SAN FRANCISCO — An unexpected, significant uptick in rheumatoid arthritis incidence among women may point to increased exposure to hormonal and environmental risk factors, although investigators remain unsure of a clear explanation.
“What we had seen over the last 50 years was a continuous decline [in RA incidence] from the 1950s to the [mid] 1990s,” Dr. Hilal Maradit Kremers said during a press briefing at the annual meeting of the American College of Rheumatology. “We were expecting that decline to continue.”
Surprisingly, the trend instead reversed quite dramatically between 1995 and 2004, according to what began as a rather routine update of incidence trends in Olmsted County, Minn., by Dr. Maradit Kremers and her associates at the Mayo Clinic, Rochester, Minn.
The age-adjusted incidence in women was 54 per 100,000 in the post-1995 analysis, compared with 36.4 per 100,000 between 1985 and 2004.
The average age of onset for women was 56.5 years, roughly the same as in previous years.
Among men, the incidence of RA remained steady between 1995 and 2004, at 28.6 per 100,000, compared with previous decades.
Although the Midwestern population included in long-term Mayo Clinic epidemiologic studies underrepresents nonwhite populations, it has the advantage of stability, allowing disease trends to be detected quite accurately. So Dr. Maradit Kremers could say with considerable confidence that “the incidence of this disease is rising again.”
What remains a mystery is why the incidence rate would change, and so rapidly. “This was purely an observational study,” she said. “At this point we can only speculate that some [unknown] risk factors may be operating to increase the occurrence of this disease.”
Smoking, the most well-established risk factor for the development of RA, actually declined among women in the United States between 1990 and 2003, from 23% of women to 19%, according to statistics from the Centers for Disease Control and Prevention.
Obesity, which did escalate during the years of the study, is not generally associated with development of RA, said Dr. Maradit Kremers, a clinical epidemiologist.
Genetics, hormones, diet, and viral exposure have all been proposed as potential risk factors for RA (Scand. J. Rheumatol. 2006;35:169–74).
Since cases in women appear to be driving the recent surge in incidence, hormonal and reproductive factors will undoubtedly be the focus of new scrutiny, she said.
Some 20 studies have explored such risk factors over the years, generally pointing to pregnancy and oral contraceptive use as protective.
The respective roles of childbearing age, total number of children, breast-feeding, and use of hormone therapy are as yet unclear, she said.
Dr. Maradit Kremers said the study has “important implications” for policy makers, especially with regard to resource allocation for a disease suddenly on the rise after years of decline.
“This worrisome increase in occurrence of RA not only offers us clues into the causes of RA, but also highlights the need for more research into the causes and treatment of this devastating disease,” Dr. Sherine Gabriel, a Mayo Clinic rheumatologist and lead author of the study, said in a statement.
Dr. Maradit Kremers disclosed that she has received research grants and/or consultant fees from Pfizer Inc. and Amgen Inc., makers of drugs prescribed for rheumatoid arthritis. Neither Dr. Gabriel nor any of the other coinvestigators reported any financial disclosures.