What is Arava?
Arava is a medicine that contains the active substance leflunomide. It is available as tablets (white and round: 10 and 100 mg; yellow and triangular: 20 mg).
What is Arava used for?
Arava is used for the treatment of adults with active rheumatoid arthritis (a disease of the immune system that causes inflammation of the joints) or active psoriatic arthritis (a disease that causes red and scaly patches on the skin and inflammation of the joints).
The medicine can only be obtained with a prescription.
How is Arava used?
Treatment with Arava should be started and kept under control by a specialist experienced in the treatment of rheumatoid arthritis and psoriatic arthritis. The doctor must perform blood tests to check the patient's liver, white blood cell and platelet counts before prescribing Arava, and regularly during treatment.
Treatment with Arava should be started with a "loading dose" of 100 mg once a day for three days, followed by a maintenance dose. The recommended maintenance dose is between 10 and 20 mg once a day in patients with rheumatoid arthritis, and 20 mg once a day in patients with psoriatic arthritis. Usually the medicine begins to take effect after four to six weeks. Its effect can further improve for up to six months.
How does Arava work?
The active substance in Arava, leflunomide, is an immunosuppressant. This substance reduces inflammation by reducing the production of immune cells called "lymphocytes", which are responsible for inflammation. Leflunomide exerts this action by blocking an enzyme called "dihydroorotate dehydrogenase", which is necessary for the lymphocytes to multiply. With less lymphocytes, there is less inflammation and it helps control the symptoms of arthritis.
What studies have been carried out on Arava?
For rheumatoid arthritis Arava has been studied in four main studies involving over 2, 000 patients in which it was compared with a placebo (a dummy treatment), or with methotrexate or sulfasalazine (other medicines used to treat arthritis rheumatoid). Two of the studies lasted six months and two lasted a year. The two longer studies were subsequently prolonged and the patients continued to take the medicines for at least another year.
Arava was compared with placebo for six months in 186 patients with psoriatic arthritis.
In all the studies, the main measure of effectiveness was the number of patients who responded to treatment, identified by specific criteria for the disease (response rates of the American College of Rheumatology for rheumatoid arthritis and the criteria for response to treatment for psoriatic arthritis).
What benefit has Arava shown during the studies?
In rheumatoid arthritis, Arava showed an efficacy superior to that of placebo and equivalent to that of sulfasalazine. Between 49 and 55% of patients taking Arava responded to treatment compared to 26 - 28% of those taking placebo and 54% of those taking sulfasalazine. These results were maintained in the extension studies. During the first year of therapy, Arava showed an efficacy equivalent to that of methotrexate, but only if it was taken together with folate (a type of vitamin B). In the extension study, Arava did not have an efficacy equivalent to that of methotrexate.
In psoriatic arthritis, Arava was more effective than placebo, with a treatment response rate of 59% of the patients taking Arava compared to 30% of those taking placebo.
What is the risk associated with Arava?
The most common side effects of Arava (seen in between 1 and 10 patients in 100) are leukopenia (low level of white blood cells), mild allergic reactions, increased levels of creatine phosphokinase (a marker of muscle lesions), paresthesia (sensitivity disorders such as pins and needles), headache, dizziness, slight increases in blood pressure, diarrhea, nausea, vomiting, inflammation of the mouth (eg mouth ulceration), abdominal pain (stomach ache), increased levels of liver enzymes, hair loss, eczema, rash, itching, dry skin, tenosynovitis (inflammation of the sheath that covers the tendons), loss of appetite, weight loss and asthenia (weakness). For the full list of all side effects reported with Arava, see the Package Leaflet.
Arava should not be used in people who may be hypersensitive (allergic) to leflunomide or any of the other substances. Arava should not be used in patients with:
- liver disease;
- states of severe immunodeficiency, e.g. acquired immunodeficiency syndrome (AIDS);
- poor bone marrow function or low level of blood cells (red blood cells, white blood cells or platelets) due to diseases other than rheumatoid or psoriatic arthritis;
- serious infections;
- moderate to severe kidney disease;
- severe hypoproteinemia (low levels of protein in the blood).
Arava should not be used in pregnant women, women of childbearing age or during breastfeeding.
Doctors who prescribe Arava should be aware of the risk of liver problems associated with the medicine. They must also take special care when passing a patient to Arava or passing a patient taking Arava to another treatment.
Why has Arava been approved?
The Committee for Medicinal Products for Human Use (CHMP) has determined that the benefits of Arava outweigh its risks for the treatment of adult patients with active rheumatoid arthritis as a "disease-modifying antirheumatic drug" (DMARD) is
active psoriatic arthritis. The committee recommended the granting of the marketing authorization for Arava.
More information on Arava:
On 2 September 1999, the European Commission issued a marketing authorization for Arava, valid throughout the European Union, to Sanofi-Aventis Deutschland GmbH. The marketing authorization was renewed on 2 September 2004 and 2 September 2009.
The full EPAR for Arava can be found here.
Last update of this summary: 09-2009.
