RESEARCH - TNF inhibitors, MTX reduce RA cardiovascular deaths

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TNF inhibitors, MTX reduce RA cardiovascular deaths

Nov 25, 2005

Janis

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, MS

(Stanford University, California) 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

---

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 to 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

1. 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.

Not an MD

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Mayo Clinic in Rochester

http://www.mayoclinic.org/rochester

s Hopkins Medicine

http://www.hopkinsmedicine.org