A meta-analysis of biologic therapies on risk of new or recurrent cancer in patients with rheumatoid arthritis and a prior malignancy

OBJECTIVES: To explore the risk of new and recurrent cancer in adult RA patients with prior malignancy and subsequently exposed to biologic therapies. METHODS: Separate searches were performed of PubMed, EMBASE and Cochrane Library and conference proceedings for observational studies reporting cancer incidence or recurrence in patients with RA and prior malignancy treated with biologics and conventional synthetic DMARDs (csDMARDs). Mantel-Haenszel fixed-effects method was conducted to calculate relative risk and 95% CI. RESULTS: A total of 12 studies involving 13 598 patients and 32 473 patient-years of follow-up were included (10, 3 and 1 studies for TNF inhibitors [TNFi], rituximab and anakinra, respectively). The crude incidence of new and recurrent cancer per 1000 patient-years were 34.4 for TNFi, 32.3 for rituximab, 32.3 for anakinra and 31.8 for csDMARDs. In the quantitative meta-analysis, biologics were not associated with an increased risk of new or recurrent cancer compared with csDMARDs in patients with RA and prior cancer (TNFi: relative risk = 0.95, 95% CI = 0.83, 1.09; rituximab: relative risk = 0.89, 95% CI = 0.52, 1.53). Secondary analyses of stratification of cancer types, the interval between initiation of TNFi and prior cancer diagnosis, and duration of TNFi exposure, found similar results. CONCLUSION: Compared with csDMARDs, there is no increased risk of developing cancer overall or some specific subtypes in RA patients with a prior cancer receiving biologics. More investigations are warranted to explore the risk of cancer development in individual cancer as well as to determine optimal time to initiate biologic therapy after the diagnosis of cancer or completion of cancer treatment.