Evaluation of  tuberculosis frequency in children using biological agents

Purpose: Anti-TNF drugs increase the risk of tuberculosis. In this study we aimed to investigate the incidence of tuberculosis in patients using anti-TNF drugs.Methods: One hundred and fifteen pediatric cases which were received anti-TNF drugs were included in the study. The clinical and epidemiological characteristics of the cases were analyzed retrospectively.Results: One hundred and fifteen cases using anti-TNF drugs were included in the study. The diagnoses of the cases were as follows; Juvenile Rheumatoid Arthritis 76 (66%), Ulcerative Colitis 11 (9.6%), Crohn's 7 (6%), Ankylosing Spondylitis 6 (5.2%), FMF 5 (4.3%), Psoriasis 4 (%3.5). The distribution of the agents used by the patients was; etanercept 74 (64.3%), infliximab 17 (14.8%), adalimumab 17 (14.8%), anakinra 5 (4.3%), and canakinumab 2 (%1.7). It was learned that all cases had BCG vaccinations when they were two months old, confirmed by the vaccination cards and the ministry of health's vaccination follow-up system. TST was performed in all of the cases and TST response was measured as <5mm in 89 (77.4%), 5-9 mm in 11 (8.7%), 10-14 mm in 8 (7.4%), >15 mm in 7 (5.6%) cases. Isoniazid (INH) prophylaxis was started for nine months in 17 cases with the diagnosis of latent tuberculosis. Active tuberculosis was not detected in any of the cases.Conclusion: All patients receiving anti-TNF need to be evaluated for tuberculosis. Although it is not detected at the beginning of the treatment, regular tuberculosis screening should be continued during the treatment with contact history, symptoms, physical examination, chest X-ray, and TST/IGRA in light of current guidelines.

Anahtar Kelime: tubercolosis pediatric anti-TNF

Biyolojik ajan kullanan çocuklarda tüberküloz sıklığının değerlendirilmesi

Öz:

Amaç: Anti-TNF ilaçlar tüberküloz enfeksiyon riskini arttırırlar. Bu çalışmayla Anti-TNF ilaç kullanan hastalarda, tüberküloz gelişme sıklığını araştırmayı amaçladık. Gereç ve yöntem: Çalışmaya anti-TNF ilaç kullanan 115 çocuk hasta dahil edildi. Olguların klinik ve epidemiyolojik özellikleri retrospektif olarak değerlendirildi. Bulgular: Anti-TNF ilaç kullanan 115 olgu çalışmaya dahil edildi. Olguların tanıları; Juvenil Romatoid Artrit 76 (%66), Ülseratif Kolit 11 (%9,6), Crohn's 7 (%6), Ankilozan Spondilit 6 (%5,2), FMF 5 (%4,3), Psoriasis 4 (%3,5) şeklindeydi. Hastaların kullandığı ajanların dağılımı ise; etanersept 74 (%64,3), infliximab 17 (%14,8), adalimumab 17 (%14,8), anakinra 5 (%4,3) ve kanakinumab 2 (%1,7) şeklindeydi. Tüm vakaların iki aylıkken BCG aşısı olduğu öğrenildi, aşı kartları ve sağlık bakanlığının aşı takip sisteminden teyit edildi. Tüm olgulara TDT yapıldı ve TDT yanıtı <5mm 89 (%77,4), 5-9 mm 11 (%8,7), 10-14 mm 8 (%7,4), >15 mm 7 (%5,6) olarak ölçüldü. Latent tüberküloz tanısı alan 17 olguya 9 ay izoniazid (INH) profilaksisi başlandı. Olguların hiçbirinde aktif tüberküloz saptanmadı.Sonuç: Anti-TNF alan tüm hastaların tüberküloz açısından değerlendirilmesi gerekmektedir. Tedavi başlangıcında saptanmasa da tedavi süresince güncel kılavuzlar ışığında temas öyküsü, semptomlar, fizik muayene, akciğer grafisi ve TDT/IGRA ile düzenli tüberküloz taramasına devam edilmelidir.

Anahtar Kelime: Tüberküloz çocuk anti-TNF.

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık

1. Tracey D, Klareskog L, Sasso EH, Salfeld JG, Tak PP. Tumor necrosis factor antagonist mechanis- ms of action: a comprehensive review. Pharmacol Ther 2008;117:244-279. https://doi.org/10.1016/j. pharmthera.2007.10.001
2. Philips JA, Ernst JD. Tuberculosis pathogenesis and immunity. Annu Rev Pathol 2012;7:353-384. https:// doi.org/10.1146/annurev-pathol-011811-132458
3. Wallis RS, Broder MS, Wong JY, Hanson ME, Be- enhouwer DO. Granulomatous infectious disea- ses associated with tumor necrosis factor antago- nists. Clin Infect Dis 2004;38:1261-1265. https://doi. org/10.1086/383317
4. Wallis RS. Reactivation of latent tuberculosis by TNF blockade: the role of interferon gamma. J Inves- tig Dermatol Symp Proc 2007;12:16-21. http://doi. org/10.1038/sj.jidsymp.5650031
5. Taylor PC. Tumor necrosis factor-blocking therapies. In: Hochberg MC, Silman AJ, Smolen JS, Weinblatt ME, Weisman MH, editors. Rheumatology. 5th ed. Philadelphia, PA: Mosby, Elsevier 2015:492-510.
6. Caso F, Costa L, Del Puente A, et al. Pharmacological treatment of spondyloarthritis: exploring the effective- ness of nonsteroidal anti-inflammatory drugs, traditio- nal disease-modifying antirheumatic drugs and biologi- cal therapies. Ther Adv Chronic Dis 2015;6:328-338. http:/doi.org/10.1177/2040622315608647
7. Ungprasert P, Thongprayoon C, Davis JM. Indirect comparisons of the efficacy of biological agents in pa- tients with psoriatic arthritis with an inadequate respon- se to traditional disease-modifying anti-rheumatic dru- gs or to non-steroidal anti-inflammatory drugs: a me- ta-analysis. Semin Arthritis Rheum 2016;45:428-438. https:/doi.org/10.1016/j.semarthrit.2015.09.004
8. Steigerwald KA, Ilowite NT. Novel treatment options for juvenile idiopathic arthritis. Expert Rev Clin Pharma- col 2015;8:559-573. https:/doi.org/10.1586/17512433. 2015.1061428
9. Turkish Ministry of Health, Public Health Institution of Turkey, Tuberculosis Guide for Patients Using Anti- TNF, Ankara, 2016;107-109.
10. British Thoracic Society Standards of Care Commit- tee. B.T.S. recommendations for assessing risk and for managing Mycobacterium tuberculosis infection and disease in patients due to start anti-TNF-alpha treat- ment. Thorax 2005;60:800-805. https:/doi.org/10.1136/ thx.2005.046797
11. Targeted tuberculin testing and treatment of latent tuberculosis infection. American Thoracic Society. MMWR Recomm Rep 2000;49:1-51.
12. Borekci S, Atahan, E, Demir Yilmaz D, et al. Factors affecting the tuberculosis risk in patients receiving anti-tumor necrosis factor-α treatment. Respiration 2015;90:191-198. https:/doi.org/10.1159/000434684
13. Kilic O, Kasapcopur O, Camcioglu Y, Cokugras H, Ari- soy N, Akcakaya N. Is it safe to use anti-TNF-α agents for tuberculosis in children suffering with chronic rheu- matic disease? Rheumatol Int 2012;32:2675-2679. https://doi.org/10.1007/s00296-011-2030-8
14. Girit S, Ayzit Atabek A, Şenol E. et al. Screening for latent tuberculosis in children with ımmune-media- ted ınflammatory diseases treated with anti-tumor necrosis factor therapy: comparison of tuberculin skin and T-SPOT tuberculosis tests. Arch Rheumatol 2019;35:20-28. https:/doi.org/10.5606/ArchRheumatol. 2020.7294
15. Lewinsohn DM, Leonard MK, LoBue PA, et al. Official American Thoracic Society/Infectious Diseases Society of America/Centers for Disease Control and Prevention Clinical Practice Guidelines: Diagnosis of Tuberculosis in Adults and Children. Clin Infect Dis 2017;64:1-33. https://doi.org/10.1093/cid/ciw694
16. Solovic I, Sester M, Gomez Reino JJ, et al. The risk of tuberculosis related to tumour necrosis factor antagonist therapies: a TBNET consensus state- ment. Eur Respir J 2010;36:1185-1206. https://doi. org/10.1183/09031936.00028510
17. Cagatay T. The Role of IGRA tests and tuberculin test for determination of latent tuberculosis in TNF-α anta- gonist users (Candidates). Turk J Dermatol 2012;6:62- 64. https://doi.org/10.5152/tdd.2012.16
18. Cagatay T, Aydin M, Sunmez S, et al. Follow-up results of 702 patients receiving tumor necrosis factor-α an- tagonists and evaluation of risk of tuberculosis. Rheu- matol Int 2010;30:1459-1463. https://doi.org/10.1007/ s00296-009-1170-6
19. Hanta I, Ozbek S, Kuleci S, Kocabas A. The evalua- tion of latent tuberculosis in rheumatologic diseases for anti-TNF therapy: experience with 192 patients. Clin Rheumatol 2008;27:1083-1086. https://doi. org/10.1007/s10067-008-0867-3
20. Kurt OK, Kurt B, Talay F, et al. Intermediate to long- term follow-up results of INH chemoprophylaxis prior to anti-TNF-alpha therapy in a high-risk area for tu- berculosis. Wien Klin Wochenschr 2013;125:616-620. https://doi.org/10.1007/s00508-013-0417-0
21. Kaptan Y, Suner A, Taş MN, Oksel F, Aksu K, Sayi- ner A. Tuberculosis despite latent infection screening and treatment in patients receiving TNF inhibitor the- rapy. Clin Rheumatol 2021;40:3783-3788. https://doi. org/10.1007/s10067-021-05697-5
22. Noguera Julian A, Calzada Hernández J, Brinkmann F, et al. Tuberculosis disease in children and adolescents on therapy with antitumor necrosis factor-ɑ agents: a collaborative, multicenter paediatric tuberculosis network european trials group (ptbnet) study. Clin Infe- ct Dis 2020;71:2561-2569. https://doi.org/10.1093/cid/ ciz1138
23. Dixon WG, Hyrich KL, Watson KD, Lunt M, Galloway J, Ustianowski A. B S R B R Control Centre Consortium, D P M Symmons, B.S.R. Biologics Register. Drug-spe- cific risk of tuberculosis in patients with rheumatoid arthritis treated with anti-TNF therapy: results from the British Society for Rheumatology Biologics Register (BSRBR). Ann Rheum Dis 2010;69:522-528. https:// doi.org/10.1136/ard.2009.118935
24. Miller EA, Ernst JD. Anti-TNF immunotherapy and tuberculosis reactivation: another mechanism reve- aled. J Clin Invest 2009;119:1079-1082. https://doi. org/10.1172/jci39143
25. Bruns H, Meinken C, Schauenberg P, et al. Anti-TNF immunotherapy reduces CD8+ T cell-mediated anti- microbial activity against Mycobacterium tuberculosis in humans. J Clin Invest 2009;119:1167-1177. https:// doi.org/10.1172/JCI38482
26. Paluch Oleś J, Magryś A, Kozioł Montewka M, Koszarny A, Majdan M. Identification of latent tuberculosis infecti- on in rheumatic patients under consideration for treat- ment with anti-TNF-α agents. Arch Med Sci 2013;9:112- 117. http://doi.org/10.5114/aoms.2013.33352

APA	kara y, KIZIL M, İŞERİ NEPESOV M, KAVAZ TUFAN A, CETIN N, aydemir y, BARİS Z, Uzun S, Kilic O, Dinleyici E (2023). Evaluation of tuberculosis frequency in children using biological agents. , 238 - 246. 10.31362/patd.1189676
Chicago	kara yalçın,KIZIL MAHMUT CAN,İŞERİ NEPESOV MERVE,KAVAZ TUFAN ASLI,CETIN NURAN,aydemir yusuf,BARİS Zeren,Uzun Soner,Kilic Omer,Dinleyici Ener Cagri Evaluation of tuberculosis frequency in children using biological agents. (2023): 238 - 246. 10.31362/patd.1189676
MLA	kara yalçın,KIZIL MAHMUT CAN,İŞERİ NEPESOV MERVE,KAVAZ TUFAN ASLI,CETIN NURAN,aydemir yusuf,BARİS Zeren,Uzun Soner,Kilic Omer,Dinleyici Ener Cagri Evaluation of tuberculosis frequency in children using biological agents. , 2023, ss.238 - 246. 10.31362/patd.1189676
AMA	kara y,KIZIL M,İŞERİ NEPESOV M,KAVAZ TUFAN A,CETIN N,aydemir y,BARİS Z,Uzun S,Kilic O,Dinleyici E Evaluation of tuberculosis frequency in children using biological agents. . 2023; 238 - 246. 10.31362/patd.1189676
Vancouver	kara y,KIZIL M,İŞERİ NEPESOV M,KAVAZ TUFAN A,CETIN N,aydemir y,BARİS Z,Uzun S,Kilic O,Dinleyici E Evaluation of tuberculosis frequency in children using biological agents. . 2023; 238 - 246. 10.31362/patd.1189676
IEEE	kara y,KIZIL M,İŞERİ NEPESOV M,KAVAZ TUFAN A,CETIN N,aydemir y,BARİS Z,Uzun S,Kilic O,Dinleyici E "Evaluation of tuberculosis frequency in children using biological agents." , ss.238 - 246, 2023. 10.31362/patd.1189676
ISNAD	kara, yalçın vd. "Evaluation of tuberculosis frequency in children using biological agents". (2023), 238-246. https://doi.org/10.31362/patd.1189676

APA	kara y, KIZIL M, İŞERİ NEPESOV M, KAVAZ TUFAN A, CETIN N, aydemir y, BARİS Z, Uzun S, Kilic O, Dinleyici E (2023). Evaluation of tuberculosis frequency in children using biological agents. Pamukkale Tıp Dergisi, 16(2), 238 - 246. 10.31362/patd.1189676
Chicago	kara yalçın,KIZIL MAHMUT CAN,İŞERİ NEPESOV MERVE,KAVAZ TUFAN ASLI,CETIN NURAN,aydemir yusuf,BARİS Zeren,Uzun Soner,Kilic Omer,Dinleyici Ener Cagri Evaluation of tuberculosis frequency in children using biological agents. Pamukkale Tıp Dergisi 16, no.2 (2023): 238 - 246. 10.31362/patd.1189676
MLA	kara yalçın,KIZIL MAHMUT CAN,İŞERİ NEPESOV MERVE,KAVAZ TUFAN ASLI,CETIN NURAN,aydemir yusuf,BARİS Zeren,Uzun Soner,Kilic Omer,Dinleyici Ener Cagri Evaluation of tuberculosis frequency in children using biological agents. Pamukkale Tıp Dergisi, vol.16, no.2, 2023, ss.238 - 246. 10.31362/patd.1189676
AMA	kara y,KIZIL M,İŞERİ NEPESOV M,KAVAZ TUFAN A,CETIN N,aydemir y,BARİS Z,Uzun S,Kilic O,Dinleyici E Evaluation of tuberculosis frequency in children using biological agents. Pamukkale Tıp Dergisi. 2023; 16(2): 238 - 246. 10.31362/patd.1189676
Vancouver	kara y,KIZIL M,İŞERİ NEPESOV M,KAVAZ TUFAN A,CETIN N,aydemir y,BARİS Z,Uzun S,Kilic O,Dinleyici E Evaluation of tuberculosis frequency in children using biological agents. Pamukkale Tıp Dergisi. 2023; 16(2): 238 - 246. 10.31362/patd.1189676
IEEE	kara y,KIZIL M,İŞERİ NEPESOV M,KAVAZ TUFAN A,CETIN N,aydemir y,BARİS Z,Uzun S,Kilic O,Dinleyici E "Evaluation of tuberculosis frequency in children using biological agents." Pamukkale Tıp Dergisi, 16, ss.238 - 246, 2023. 10.31362/patd.1189676
ISNAD	kara, yalçın vd. "Evaluation of tuberculosis frequency in children using biological agents". Pamukkale Tıp Dergisi 16/2 (2023), 238-246. https://doi.org/10.31362/patd.1189676