TNF inhibitors, MTX reduce RA cardiovascular deaths
Nov 25, 2005 Janis Kelly
San Diego, CA - TNF inhibitors and methotrexate (MTX) decrease the risk of death, especially cardiovascular (CV) death, in rheumatoid-arthritis (RA) patients, whereas prednisone increases mortality, Kaleb Michaud (Stanford University, CA) reported at the 2005 ACR/ARHP Annual Scientific Meeting [1].
According to Michaud, anti-TNF use was associated with a reduced risk of mortality (hazard ratio [HR] 0.69), as was MTX (HR 0.84). Prednisone use, however, was associated with increased mortality (HR 1.63). "Despite more severe RA at onset, anti-TNF and MTX therapies appear to convey a mortality benefit," said Michaud.
First study to show survival benefit
Michaud and coauthor Dr Frederick Wolfe (National Data Bank for Rheumatic Diseases, Wichita, KS) analyzed data from a long-term outcome study of 19 580 patients with RA. During 63 811 patient-years of follow-up, there were 1129 deaths. The researchers used initial Health Assessment Questionnaire (HAQ) scores to adjust for baseline severity, time-varying HAQ scores to account for changes in severity as the result of therapy, and a baseline comorbidity index of 13 medical conditions to adjust for baseline concomitant diseases.
"In clinical trials, anti-TNF therapy is superior to conventional therapies for the treatment of rheumatoid arthritis. However, there is, as yet, no evidence of long-term benefit for this treatment, and there is concern regarding long-term toxicity. Studies of mortality can provide a 'hard' end point that can provide evidence regarding these issues. Such studies usually require many years of follow-up, unless a very large sample is available. We used such a sample to assess the effect of contemporary treatment on mortality in RA," Michaud said.
The analysis showed that 45% of deaths were due to cardiovascular disorders, 29% to lung disorders, 23% to malignancies, and 8% to infections. Prednisone was associated with increased mortality (HR 1.63). TNF inhibitors were associated with reduced mortality (HR 0.69), as was MTX (HR 0.84).
Given the importance of CV risk in this population, the effect of treatment on risk of CV death was particularly interesting. Michaud reported that MTX, infliximab, and etanercept were all strongly associated with a decreased risk of CV mortality (HR 0.61-0.74), whereas prednisone was associated with an increased risk of CV mortality.
This raises the intriguing question of whether the improvement in CV risk observed in patients taking TNF inhibitors or MTX was due to treatment or reflected a lowering of CV risk attributable to less use of prednisone.
"It is well documented that rheumatoid-arthritis patients have [higher mortality rates than] the general population. Although these patients and their physicians should continue to monitor and make sound and personalized decisions about their prescribed therapies, . . . they should note that the use of methotrexate and anti-TNF therapy improves survival," Michaud concluded.
Source
Michaud K, Wolfe F. Reduced mortality among RA patients treated with anti-TNF therapy and methotrexate. 2005 ACR/ARHP Annual Scientific Meeting; November 12-17; San Diego, CA. Poster 296.
San Diego, CA - TNF inhibitors and methotrexate (MTX) decrease the risk of death, especially cardiovascular (CV) death, in rheumatoid-arthritis (RA) patients, whereas prednisone increases mortality, Kaleb Michaud (Stanford University, CA) reported at the 2005 ACR/ARHP Annual Scientific Meeting [1].
According to Michaud, anti-TNF use was associated with a reduced risk of mortality (hazard ratio [HR] 0.69), as was MTX (HR 0.84). Prednisone use, however, was associated with increased mortality (HR 1.63). "Despite more severe RA at onset, anti-TNF and MTX therapies appear to convey a mortality benefit," said Michaud.
First study to show survival benefit
Michaud and coauthor Dr Frederick Wolfe (National Data Bank for Rheumatic Diseases, Wichita, KS) analyzed data from a long-term outcome study of 19 580 patients with RA. During 63 811 patient-years of follow-up, there were 1129 deaths. The researchers used initial Health Assessment Questionnaire (HAQ) scores to adjust for baseline severity, time-varying HAQ scores to account for changes in severity as the result of therapy, and a baseline comorbidity index of 13 medical conditions to adjust for baseline concomitant diseases.
"In clinical trials, anti-TNF therapy is superior to conventional therapies for the treatment of rheumatoid arthritis. However, there is, as yet, no evidence of long-term benefit for this treatment, and there is concern regarding long-term toxicity. Studies of mortality can provide a 'hard' end point that can provide evidence regarding these issues. Such studies usually require many years of follow-up, unless a very large sample is available. We used such a sample to assess the effect of contemporary treatment on mortality in RA," Michaud said.
The analysis showed that 45% of deaths were due to cardiovascular disorders, 29% to lung disorders, 23% to malignancies, and 8% to infections. Prednisone was associated with increased mortality (HR 1.63). TNF inhibitors were associated with reduced mortality (HR 0.69), as was MTX (HR 0.84).
Given the importance of CV risk in this population, the effect of treatment on risk of CV death was particularly interesting. Michaud reported that MTX, infliximab, and etanercept were all strongly associated with a decreased risk of CV mortality (HR 0.61-0.74), whereas prednisone was associated with an increased risk of CV mortality.
This raises the intriguing question of whether the improvement in CV risk observed in patients taking TNF inhibitors or MTX was due to treatment or reflected a lowering of CV risk attributable to less use of prednisone.
"It is well documented that rheumatoid-arthritis patients have [higher mortality rates than] the general population. Although these patients and their physicians should continue to monitor and make sound and personalized decisions about their prescribed therapies, . . . they should note that the use of methotrexate and anti-TNF therapy improves survival," Michaud concluded.
Source
Michaud K, Wolfe F. Reduced mortality among RA patients treated with anti-TNF therapy and methotrexate. 2005 ACR/ARHP Annual Scientific Meeting; November 12-17; San Diego, CA. Poster 296.
posted by Ricardo Pocurull at 7:03 AM
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