The decision to use biologic disease-modifying antirheumatic drugs (bDMARDs) to treat arthritis is made after assessing the unique risk profile of a given patient. The risks that have been associated with bDMARD use, including risk of malignancy, should be weighed against the benefits of treatment.
Clinical data on the risk of lymphomas, leukemias, and solid malignancies associated with the use of tumor necrosis factor inhibitors have been mixed. The US Food and Drug Administration has issued several warnings regarding the risks. Although standardized incidence ratios (SIR) have been used to estimate the risk of malignancy associated with bDMARDs, proving a direct association is difficult because SIRs cannot differentiate between the risk associated with treatment and the risk associated with the diagnosis itself.
To investigate whether female patients receiving bDMARDs for management of inflammatory arthritis are at increased risk of virus-associated cancers, researchers from the Herlev and Gentoffe University Hospital, Herlev, Denmark, analyzed results from DANBIO, a Danish registry that provides nationwide data on the disease course of inflammatory rheumatic diseases. They found no apparent overall excess of virus-associated cancers in the study cohort.
The study, published in Rheumatology, compared virus-associated cancer rates among bDMARD users (n = 5,647) and nonusers (n = 10,331) among women with rheumatoid arthritis (72%), psoriatic arthritis (12%), ankylosing spondylitis (4%), and other arthritides (12%) identified in the DANBIO registry. The researchers found 24 virus-associated cancers in the patients taking bDMARDs compared with 32 in the patients who were bDMARD-naïve. No overall increased risk of virus-associated cancers was seen when bDMARD and DMARD-naive patients were compared (hazard ratio = 0.9, 95% CI: 0.7, 1.2).
When bDMARD patients and bDMARD-naïve patients were compared to women in the general population, no increased risk for cervical cancer was found. However, patients who were bDMARD-naïve were at increased risk for lymphoma (SIR = 2.5, 95% CI: 1.5, 4.0). A trend towards increased incidence of oropharyngeal cancer also was found in patients taking bDMARDS (n = 3, SIR = 4.0, 95% CI: 1.3, 12.4).
Summary and Clinical Applicability
In this study, female patients with inflammatory arthritis who were never treated with bDMARDs were at increased risk for lymphoma. No other differences in incidence rates of virus-associated cancers were found between the bDMARD-treated and the bDMARD-naïve patients.
The statistical power of this study was limited by the relatively smaller number of specifically identified malignancies that occurred in women during the study period. The apparent increased risk of oropharyngeal cancer in bDMARD-treated patients compared with the general population warrants further study.
Cordtz R, Mellemkjær L, Glintborg B, et al. Risk of virus-associated cancer in female arthritis patients treated with biological DMARDs-a cohort study. Rheumatology (Oxford). 2016; Feb 24. pii: kew012. [Epub ahead of print]