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Tristan Manalac
21 Jul 2019

Rheumatoid arthritis (RA) patients appear to be at higher risk of developing malignancies, particularly lymphomas and lung and cervical malignancies, according to a recent Singapore study.

Accessing the prospective RA registry of the Tan Tock Seng Hospital in Singapore, researchers identified 1,117 RA patients (mean age at onset, 44.9±13.4 years; 84.1 percent female), of whom 132 developed malignancies after 1,752 person-years of follow-up. The corresponding incidence rates for specific malignancy types were obtained from the Singapore Cancer Registry, for both the study and the general populations. [Int J Rheum Dis 2019;doi:10.1111/1756-185X.13655]

Compared with their cancer-free counterparts, RA patients who developed malignancies were less likely to be female (79.7 percent vs 84.6 percent), more likely to be Chinese (84.1 percent vs 75.5 percent) and received their RA diagnosis at an older age (mean, 51.7±13.9 vs 46.7±13.1 years). Smoking was more common among participants with malignancies (17.4 percent vs 13.1 percent).

After a total of 19,839 person-years of follow-up, 53 deaths were reported in the malignancy group, resulting in a mortality rate of 40.2 percent. In comparison, 74 died in the cancer-free group, yielding a mortality rate of only 7.5 percent.

Relative to the general population, RA patients showed a trend toward a higher risk of malignancy. However, this was only statistically significant in females (standardized incident ratio [SIR], 1.21, 95 percent CI, 1.00–1.46) and not in males (SIR, 1.28, 0.88–1.87).

Of these malignancies, majority (86.4 percent; n=114) were solid-organ tumours while 13.6 percent (n=18) were haematological in nature. Breast (n=21), lung (n=19), colorectal (n=17), cervical (n=14) and skin (n=10) cancers were the most common solid-organ tumours, while non-Hodgkin’s lymphoma (n=12) dominated the haematological malignancies. There was only one case of Hodgkin’s lymphoma.

Stratifying the findings according to sex, researchers found that lymphomas were partly responsible for the elevated cancer risk in RA patients. Both male (SIR, 5.05, 1.90–13.46) and female (SIR, 3.75, 1.95–7.20) patients were significantly more likely to develop the haematological malignancy. Moreover, lung cancer was more likely to occur in male RA patients (SIR, 2.36, 1.23–4.53), while females were at greater risk of cervical cancer (SIR, 3.72, 2.20–6.23).

“The epidemiology of malignancy varies between countries,” said researchers. “This could be due to differences in exposure to risk factors or in study design. Despite this, numerous studies have found that the overall incidence of malignancy in RA patients is higher than in the general population, consistent with our finding.”

“In our cohort, patients who developed malignancies had a longer delay in the diagnosis of RA and longer time to initiation of disease‐modifying antirheumatic drugs,” they pointed out. This delay may have resulted in greater cumulative disease activity, ultimately leading to cancer.

“In this cohort of Singaporean RA patients, we found a trend toward increased overall malignancy rates in women compared with the general Singapore population controlled for age,” researchers concluded. “[T]his paper adds information about RA‐associated malignancy among Singaporean and Asian RA patients, which hitherto has been very sparse.”

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