FDA Issues Advisory for Increased Risk of Lymphoma in Patients Treated With Golimumab

The FDA has issued new warnings on the increased incidence of lymphoma among patients receiving golimumab in clinical trials.

The US Food and Drug Administration (FDA) issued new warnings for golimumab, including an advisory of the increased incidence of lymphoma among patients receiving the drug during clinical trials.1 Golimumab is a human IgG1 kappa monoclonal antibody specific for human tumor necrosis factor (TNF)-alpha that neutralizes TNF-alpha activity. Golimumab binds to both the soluble and transmembrane bioactive forms of human TNF-alpha. It is administered once monthly by subcutaneous injection. Golimumab has been approved for use in patients with rheumatoid arthritis (RA), psoriatic arthritis, and ankylosing spondylitis.

Currently 5 TNF inhibitors are approved by the FDA for the treatment of selected rheumatic diseases. A systematic review of synthetic and biologic disease-modifying antirheumatic drug (DMARD) therapy for RA concluded that anti-TNF monotherapy was similar in efficacy to treatment with methotrexate alone, while the combination of an anti-TNF agent with methotrexate reduced disease activity more and slowed radiographic progression to a greater extent than did anti-TNF monotherapy or methotrexate alone.2,3

The analysis of lymphoma risk in association with anti-TNF agents is confounded by the strong association between high cumulative disease activity and development of lymphoma. Additionally, as TNF-inhibitor therapies are often reserved for those with the most severe disease, it is likely that those patients with inherently higher risk of lymphoma due to their underlying disease states will be treated with TNF inhibitors.  The true magnitude of risk between TNF inhibitor use and development of malignancy is also further confounded by the concomitant use of other medications that independently increase malignancy risk (eg, cyclophosphamide) and a lack of data from randomized trials to address the risk of new or recurring malignancies in patients with a prior history of cancer.

 The new label states the incidence of lymphoma among patients receiving golimumab in clinical trials was 0.21 per 100 patient-years as compared with 0 per 100 patient-years in groups of patients who received placebo. The advisory also states that there is a 3.8-fold higher rate of lymphoma in the 2347 patients who were treated with golimumab and followed for a median of 1.4 years compared to the risk in the general population.

This labeling is generally consistent with a longitudinal study in outcomes in RA from the National Data Bank for Rheumatic Diseases in which patients completed questionnaires every 6 months.2 The study included 19,591 participants and a total of 89,710 patient-years of follow-up, which found that the incidence rate of lymphoma for the overall cohort was 106 per 100,000 person-years of exposure (95% confidence interval [CI], 87-130). The odds ratio for lymphoma among RA patients who received a TNF inhibitor compared with RA patients who did not receive anti-TNF therapy was 1.0 (95% CI, 0.6-1.8). The odds ratio for lymphoma in patients who received a TNF inhibitor plus methotrexate compared with patients who received methotrexate alone was 1.1 (95% CI, 0.6-2). 

The warning does also concede that patients with RA and other inflammatory diseases may likely have a higher risk for lymphoma in the absence of TNF inhibitors. In addition, most patients who developed lymphoma also received azathioprine or 9-mercaptopurine; therefore, a  synergistic effect may be driving the increased malignancy risk.

Ultimately, the decision to use a TNF inhibitor must be based upon the specific clinical features and unique risk profile of a given patient. The risks associated with TNF inhibitor use must be interpreted in the context of the potential benefits associated with these medications, as well as the adverse effects associated with conventional treatments for immune-mediated diseases.


1. US Food and Drug Administration. FDA-approved drug products: Simponi Aria. Available at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/125433s015lbl.pdf. Accessed January 19, 2016.

2. Wolfe F, Michaud K. The effect of methotrexate and anti-tumor necrosis factor therapy on the risk of lymphoma in rheumatoid arthritis in 19,562 patients during 89,710 person-years of observation. Arthritis Rheum. 2007;56:1433-1439. 

3. Bongartz T, Sutton AJ, Sweeting MJ, Buchan I, Matteson EL, Montori V. Anti-TNF antibody therapy in rheumatoid arthritis and the risk of serious infections and malignancies: systematic review and meta-analysis of rare harmful effects in randomized controlled trials. JAMA. 2006;295:2275-2285.