Incidence of malignancy in adult patients with rheumatoid arthritis: a meta-analysis

Abstract

Introduction: Patients with rheumatoid arthritis (RA) are at an increased risk of malignancies compared with the general population. This has raised concerns regarding these patients, particularly with the widespread use of immunomodulating therapies, including biologic disease-modifying antirheumatic drugs (DMARDs). We performed a systematic literature review and analysis to quantify the incidence of malignancies in patients with RA and the general population to update previously published data.

Methods: A literature search was conducted that was consistent with and similar to that in a meta-analysis published in 2008. MEDLINE, BIOSIS Previews, Embase, Derwent Drug File and SciSearch databases were searched using specified search terms. Predefined inclusion criteria identified the relevant observational studies published between 2008 and 2014 that provided estimates of relative risk of malignancy in patients with RA compared with the general population. Risk data on overall malignancy and site-specific malignancies (lymphoma, melanoma and lung, colorectal, breast, cervical and prostate cancer) were extracted. The standardized incidence ratios (SIRs; a measure of risk) relative to the general population were evaluated and compared with published rates.

Results: A total of nine publications met the inclusion criteria. Seven of these reported SIRs for overall malignancy; eight for lymphoma, melanoma, and lung, colorectal and breast cancer; seven for prostate cancer; and four for cervical cancer. Compared with those in the general population, the SIR estimates for patients with RA suggest a modest increased risk in overall malignancy, as previously observed. Patients with RA continued to show an increased risk of lymphoma and lung cancer compared with the general population. Overall, SIR estimates for colorectal and breast cancers continued to show a decrease in risk, whereas cervical cancer, prostate cancer and melanoma appeared to show no consistent trend in risk among patients with RA compared with the general population.

Conclusions: The additional data evaluated here are consistent with previously reported data. Patients with RA are at an increased risk of lung and lymphoma malignancies compared with the general population. Quantifying differences in malignancy rates between non-biologic and biologic DMARD-treated patients with RA may further highlight which malignancies may be related to treatment rather than to the underlying disease.

Fig. 1

Literature search data

Fig. 2

Relative risk of overall malignancy in patients with rheumatoid arthritis (RA) compared with the general population. CI, confidence interval; DMARD, disease-modifying antirheumatic drug; n, number of malignancies; N, population size; RR, relative risk; SIR, standardized incidence ratio; TNF, tumor necrosis factor. *SIRs by sex are not included in the total pooled SIR. ^†Excluding non-melanoma skin cancer. ^‡All solid tumors. ^§Excluding lymphatic and hematopoietic

Fig. 3

Relative risk of malignant lymphoma in patients with rheumatoid arthritis (RA) compared with the general population. CI, confidence interval; n, number of malignancies; N, population size; OR, odds ratio; SIR, standardized incidence ratio; TNF, tumor necrosis factor. *SIRs by sex are not included in the total pooled SIR. ^†Reported as odds ratio

Fig. 4

Relative risk of Hodgkin disease in patients with rheumatoid arthritis (RA) compared with the general population. CI, confidence interval; n, number of malignancies; N, population size; MTX, methotrexate; SIR, standardized incidence ratio. *SIRs by sex for Parikh-Patel et al. [16] are included in the total pooled SIR, as overall SIR was not available in their study

Fig. 5

Relative risk of non-Hodgkin lymphoma in patients with rheumatoid arthritis (RA) compared with the general population. CI, confidence interval; DMARD, disease-modifying antirheumatic drug; n, number of malignancies; N, population size; SIR, standardized incidence ratio. *SIRs by sex included in total pooled SIR only if overall SIR was not available

Fig. 6

Relative risk of lung cancer in patients with rheumatoid arthritis (RA) compared with the general population. CI, confidence interval; DMARD, disease-modifying antirheumatic drug; MTX, methotrexate; n, number of malignancies; N, population size; SIR, standardized incidence ratio; TNF, tumor necrosis factor. *SIRs by sex are included in total pooled SIR only if overall SIR was not available. ^†Reported as odds ratio

Fig. 7

Relative risk of colorectal cancer in patients with rheumatoid arthritis (RA) compared with the general population. CI, confidence interval; DMARD, disease-modifying antirheumatic drug; n, number of malignancies; N, population size; SIR, standardized incidence ratio; TNF, tumor necrosis factor. *SIRs by sex are included in total pooled SIR only if overall SIR was not available. ^†Reported as odds ratio

Fig. 8

Relative risk of breast cancer in patients with rheumatoid arthritis (RA) compared with the general population. CI, confidence interval; DMARD, disease-modifying antirheumatic drug; n, number of malignancies; N, population size; SIR, standardized incidence ratio; TNF, tumor necrosis factor. *Reported as odds ratio

Fig. 9

Relative risk of melanoma in patients with rheumatoid arthritis (RA) compared with the general population. CI, confidence interval; DMARD, disease-modifying antirheumatic drug; n, number of malignancies; N, population size; SIR, standardized incidence ratio; TNF, tumor necrosis factor. *SIRs by sex are included in total pooled SIR only if overall SIR was not available. ^†Reported as odds ratio

Fig. 10

Relative risk of cervical cancer in patients with rheumatoid arthritis (RA) compared with the general population. CI, confidence interval; DMARD, disease-modifying antirheumatic drug; n, number of malignancies; N, population size; SIR, standardized incidence ratio; TNF, tumor necrosis factor

Fig. 11

Relative risk of prostate cancer in patients with rheumatoid arthritis (RA) compared with the general population. CI, confidence interval; n, number of malignancies; N, population size; SIR, standardized incidence ratio. *Reported as odds ratio