Rheumatology Advance Access originally published online on April 4, 2007
Rheumatology 2007 46(6):1035-1036; doi:10.1093/rheumatology/kem064
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LETTERS TO THE EDITOR |
Use of the QuantiFERON TB Gold test as part of a screening programme in patients with RA under consideration for treatment with anti-TNF-
agents: the Newcastle (UK) experience
1Musculoskeletal Research Group, Institute of Cellular Medicine, Newcastle University, Newcastle-upon-Tyne NE2 4HH and 2Musculoskeletal Unit, Freeman Hospital, High Heaton, Newcastle-upon-Tyne NE7 7DN, UK
Correspondence to: Arthur Pratt, Floor 4, Catherine Cookson Building, The Medical School, Framlington Place, Newcastle-upon-Tyne NE2 4HH, UK. E-mail: arthur.pratt{at}ncl.ac.uk
SIR, RA patients treated with anti-TNF-
agents have an increased risk of developing Mycobacterium tuberculosis (MTB) infection, the magnitude of which (compared with background risk) depends on the agent used, approaching 10-fold for infliximab-treated patients [1]. Such cases are likely predominately to represent reactivation of latent infection, as opposed to the de novo cases, which are thought to account for most etanercept-associated infections [2]. For the purposes of latent MTB infection screening the tuberculin skin test (TST) has well-recognized shortcomings [3], and the development of blood tests whose basis is the detection of IFN-
released by T-cells in response to MTB-specific antigens, including the commercially available QuantiFERON-TB Gold (QTG) test (Cellestis, Carnegie, Australia), has been cautiously welcomed. These are more specific than the TST, especially amongst patients previously exposed to BCG, and may also be more sensitive, as well as having operational advantages over the TST [4]. Lack of a gold standard test for latent TB makes validation of such tests difficult though it would seem that their sensitivities and specificities vary according to the characteristics of the population studied [4, 5]. The same probably applies to the tests’ informativeness, and, of note, the rate of indeterminate QTG test results amongst cancer chemotherapy patients has been noted to be significantly higher than that seen amongst relatively immunocompetent individuals in an Italian study (36% vs 9%) [6]. This raises the question of whether the test might be similarly uninformative in RA patients under consideration for anti-TNF- therapy, who are invariably immunosuppressed (albeit to a lesser extent). The QTG test has been employed by the Rheumatology department at The Freeman Hospital, Newcastle-upon-Tyne, UK, since March 2004 as part of the TB screening programme for just such a patient group. We have audited its use amongst 101 consecutive RA patients, recruited over a 2 year period, who fulfilled published criteria permitting use of a biologic drug [3], and we present data addressing the feasibility, informativeness and, so far as possible, the prospective accuracy of the QTG test in this highly relevant clinical context.
Prior to treatment all patients were screened for MTB infection as per published guidelines [3]. In addition a QTG test was undertaken, employing Newcastle's Public Health Laboratory Service (PHLS) and according to the test manufacturer's instructions [7].
Mean age of recruited patients was 55 (S.D. 44–66), 77% were female and 99% were white Caucasian; mean disease activity score (DAS28) was 6.6 (S.D. 5.86–7.34). BCG status was known in 93 (92%) of the patients, and amongst this group 78.5% had undergone vaccination. Recruited patients were invariably exposed to DMARDs including methotrexate at maximum tolerated dose (up to 25 mg) at the time of QTG testing, and 
40% of them had been recipients of systemic corticosteroid therapy prior to recruitment. Test results, recorded as positive, negative or, in instances where no IFN- response was seen to a positive control mitogen, indeterminate, are summarized in Fig. 1. Seven patients who had positive results were immediately referred to a respiratory physician for the direction of appropriate MTB chemoprohylaxis. None of these had signs of active tuberculosis, and all but three went on to receive an anti-TNF- agent. Of the 98 patients subsequently administered a biologic, 68.3% received etanercept, 18.3% adalimumab and 13.3% infliximab. All of the patients have been followed up for between 6 and 30 months (average 18.3 months) following initiation of an anti-TNF- agent. No cases of MTB reactivation or de novo infection have been observed in our cohort during this period regardless of the agent used.
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An infrastructure within which routine use of the QTG test is established has been developed with relative ease in our centre, thanks to effective cooperation between the Rheumatology department and the PHLS. Blood samples must be processed in the laboratory within 12 h, and blood is therefore drawn on a week-day morning, with results available within 48 h. The laboratory charges £35.00 for the service. An excessive proportion of uninformative results was not seen in our cohort (9.9% indeterminate test results) and this was encouraging. BCG status did not significantly influence likelihood of an indeterminate test result (P > 0.05), and the relatively high proportion of negative QTG test results overall (83%), whilst not proof of a complete lack of BCG-associated false positives, is supportive of a specificity unconfounded by BCG status. Furthermore the absence of any cases of MTB, whether reactivation or de novo, over a relatively long period of follow-up, points to a favourable, albeit unquantifiable, test sensitivity.
We conclude that use of the QTG test as a screening tool amongst RA patients due to start anti-TNF- treatment is feasible, that its informativeness appears unaffected by any impaired immunocompetence of our patient group, and that it is a useful and potentially cost-effective adjunct to existing protocols.
Conflict of Interest: AP has been funded to attend a conference by Schering Plough Ltd. KN has received honoraria from Abbott Laboratories, Schering Plough Ltd and Wyeth Biotechnology Ltd, and has received a research grant (March 2003 to March 2005) from Schering Plough Ltd. LK has participated in clinical trials by Abbott Laboratories and Wyeth Pharmaceuticals.
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[Abstract/Free Full Text] - Ferrara G, Losi M, D'Amico R, et al. Use in routine clinical practice of two commercial blood tests for diagnosis of infection with Mycobacterium tuberculosis: a prospective study. Lancet (2006) 367:1328–34.[CrossRef][Web of Science][Medline]
- http://www.cellestis.com/IRM/contentAU/gold/Gold_PackageInsert.pdf.
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