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Background: Tuberculin skin test (PPD) or interferon gamma release assays (IGRAs) are used to detect latent tuberculosis infection. Induration of 15 mm or more is considered positive in any person whereas this cut-off is ≥5 mm for immunosuppressed individuals such as Rheumatoid arthritis. Since IGRAs are dependent on normal T-cell function, it may result in false-negatives for among RA patients due to disease itself and immunosuppressive drugs.
Objectives: We aimed to compare IGRA results of RA patients using high dose DMARDS vs. not using any of them.
Methods: Totally 534 RA patients among Hacettepe University Rheumatology Biologic Registry Database (HURBIO) database was enrolled into this study. QFT-Plus test of patients with rheumatoid arthritis (RA) between January 2018 and March 2021 during work up before biologic/targeted therapy were analysed, retrospectively. The patient group was divided into two according to the drugs have been using at the time of IGRA test. Patients using methotrexate ≥ 10 mg or leflunomide (any dose) or steroids (≥7.5 mg prednisolone) or any combination thereof were classified as the “High Dose” group. The other group consisted of patients who did not take these drug doses. Demographic characteristics, comorbidities, drugs and doses used, and hemogram, sedimentation, and CRP values of the patients were recorded. QuantiFERON test was recorded as positive, negative, indeterminate.
Results: 353(66.1%) RA patients were in the high dose patient group and also 287(81.3%) of these patients were female, the median age was 55 years (min:19- max:82). The high dose group was older than the other group. When the two groups were compared, no statistically significant difference was found between comorbidity, and smoking (
Comparison of RA patients’ groups using high-dose immunosuppressives and not using any of them
| High Dose Methotrexate or Leflunomide or Steroid (+), (% )66.1 | High Dose Methotrexate or Leflunomide or Steroid (-), (% )33.9 | P Value | ||
|---|---|---|---|---|
| Female | 81.3 | 75.1 | 0.09 | |
| Age, med (min-max) | 55 (19-82) | 52 (19-81) | 0.01 | |
| Diabetes Mellitus | 11 | 10.5 | 0.84 | |
| Hypertension | 30.6 | 24.9 | 0.16 | |
| Chronic Renal Failure | 0.3 | 0 | 0.66 | |
| Chronic Obstructive Pulmonary Disease | 4.2 | 3.3 | 0.59 | |
| Coronary Artery Disease | 3.7 | 6.1 | 0.20 | |
| History of malignancy | 0.8 | 1.7 | 0.40 | |
| Smoking | Never | 49 | 52.5 | 0.19 |
| Ever | 24.1 | 27.6 | ||
| Quit | 26.3 | 18.8 | ||
| Leukocyte,*10 3 /ml | Median (min-max) | 7.6 (2.8-28.8) | 7.9 (3.5 – 20.8) | 0.26 |
| Neutrophil,*10 3 /ml | 4.8 (0.2-23.0) | 5.0 (1.5-19.1) | 0.18 | |
| Lymphocyte,*10 3 /ml | 1.9 (0.4-5.9) | 1.8 (0.5-5.3) | 0.67 | |
| Thrombocyte,*10 3 /ml | 285 (117-669) | 285.5 (60-724) | 0.79 | |
| Hemoglobine,g/dL | 12.8 (7.7-17.9) | 12.8 (9.3-16.6) | 0.41 | |
| Sedimentation,mm/saat | 30 (2-294) | 28 (2-104) | 0.27 | |
| C Reactive Protein,mg/dl | 1.1 (0.1-62.8) | 1.1 (0-20.7) | 0.96 | |
| QuantiFERON-TB Gold-Plus (QFT-Plus ) | 10.5 | 20.4 | 0.00 | |
| Nil med (min-max) | 0.07 (0-2.7) | 0.05 (0-0.85) | 0.48 | |
| QFT-Plus TB-1 med (min-max) | 1 (0->10) | 0.99 (0->10) | 0.25 | |
| QFT-Plus TB-2 med (min-max) | 1 (0->10) | 1.1 (0->10) | 0.42 | |
| Mitogen med (min-max) | 10 (0->10) | 9.5 (0->10) | 0.27 | |
| Methotrexate | Not Taking | 31.4 | 33.7 | |
| Less than 10 mg | 44.2 | 66.3 | ||
| 10 mg and more | 24.4 | 0 | ||
| Leflunomide | Not Taking | 25.8 | 100 | |
| Taking | 74.2 | 0 | ||
| Hydroxychloroquine | Not Taking | 25.2 | 40.9 | |
| Taking | 74.8 | 59.1 | ||
| Sulfasalazine | Not Taking | 62.6 | 61.9 | |
| Taking | 37.4 | 38.1 | ||
| Steroids | Not Taking | 4.2 | 19.9 | |
| Less than 7.5 mg | 66.3 | 80.1 | ||
| 7.5 mg and more | 29.5 | 0 | ||
Conclusion: Our results confirmed a significantly lower QFT-Plus positivity in patients with RA taking methotrexate ≥ 10 mg or leflunomide (any dose) or steroids (≥7.5 mg prednisolone). Physicians should be careful in interpretation of QFT-Plus in patients with rheumatoid arthritis. Further analysis including flow cytometry analysis is required to better identifying cut-offs for immunosuppressive individuals and patients with inflammatory rheumatic diseases.
Disclosure of Interests: None declared