Combination therapy reduces symptoms and joint erosion in rheumatoid arthritis
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《英国医生杂志》
The combination of etanercept (a drug that blocks tumour necrosis factor) and methotrexate achieves significantly greater reduction in symptoms and joint erosion than either drug used alone, a trial published in the Lancet last week has found.
The study randomised 686 participants with active, adult onset, rheumatoid arthritis to etanercept (25 mg subcutaneously twice a week) or oral methotrexate (up to 20 mg every week), or a combination of both drugs.
The mean age of the participants was about 53 years, with mean disease duration of 6.3 to 6.8 years (range 6 months to 20 years). All participants had previously had a less than satisfactory response to at least one disease modifying drug other than methotrexate.
Clinical response was assessed by criteria of the American College of Rheumatology (ACR) The primary end point of symptom relief was the numeric index of the ACR response area under the curve over the first 24 weeks. The proportion of participants who attained symptom relief was significantly greater among those treated with etanercept plus methotrexate (18.3% over time (years); 95% confidence interval 17.1 to 19.6) than among those taking etanercept alone (14.7%; 13.5 to 16.0) (P<0.0001) or methotrexate alone (12.2%; 11.0-13.4) (P<0.0001) (Lancet 2004;363:675-81).
Remission (defined by disease activity score) after one year was also significantly greater in patients treated with both drugs combined. More than a third (35%) of participants taking the combination had disease remission, compared with 16% of those taking only etanercept and 13% of patients taking only methotrexate.
Combination treatment was also more effective in slowing joint destruction, assessed by radiography, resulting in a significant improvement in a score for joint erosion. More than three quarters (80%) of participants taking combination treatment had no radiological progression during the first year of treatment, compared with 68% of those taking methotrexate and 57% taking etanercept.
Professor Lars Klareskog, professor of rheumatology, Karolinska Institute, Stockholm, Sweden, and lead author of the study, said: "This is the first demonstration in a randomised, controlled clinical trial that erosions in established rheumatoid arthritis can improve in a group of patients over time. The results suggest that repair of joints destroyed by the disease may be a biological and clinical possibility."
The study, which was sponsored by Wyeth Research, the company that developed etanercept, confirmed that the drug has a different mode of action from methotrexate (which acts as an antimetabolite) in rheumatoid arthritis and that using the two drugs together had a synergistic effect in the disease.
Professor Klareskog added. "Results also confirmed that beneficial effects could be obtained in patients with rather advanced disease梬ith an average duration of seven years. It would be expected that patients with earlier disease might do even better," he said.
He concluded that patients with rheumatoid arthritis should continue to be treated with a drug such as methotrexate as first line therapy and that a combination, such as etanercept plus methotrexate, should be considered in those not responding.(London Susan Mayor)
The study randomised 686 participants with active, adult onset, rheumatoid arthritis to etanercept (25 mg subcutaneously twice a week) or oral methotrexate (up to 20 mg every week), or a combination of both drugs.
The mean age of the participants was about 53 years, with mean disease duration of 6.3 to 6.8 years (range 6 months to 20 years). All participants had previously had a less than satisfactory response to at least one disease modifying drug other than methotrexate.
Clinical response was assessed by criteria of the American College of Rheumatology (ACR) The primary end point of symptom relief was the numeric index of the ACR response area under the curve over the first 24 weeks. The proportion of participants who attained symptom relief was significantly greater among those treated with etanercept plus methotrexate (18.3% over time (years); 95% confidence interval 17.1 to 19.6) than among those taking etanercept alone (14.7%; 13.5 to 16.0) (P<0.0001) or methotrexate alone (12.2%; 11.0-13.4) (P<0.0001) (Lancet 2004;363:675-81).
Remission (defined by disease activity score) after one year was also significantly greater in patients treated with both drugs combined. More than a third (35%) of participants taking the combination had disease remission, compared with 16% of those taking only etanercept and 13% of patients taking only methotrexate.
Combination treatment was also more effective in slowing joint destruction, assessed by radiography, resulting in a significant improvement in a score for joint erosion. More than three quarters (80%) of participants taking combination treatment had no radiological progression during the first year of treatment, compared with 68% of those taking methotrexate and 57% taking etanercept.
Professor Lars Klareskog, professor of rheumatology, Karolinska Institute, Stockholm, Sweden, and lead author of the study, said: "This is the first demonstration in a randomised, controlled clinical trial that erosions in established rheumatoid arthritis can improve in a group of patients over time. The results suggest that repair of joints destroyed by the disease may be a biological and clinical possibility."
The study, which was sponsored by Wyeth Research, the company that developed etanercept, confirmed that the drug has a different mode of action from methotrexate (which acts as an antimetabolite) in rheumatoid arthritis and that using the two drugs together had a synergistic effect in the disease.
Professor Klareskog added. "Results also confirmed that beneficial effects could be obtained in patients with rather advanced disease梬ith an average duration of seven years. It would be expected that patients with earlier disease might do even better," he said.
He concluded that patients with rheumatoid arthritis should continue to be treated with a drug such as methotrexate as first line therapy and that a combination, such as etanercept plus methotrexate, should be considered in those not responding.(London Susan Mayor)