Inflammatory Polyarthritis Linked to Cancer Mortality Risk

MANCHESTER, England, March 2 -- Patients with inflammatory polyarthritis, often a precursor to rheumatoid arthritis, are 40% more likely than the general population to die of cancer, according to a prospective cohort study.

These patients are also 60% more likely to develop hematopoietic cancers, including lymphoma, said Alan Silman, M.D., of the Manchester University Medical School here, and colleagues, in the March issue of Arthritis & Rheumatism. The overall occurrence rate of all types of cancer, however, was not higher in inflammatory polyarthritis patients than in the general population.

Several studies have found a "modest" increase in risk of cancer death among patients with rheumatoid arthritis, while others have demonstrated as much as a 2.5-fold increase in risk, Dr. Silman and colleagues said. However, these studies generally included patients with severe rheumatoid arthritis, who would be expected to fare less well with cancer, they said.

One strategy to overcome this limitation is to follow a cohort of patients with new-onset inflammatory polyarthritis, the authors said. "Over time, an increasing proportion of new inset inflammatory polyarthritis evolves into rheumatoid arthritis," they said. In fact, 60% of the study patients developed rheumatoid arthritis during the first five years of follow up.

The current study is the first to assess the long-term risk of cancer mortality in patients with inflammatory polyarthritis, including those who go on to develop rheumatoid arthritis, the authors said. The cohort of 2,105 patients included those 16 and older newly diagnosed with inflammatory polyarthritis in the region around Norwich, England. They were followed from 1990 through 1999, with an average follow up of 8.4 years.

A total of 123 patients in the inflammatory polyarthritis cohort was diagnosed with cancer during the study period. Comparing cancer incidence and morality rates in the cohort with data from the Eastern Cancer Registration and Information Center, which covers the general population in the Norwich area, revealed no increased incidence of all cancers in the IP cohort (relative risk=0.9; 95% confidence interval=0.7 to 1.1).

However, the researchers found a higher occurrence rate of hematopoietic cancers in the inflammatory polyarthritis cohort (RR=1.6; 95% CI=1.0 to 2.7). This result was expected, given that previous studies have linked rheumatoid arthritis and lymphoma risk, the authors said.

There were also trends toward higher incidences of cancers of the digestive system (RR=1.3; 95% CI=0.8 to 2.1) and secondary tumors (RR=1.4; 95% CI=0.5 to 3.7), but these did not reach statistical significance.

Mortality risk was another story, however. After adjusting for age, sex, and type of cancer, the researchers found that the inflammatory polyarthritis cohort was significantly more likely to die from any type of cancer (RR=1.4; 95% CI=1.1 to 1.7).

The risk of dying from hematopoietic cancers (RR=1.8; 95% CI=0.8 to 3.9) and digestive system cancers (RR=1.9; 95% CI=1.2 to 3.0) "was of an order of magnitude similar to that for the overall risk of cancer," the authors said.

Higher mortality risk was linked with markers of disease severity such as rheumatoid factor positivity (RR= 1.29; 95% CI=0.84 to 1.99) and overall health assessment scores (RR=1.14; 95% CI=0.95 to 1.37), but none of these links reached statistical significance.

Use of disease-modifying, anti-rheumatic drugs (DMARDs), another marker of disease severity, was not linked with mortality risk (RR=0.97; 95% CI=0.55 to 1.71).

In the subgroup of inflammatory polyarthritis patients who developed rheumatoid arthritis, the overall cancer incidence risk (RR=1.1; 95% CI=0.9 to 1.3) and the cancer mortality risk (RR=1.3; 95% CI=1.0 to 1.8) was similar to the cohort as a whole, the authors said.

"It remains unclear why patients with inflammatory polyarthritis experience reduced cancer survival compared with the general population," the authors said. "Possible candidates include a role for general ill health, which might also limit the aggression of cancer therapy adopted, and an increased likelihood of infection, although the latter was not an important factor in the cancer deaths in this cohort."

"Future research into identifying risk factors associated with poorer cancer survival in such patients is needed so as to recognize individuals at the greatest risk," the authors concluded.

An important limitation of the study is that the cohort samples of specific types of cancers were probably "too small for a robust analysis," the authors said. For example, the inflammatory polyarthritis cohort included only 15 patients with hematopoietic cancers and only 15 patients with cancers of the digestive system.