Conversion and Reversion Rates of Tuberculosis Screening Assays in Patients With Rheumatic Diseases and Negative Baseline Screening Under Long-Term Biologic Treatment.

BACKGROUND: To determine the conversion and reversion rates of tuberculosis (TB) screening tests (Tuberculin Skin Test-TST, Interferon Gamma Release Assay-IGRA: T-SPOT.TB) during biologic treatment in patients with rheumatic diseases and negative baseline screening. METHODS: This was a long-term, longitudinal cohort study of 50 patients with rheumatic diseases and negative baseline TB screening (TST: < 5 mm, negative T-SPOT.TB) treated with tumor necrosis factor inhibitors (TNFi) or other non-TNFi biologics. Patients were rescreened at a mean time of 1.4 (first rescreening) and 6.9 (second rescreening) years from baseline, with both assays. The conversion (negative to positive) and reversion (positive to negative) rate was calculated for each TB screening test. RESULTS: Fifty patients (mean age = 60 years) with various rheumatic diseases (rheumatoid arthritis: n = 24, spondyloarthropathies: n = 23, other: n = 3) were enrolled. During the first phase (baseline to first rescreening), all patients were treated with TNFi while during the second phase (first to second rescreening), TNFi (54%) and non-TNFi (46%) were used. Fifteen patients (30%) displayed conversion of at least 1 screening assay during follow-up (10 at the first and 5 at the second rescreening). This conversion rate was higher with TST (n = 11, 22% or 3.47/100 patient-years) compared to T-SPOT.TB (n = 4, 8% or 1.74/100 patient-years). Among the 10 converters at the first rescreening, 5 received isoniazid (INH) preventive therapy and 5 did not; an equal number of patients (3/5, 60%) reverted to negative with or without INH therapy. None of the patients developed active TB during follow-up (6.9 ± 1.0 years). CONCLUSIONS: Approximately one-third of patients with rheumatic diseases and negative baseline TB screening developed conversion of at least 1 screening test during long-term biologic treatment. This occurred most often with TST and was usually a transient event. These findings do not support routine serial TB retesting in biologic-treated patients with rheumatic diseases in the absence of TB risk factors.

Frequent conversion of tuberculosis screening tests during anti-tumour necrosis factor therapy in patients with rheumatic diseases.

OBJECTIVES: To determine the rate of tuberculosis (TB) screening test conversion during anti-tumour necrosis factor (TNF) therapy in rheumatic patients with negative baseline screening. METHODS: This was a prospective study of rheumatic patients with negative baseline TB screening (tuberculin skin test (TST): <5 mm, and negative T-SPOT.TB, QuantiFERON-TB Gold In Tube (QFT-GIT) and chest X-ray) treated with anti-TNF agents. All patients underwent re-screening for TB with all assays 1 year later. Factors associated with TB test conversion were analysed and compared between 'converters' and 'non-converters'. RESULTS: Seventy patients (mean age 50.6±15.5 years) with rheumatic disease (33 with rheumatoid arthritis, 33 with spondyloarthropathies and 4 with other conditions) were enrolled. Patients were treated with different anti-TNFs (27 with adalimumab, 14 etanercept, 16 infliximab, 8 golimumab, 5 certolizumab pegol) for 1 year. Twenty patients (29%) displayed conversion of at least one screening assay 12 months after anti-TNF therapy: conversion of TST occurred in 9 (13%), T-SPOT.TB in 7 (10%) and QFT-GIT in 5 (7%). Only one patient had concomitant conversion of more than one screening test. Univariate and multivariate analysis revealed that only infliximab was associated with a decreased rate of TB screening assay conversion (OR 0.048, 95% CI 0.004 to 0.606, p=0.017). No patient (40% received isoniazid therapy) developed active TB during follow-up (27±12 months). CONCLUSIONS: Approximately one third of patients with negative baseline TB screening develop conversion of at least one screening test during anti-TNF treatment. These findings should be considered when designing re-screening strategies and contemplating latent TB therapy.

Comparison of two gamma interferon release assays and tuberculin skin testing for tuberculosis screening in a cohort of patients with rheumatic diseases starting anti-tumor necrosis factor therapy.

Gamma interferon release assays (IGRAs) are increasingly used for latent Mycobacterium tuberculosis infection (LTBI) screening in patients with rheumatic diseases starting anti-tumor necrosis factor (anti-TNF) therapies. We compared the performances of two IGRAs, an enzyme-linked immunospot release assay (T-SPOT.TB) and an enzyme-linked immunosorbent assay (QuantiFERON-TB Gold In Tube [QFT-GIT]), to that of tuberculin skin testing (TST) for LTBI screening of 157 consecutive rheumatic patients starting anti-TNF therapies. Among 155 patients with valid results, 58 (37%) were positive by TST, 39 (25%) by T-SPOT.TB assay, and 32 (21%) by QFT-GIT assay. IGRAs were associated more strongly with at least one risk factor for tuberculosis (TB) than TST. Risk factors for a positive assay included chest X-ray findings of old TB (TST), advanced age (both IGRAs), origin from a country with a high TB prevalence, and a positive TST (T-SPOT.TB assay). Steroid use was negatively associated with a positive QFT-GIT assay. The agreement rate between IGRAs was 81% (kappa rate = 0.47), which was much higher than that observed between an IGRA and TST. If positivity by either TST or an IGRA was required for LTBI diagnosis, then the rate of LTBI would have been 46 to 47%, while if an IGRA was performed only for TST-positive patients, the respective rate would have been 11 to 17%. In conclusion, IGRAs appear to correlate better with TB risk than TST and should be included in TB screening of patients starting anti-TNF therapies. In view of the high risk of TB in these patients, a combination of one IGRA and TST is probably more appropriate for LTBI diagnosis.