Journal List > J Rheum Dis > v.22(4) > 1064197

Sung, Cho, Won, Choi, Kim, Jun, Yoo, and Bae: Incidence of Tuberculosis in Rheumatoid Arthritis Patients Using Anti-Tumor Necrosis Factor Agents following Latent Tuberculosis Infection Screening Strategies

Abstract

Objective

To compare the incidence of tuberculosis (TB) in rheumatoid arthritis (RA) patients using tumor necrosis factor (TNF) inhibitors following two strategies for latent tuberculosis infection (LTBI) screening: Tuberculin skin test (TST) only vs. TST plus Qauntiferron-TB gold in tube (QFT-GIT).

Methods

Data was extracted from a retrospective cohort of Korean RA patients who used biologic agents. Of the 406 RA patients who underwent TST before starting TNF inhibitor, we selected 355 patients who strictly followed LTBI screening and treatment strategies. Two hundred and twenty-two patients were classified as TST only group and the remaining 133 patients as TST plus QFT-GIT group. We calculated the standardized incidence ratio of TB in the entire sample and compared the TB incidence between groups.

Results

Among the patients who received the TST only strategy (n=222, 538.6 person-year [PY]), two patients developed TB during anti-TNF therapy, while of those who followed the TST plus QFT-GIT strategy, none developed TB (n=133, 108.8 PY). The overall crude incidence of TB in RA patients using TNF inhibitors was 314 per 100,000 PY. Compared with the general population, the overall age standardized incidence of TB in TNF inhibitor users who followed management guideline for LTBI was 3.9.

Conclusion

Despite following screening and management guidelines for LTBI, TB incidence for RA patients during anti-TNF therapy is higher than in the general population. Combining QFT-GIT with TST as a screening for LTBI might be reduce the risk of TB.

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Figure 1.
Patient selection flow. TST: tuberculin skin test, IGRA: interferon-gamma release assay, LTBI: latent tuberculosis infection, TB: tuberculosis.
jrd-22-223f1.tif
Table 1.
Demographic and clinical features in rheumatoid arthritis using TNF inhibitors according to LTBI screening strategy
Characteristic Total (n=355) TST only (n=222) TST plus IGRA (n=133) p
Age (yr) 49.7±13.2 49.6±12.9 49.9±13.8 0.83
Female 311 (87.6) 199 (89.6) 112 (84.2) 0.18
Disease duration 8.7±6.8 9.0±6.5 8.4±7.1 0.45
Follow-up duration from starting TNF inhibitor (mo) 22.0±22.7 29.3±25.7 10.0±6.8 <0.01
DAS 28-ESR 6.0±0.9 6.0±0.9 5.9±0.9 0.33
RF positive 271 (76.3) 165 (74.3) 106 (79.7) 0.31
TNF inhibitors       <0.01
 Etanercept 219 (61.7) 150 (67.6) 69 (51.9)  
 Adalimumab 98 (27.6) 44 (19.8) 54 (40.6)  
 Infliximab 38 (10.7) 28 (12.6) 10 (7.5)  
Glucocorticoid user 286 (80.6) 173 (77.9) 113 (85.0) 0.14
Glucocorticoid dose (mg/d) 3.9±2.3 3.9±2.2 4.0±2.5 0.55
Methotrexate user 268 (75.5) 162 (73.0) 106 (79.7) 0.19
Methotrexate dose (mg/wk) 13.8±3.2 14.4±3.3 13.1±3.0 <0.01
The number of previous non-biologic DMARDs 4.2±1.5 4.4±1.6 3.8±1.3 <0.01
Tuberculosis related information        
 Tuberculosis prophylaxis 105 (29.6) 68 (30.6) 37 (27.8) 0.48
  Isoniazid 102 65 37  
  Rifampicin and pyrazinamide 3 3 0  
 Chest X-ray or CT at enrollment 347 (97.8) 218 (98.2) 129 (97.0) 0.48
  Abnormal finding* in Chest X-ray or CT 83 (23.9) 52 (23.9) 31 (24.0) 1.00
Positivity of TST        
 >5 mm 93 (26.2) 68 (30.6) 25 (18.8) 0.02
 ≥10 mm 69 (19.4) 47 (21.2) 22 (16.5) 0.35
 ≥15 mm 36 (10.1) 23 (10.4) 13 (9.8) 1.00

Values are presented as mean±standard deviation or number (%).

* Old tuberculosis, interstitial lung diseases, bronchiectasis, etc. was included. CT: computed tomography, DAS: disease activity score, DMARD: disease modifying anti-rheumatic drug, ESR: erythrocyte sedimentation rate, IGRA: interferon-gamma release assay, LTBI: latent tuberculosis infection, RF: rheumatoid factor, TNF: tumor necrosis factor, TST: tuberculin skin test.

Table 2.
Agreement between TST and IGRA in RA patients using TNF inhibitor
Population IGRA positive IGRA negative Kappa
TST positive >5 mm      
 TST (+) 19 (14.3) 6 (4.5) 0.59
 TST (−) 12 (9.0) 96 (72.2)  
TST positive≥10 mm      
 TST (+) 17 (12.8) 5 (3.8) 0.56
 TST (−) 14 (10.5) 97 (72.9)  
TST positive≥15 mm      
 TST (+) 10 (7.5) 3 (2.3) 0.37
 TST (−) 21 (15.8) 99 (74.4)  

Values are presented as number (%). IGRA: interferon-gamma release assay, RA: rheumatoid arthritis, TNF: tumor necrosis factor, TST: tuberculin skin test.

Table 3.
Standardized incidence rate of tuberculosis in RA patients using TNF inhibitor
Population Observational period (PY) Incidence rate (/100,000 PY) SIR*
Patients who followed screening guideline for LTBI (n=355) 637.4 314 3.9
 TST only (n=222) 538.6 371 4.6
 TST and IGRA (n=133) 108.8 NA NA

* Compared with the general population, the overall age standardized incidence. IGRA: interferon-gamma release assay, LTBI: latent tuberculosis infection, NA: not available, PY: person-year, RA: rheumatoid arthritis, SIR: standardized incidence ratio, TNF: tumor necrosis factor, TST: tuberculin skin test.

Table 4.
Clinical characteristics of patients who developed tuberculosis during TNF inhibitor use
Characteristic Case 1 Case 2
Age at starting TNF inhibitors (yr) 35 39
Gender Female Female
LTBI screening strategy TST only TST only
TST positivity Positive Negative
IGRA positivity NA NA
LTBI treatment Yes No
TNF inhibitor Adalimumab Adalimumab
Concomitant medication at enrollment    
 Prednisolone (mg/d) No 5
 Methotrexate use (mg/wk) No 12.5
The number of previous non-biologic DMARDs 4 4
Laboratory data    
 ANA Positive Positive
 RF Positive Negative
 ESR (mm/h) 59 33
 CRP (mg/dL) 1.63 1.90
Time to tuberculosis occurrence from starting TNF inhibitor (mo) 19 19
Method of tuberculosis diagnosis Active tuberculosis in chest X-ray Tuberculosis in lymph node biopsy
Location of tuberculosis Lung Lymph node

ANA: antinuclear antibody, CRP: C-reactive protein, DMARD: disease modifying anti-rheumatic drug, ESR: erythrocyte sedimentation rate, IGRA: interferon-gamma release assay, LTBI: latent tuberculosis infection, NA: not available, RF: rheumatoid factor, TNF: tumor necrosis factor, TST: tuberculin skin test.

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