Likelihood Of Detecting Latent Tuberculosis Infection Before And During Infliximab Therapy

Screening and treatment for latent tuberculosis (TB) before the use of anti-TNF therapy has decreased the risk of active TB. Despite preventive actions new cases of active TB still occur in patients on anti-TNF therapy. The aim of this study was to determine the likelihood of detecting latent TB in IBD patients before starting infliximab (according to 2-step tuberculin skin test [TST] and chest X-ray results) and during infliximab therapy (by the positive conversion of sequential TST). The outcome of patients with a positive result in any TST was also investigated. This prospective single-center study included all consecutive IBD patients screened for latent TB with 2-step TST before starting infliximab treatment. TST was positive if induration was ≥5 mm in any basal or sequential test. Patients with a positive basal TST or with criteria of latent TB in chest X-ray received a complete therapeutic regimen for latent TB with isoniazid and infliximab was delayed for 1 month. We performed annual sequential 1-step TST in all patients with basal negative 2-step TST and still on infliximab. Only the patients with at least the one-year sequential TST were evaluated to assess the rate of positive conversion of TST during follow-up. Patients with a positive result in any sequential TST were treated with a complete therapeutic regimen for latent TB while continuing on infliximab, and were followed to assess clinical outcomes. One hundred patients (mean age 42 years, 50% male) with either Crohn's disease (n=67) or ulcerative colitis (n=33) were enrolled. Fifteen patients had a positive TST at baseline (13 in 1-test and 2 in booster; mean TST induration 15 mm, range 8-34 mm). Eighty-five patients had a negative 2-step TST at baseline, and of those 76 had at least the one-year TST. Nine out of 76 patients had a positive TST during follow-up (mean TST induration 13 mm, range 9-20 mm). During follow-up, 135 serial TST were performed. Positive conversion had occurred in 6/76 (7.9%; 95% CI: 1.2-14.6) patients, 2/35 (5.7%; 95% CI: 0.7-25.1) patients and 1/14 (9.1%; 95% CI: 0.2-33.9) patients at one, two and three years, respectively. At four and five years, 0/6 and 0/4 patients had a positive TST. The cumulative probability of continuing with a negative TST during follow-up was 0.921, 0.849 and 0.768 at one, two, three and successive years, respectively. After a median of 23 months (range 3-54 months) follow-up, none of the patients with positive TST had clinical or radiological signs of active TB. One in four IBD patients showed a positive TST before or during infliximab treatment. Nine out of 24 (37%) latent TB infections were diagnosed by the positive conversion of sequential annual TST. Although the exact significance of these positive conversions is not well known, annual TST is advisable as false negative responses to latent TB or new TB contacts are possible in IBD patients receiving long-term infliximab therapy, especially in countries with a high prevalence of TB.