Risk of incident or recurrent malignancies among patients with rheumatoid arthritis exposed to biologic therapy in the German biologics register RABBIT

Introduction We used the data of the German biologics register RABBIT, a nationwide prospective cohort study, to investigate the risk of new or recurrent malignancy in patients with rheumatoid arthritis (RA) receiving biologics compared to conventional disease modifying anti-rheumatic drugs (DMARDs). Methods The analysis was based on patients with RA enrolled in RABBIT at the start of a biologic or conventional DMARD therapy between 01 May 2001 and 31 December 2006. Incidences of first or recurrent malignancies were analysed separately. A nested case-control design was used to investigate the risk of developing a first malignancy. Matching criteria were: age, gender, follow-up time, disease activity score based on 28 joint counts (DAS28) at study entry, smoking status, and selected chronic co-morbid conditions (obstructive or other lung disease, kidney, liver or gastrointestinal disease, psoriasis). Results A prior malignancy was reported in 122 out of 5,120 patients. Fifty-eight of these patients had received anti-TNFα agents, 9 anakinra, and 55 conventional DMARDs at study entry. In 14 patients (ever exposed to anti-TNFα: eight, to anakinra: one) 15 recurrent cancers were observed. The average time period since the onset of the first malignancy was nine years. Crude recurrence rates per 1,000 patient-years (pyrs) were 45.5 for patients exposed to anti-TNFα agents, 32.3 for anakinra patients and 31.4 for patients exposed to DMARDs only (Incidence rate ratio anti-TNFα vs. DMARD = 1.4, P = 0.6.). In patients without prior cancer, 74 patients (70% female, mean age: 61.3) developed a first malignancy during the observation. This corresponds to an incidence rate (IR) of 6.0/1,000 pyrs. Forty-four of these patients were ever exposed to anti-TNFα treatment (IR = 5.1/1,000 pyrs). In a nested case-control study comparing cancer patients to cancer-free controls, 44 of the cancer patients and 44 of the cancer-free controls were ever exposed to anti-TNFα agents ( P = 1.0). Conclusions No significant differences in the overall incidence of malignancies in patients exposed or unexposed to anti-TNFα or anakinra treatment were found. The same applied to the risk of recurrent malignancies. However, in particular this last finding needs further validation in larger data sets.