Background/Purpose

Reactivation of latent tuberculosis infection (LTBI) is a serious concern in patients treated with TNF-α inhibitors (TNFi). Conversely, TB chemoprophylaxis (CP) is time consuming, delays the initiation of required treatment, adds to the overall cost of treatment, and carries risk of adverse events itself. Since 2002 our national guidelines require following a two-step screening algorithm prior to the initiation of the first TNFi. The first step includes tuberculin skin test (TST), and a chest X-ray (CXR). If TST < 5 mm, and the radiologist finds no changes consistent with TB on CXR TNFi is prescribed. If any test is abnormal, the patient is evaluated by a pulmonologist who usually orders QuantiFERON TB Gold IT (QF) and decides whether TB CP (rifampicin/isoniazid 600/300 mg qd for 3 months) is required prior to TNFi treatment.

In February 2002 we showed that in a setting with low background annual TB incidence rate (IR) (i.e. 8.4 per 10⁵) following of this algorithm resulted in TB IR of 0.11 (95% CI 0.01–0.38), and 0.16 (95% CI 0.02–0.58) per 100 person years (PY) overall, and in RA patients, respectively. The costly QF and CP were required in 13.9%, and 5.2% of patients, respectively. Our aim was to reevaluate the performance of this algorithm.

Methods

In March 2014 we cross-linked the data from the obligatory national registry of patients treated with biological DMARDs and the national TB registry to identify cases of TB in patients who were ever treated with TNFi.

Results

1533 patients were treated with at least one TNFi for 3,846 PY (Table 1). Flow of patients through the screening algorithm and case patient characteristics are depicted in Figure 1. QF was performed in273/1500 (18.2%). 96/1533 (6.3%) patients received CP. Four cases of TB were identified, hence IR was 0.10 (95% CI 0.03–0.27), and 0.19 (95% CI 0.05–0.48) per 100 PY overall, and in RA patients, respectively. Only RA patients developed TB. The TB IR for certolizumab vs. other TNFi prescribed for RA was 1.3 (95% CI 0.16–0.47) vs. 0.1 (95% CI 0.01–0.37) per 100 PY (p=0.027 Fisher’s exact test). The first two received appropriate CP (adherence was good, isolated M. tuberculosis strains were susceptible to CP) prior to TNFi, in the third patient the screening was stopped after 1^st step and in the fourth one after the 2^nd step. Interestingly, the 3^rd case was screened for TB again before switching to rituximab. At repeated screening two months prior to TB diagnosis the TST was 10 mm, CXR neg. and QF–.

Conclusion

At follow-up our two-step algorithm is still performing well. Further vigilance is warranted, especially in RA patients and those treated with CZP.