Infliximab (Remicade) has been licenced for the treatment of rheumatoid arthritis. Infliximab is a monoclonal antibody that blocks tumour necrosis factor alpha (TNFa), a proinflammatory mediator. It was previously launched for the treatment of Crohn's disease in December, 1999.
The use of anti-TNF drugs was discussed at a Schering-Plough-sponsored satellite symposium at the annual European congress of the European League Against Rheumatism in Nice, France, on June 23.
Professor Ravinder Maini (director, Kennedy Institute of rheumatology, Imperial College school of medicine, London) presented data from an ongoing study - the ATTRACT trial (anti-TNFa trial in rheumatoid arthritis with concomitant therapy). The results indicated that infliximab produced an arrest of structural damage, he said.
In the study, 428 patients received methotrexate (15mg per week) and were randomised to receive in addition placebo or infliximab at doses of 3mg/kg or 10mg/kg every four or every eight weeks. Radiographical damage was analysed at 30 weeks (see PJ, December 11, p937), 54 weeks and at two years using the van der Heidje-Sharp score. At 54 weeks, the group receiving methotrexate alone had a median disease progression score of four points. The four infliximab groups had scores of between 0.5 and –0.5 points, which Professor Maini described as a "striking difference". The results showed that all four infliximab regimens provided a clinically and statistically significant benefit in the prevention of structural joint damage, he said. This result was regardless of whether a benefit was observed in the control of signs and symptoms of the disease.
The two-year data was currently being evaluated and the results were not yet available. However, Dr Peter Lipsky (national institute of arthritis and musculoskeletal and skin diseases, National Institutes of Health, Bethesda, US) commented that it was known that effects on signs and symptoms "demonstrate clearly that the impact is sustained throughout the second year of the trial".
Infliximab is now licensed for use in patients with active rheumatoid arthritis where response to disease modifying anti-rheumatic drugs (DMARDs), including methotrexate, has been inadequate (see p33). The proportion of patients who respond to anti-TNF therapy was between 60 and 70 per cent, said Professor Maini. It was not possible to extrapolate data to compare infliximab with the other currently available anti-TNF drug, etanercept. Once treatment with infliximab was stopped, there was no rebound effect but the disease did, almost inevitably, return slowly, he said. However, the fact that previous non-responders to DMARDs apparently became responsive following infliximab treatment needed to be investigated.
In terms of adverse drug reactions, Professor Maini described symptoms of flushing and rash following infusion of infliximab. This was, he said, some kind of cytokine reaction, which responded to slowing the infusion rate or could be prevented by giving an antihistamine before infusion. In clinical trials, some patients developed serious infections. While Professor Maini did not think this was a particular problem, he said that if a patient were to need surgery or develop an infection then infliximab treatment should be discontinued.