Issue 17

Clinical Question

What is the risk of infection with anti-tumour necrosis factor (anti-TNF) or thiopurine monotherapy or combination therapy?

Editor’s Bottom Line

Although residual confounding by indication cannot be excluded, both thiopurines and anti-TNF agents appear to increase the risk of infection. Clinicians must weigh this risk against efficacy when making treatment decisions.

Reference

Kirchgesner J, Lemaitre M, Carrat F, et al. Risk of Serious and Opportunistic Infections Associated with Treatment of Inflammatory Bowel Diseases. Gastroenterol. 2018;155(2):337–46. https://www.gastrojournal.org/article/S0016-5085(18)30445-1/fulltext

Synopsis

To assess the risk of infection associated with anti-TNF therapy (infliximab or adalimumab) and thiopurines, either alone or in combination, French researchers examined data from 190,694 adult inflammatory bowel disease (IBD) patients enrolled in the country’s national health insurance database between 2009 and 2014. Patients were a mean of 45 years of age. The distribution of Crohn’s disease and ulcerative colitis cases was roughly even. Approximately 25%, 14% and 6% of patients had been exposed to thiopurine monotherapy, anti-TNF monotherapy and combination therapy, respectively.

The investigators found 8,561 serious infections and 674 opportunistic infections in the cohort. Whereas serious infections occurred after an average of roughly one year of treatment with monotherapy using either thiopurines or anti-TNF drugs, the average time to serious infection with combination therapy was 136 days. The most common infections were respiratory, gastrointestinal and dermatological. Roughly 4% of patients died within three months of infection.

Analyses corrected for corticosteroid exposure and disease activity showed that combination therapy increased the risk of serious infection compared to anti-TNF monotherapy (hazard ratio [HR]: 1.23; 95% confidence interval [CI]: 1.05–1.45) and thiopurine monotherapy (HR: 2.11; 95% CI: 1.80–2.48). Those receiving combination therapy also had a higher risk of opportunistic infections compared to anti-TNF monotherapy (HR: 1.96; 95% CI: 1.32–2.91) and thiopurine monotherapy (HR: 2.11; 95% CI: 1.45–3.08).

Additionally, anti-TNF monotherapy was linked with a higher risk of serious infections (HR: 1.71; 95% CI: 1.56–1.88), mycobacterial infection (HR, 1.98; 95% CI, 1.15–3.40) and bacterial infection (HR, 2.38; 95% CI, 1.23–4.58), compared to thiopurine monotherapy. However, anti-TNF monotherapy was associated with a lower risk of opportunistic viral infection than thiopurine monotherapy (HR: 0.57; 95% CI: 0.38–0.87).

Details

Study Design: Observational analytic
Funding: Unfunded
Allocation: Cohort
Setting: Database
Level of Evidence: 2b (Oxford Levels of Evidence)

The summary and conclusion in this issue of E-mentoring in IBD pertains to the manuscript(s) being reviewed, and should be considered in the context of what is already known surrounding the topic and incorporated into practice as deemed appropriate by the individual learner.