Do biologic disease modifying antirheumatic drugs (bDMARDs) used to treat rheumatic diseases cause malignancy?
There is conflicting data on the risk of bDMARD treatment causing malignancies in patients with rheumatic disease or reactivating malignancies in these patients with a prior history of cancer. The challenges for establishing or refuting an increased risk stem from: 1) the possible increased predisposition to cancer based on the patient’s underlying rheumatic disease; 2) concomitant or prior use of other immunosuppressive medications that can increase malignancy risk (e.g., cyclophosphamide); 3) the exclusion of patients with prior cancer history from controlled clinical trials; and 4) relative lack of long-term bDMARD exposure data. Several anecdotal case reports, flawed case series, and Food and Drug Administration-issued warnings make it difficult to assure the patient that there is no increased risk. However, recent large observational studies and reports from large registry databases primarily examining anti-tumor necrosis factor (TNF) agents indicate that malignancies are not significantly increased. To summarize the findings:
- • Lymphoma and leukemia: bDMARDs do not appear to increase the risk above that conferred by the underlying disease. Patients with exposure to cyclophosphamide or azathioprine may be at increased risk if they receive anti-TNF agents. High-dose infliximab (10 mg/kg per month) may have an increased risk regardless of previous therapies. All patients should be examined for lymph node enlargement and splenomegaly periodically.
- • Patients with a prior history of lymphoma who require a bDMARD should probably not be given an anti-TNF agent unless another alternative cannot be used.
- • Solid organ malignancies: bDMARDs do not appear to increase the risk above that conferred by the underlying disease or past nonbiologic therapies. Patients who develop a malignancy while receiving a bDMARD do not appear to have a worse histology, more extensive disease, or worse prognosis than patients who did not receive a bDMARD. All patients should have routine age-appropriate preventative cancer screening.
- • Patients with a prior history of solid organ malignancy are not more likely to get a recurrence of that cancer if treated with a bDMARD. The data for this is strongest in patients who are cancer-free for at least 5 years before starting a bDMARD.
- • Skin cancers (nonmelanoma and melanoma) appear to be increased in patients on bDMARDs, particularly anti-TNF agents. Patients should have routine skin exams while on bDMARDs. Patients with a history of melanoma should probably not receive an anti-TNF agent if another bDMARD can be used.
- • Due to the lack of definitive data, all patients who are starting on a bDMARD need to be counseled on the possible risks compared with benefits. In patients with a prior history of malignancy, the patient’s oncologist should also approve of the use of the bDMARD.
