Remicade

infliximab

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

What is Remicade?

Remicade is a powder that is made up into a solution for infusion (drip into a vein). It contains the active substance infliximab.

What is Remicade used for?

Remicade is an anti-inflammatory medicine. It is usually used when other medicines or treatments have failed, in adults with the following diseases:

• rheumatoid arthritis (an immune system disease causing inflammation of the joints). Remicade is used with methotrexate (a medicine that acts on the immune system);
• Crohn’s disease (a disease causing inflammation of the digestive tract), when the disease is moderate to severe or fistulising (with the formation of fistulae, abnormal passageways between the gut and other organs);
• ulcerative colitis (a disease causing inflammation and ulcers in the lining of the gut);
• ankylosing spondylitis (a disease causing inflammation and pain in the joints of the spine);
• psoriatic arthritis (a disease causing red, scaly patches on the skin and inflammation of the joints);
• psoriasis (a disease causing red, scaly patches on the skin).

Remicade is also used in patients aged between six and 17 years with severe, active Crohn’s disease, when they have not responded to or cannot take other medicines or treatments.

See the summary of product characteristics (also part of the EPAR) for full details.

The medicine can only be obtained with a prescription.

How is Remicade used?

Remicade must be given under the supervision and monitoring of a specialised doctor who has experience in the diagnosis and treatment of the diseases that Remicade can be used to treat.

Remicade is usually given as 3 mg per kilogram bodyweight in rheumatoid arthritis, although the dose can be increased if necessary. The dose is 5 mg per kilogram for the other diseases. How often the treatment is repeated depends on which disease is being treated, and on the patient’s response to the medicine.

Remicade is given as an infusion lasting one or two hours. All patients are monitored for any reactions during the infusion and for at least one to two hours afterwards. They may be given other medicines before or during treatment with Remicade to reduce the risk of infusion-related reactions. For more information, see the package leaflet.

Patients who receive Remicade must be given the special alert card that summarises the safety information about the medicine.

How does Remicade work?

The active substance in Remicade, infliximab, 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) in the body. Infliximab has been designed to attach to a chemical messenger in the body called tumour necrosis factor-alpha (TNF-alpha). This messenger is involved in causing inflammation and is found at high levels in patients with the diseases that Remicade is used to treat. By blocking TNF-alpha, infliximab improves the inflammation and other symptoms of the diseases.

How has Remicade been studied?

For rheumatoid arthritis, Remicade has been studied in a total of 1,432 patients in two studies. Remicade was given with methotrexate and compared with methotrexate alone. The main measure of effectiveness was the change in the symptoms, joint damage and physical function after up to 54 weeks.

For Crohn’s disease, Remicade has been compared with placebo (a dummy treatment) in 1,090 adults in four studies. The main measures of effectiveness were the improvement in the severity of symptoms or the healing of fistulae. The effects of adding Remicade to existing treatment have also been studied in 103 children and adolescents with Crohn’s disease who were aged between six and 17 years. A sixth study in 508 adult patients looked at the number of patients whose symptoms improved and who did not need additional treatment with corticosteroids (other medicines used in Crohn’s disease). The patients were treated for 6 months with Remicade, another medicine azathioprine, or the combination of Remicade and azathioprine.

For ulcerative colitis (728 patients), ankylosing spondylitis (70 patients), psoriatic arthritis (104 patients) and psoriasis (627 patients), Remicade has been compared with placebo. In all of these studies, the main measure of effectiveness was the change in symptoms after up to 16 weeks.

What benefit has Remicade shown during the studies?

Remicade was more effective than the comparator medicines in all of the studies:

• in rheumatoid arthritis, more patients taking Remicade in combination with methotrexate showed a reduction in symptoms than those taking methotrexate alone, as well as less damage to the joints and greater improvements in physical function;
• in Crohn’s disease in adults, compared with placebo, Remicade produced a greater improvement in symptoms, led to fistulae healing in more patients and increased the time that patients continued to respond to treatment. Most of the children and adolescents with Crohn’s disease also showed a reduction in symptoms after adding Remicade to their existing treatment. In the sixth study, Remicade alone and in combination with azathioprine was more effective than azathioprine alone;
• in ulcerative colitis, ankylosing spondylitis and psoriatic arthritis, more patients receiving Remicade had a reduction in symptoms than those receiving placebo;
• in psoriasis, Remicade led to a greater improvement in symptoms than placebo.

What is the risk associated with Remicade?

Most side effects seen in patients taking Remicade are related to the infusion and not to the medicine itself, including dyspnoea (breathlessness), urticaria (hives) and headache. Some patients can experience anaphylactic shock (a severe allergic reaction) during infusion, or delayed hypersensitivity (allergic reaction after the first exposure to the medicine). Patients experiencing these symptoms should have their infusion slowed down or treatment interrupted.

The most common side effects with Remicade (seen in between 1 and 10 patients in 100) are viral infections (such as flu or cold sores), serum sickness-like reactions (including skin rash, joint pain or fever), headache, vertigo (dizziness), flushing, upper respiratory tract infection (colds), lower respiratory tract infection (such as bronchitis or pneumonia), dyspnoea, sinusitis (inflammation of the sinuses), nausea (feeling sick), diarrhoea, abdominal (tummy) pain, dyspepsia (heartburn), rash, pruritus (itching), urticaria, increased sweating, dry skin, fatigue (tiredness), chest pain, fever and elevated liver enzymes in the blood. Some side effects, including infections, may be more common in children than in adults. For the full list of all side effects reported with Remicade, see the package leaflet.

Remicade should not be used in patients who have experienced hypersensitivity (allergy) to infliximab in the past, or who are hypersensitive (allergic) to mouse proteins or any of the other ingredients of Remicade. Remicade must not be used in patients with tuberculosis, other severe infections, or moderate or severe heart failure (an inability of the heart to pump enough blood around the body).

Why has Remicade been approved?

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

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

The company that makes Remicade will set up an educational programme for doctors who intend to prescribe the medicine to children with Crohn’s disease, to explain the risks of treatment.

Other information about Remicade

The European Commission granted a marketing authorisation valid throughout the European Union on 13 August 1999. The marketing authorisation holder is to Janssen Biologics B.V. The marketing authorisation is valid for an unlimited period.

For more information about treatment with Remicade, read the package leaflet (also part of the EPAR) or contact your doctor or pharmacist.

This EPAR was last updated on 13/12/2011 .

More detail is available in the Summary of Product Characteristics

Product details

Publication details

Product information

30/09/2011  Remicade -EMEA/H/C/000240 -IA/0160/G

Contents

• Annex I - Summary of product Characteristics
• Annex IIA - Manufacturing Authorisation Holder responsible for Batch Release
• Annex IIB - Conditions of the Marketing Authorisation
• Annex IIIA - Labelling
• Annex IIIB - Package Leaflet

Please note that the size of the above document can exceed 50 pages.

You are therefore advised to be selective about which sections or pages you wish to print.

Pharmaco-therapeutic Group

Immunosuppressants

Therapeutic Indication

Rheumatoid arthritis:
Remicade, in combination with methotrexate, is indicated for the reduction of signs and symptoms as well as the improvement in physical function in:

• adult patients with active disease when the response to disease-modifying anti-rheumatic drugs (DMARDs), including methotrexate, has been inadequate.
• adult patients with severe, active and progressive disease not previously treated with methotrexate or other DMARDs.

In these patient populations, a reduction in the rate of the progression of joint damage, as measured by X-ray, has been demonstrated.

Adult Crohn's disease:
Remicade is indicated for:

• treatment of moderately to severely active Crohn's disease, in adult patients who have not responded despite a full and adequate course of therapy with a corticosteroid and/or an immunosuppressant; or who are intolerant to or have medical contraindications for such therapies.
• treatment of fistulising, active Crohn's disease, in adult patients who have not responded despite a full and adequate course of therapy with conventional treatment (including antibiotics, drainage and immunosuppressive therapy).

Paediatric Crohn's disease:

• Remicade is indicated for treatment of severe, active Crohn's disease, in paediatric patients aged 6 to 17 years, who have not responded to conventional therapy including a corticosteroid, an immunomodulator and primary nutrition therapy; or who are intolerant to or have contraindications for such therapies. Remicade has been studied only in combination with conventional immunosuppressive therapy.

Ulcerative colitis:

• Remicade is indicated for treatment of moderately to severely active ulcerative colitis in adult patients who have had an inadequate response to conventional therapy including corticosteroids and 6-mercaptopurine (6-MP) or azathioprine (AZA), or who are intolerant to or have medical contraindications for such therapies.

Ankylosing spondylitis:
Remicade is indicated for treatment of severe, active ankylosing spondylitis, in adult patients who have responded inadequately to conventional therapy.
Psoriatic arthritis:

• Remicade is indicated for treatment of active and progressive psoriatic arthritis in adult patients when the response to previous DMARD therapy has been inadequate.
• Remicade should be administered
  • in combination with methotrexate
  • or alone in patients who show intolerance to methotrexate or for whom methotrexate is contraindicated

Remicade has been shown to improve physical function in patients with psoriatic arthritis, and to reduce the rate of progression of peripheral joint damage as measured by X-ray in patients with polyarticular symmetrical subtypes of the disease.

Psoriasis:
Remicade is indicated for treatment of moderate to severe plaque psoriasis in adult patients who failed to respond to, or who have a contraindication to, or are intolerant to other systemic therapy including cyclosporine, methotrexate or PUVA.

Changes since initial authorisation of medicine

Initial Marketing authorisation documents