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ORIGINAL ARTICLE
Year : 2022  |  Volume : 67  |  Issue : 1  |  Page : 1-4
Conversion rate of tuberculosis screening tests among dermatology patients treated with tumor necrosis factor inhibitors


Department of Dermatology, College of Medicine, King Saud University, Riyadh, Saudi Arabia

Date of Web Publication19-Apr-2022

Correspondence Address:
Sarah F Alsukait
Department of Dermatology, College of Medicine, King Saud University, Riyadh - 12372
Saudi Arabia
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijd.ijd_201_21

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   Abstract 


Background: The use of tumor necrosis factor-α inhibitors (TNFi) has been associated with an increased risk latent tuberculosis (TB) reactivation. The role of TB screening assays in monitoring patients during TNFi therapy remains uncertain. Spontaneous conversions and reversions have been described. Aims: This study aims to determine the conversion and reversion rate of TB screening tests among dermatology patients receiving TNFi in a country with moderate TB incidence. Subjects and Methods: A retrospective single-center study conducted on all patients in whom treatment with TNFi was initiated in our dermatology clinic in a tertiary university hospital, Riyadh, Saudi Arabia, until September 2018. Data were collected from the hospital electronic patient information system. Results: One hundred and eighteen patients were included. Majority (79.9%) of patients used adalimumab. Psoriasis was the most common indication (90%). Among patients with negative baseline TB screening who had been retested during TNFi therapy (n = 65; 55%), conversion to positive was observed in nine patients (13.8%) with a mean duration of exposure of 39.7 months, whereas among patients with positive TB testing result (n = 18), 10 (55.5%) reverted to negative. Conclusions: This study emphasizes the need for prospective large-scale multispecialty studies assessing the significance of TB retesting, which should be considered when designing rescreening protocols.


Keywords: Biologics, dermatology, tuberculosis


How to cite this article:
Alsukait SF, Alsaad AB, Alotaibi GF, Alsaif FM, Alotaibi HM. Conversion rate of tuberculosis screening tests among dermatology patients treated with tumor necrosis factor inhibitors. Indian J Dermatol 2022;67:1-4

How to cite this URL:
Alsukait SF, Alsaad AB, Alotaibi GF, Alsaif FM, Alotaibi HM. Conversion rate of tuberculosis screening tests among dermatology patients treated with tumor necrosis factor inhibitors. Indian J Dermatol [serial online] 2022 [cited 2022 May 25];67:1-4. Available from: https://www.e-ijd.org/text.asp?2022/67/1/1/343268





   Introduction Top


Tumor necrosis factor-α (TNFα) is an important cytokine in preventing reactivation of latent tuberculosis (TB) infection (LTBI). The use of tumor necrosis factor-α inhibitors (TNFi) has been associated with an increased risk of active TB.[1] LTBI can be demonstrated by tuberculin skin test (TST) and/or interferon-gamma release assays (IGRAs), which include QuantiFERON-TB Gold in tube (QFT-GIT) and T-SPOT.TB.[2] IGRAs are more specific than TST as their results are not influenced by previous bacillus Calmette–Guerin vaccination.[3] The value of IGRAs for baseline screening has been recognized; however, their role in monitoring patients during TNFi therapy remains uncertain.[4] There is increasing concern regarding the significance of these TB screening assay conversions during retesting. Conflicting guidelines exist regarding the frequency of TB retesting in patients undergoing TNFi therapy. The National Psoriasis Foundation recommends annual TB screening in all patients,[5] whereas the American College of Rheumatology recommends annual screening in only patients with risk factors for TB.[6] Few studies examined the performance of these assays as monitoring tools for TB during biologic therapy among dermatology patients.[7],[8],[9],[10] This study aims to determine the conversion rate of TB screening tests among dermatology patients receiving TNFi agents with negative baseline screening results at our institution, in addition to determine the reversion rate among those with positive TB testing result, and the prevalence of TB infection in dermatology patients before and after initiation of TNFi.


   Subjects and Methods Top


We conducted a single-center retrospective study from October 2018 to March 2019 in all patients to whom treatment with TNFi was initiated until September 2018 in dermatology outpatient clinics of King Khalid University Hospital, a tertiary hospital in Riyadh, Saudi Arabia. The data were collected from the hospital electronic patient information system. We included patients who were naïve to TNFα blockers before their first visit to our clinics and those with a total duration of TNFi use of 30 days or longer. Patients with missing data and patients who were on TNFi for nondermatological conditions were excluded. Data items recorded included patients' demographic data, indication of treatment, type of TNFi used, duration of treatment, type of TB screening test used, results of TB screening tests before and after initiation of TNFi, and LTBI treatment provided, and for those who converted from negative to positive, we recorded duration of exposure to TNFα blockers. Diagnosis of LTBI by infectious diseases or pulmonology specialists was made based on positive QFT and/or TST result and negative chest X-ray. Conversion was defined as a negative TB testing at baseline and a positive IGRA at follow-up, and reversion was defined as a positive TB testing at baseline or follow-up and negative IGRA upon further retesting.

This study was approved by the Institutional Review Board of College of Medicine, King Saud University, Riyadh. The ethics committee approval, it was obtained in October 2018. Data were collected, stored, managed, and coded in a spreadsheet using Excel 2010 software. Data were analyzed using SPSS version 21.0 (IBM Inc., Chicago, IL, USA). Descriptive analysis was done, where categorical variables were presented in the form of frequencies and percentages and continuous variables in the form of means. Chi-square test was used to compare categorical data. For comparing continuous data, Student's t-test was used for variables with normal distribution. A P value <0.05 was considered significant.


   Results Top


Patients' demographic and clinical characteristics

A total of 118 patients were included in the study with a mean age of 34.66 (minimum 8, maximum 71) years. [Table 1] demonstrates patients' demographic and clinical characteristics. Adalimumab (n = 94; 79.9%) was the most common TNFi used, followed by etanercept (n = 18; 15.3%), and only one patient was on infliximab (n = 0.8%). Five patients (4.2%) were on etanercept and then switched to adalimumab. The most common indication for starting TNFi was psoriasis (n = 106; 89.9%), followed by hidradenitis supprativa (n = 11; 9.3%), and one patient dissecting cellulitis (0.8%).
Table 1: Demographic and clinical characteristics of the patients

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Baseline TB screening tests

TB screening tests prior to TNFi initiation were conducted in 96 (81.4%) patients; the majority (n = 83; 86.45%) had a negative testing result, with a minority of positive (n = 9; 9.37%) and indeterminate results (n = 4; 4.16%). TST alone was used as an initial screening test in 33 patients (34.3%), both TST and IGRAs in 12 patients (12.5%), and IGRA alone in 51 patients (53.12%). Those with a positive baseline TB testing (n = 9) were subsequently diagnosed with LTBI by infectious diseases or pulmonology specialists. Therefore, the prevalence of LTBI before starting TNFi in our study was 9.37%. No patients with active TB were detected prior to initiation of treatment. Eight patients received isoniazid for 9 months, and one received isoniazid and rifampicin for 3 months, which were completed 1 month before initiating TNFi therapy.

Follow-up TB tests

Seventy-eight patients (66%) underwent retesting of TB after initiation of TNFi, all of which using IGRA. The mean duration between TB testing was 21 months. Among those with a positive baseline TB testing (n = 9), three patients remained positive (33.3%), four patients reverted to negative (44.4%), one patient reverted to indeterminate (1.01%), and one did not undergo further retesting (1.01%). Those with a negative baseline (n = 83; 70.3%) had been retested (n = 65; 78.3%); conversion to positive was observed in nine patients (13.8%) during TNFi therapy. Mean duration of exposure to TNFi prior to positive conversion was found to be 39.7 months. Four patients were on etanercept, four on adalimumab, and only one patient switched from etanercept to adalimumab. Six of them reverted back to negative, and three of them did not undergo further retesting. LTBI was diagnosed by infectious diseases or pulmonology specialists in all nine patients. All patients received isoniazid prophylaxis for 9 months except for one due to pregnancy-related concern. None of the patients developed active TB during TNFi therapy. Among those with a positive TB testing result whether at baseline or follow-up (n = 18), reversion rate to negative was found to be 55.5% (n = 10). [Table 2] demonstrates patient characteristics with positive conversion during TNFi therapy. None of the characteristics described were found to have statistically significant associations when compared with those who did not convert (P < 0.05). All of those with an indeterminate baseline (n = 4) reverted to negative upon retesting. [Figure 1] demonstrates the distribution of baseline TB screening testing results prior to initiation of TNFi therapy and follow-up retesting results after initiation of TNFi treatment.
Figure 1: Flow-chart distribution of baseline tuberculosis (TB) screening testing results prior to initiation of TNF inhibitor therapy and follow-up retesting results after initiation of TNF inhibitors treatment

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Table 2: Characteristics of patients with positive conversion during TNFi therapy (n=9)

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   Discussion Top


TNFi are used commonly in dermatology practice, especially among psoriatic patients.[11] Increased risk of infections such as TB is a well-known risk.[1] Few studies examined the performance of these assays as monitoring tools for TB during biologic therapy among dermatology patients.[7],[8],[9],[10] In addition, no previous studies addressing the rate of conversion and/or reversion of TB screening tests were conducted in Saudi Arabia, a country with moderate TB incidence (TB case rate of 10 per 100,000 population) according to the World Health Organization reports in 2017.[12] The conversion rate in our study was 13.8%, which is similar to the results of other studies addressing the performance of IGRAs among psoriasis patients on TNFi in intermediate TB burden countries such as Taiwan 14.3%.[7] In comparison to the United States (a low-burden TB country), two separate studies were conducted among psoriasis patients on TNFi both reporting similar results with only 0.4%[8] and 0.5%[13] conversion rates from negative to positive QFT during TNFi therapy. The authors of these studies argue that serial TB testing in low-risk TB countries in patients on TNFi with no known risk factors is unnecessary. However, in another Italian cohort also, a low-risk TB country of 50 patients with psoriasis on TNF blockers, 10% converted to positive.[10] Our study also reported an overall reversion rate of 55.5% among those tested with positive TB screening result whether prior to or during TNFi therapy. In a meta-analysis that evaluated TB testing reversion among individuals with or without prophylactic treatment,[14] findings of the included studies were found to be heterogeneous. Summarized QFT reversion rate was found to be 24.9% in participants completed preventive therapy and 25.3% among those without preventive treatment, respectively. The authors suggest that the reversion of TB infection testing might not be a reliable tool for monitoring LTBI treatment efficacy and they did not support to use serial QFT test for prophylactic treatment efficacy evaluation.

Our study is limited by its retrospective design, also that it included patients from a single center and a single specialty.

In conclusion, due to a considerable conversion rate of 13.8% among our study population which was consistent with results of other studies conducted in intermediate TB burden countries, annual TB screening testing is recommended particularly in such countries. This study also emphasizes the need for prospective multispecialty large-scale studies assessing the clinical utility and cost-effectiveness of repeat LTBI testing in long-term screening of psoriatic patients on TNFi therapy, which should be considered when designing rescreening strategies that can be based on a country's TB burden.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Sester M, van Leth F, Bruchfeld J, Bumbacea D, Cirillo DM, Dilektasli AG, et al. Risk assessment of tuberculosis in immunocompromised patients. A TBNET study. Am J Respir Crit Care Med 2014;190:1168-76.  Back to cited text no. 1
    
2.
Hernandez C, Cetner AS, Jordan JE, Puangsuvan SN, Robinson JK. Tuberculosis in the age of biologic therapy. J Am Acad Dermatol 2008;59:363-80.  Back to cited text no. 2
    
3.
Chang KC, Leung CC. Systematic review of interferon-gamma release assays in tuberculosis: Focus on likelihood ratios. Thorax 2010;65:271-6.  Back to cited text no. 3
    
4.
Hatzara C, Hadziyannis E, Kandili A, Koutsianas C, Makris A, Georgiopoulos G, et al. Frequent conversion of tuberculosis screening tests during anti-tumour necrosis factor therapy in patients with rheumatic diseases. Ann Rheum Dis 2014;74:1848-53.  Back to cited text no. 4
    
5.
Doherty SD, Van Voorhees A, Lebwohl MG, Korman NJ, Young MS, Hsu S, et al. National Psoriasis Foundation consensus statement on screening for latent tuberculosis infection in patients with psoriasis treated with systemic and biologic agents. J Am Acad Dermatol 2008;59:209-17.  Back to cited text no. 5
    
6.
Singh JA, Saag KG, Bridges SL Jr, Akl EA, Bannuru RR, Sullivan MC, et al. 2015 American college of rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Rheumatol 2015;68:1-26.  Back to cited text no. 6
    
7.
Cheng C-Y, Hui RC-Y, Hu S, Hsieh M-H, Huang Y-H. Serial QuantiFERON-TB gold in-tube testing for psoriatic patients receiving antitumor necrosis factor-alpha therapy. Dermatologica Sinica 2015;33:124-9.  Back to cited text no. 7
    
8.
Chung J, Aronson A, Srikantha R, Vogelgesang S, Wanat K. Low conversion rate of QuantiFERON-TB gold screening tests in patients treated with tumor necrosis factor inhibitors: A retrospective cohort study identifying an important practice gap. J Am Acad Dermatol 2018;79:169-171.  Back to cited text no. 8
    
9.
Sauzullo I, Mengoni F, Marocco R, Potenza C, Skroza N, Tieghi T, et al. Interferon-γ release assay for tuberculosis in patients with psoriasis treated with tumour necrosis factor antagonists: In vivo and in vitro analysis. Br J Dermatol 2013;169:1133-40.  Back to cited text no. 9
    
10.
Garcovich S, Ruggeri A, D'Agostino M, Ardito F, De Simone C, Delogu G, et al. Clinical applicability of Quantiferon-TB-Gold testing in psoriasis patients during long-term anti-TNF-alpha treatment: A prospective, observational study. J Eur Acad Dermatol Venereol 2012;26:1572-6.  Back to cited text no. 10
    
11.
Menter A, Strober BE, Kaplan DH, Kivelevitch D, Prater EF, Stoff B, et al. Joint AAD-NPF guidelines of care for the management and treatment of psoriasis with biologics. J Am Acad Dermatol 2019;80:1029-72.  Back to cited text no. 11
    
12.
World Health Organization. Global Tuberculosis Report 2017. World Health Organization; 2017.  Back to cited text no. 12
    
13.
Ya J, Khanna U, Havele S, Fernandez AP. Utility of repeat latent tuberculosis testing with the QuantiFERON-TB gold test in patients with psoriasis treated with tumour necrosis factor-α inhibitors at a single U.S. institution. Br J Dermatol 2019;182:800-2.  Back to cited text no. 13
    
14.
Zhang Z, Fan W, Yang G, Xu Z, Wang J, Cheng Q, et al. Risk of tuberculosis in patients treated with TNF-α antagonists: A systematic review and meta-analysis of randomised controlled trials. BMJ Open 2017;7:e012567.  Back to cited text no. 14
    


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