Factors Affecting the Tuberculosis Risk in Patients Receiving Anti-Tumor Necrosis Factor-α Treatment

Abstract

Background: Tumor necrosis factor (TNF)-α inhibitors are known to increase the risk of tuberculosis (TB). Objectives: To examine the factors associated with an increased risk of TB in patients receiving anti-TNF-α treatment (aTNF-α-T). Method: Of 3,094 patients who received aTNF-α-T between 2003 and 2013, a total of 1,964 subjects with a follow-up time longer than 6 months were identified and included in this retrospective analysis. Potential risk factors for the development of TB in patients receiving aTNF-α-T were evaluated. Results: Of the 1,964 patients, 1,009 (51%) were male and 955 (49%) were female, with a mean age of 39.7 ± 13.9 years. The primary conditions requiring aTNF-α-T included ankylosing spondylitis (n = 875), rheumatoid arthritis (n = 711), Behçet's disease (n = 83), and others (n = 295). Sixteen patients [8 (50%) males and 8 (50%) females; 5 (31.2%) with pulmonary TB and 11 (68.8%) with extrapulmonary TB] developed TB, with a corresponding TB incidence of 466/100,000. No significant associations were found between age, gender, smoking history, pack-years of smoking, isoniazid (INH) chemoprophylaxis, type of anti-TNF-α agent, use of other immunosuppressive drugs, and the risk of TB (p > 0.05). Multivariate logistic regression analysis showed a significantly higher risk of TB in patients diagnosed with Behçet's disease, and a significantly lower risk of TB in patients with a tuberculin skin test wheal ≥10 mm in diameter (p < 0.05). Conclusion: aTNF-α-T is associated with an increased risk of pulmonary or extrapulmonary TB, even when follow-up protocols and INH chemoprophylaxis are implemented, and TB often develops in the later stages of treatment. The risk of TB was higher in patients with Behçet's disease and lower in patients who had a strong tuberculin skin test reaction.

Relative risk of tuberculosis in patients with rheumatic diseases managed with anti-tumour necrosis factor-alpha therapy: A nationwide cohort study

“…In our study, men were more likely to develop TB in anti‐TNF‐α‐naïve group whereas a non‐significant tendency of having TB was observed in male anti‐TNF‐α users, implying no confounding effect of being male on anti‐TNF‐α therapy‐related TB risk. In fact, previous studies from Turkey reported no effect of gender in RD patients under anti‐TNF‐α therapy . On the other hand, analysis of the RR in gender subgroups showed significantly elevated risk only in men.…”

“…In addition, we were not able to collect data regarding isoniazid use as the drug is distributed from tuberculosis control dispensaries which do not submit their electronic prescriptions to PIS. Although this might have influenced the observed risk of TB, a recent study in Turkey reported no association between isoniazid chemoprophylaxis and TB . We also did not assess continuity of anti‐TNF‐α therapy or its doses, or concomitant corticosteroid dosages among anti‐TNF‐α users, which could differentially create a background risk for TB.…”

“…In fact, with a background of serious TB epidemic experience during the first half of the 20th century, the country showed around 2‐fold diminishing TB incidence trend over last 25 years with a resultant incidence rate of 18/100 000 in an about 79 millions of population in 2016, but still considered among high‐priority countries by WHO . However, several studies reported substantial elevation of TB incidence associated with anti‐TNF‐α agents despite the presence of a risk management strategy . This requires evaluation of the TB risk at the national level that would not only reflect the relative risk (RR) but also help to address potential areas of development or contributions to existing risk management strategy.…”

“…18,19 However, several studies reported substantial elevation of TB incidence associated with anti-TNF-α agents despite the presence of a risk management strategy. [20][21][22][23][24] This requires evaluation of the TB risk at the national level that would not only reflect the relative risk (RR) but also help to address potential areas of development or contributions to existing risk management strategy.…”

Risk Factors for Tuberculosis in Patients Receiving Tumour Necrosis Factor-α Blockers: What Do We Really Know?

“…In this issue of Respiration , Borekci et al [6 ]report their retrospective analysis of patients who were treated with a TNF-α blocker and followed up for at least 6 months during 2003-2013 at a single centre in Turkey. The most common underlying autoimmune inflammatory conditions were ankylosing spondylitis, rheumatoid arthritis and Behçet's disease.…”