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Risk of active tuberculosis in patients with inflammatory arthritis receiving TNF inhibitors: a look beyond the baseline tuberculosis screening protocol

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Abstract

Tuberculosis (TB) is a major concern in patients receiving TNF inhibitors (TNFi). This study aimed to assess the incidence of active TB and the efficacy of TB prevention measures used over the years, and to determine risk factors for developing TB, in a single-centre cohort of patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS) receiving TNFi. Data of all patients in whom treatment with TNFi was initiated in our rheumatology clinic until December 1st 2014 have been retrospectively analysed. The cohort was divided into 3 groups per the mandatory LTBI screening method at baseline: tuberculin skin test (TST) with a positive threshold of either 10 mm (group TST1), or 5 mm (group TST2), and QuantiFERON®-TB Gold test (group QFT). The incidence of active TB was analysed for each group and compared to TB incidence data in general population. Five hundred fifty patients were included (305 RA, 42 PsA, 203 AS); 97 patients belonged to the TST1, 229 to the TST2 and 224 to the QFT group. The number of active TB cases/time of exposure to TNFi (person-years, PY) was 8/593.5, 9/1044.0 and 3/555.3, respectively, accounting for an incidence of 1348.0, 862.1 and 540.2 cases per 105 PY. Active TB cases occurring in the first year of TNFi treatment (early TB) per total TB cases were only 3/8, 1/9 and 1/3, respectively, too few to identify statistically significant differences between the 3 LTBI screening protocols. However, less TB cases per total observation time were registered in the QFT group, probably due to the reduced duration of exposure to TNFi. All cases of active TB were registered among patients receiving monoclonal antibodies TNFi agents. We have found no significant risk factors for developing active TB. In our cohort, TB occurring after 1 year of TNFi treatment exceeds ‘early TB’, suggesting the necessity of further TB prevention measures besides baseline screening for LTBI.

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Author notes

  1. Ana Maria Gheorghiu and Alina Soare contributed equally to this work.

Authors and Affiliations

  1. Department of Internal Medicine and Rheumatology, Cantacuzino Clinical Hospital, Ion Movila 5-7, 020475, Bucharest, Romania

    Alina Soare, Ana Maria Gheorghiu, Rucsandra Dobrotă, Raida Oneaţă, Simona Pintilie, Mihaela Milicescu, Ioan Ancuţa, Andrei Martin, Mariana Sasu, Claudia Ciofu, Liviu Macovei, Victor Stoica, Mihai Bojincă & Carina Mihai

  2. Carol Davila University of Medicine and Pharmacy, Bucharest, Romania

    Alina Soare, Ana Maria Gheorghiu, Victoria Aramă, Dragoș Bumbăcea, Rucsandra Dobrotă, Raida Oneaţă, Simona Pintilie, Mihaela Milicescu, Ioan Ancuţa, Andrei Martin, Claudia Ciofu, Liviu Macovei, Victor Stoica, Mihai Bojincă & Carina Mihai

  3. Infectious Diseases 3 Department, Matei Bals National Institute for Infectious Diseases, Bucharest, Romania

    Victoria Aramă

  4. Department of Pneumology, Elias Emergency University Hospital, Bucharest, Romania

    Dragoș Bumbăcea

Authors
  1. Alina Soare
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  2. Ana Maria Gheorghiu
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Contributions

All authors participated in study design. MM, IA, AM, MS, CC, LM, MB, VS and CM recruited patients. AS, AMG, RD, RO and SP collected data. AS, AMG, DB and CM conducted the statistical analyses. VA and DB analysed TB cases and offered expert opinion in the area of TB. AS, AMG, DB and CM drafted the manuscript, which was critically reviewed, edited and approved for submission by all authors.

Corresponding author

Correspondence to Ana Maria Gheorghiu.

Ethics declarations

All patients receiving TNFi in our centre gave written informed consent enabling the centre to use their de-identified medical data in research projects, and this study was approved by the local ethics committee.

Disclosure of interest

A. M. Gheorghiu: none declared. A. Soare: none declared. V. Aramă has received research support and/or honoraria and has/had consultancy relationship from Abbvie, MSD, BMS, Roche and Pfizer. D. Bumbăcea: none declared. R. Dobrotă: none declared. R. Oneață: none declared. S. Pintilie: none declared. M. Milicescu has received research support and/or honoraria from Abbvie, MSD and Pfizer. I. Ancuta has received research support and/or honoraria and has/had consultancy relationship from Abbvie, Pfizer, Roche, UCB and BMS. A. Martin has received research support and/or honoraria from Abbvie, MSD, Pfizer, Roche, UCB and BMS. M. Sasu has received research support and/or honoraria from Abbvie, MSD, Pfizer, Roche, UCB and BMS. C. Ciofu has received research support and/or honoraria from Abbvie and MSD. L. Macovei has received research support and/or honoraria from MSD, Pfizer and Roche. V. Stoica has received research support and/or honoraria from GSK, PSI Pharma Support, M&M CRE, Kendle International Inc. and Clintec International. M. Bojincă has served as a consultant for Abbvie, BMS, MSD, Pfizer, Roche, Sandoz and has received speaker fees from Abbvie, BMS, MSD, Pfizer, Roche, Gedeon Richter, Sandoz, UCB and Zentiva. C. Mihai has received research support and/or honoraria and has/had consultancy relationship from Abbvie, Abbott, BMS, MSD, Pfizer, Roche, Sandoz, Teva and UCB.

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Soare, A., Gheorghiu, A.M., Aramă, V. et al. Risk of active tuberculosis in patients with inflammatory arthritis receiving TNF inhibitors: a look beyond the baseline tuberculosis screening protocol. Clin Rheumatol 37, 2391–2397 (2018). https://doi.org/10.1007/s10067-017-3916-y

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