AMSTERDAM — Rheumatoid arthritis patients on tumor necrosis factor inhibitors appear to have a twofold reduction in stroke incidence, compared with similarly ill patients being treated with methotrexate or other traditional disease-modifying antirheumatic drugs, Dr. Will G. Dixon reported at the annual European Congress of Rheumatology.
There is evidence to suggest that rheumatoid arthritis (RA) patients on tumor necrosis factor (TNF) inhibitors may also have a reduced MI rate. This benefit appears to be confined to patients whose joint disease responds well to the medication, said Dr. Dixon of the University of Manchester (England).
He presented the first report from the British Society of Rheumatology Biologics Register, an ongoing observational database that in 2001 began prospectively enrolling all RA patients in the United Kingdom who were prescribed etanercept, infliximab, or adalimumab.
RA patients are known to have an overall mortality twice that of the general population, with most of the excess attributed to a steep increase in cardiovascular deaths, explained Dr. Dixon at the meeting, which was sponsored by the European League Against Rheumatism. Inflammation is known to play a central role both in RA and in atherosclerotic cardiovascular disease.
The study hypothesis was that inhibition of joint inflammation using powerful anti-TNF agents might produce a parallel reduction in the inflammation that triggers atherosclerotic plaque rupture and acute coronary and cerebrovascular events, he continued.
This first analysis of the British national registry data included 10,989 patients on a TNF antagonist for at least 6 months and a comparison arm that consisted of 2,097 RA patients treated with traditional disease-modifying antirheumatic drugs (DMARDs).
There were 42 strokes in the TNF blocker group and 12 in the DMARD group, translating into a crude incidence of 3.9 strokes per 1,000 person-years in RA patients on TNF inhibitors, compared with 5.7 strokes per 1,000 person-years in the DMARD group. After statistical adjustment for baseline differences between the two populations in terms of age, gender, RA severity, comorbidities, smoking status, and body mass index, being on a TNF inhibitor was independently associated with a 49% stroke risk reduction.
The MI analysis was done earlier, at a point when the TNF inhibitor group was smaller by roughly 2,000 patients. No difference in the MI rate between the two groups was found.
However, by restricting the analysis to patients whose RA responded well to anti-TNF therapy, a favorable trend was found. And upon further restricting the analysis to the first 6 months of follow-up—a prespecified secondary study end point on the grounds that marked inhibition of atherosclerotic inflammation might be expected to rapidly quell coronary plaque rupture—being on a TNF inhibitor was associated with a 72% reduction in MI. This difference didn't achieve statistical significance, however, because of small numbers, said Dr. Dixon.
“The clinical implication of these findings is that if we're able with the anti-TNF drugs to reduce rates of heart attacks and strokes in our patients, which are their leading cause of death, then it may be that in addition to improving their joint symptoms we may be reducing their mortality,” he concluded.
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