Leflunomide (Arava), a disease modifying antirheumatic drug (DMARD), has been launched by Hoechst Marion Roussel. The drug is indicated for the treatment of adult patients with active rheumatoid arthritis. It is licensed as a first line disease modifying drug or for patients who have failed on previous DMARD therapy.
At a company meeting on November 18 to launch the drug, Professor Paul Emery (professor of rheumatology, Leeds General infirmary) described leflunomide as a "real alternative for patients" and said that it was "equivalent or superior to current gold standards" of efficacy in treatment, which were methotrexate and sulphasalazine.
Leflunomide was an immunodulatory agent, explained Professor Emery. It inhibited the production of pyrimidines through selective inhibition of an enzyme, dihydroorotate dehydrogenase. In susceptible cells, including T-lymphocytes, the loss of pyrimidine caused the cell cycle to arrest, he said, which stopped the production of T-lymphocytes. Hoechst Marion Roussel says that, by reducing the number of active lymphocytes in joints, inflammation and damage is reduced.
Professor Emery said that it was too early to say if leflunomide could be used in combination with other DMARDs. The summary of product characteristics (SPC) of the drug says that combinations should be avoided because of the risk of additive or synergistic side effects (see PJ, November 13, p800). It recommends a washout regime before starting therapy with another DMARD. The suggested washout procedure is 8g cholestyramine three times daily, or 50g activated powdered charcoal four times daily, for 11 days.
Professor David Scott (professor of rheumatology, King's College hospital, London) said at the launch that he believed leflunomide would have no more side effects than methotrexate or sulphasalazine and may even be safer. Hoechst Marion Roussel says that the most common side effects in trials were diarrhoea (17 per cent), rash (10 per cent), hair loss (10 per cent), nausea (9 per cent) and elevated liver enzymes (5 per cent). Possible haematological reactions and skin reactions are also mentioned in the SPC. Pregnancy must be excluded before the start of treatment and leflunomide should not be given to women of child bearing potential who are not using reliable contraception.
Professor Gabriel Panayi (president-elect of the British Society of Rhematology and professor of rheumatology, Guy's hospital, London) told The Journal on November 22 that there was a financial "crisis" approaching in rheumatology. The cost of treating rheumatoid arthritis had always been very low (because most drugs used were generic), but after years of scientific research, new drugs were coming onto the market. Anti-TNF therapy, which would be expensive but was very effective, and leflunomide would be referred to the National Institute for Clinical Evidence (NICE) for evaluation. It would be a great pity if these developments were not seen in clinical practice, Professor Panayi indicated.