra given by infusion, showed that RoActemra injected under the skin was no less effective in achieving a response after 6 months.

In systemic juvenile idiopathic arthritis, RoActemra given by infusion has been compared with placebo in one main study involving 112 children who had inadequate responses to NSAID and systemic corticosteroid treatment. In this study 85% (64 out of 75) patients treated with RoActemra responded to treatment and no longer had fever after three months, compared with 24% (9 out of 37) patients receiving placebo.

In juvenile idiopathic polyarthritis, RoActemra given by infusion has been compared with placebo in one main study involving 166 children from 2 years of age who could not take or had inadequate response to methotrexate. Patients were allowed to continue treatment with methotrexate during the study. After four to six months of treatment, 26% of patients on RoActemra (21 out of 82) had a flare-up of symptoms during treatment, compared with 48% of patients taking placebo (39 out of 81).

What are the risks associated with RoActemra?

The most common side effects (seen in more than 5 patients in 100) with RoActemra are upper respiratory tract infections (nose and throat infection), nasopharyngitis (inflammation of the nose and throat), headache, hypertension (high blood pressure) and abnormal liver function tests. The most serious side effects are serious infections, complications of diverticulitis (inflammation of the gut) and hypersensitivity (allergic) reactions. For the full list of all side effects reported with RoActemra, see the package leaflet.

RoActemra must not be used in patients who have an active, severe infection. Doctors should monitor patients carefully for signs of infection during treatment, and should prescribe RoActemra with caution in patients who have had recurring or long-term infections, or diseases that could increase the risk of infections, such as diverticulitis (a disease affecting the gut) or diabetes. For the full list of restrictions, see the package leaflet.

Why is RoActemra approved?

The CHMP decided that RoActemra's benefits are greater than its risks and recommended that it be given marketing authorisation.

What measures are being taken to ensure the safe and effective use of RoActemra?

The company that makes RoActemra must supply all doctors expected to prescribe the medicine with an educational pack containing important information tailored to the needs of doctors, nurses and patients on the safety and correct use of RoActemra. The pack will also include a patient alert card with key safety information for patients.

Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of RoActemra have also been included in the summary of product characteristics and the package leaflet.

Other information about RoActemra:

The European Commission granted a marketing authorisation valid throughout the European Union for RoActemra on 16 January 2009.

The full EPAR for RoActemra 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 RoActemra, read the Package Leaflet (also part of the EPAR) or contact your doctor or pharmacist.

This summary was last updated in 07-2016.

RoActemra

EMA/462803/2016

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