According to the results of a study published in Arthritis and Rheumatism, the use of anti-tumour necrosis factor (anti-TNF) therapy with methotrexate in treating rheumatoid arthritis (RA) is not associated with an increased risk of developing lymphoma.
The authors present an update of a previous report in 2004 (29,314 person-years of follow-up), in which they concluded that lymphomas were increased in RA (standardised incidence ratio [SIR] 1.9, 95% confidence interval [95% CI] 1.3–2.7), and that the SIR was greatest for anti-TNF therapies. In the current report, they extend these data to 89,710 person-years and use conditional logistic regression to analyse the association between lymphoma risk and treatment with anti-TNF agents and methotrexate (MTX).
Patients included in the study were participants in the National Data Bank for Rheumatic Diseases (NDB) longitudinal study of long-term outcomes of RA, who completed semi-annual questionnaires from 1998 to 2005. A total of 19,591 participants met the inclusion criteria, and their data were used to calculate the lymphoma incidence rate and SIR. The US Surveillance, Epidemiology, and End-Results (SEER) database was used as a comparison population to determine expected rates of lymphoma.
The main findings were:
• The lymphoma incidence rate was 105.9 (95% CI 86.6–129.5) per 100,000 person-years of exposure. Compared with the SEER lymphoma database, the SIR was 1.8 (95% CI 1.5–2.2) based on 52.2 cases and 95 actual cases.
• After a median follow-up of 3.4 years, the use of anti-TNF agents overall was not associated with an increased lymphoma risk (odds ratio [OR] 1.0, 95% CI 0.6–1.8; p=NS).
• The use of anti-TNF therapy and MTX did not increase the risk of lymphoma above that associated with MTX alone (OR 1.1, 95% CI 0.6–2.0; p=NS).
• MTX was not associated with an increased risk of lymphoma compared to other DMARDs (OR 1.3; 95% CI 0.6–2.7, p=NS).
• When specific anti-TNF agents were analysed separately, neither etanercept (OR 0.7, 95% CI 0.3–1.6; p=NS) nor infliximab (OR 1.2, 95% CI 0.6-2.2; p=NS) were associated with an increased lymphoma risk. Although a statistically significant association was found between adalimumab treatment and lymphoma, this association was based on a limited number of cases (56 patients and two lymphomas).
The authors conclude: “The results of this study provide strong evidence that lymphoma is not increased among RA patients treated with anti-TNF agents in routine clinical practice.” They note that “these results are substantially different from results of clinical trials. It has been suggested that one explanation for this discrepancy is that the effect seen in clinical trials might represent an unmasking of cases that will be identified later in observational studies”.
Arthritis Rheum 2007;56:1433-9.