Iranian Journal of Pathology

Assessment of PPD Conversion Rate in Patients Receiving Tumor Necrosis Factor-alpha Inhibitor Drugs

Articles in Press

Document Type : Original Research

Authors

Mohsen Meidani 1
Faranak Nasseri 2
Abdolrahman Rostamian 2
Zahra Saffarian 3
Neda Alijani 4
Parvin Rezaie 5
Ali Ferdosi 6
Amirhossein Hajialigol 7
Mohammadreza Shafiei 8
Shila Aghayani 8

1 Department of Infectious Diseases, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran

2 Department of Rheumatology, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran

3 Dermatology Department of Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran

4 Department of Infectious Diseases, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran

5 Master of Nursing, Community Health Management Nursing, Infection Control Department, Shariati Hospital, Tehran, Iran

6 Department of Pharmacology, Tehran Medical Sciences Branch, Islamic Azad University, Tehran, Iran

7 Alborz Office of Universal Scientific Education and Research Network (USERN), Alborz University of Medical Sciences, Karaj, Iran

8 Student Research Committee, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran.

10.30699/ijp.2026.2076748.3574
Abstract
Background & Objective: Tumor necrosis factor-alpha (TNF-α) inhibitors are widely used in rheumatologic diseases but may increase the risk of primary tuberculosis (TB) infection or reactivation. Purified protein derivative (PPD) conversion is an important indicator of latent TB in immunosuppressed patients. This study aimed to determine the rate of PPD conversion and associated factors in patients receiving anti-TNF therapy.
Methods: This prospective study included adults with rheumatologic diseases who initiated anti-TNF therapy between March 2021 and September 2023. Patients with prior TB, previous anti-TNF exposure, or a positive baseline PPD were excluded. A PPD test was performed before treatment and repeated one year later. An induration ≥5 mm at follow-up was considered conversion.
Results: Sixty patients completed the study (mean age 44.29 ± 14.70 years; 56.7% male). Six patients (10.0%) demonstrated PPD conversion after one year of anti-TNF therapy. Most conversions occurred in individuals with psoriatic arthritis (66.6%). No cases of active TB were detected clinically or radiologically. Statistical analysis showed no significant association between PPD conversion and age, sex, disease duration, anti-TNF type, methotrexate or corticosteroid use, diabetes mellitus, or hypertension. Psoriatic arthritis was the only factor significantly associated with conversion (P = 0.03).
Conclusion: Ten percent of patients receiving anti-TNF therapy developed PPD conversion, indicating new latent TB infection. Psoriatic arthritis was significantly associated with conversion, while medication type and other clinical factors were not. These findings support routine annual TB screening in anti-TNF recipients, particularly in regions with moderate or high TB prevalence.

Keywords

anti-TNF drugs, Tuberculosis, PPD, Biological drugs

Subjects

1.      Mardi S, Shojaeian S, Shadabi S, et al. Zidovudine and interferon alfa-based regimens for the treatment of adult T-cell leukemia/lymphoma: a systematic review and meta-analysis. Virol J. 2023;20(1):118. [DOI:10.1186/s12985-023-02077-0] [PMID] [PMCID]
2.      Mahdavi FS, Mardi S, Mohammadi S, Ansari S, Yaslianifard S, Fallah P, et al. MicroRNA-146: biomarker and mediator of cardiovascular disease. Dis Markers. 2022;2022:1-10.          [DOI:10.1155/2022/7767598] [PMID] [PMCID]
3.      Papamichael K, Cheifetz AS. Use of anti-TNF drug levels to optimise patient management. Frontline Gastroenterol. 2016;7(4):289-300. [PMCID] [DOI:10.1136/flgastro-2016-100685] [PMID]
4.      Sartori NS, de Andrade NPB, da Silva Chakr RM. Incidence of tuberculosis in patients receiving anti-TNF therapy for rheumatic diseases: a systematic review. Clin Rheumatol. 2020;39(5):1439-47. [DOI:10.1007/s10067-019-04866-x] [PMID]
5.      Natarajan A, Beena P, Devnikar AV, Mali S. A systemic review on tuberculosis. Indian J Tuberc. 2020;67(3):295-311. [DOI:10.1016/j.ijtb.2020.02.005] [PMID]
6.      Tavakoli A. Incidence and prevalence of tuberculosis in Iran and neighboring countries. Zahedan J Res Med Sci. 2017;19(7):e12345. [DOI:10.5812/zjrms.9238]
7.      Athimni S, Slouma M, Dhahri R, Gharsallah I, Metoui L, Louzir B. Tuberculosis infection under anti-TNF alpha treatment. Curr Drug Saf. 2022;17(3):235-40. [DOI:10.2174/1574886316666211109092354] [PMID]
8.      Rodríguez-Molino P, Tebruegge M, Noguera-Julian A, Neth O, Fidler K, Brinkmann F, et al. Tuberculosis disease in immunocompromised children and adolescents: a pTBnet multicentre case-control study. Clin Infect Dis. 2024;79(2):ciae158.
9.      Ketabforoush AHME, Aleahmad M, Qorbani M, Mehrpoor G, Afrashteh S, Mardi S, et al. Bone mineral density status in patients with recent-onset rheumatoid arthritis. J Diabetes Metab Disord. 2023;22(1):775-85. [DOI:10.1007/s40200-023-01200-w] [PMID] [PMCID]
10.    Jensen PA, Lambert LA, Iademarco MF, Ridzon R. Guidelines for preventing the transmission of Mycobacterium tuberculosis in health-care settings, 2005. MMWR Recomm Rep. 2005;54(RR-17):1-141.
11.    Park HJ, Choi BY, Sohn M, Han NY, Kim IW, Oh JM. Effects of tumor necrosis factor-alpha inhibitors on the incidence of tuberculosis. Korean J Clin Pharm. 2018;28(4):333-41. [DOI:10.24304/kjcp.2018.28.4.333]
12.    Lalvani A, Millington KA. Screening for tuberculosis infection prior to initiation of anti-TNF therapy. Autoimmun Rev. 2008;8(2):147-52. [PMID] [PMCID] [DOI:10.1016/j.autrev.2008.07.011]
13.    Cuomo G, D'Abrosca V, Iacono D, Pantano I, et al. The conversion rate of tuberculosis screening tests during biological therapies in patients with rheumatoid arthritis. Clin Rheumatol. 2017;36(2):457-61. [DOI:10.1007/s10067-016-3462-z] [PMID]
14.    Lee CK, Wong SH, Lui G, Tang W, Tam LS, Ip M, et al. A prospective study to monitor for tuberculosis during anti-tumor necrosis factor therapy. J Crohns Colitis. 2018;12(8):954-62. [DOI:10.1093/ecco-jcc/jjy057] [PMID]
15.    Goel N, Torralba K, Downey C, Salto L. Screening for acquired latent tuberculosis in rheumatoid arthritis patients on TNF inhibition therapy in Southern California. Clin Rheumatol. 2020;39(8):2291-7. [DOI:10.1007/s10067-020-04991-y] [PMID]
16.    Pattanaik D, Gupta S, Islam S, Singhal K, Raza S. Conversion of tuberculosis screening tests during biologic therapy among veteran patients with rheumatic disease. ACR Open Rheumatol. 2019;1(9):542-5. [DOI:10.1002/acr2.11070] [PMID] [PMCID]
17.    Zavala Del Ángel AE, Morales-Romero J, Zenteno-Cuevas R, Enciso Moreno JA, Mata Miranda MDP, Martínez Zapata JL, et al. Prevalence of latent tuberculosis infection (LTBI) in Mexican patients with rheumatoid arthritis (RA). Cureus. 2023;15(5):e39743. [DOI:10.7759/cureus.39743] [PMID] [PMCID]
18.    Song YJ, Cho SK, Kim H, Kim HW, Nam E, Bae SC, et al. Risk of tuberculosis development in patients with rheumatoid arthritis receiving targeted therapy: a prospective single center cohort study. J Korean Med Sci. 2021;36(10):e70.            [DOI:10.3346/jkms.2021.36.e70] [PMID] [PMCID]
19.    Coşkunol İ, Turan O, Baysak A, Solmaz D, Can G. Frequency of latent tuberculosis in patients receiving anti-TNF-alpha therapy. Afr Health Sci. 2023; 23(2):128-32. [DOI:10.4314/ahs.v23i2.14] [PMID] [PMCID]
20.    Hai BB, Anh TL, Thi Thu PN, Van HN, Van GV, Van DH. Latent and active tuberculosis development in rheumatoid arthritis patients receiving biologic DMARDs: a prospective study. PLoS One. 2024; 19(1):e0295048. [PMID] [PMCID]      [DOI:10.1371/journal.pone.0295048]
Iranian Journal of Pathology

Articles in Press, Accepted Manuscript
Available Online from 20 February 2026

  • Receive Date 04 November 2025
  • Revise Date 27 November 2025
  • Accept Date 10 January 2026

Home

Guide for Authors

Submit Manuscript

Contact Us