BARCELONA — Treatment with tumor necrosis factor blocking drugs has been shown for the first time to improve mortality in rheumatoid arthritis, Dr. Lennart Jacobsson said at the annual European Congress of Rheumatology.
It is well recognized that patients with rheumatoid arthritis (RA) have an increased mortality, compared with the healthy general population, particularly from cardiovascular causes, and it has previously been demonstrated that methotrexate treatment confers a survival benefit. This benefit now has been extended to treatment with anti-tumor necrosis factor (TNF) drugs in a cohort of 921 Swedish patients enrolled in the South Swedish Arthritis Treatment Group register, said Dr. Jacobsson of the department of rheumatology, Malmö University Hospital.
They were compared with a group of 1,016 patients with RA in the same area of Sweden who were not treated with anti-TNF drugs, and were found to have an adjusted hazard ratio (HR) of 0.65 for death after controlling for age, sex, disability, and baseline comorbidities.
“In other words, there was a 35% risk reduction with treatment with anti-TNF therapy,” Dr. Jacobsson said.
A total of 188 deaths occurred in the combined groups during 7,077 patient-years. Of these, 63 deaths were in men during 1,817 patient-years, and 125 were in women during 5,260 patient-years.
After controlling for age, disability, and comorbidity, mortality was significantly reduced in women treated with anti-TNF drugs, with an adjusted HR of 0.52, but not in men, whose adjusted HR was 0.95 (Ann. Rheum. Dis. 2007;66:670–5).
When the mortality rates among women who had RA with and without anti-TNF therapy were compared with those of the general Swedish female population, an increased risk of death of 70%–80% was seen in those not treated with the drugs. “But among women with RA treated with anti-TNF therapy, the risk is comparable with that of women of the same age in the general Swedish population,” Dr. Jacobsson said.
The lack of significance in men could reflect insufficient numbers or the men's higher baseline risk for death, he said.
Numerous questions remain unanswered about the benefits of the TNF blocking drugs. “For example, can similar effects be obtained by more extensive use of statins? That is quite possible. Is there a role for TNF inhibitors in non-RA groups to prevent cardiovascular events? Are the effects of TNF blockers additive to those of methotrexate? Preliminary data from our register indicate that this is the case,” he said.
This question of potentially additive cardiovascular benefits of TNF blockers and methotrexate was addressed in a separate presentation at the meeting.
Dr. Gurkirpal Singh of Stanford (Calif.) University performed a nested case-control study using data from Medi-Cal, the Medicare program for California. All patients with RA who received a TNF inhibitor, methotrexate, or other disease-modifying antirheumatic drugs (DMARDs) between January 1999 and June 2005 were included.
Among the 19,233 RA patients who were identified, 13,383 were taking methotrexate, 14,958 were on other DMARDs, and 4,943 were receiving a TNF inhibitor.
During 74,006 patient-years of follow-up, there were 441 cases of acute myocardial infarction (MI). Cases were risk set matched with four controls for age, gender, and date of MI.
Current exposure to TNF inhibitors as monotherapy or in with methotrexate or other DMARDs was compared with methotrexate monotherapy. All analyses were adjusted for multiple potentially confounding risk factors like surrogate variables for smoking and dyslipidemia.
Analysis revealed that combination TNF inhibitor-methotrexate treatment significantly reduced the risk of acute MI, compared with methotrexate monotherapy, with an adjusted relative risk (RR) of 0.20, Dr. Singh reported.
No statistical differences were seen when combination TNF inhibitor-methotrexate therapy was compared with TNF-blocking monotherapy (RR 1.17), when compared with anti-TNF therapy combined with other DMARDs (RR 1.78), or for other DMARD therapies without methotrexate (RR 0.88).
Combined TNF inhibitor- methotrexate therapy is associated with a reduction in the risk of acute MI by 80%, compared with methotrexate monotherapy in patients with RA, Dr. Singh concluded.
“Such dramatic effects enhance the therapeutic gains of TNF-inhibitor therapy in patients with RA and should be seriously considered, particularly in high-risk patients,” he said.
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