Biologics Associated With Lower Overall Risk of Malignancy in Patients With Early RA

Patients with rheumatoid arthritis (RA) are at elevated risk for developing malignancies, including lymphoma, leukemia, and lung cancer, because of immune dysregulation and chronic inflammation. Furthermore, using synthetic disease-modifying anti-rheumatic drugs (DMARDs), such as methotrexate, is believed to increase the risk of hematologic malignancies.

Biologic DMARDs, especially anti—tumor necrosis factor (anti-TNF) biologics, have also raised concerns about malignancy, particularly because of TNF’s role in tumor progression and surveillance. In a new study, published in Arthritis Research & Therapy, a research team led by Soo-Kyung Cho, MD, sought to investigate the incidence of malignancy in early RA and found that the use of biologic DMARDs decreased the overall risk of developing malignancies, though it did not affect the risk of developing hematologic malignancies.

The study comprised a retrospective cohort of patients with incident RA who had no history of malignancy (n = 12,397) identified using the Korean National Claims Database. The investigators calculated the incidence rate (IR) of overall and individual malignancies, and the standardized incidence ratio of malignancies in biologic DMARD users was compared with that of nonusers (all biologic users were assumed to have been exposed to anti-TNFs, as only anti-TNFs were approved for first-line biologic treatment in patients with RA in the Republic of Korea through December 2013). Multivariable logistic regression analysis was used to evaluate the impact of biologic DMARDS on development of malignancies in patients with early RA.

In total, 725 malignancies were identified in 561 patients during the observation period; 140 patients had more than 1 malignancy. The IR of overall malignancies was 174.3 per 10,000 patient years (95% CI, 161.6-187.0). In patients receiving biologic DMARDs, the IR of overall malignancy was 81.5 per 10,000 patient years (95% CI, 45.8-117.2), versus 180.1 per 10,000 patient years (95% CI, 166.8-193.4) in patients who did not use biologic DMARDs.

In multivariable analysis, biologic DMARD use was associated with a low risk of malignancy (OR 0.42; 95% CI, 0.25-0.73), though use of biologic DMARDs was not found to be protective in the development of hematologic malignancies (OR 1.69; 95% CI, 0.38-7.59).

The researchers noted that, because the study was limited to patients with 3 to 4 years of follow-up, long-term effects of biologic DMARDs on hematologic malignancies cannot be confirmed with these study data. Furthermore, the study did not include subgroup analysis according to the type of biologic that was used in treating RA.

However, the authors conclude that the use of biologic DMARDs in patients with early RA is associated with a reduced risk of malignancy development, with the exception of hematologic malignancies.