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EUROPEAN MEDICINES AGENCY

SCIENCE MEDICINES HEALTH

EMA/561451/2016

EMEA/H/C/000701

EPAR summary for the public

Orencia

abatacept

This document is a summary of the European public assessment report (EPAR) for Orencia. 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 Orencia.

What is Orencia?

Orencia is a medicine that contains the active substance abatacept. It is available as a powder that is

made up into a solution for infusion (drip) into a vein and as a solution for injection under the skin in

pre-filled syringes and pre-filled pens.

What is Orencia used for?

Orencia is used in combination with methotrexate (a medicine that acts on the immune system) to

treat the following diseases:

•    moderate to severe active rheumatoid arthritis (an immune system disease causing damage and inflammation in the joints) in adults who have not had an adequate response to other medicines including methotrexate or a 'tumour necrosis factor (TNF) blocker';

•    highly active and progressive rheumatoid arthritis in adults who have not previously been treated with methotrexate;

•    moderate to severe active polyarticular juvenile idiopathic arthritis (a rare childhood disease causing inflammation of many joints) in adolescents and children from six years of age who have not had a sufficient response to other medicines including at least one TNF blocker.

The medicine can only be obtained with a prescription.

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How is Orencia used?

Treatment with Orencia should be started and supervised by a specialised doctor who has experience in the diagnosis and treatment of rheumatoid arthritis or juvenile idiopathic arthritis.

Orencia given by infusion can be used for both rheumatoid and juvenile idiopathic arthritis. The infusion should last 30 minutes. The dose depends on the patient's weight. It is given every two weeks for the first three doses, and then every four weeks. If there is no response within six months, the doctor should consider whether treatment should continue or not.

The solution for injection is only for use in rheumatoid arthritis and is given as an injection under the skin once a week. If the patient is taking Orencia for the first time, the infusion can be used for the first dose. In this case it should be followed by an injection under the skin the next day. Subsequently, the patient will have an injection under the skin once a week. After being properly trained and with the agreement of their doctor, patients may inject themselves.

How does Orencia work?

The active substance in Orencia, abatacept, is a protein that has been designed to suppress the activity of T cells, immune system cells that are involved in causing the inflammation in rheumatoid and polyarticular juvenile idiopathic arthritis. T cells must be activated before they work. This happens when signal molecules attach to receptors on the surface of the T cells. Abatacept has been designed to attach to two of these signal molecules called CD80 and CD86. This stops them activating the T cells, helping to reduce the inflammation and other symptoms of the diseases.

How has Orencia been studied?

In rheumatoid arthritis, Orencia has been studied in four main studies involving a total of 1,733 adults. The first two studies included a total of 991 patients who had not had an adequate response to methotrexate in the past, and the third included 391 patients who had not had an adequate response to TNF blockers in the past. These three studies compared the effects of adding Orencia or placebo (a dummy treatment) with the other medicines that the patients were already taking for rheumatoid arthritis: these did not include a TNF blocker. In the fourth study, Orencia in combination with methotrexate was compared with Orencia alone and methotrexate alone in 351 adults who had not been treated with methotrexate (or with any so-called biologic agents such as TNF alpha blockers) in the past, but may have been on other medicines for management of rheumatoid arthritis. The main measures of effectiveness were the reduction in symptoms of arthritis after treatment, as well as physical function (the ability to carry out everyday tasks) and the amount of damage to the joints (assessed using X-rays). In addition, Orencia given by injection under the skin has been compared with Orencia infusion in a study involving around 1,371 patients with rheumatoid arthritis.

In polyarticular juvenile idiopathic arthritis, Orencia infusion has been studied in one main study involving patients aged between six and 17 years whose previous treatment had failed. All of the patients received Orencia for four months, before the 122 who responded were then either switched to placebo or continued receiving Orencia. The main measure of effectiveness was how long it was before the patient's disease flared up again. Around three-quarters of the patients were also taking methotrexate.

What benefit has Orencia shown during the studies?

In rheumatoid arthritis, Orencia was more effective than placebo in improving symptoms in all of the studies. In the first study, 61% of the patients adding the approved dose of Orencia to methotrexate had a reduction in symptoms (70 out of 115), compared with 35% of the patients adding placebo (42 out of 119) after 6 months. The second study showed a similar effect of Orencia on symptoms of rheumatoid arthritis, as well as improved physical function and a reduced rate of joint damage after a year of treatment.

In the study of rheumatoid arthritis patients with an inadequate response to TNF blockers in the past, adding Orencia to existing treatment led to 50% of the patients having a reduction in symptoms (129 out of 256) after 6 months, compared with 20% of the patients adding placebo (26 out of 133). Patients taking Orencia also had a greater improvement in physical function after six months.

In the study of patients who had not previously received methotrexate, adding Orencia and methotrexate to existing treatment for 12 months led to a reduction in symptoms in 61% of the patients (70 out of 115), compared with 42% of the patients on Orencia alone (48 out of 113) and 45% of the patients on methotrexate alone (52 out of 115).

Orencia given by injection under the skin to patients with rheumatoid arthritis showed a similar benefit to Orencia given by infusion.

In polyarticular juvenile idiopathic arthritis, it took longer for the disease to flare up in the patients continuing to receive Orencia than those who switched to placebo. Over six months, 20% of the patients receiving Orencia had a flare-up (12 out of 60), compared with 53% of those receiving placebo (33 out of 62).

What is the risk associated with Orencia?

The most common side effects in adults taking Orencia (seen in more than 1 patient in 10) are upper respiratory tract infections (nose and throat infection). In younger patients, the most common side effects (seen in between 1 and 10 in 100 patients) are upper respiratory tract infections, ear infection, blood in the urine and fever. For the full list of all side effects reported with Orencia, see the package leaflet.

Orencia must not be used in patients with severe and uncontrolled infections, such as sepsis (when bacteria and their toxins circulate in the blood and start to damage the organs) or 'opportunistic' infections (infections seen in patients with a weakened immune system). For the full list of restrictions, see the package leaflet.

Why has Orencia been approved?

The CHMP concluded that Orencia had a modest anti-inflammatory effect in rheumatoid arthritis and, in combination with methotrexate, led to a reduction in the worsening of joint damage and an improvement in physical function. It also concluded that Orencia could be a valuable option in the treatment of polyarticular juvenile idiopathic arthritis. The Committee decided that Orencia'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 Orencia?

Patients who receive Orencia are given a special alert card explaining that Orencia must not be used in patients with certain infections and instructing patients to contact their doctor immediately if they develop an infection during a course of treatment.

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

Other information about Orencia:

The European Commission granted a marketing authorisation valid throughout the European Union for Orencia on 21 May 2007.

The full EPAR for Orencia 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 Orencia, read the package leaflet (also part of the EPAR) or contact your doctor or pharmacist.

This summary was last updated in 08-2016.