Use of TNFalpha (tumour necrosis factor alpha) inhibitors to treat rheumatoid arthritis (RA) is supported by two new trials. One suggests that etanercept is more effective than methotrexate and the other that a combination of infliximab and methotrexate is more effective than methotrexate alone. In the first study, twice-weekly subcutaneous treatment with etanercept (10mg or 25mg) was compared with weekly oral methotrexate (titrated to a mean dose of 19mg) in 632 patients with early RA by Dr Joan Bathon (Johns Hopkins university, Baltimore, United States) and colleagues. They conclude that etanercept has a more rapid treatment effect in rheumatoid arthritis than methotrexate. Patients in both etanercept groups had a rapid improvement in their condition, and differences between etanercept and methotrexate treatment were seen after two weeks, they report. After 12 months, 72 per cent of the 25mg etanercept group had no increase in erosion score compared with 60 per cent of the methotrexate group. The 25mg dose of etanercept was more effective than 10mg. Both treatments were well tolerated with most side effects classed as mild or moderate, the researchers say. Significantly more adverse reactions occurred in the methotrexate group than either etanercept group. The researchers comment: "These results underscore the importance of early intervention in slowing or arresting damage evident on radiography and support the use of the current treatment algorithm for early, aggressive treatment of active disease. Preventing the damage that occurs early in the course of the disease may be the key to better long-term functional outcomes."The study is published in the New England Journal of Medicine (2000;343:1586). In the second study, Dr Peter Lipsky (University of Texas, Dallas, US) and colleagues found that the combination of infliximab and methotrexate provided clinical benefit and halted the progression of joint damage. All 428 patients in the trial received methotrexate and were randomised to receive additionally either placebo or different doses of infliximab. Combination therapy resulted in a sustained reduction in the symptoms and signs of RA that was significantly greater than the reduction associated with methotrexate alone. It provided clinical benefit in patients with active RA despite previous therapy with methotrexate and in patients with extensive joint damage. The researchers comment: "Not only did the combination of infliximab and methotrexate prevent progressive joint damage during the one year of therapy, but in 40 to 55 per cent of the patients, the radiographic evidence of joint damage decreased, implying that some damage had been repaired." Treatment with methotrexate and infliximab was found to be well tolerated and safe. There have been concerns over an increased frequency of infections with TNFalpha inhibitors. This study found a similar frequency of serious infections with combination therapy as with methotrexate alone. However, the authors comment that the frequency of infectious complications will have to be carefully monitored when a large number of patients are treated with combination therapy. Infliximab treatment is also associated with the development of autoantibodies, although the researchers say that this has rarely been associated with symptoms suggestive of an autoimmune disease (ibid, p1594). In a leading article, Dr John Klippel (Arthritis Foundation, US) says that it is too early to know how this new information will change clinical practice. "However, it seems reasonable to argue, on the basis of this evidence, that TNFalpha inhibitors should be used as early as possible in all patients who have documented rheumatoid arthritis."In his opinion, newly reported adverse effects of etanercept (PJ, October 7, p510 and November 18, p748) were unlikely to have a major influence on the use of TNFa inhibitors (ibid, p1640).