Interferon-γ release assay screening in biologics: safe and reliable, but not perfect.

Background

Systemic biologic agents can increase the risk of re-activation of latent tuberculosis (TB). Prior to initiation, screening for latent TB using an interferon-γ release assay (IGRA) is recommended. There is concern that false-negative IGRAs may be more likely in this context.

Methods

This retrospective analysis of IGRAs, specifically T-SPOT.TB, results and outcomes of patients already on or due to start biologics identifies the rate of TB re-activation in a low TB incidence setting. Additionally, we estimate the negative predictive value (NPV) of IGRAs in this population.

Results

Patients on biologics were more likely to have a negative IGRA result than patients not on biologics. There was no statistically significant change in conversion or reversion rates between groups. Of 9263 patients on biologics, 19 developed active TB after starting biologics at an incidence rate of 55.1 per 100 000 patient-years. This occurred despite screening in half of the 16 patients for whom we were able to review medical records. Most drugs implicated were known to be high risk, although rituximab and natalizumab were being taken by five patients and one patient, respectively. The T-SPOT.TB NPV was 99.20% and dropped only slightly to 99.17% when we simulated an approach where all borderline IGRA results were regarded as being negative.

Conclusions

Negative IGRA results confer a low risk of subsequent active TB in patients on biologics in a low TB incidence setting. However, continued awareness is needed given that a number of active TB cases will have had a prior negative result.

Informations de copyright

Copyright ©The authors 2022.

Déclaration de conflit d'intérêts

Conflict of interest: J. Cafferkey reports the following relationships outside the submitted work: grants or contracts from Royal College of Emergency Medicine, NHS Lothian and University of Edinburgh; support for attending meetings and/or travel from Edinburgh Anaesthesia Research and Education Fund; current member of the Regional Ethics Committee, South East Scotland. K. Kumar received support for the present manuscript from the National Institute for Health Research Imperial Biomedical Research Centre (funding for clinical PhD and salary at Imperial College London), Lee Family endowment to the Faculty of Medicine at Imperial College London (funding for clinical PhD and salary at Imperial College London). M. Patel reports the following relationships outside the submitted work: consulting fees received from Takeda and Jansen; payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from Jansen – Guidelines in Practice; support for attending meetings and/or travel from Jansen; and participation on a Data Safety Monitoring Board or Advisory Board for Takeda, Pfizer, Jansen, Celltrion and Mylan. A. Chavda has received an honorarium for a manuscript from Shiongi for a case report on Cefidericol. M. Park received support for the present manuscript from the National Institute for Health Research Imperial Biomedical Research Centre. M. Coleman has received payment from Gilead as support for educational lecture talks. The remaining authors have nothing to disclose.