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TNF-alpha medication ups risk of tuberculosis

05 Apr 2017

Patients treated with tumour necrosis factor (TNF)-α antagonists may be at a greater risk of tuberculosis (TB), although the biological mechanism underlying this association needs to be elucidated, according to a meta-analysis.

Researchers searched databases including Medline, Embase and Cochrane library for randomised controlled trials (RCTs) reporting TB risk among patients treated with any of the currently available TNF-α antagonists: etanercept (ETN), adalimumab (ADA), infliximab (IFX), golimumab (GOL) and certolizumab pegol (CZP). Exclusion criteria included studies based on unoriginal data, those without data on TB incidence, those that did not observe TB events and articles not published in English.

A total of 29 RCTs involving 11,879 patients were included (n=14 for IFX; n=9 for ADA; n=2 for GOL; n=1 for ETN; n=3 for CZP). A random-effect model was used to calculate odds ratios (ORs) with 95 percent CIs, and subgroup analyses were performed based on type of medication, disease under treatment and TB endemicity. Quality of evidence was evaluated using the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach.

Pooled data revealed that TB developed in 45 of 7,912 patients in the TNF-α arms and in three of 3,967 patients in the control arms, yielding an OR of 1.94 (1.10 to 3.44; p=0.02). Results from the subgroup analyses indicated that the effect of TNF-α treatment on TB risk was greater among patients treated for rheumatoid arthritis (OR, 2.29; 1.09 to 4.78; p=0.03). The quality of evidence was low as per the GRADE system.

The present data highlight the importance of considering the potential increase in the risk of TB in the clinical decision concerning treatment with anti-TNF-α drugs; patients should be screened for LTBI and anti-TB prophylaxis before making any decision.

TNF-α antagonists are widely used in in the treatment of rheumatoid arthritis, inflammatory bowel disease, ankylosing spondylitis and other immune-mediated or inflammation-related diseases. These agents potentially impact on the protective mechanism against infections, especially TB, by increasing the phagocytic capacity of macrophages and enhancing intracellular killing of mycobacterium via the generation of reactive nitrogen and oxygen intermediates. [J Pathol 2008;214:149–60; Ann Rheum Dis 2015;74:1212–17]

“TNF-α is also involved in the pathological changes of latent tuberculous infection, especially in maintaining the formation and function of granuloma which prevents mycobacterium from disseminating into the blood. These TNF-mediated immune mechanisms may explain the reason for the increased risk of TB in patients receiving anti-TNF agents’ treatment,” researchers said.

“Further high-quality research regarding the long-term safety of biologics is needed to improve the safety of biological treatment in clinical use,” they added.

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Most Read Articles
01 Oct 2013

Heart disease is still New Zealand’s biggest killer, with one Kiwi dying from coronary heart disease every 90 minutes. Pharmacy Today New Zealand looks at how pharmacists can help

Dr. James Salisi, 01 Jul 2014

The recent spike in the number of new cases of human immunodeficiency virus (HIV) infection in the Philippines means that clinicians and pharmacists alike may need to increase their awareness and competency in prescribing and monitoring HIV treatment. Although taught in medical and pharmacy schools, the scarcity in exposure to clinical cases before highlights the need to for physicians and pharmacist to review HIV pharmacotherapy in order to cater to the increasing HIV patient population.

01 Sep 2017
Complementary medicines can play an important part in maintaining wellness, preventing deficiencies and optimizing health outcomes, says Dr Lesley Braun PhD, Director of the Blackmores Institute. 
08 Oct 2017
Tumour necrosis factor inhibitors (TNFIs) may inhibit spinal radiographic progression in patients with ankylosing spondylitis (AS) through the inhibiting effect of the drugs on disease activity, a study suggests.