Use of non‐steroidal anti‐inflammatory drugs and risk of non‐Hodgkin lymphoma: a systematic review and meta‐analysis

Abstract

Epidemiological study findings regarding the association between use of non-steroidal anti-inflammatory drugs (NSAIDs) and risk of non-Hodgkin lymphoma (NHL) have been inconsistent. We aimed to systematically review epidemiological studies of the association and calculate pooled relative risks using meta-analytic methods. We searched eight electronic literature databases and three clinical trial registers to identify all studies (including observational studies and randomized clinical trials) of the association published prior to October 2013. Identified studies were independently reviewed by two researchers. We used a random effects model to calculate pooled odds ratio (PORs). Heterogeneity amongst studies was examined using Cochran's Q and I-squared (I(2)) tests; and sources of heterogeneity were explored using subgroup and meta-regression analyses. A total of 17 studies (12 case-control studies and five cohort studies), all adult studies, were included. Use of NSAIDs was not associated with overall risk of NHL [POR = 1.05, and 95% confidence interval (95% CI) 0.90-1.22] or NHL subtypes including B-cell lymphoma, T-cell lymphoma, follicular lymphoma, diffuse large B-cell lymphoma and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). Aspirin use was associated with reduced risk of CLL/SLL (POR = 0.70, 95% CI 0.54-0.91) but not with the risk of all NHLs (POR = 1.02, 95% CI 0.89-1.17). Use of non-aspirin NSAIDs was associated with increased risk of NHL (POR = 1.41, 95% CI 1.01-1.97) amongst females only. The epidemiologic evidence remains inconclusive. Effects of NSAIDs may differ by drug type, NHL subtype, and sex and more studies taking into consideration these differences are needed.

Impact of potential inappropriate NSAIDs use in chronic pain

“…Use of non-aspirin NSAIDs is associated with increased risk of non-Hodgkin lymphoma, 16 and about one-third of people with chronic urticaria have severe reactions to NSAIDs, involving angioedema and anaphylaxis after their administration. 17 NSAIDs use may mask initial pneumococcal pneumonia symptoms and delay antimicrobial therapy, thus predisposing patients to worse outcomes.…”

Aspirin and other nonsteroidal anti‐inflammatory drugs, statins and risk of non‐Hodgkin lymphoma

“…[CI] 0.89-1.17) nor nonaspirin NSAIDs (OR = 1.26, 95% CI 0.86-1.85) were associated with NHL risk, although aspirin use was protective for CLL/SLL (OR = 0.70, 95% CI 0.54-0.91) and nonaspirin NSAIDs use was associated with NHL risk in women (OR = 1.41, 95% CI 1.01-1.97). 5 In a meta-analysis of 10 studies (5 case-control, 4 cohort and 1 randomized trial), statin use was inversely associated with overall NHL risk (OR = 0.82, 95% CI 0.69-0.99); an inverse association was also observed for chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma and T-cell lymphoma, but was only statistically significant for marginal zone lymphoma (MZL; OR = 0.54, 95% CI 0.31-0.94). 6 Of particular note, however, excluding statin use within one year of diagnosis attenuated the association with NHL risk (OR = 0.92, 95% CI 0.80-1.06).…”