Background/Purpose: During the development of algorythms for screening latent tuberculosis before starting TNF-alpha antagonists, it is assumed that BCG vaccination causes false positive PPD and that concomitant medications such as corticosteroids cause false negative PPD results, favoring the use of Quantiferon or Elispot in these patients. Moreover it is assumed that INH is difficult to tolerate in this patient group. However we hypothesized that these assumptions may be wrong since there is a long time between BCG vaccination and TNF-alpha antagonist use in most of the rheumatology patients; there is no consistent data to show that disease modifying agents and corticosteroids in doses used for rheumatologic conditions are associated with negative PPD results; and INH is usually well tolerated by most of our patients.

Methods: We included patients who were prescribed a TNF-alpha antagonist for the first time between January 2011 and December 2012 in our clinic. Patients who had a previous tuberculosis infection were excluded since this could cause PPD positivity. We used logistic regression to analyse the determinants of a positive PPD (≥ 5mm). The variables were having a BCG scar, drugs (prednisolone, methotrexate, leflunomide, azathioprine, cyclosporine-A and cyclophosphamide), age, gender, diagnosis and disease duration. We also evaluated the frequency of being able to complete 9 months of INH treatment, the reasons for discontinuation and the frequency of developing tuberculosis among those who used and who did not use INH.

Results: A TNF-alpha antagonist was started in 961 patients (503 men, 458 women, mean age 41.28 ± 13.10 years, disease duration 6.54 ± 6.80 years). We excluded 75 patients who had previously used a TNF-alpha antagonist and 33 patients who had previous tuberculosis treatment. Among the remaining 853, an initial PPD test was available in 671 patients. At least one BCG scar was present in 592 patients. Logistic regression showed that BCG vaccination (OR=3.45, 95%CI 2.51-4.75, p<0.0001) and a diagnosis of ankylosing spondylitis (OR=1.79, 95%CI 1.21-2.65, p=0. 003) were associated with PPD positivity, while corticosteroid use was associated with a negative PPD (OR=1.96, 95%CI 1.09-3.51, p=0.023). INH was started in 525 patients and 391 had reliable data regarding INH use. 346 patients (87%) completed 9 months of treatment, 22 with interruptions. 45 had to stop INH after 3.85 ± 2.46 months. The reasons for discontinuation were hepatotoxicity in 26, allergic dermal reactions in 2, nausea in 2, dizziness in 2, pregnancy in 1, shortness of breath in 1, pancreatitis in 1 patient and non-willingness in 10 patients. Among the 26 who had to stop INH for transaminase elevation 13 were using concomitant methotrexate. None of the patients developed tuberculosis during our follow-up of up to 3 years.

Conclusion: BCG vaccination may still be a cause of false positive PPD in candidates for treatment with TNF-alpha antagonists. Corticosteroids seem to be associated with negative PPD while DMARDs are not. INH prophylaxis is generally well tolerated despite concomitant methotrexate. Longitudinal follow-up is necessary to determine the long term efficacy of INH treatment for preventing tuberculosis in these patients.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/how-correct-are-the-assumptions-made-for-tuberculosis-screening-algorythms-before-tnf-alpha-antagonists/