Risk of incident active tuberculosis disease in patients treated with non-steroidal anti-inflammatory drugs: a population-based study

Abstract

Background Mycobacterium tuberculosis (TB) is one of the world’s most devastating public health threats. Our goal is to evaluate whether the use of non-steroidal anti-inflammatory drugs (NSAIDs) affect the risk of new incident active TB disease.MethodsWe conducted a nested case-control analysis by using a 1 million longitudinally followed cohort, from Taiwan’s national health insurance research database. Effects of NSAIDs on active TB were estimated by conditional logistic regression and adjusted using a TB-specific disease risk score (DRS). NSAIDs exposures were defined as having a prescription record of NSAIDs ≧ 7 days that ended between 31 and 90 days prior to the index date.ResultsA total of 123,419 users of traditional NSAIDs, 16,392 users of cyclooxygenase-2 selective inhibitor (Coxibs), and 4706 incident cases of active TB were identified. Compared with nonusers, use of traditional NSAIDs was associated with an increased risk of TB in the unadjusted analysis ([RR], 1.39; 95% [CI], 1.24 – 1.57 and DRS adjusted analysis ([ARR], 1.30; 95% [CI], 1.15– 1.47). However, use of Coxibs was not associated with a significant increase in the risk of TB after DRS adjustment ([ARR], 1.23; 95% [CI], 0.89 – 1.70).ConclusionsIn this large population-based study, we found that subjects using traditional NSAIDs were associated with increased risk for active TB. We did not find evidence for a causative mechanism between traditional NSAIDs and TB, and more research is required to verify whether the association between traditional NSAIDs and TB is causal, or simply reflects an increased use of anti-inflammatory drugs in the early phases of TB onset.Electronic supplementary materialThe online version of this article (doi:10.1186/s12890-017-0425-3) contains supplementary material, which is available to authorized users.

Metformin use is associated with a low risk of tuberculosis among newly diagnosed diabetes mellitus patients with normal renal function: A nationwide cohort study with validated diagnostic criteria

“…Those patients may have a poor-controlled blood sugar, which could increase the risk of active TB diseases [ 36 ] and counteract the protective effects of metformin use. In our study, NSAIDs increased the risk of TB, which is a similar finding in a previous study [ 37 ]. Whether the association between traditional NSAIDs and TB is causal, or simply reflects an increased use of anti-inflammatory drugs in the early phases of TB onset remains to debate [ 37 ].…”

“…In our study, NSAIDs increased the risk of TB, which is a similar finding in a previous study [ 37 ]. Whether the association between traditional NSAIDs and TB is causal, or simply reflects an increased use of anti-inflammatory drugs in the early phases of TB onset remains to debate [ 37 ]. A systemic review, however, indicated an opposite result, showing a beneficial effect of NSAIDs as an adjunct to current TB therapy regimens [ 38 ].…”

Cyclooxygenase inhibitors impair CD4 T cell immunity and exacerbate Mycobacterium tuberculosis infection in aerosol-challenged mice

“…Two old case reports and a small retrospective case-control study express a concern for risk of progression to TB in patients using NSAIDs although these provide weak, if any evidence for this concern 41–43 . However, a recent population-wide retrospective case-control study from Taiwan suggested an association between NSAID prescriptions and increased risk of TB, but was unable to demonstrate an association for COXi specifically in the adjusted analysis 44 . This study was corroborated by another Taiwanese study focusing on patients with psoriasis 45 , but a similar association was not found in a Canadian study of patients with rheumatoid arthritis 46 .…”

Therapeutic host-directed strategies to improve outcome in tuberculosis

“…Compared with nonusers, use of traditional NSAID was associated with an increased risk of TB in an unadjusted analysis of a population-based study. 17 Results from carefully controlled trials should provide more conclusive findings on the effect of these inexpensive and widely available compounds on TB treatment outcomes.…”