THU0543 LATENT TUBERCULOSIS INFECTION IN CHILDREN WITH PEDIATRIC RHEUMATOLOGIC DISEASES TREATED WITH CANAKINUMAB

Abstract

Background: Little is known about the long-term safety of canakinumab about tuberculosis (TB) risk in paediatric rheumatologic diseases. Objectives: To determine the incidence of latent tuberculosis infection and evaluate the follow-up protocol of the patients treated with canakinumab in a single pediatric rheumatology center from a TB-medium burden country. Methods: The hospital charts of patients treated with canakinumab between 2012 and 2019 were retrospectively reviewed. The patients were screened for TB using tuberculin skin test (TST) and/or QuantiFERON-TB Gold (QFT-G) test. They had no history of active TB prior to screening and no signs or symptoms of active TB. None of the patients had recent close contact with a person diagnosed as active TB. At initial evaluation, in patients who had never been given immunosuppressive therapy, TST ≥15 mm (if BCG vaccinated) and TST ≥10 mm (if BCG unvaccinated) were considered as positive. In the case of prior immunosuppressive drug use TST cut-off limit was accepted as 5 mm. Patients with either a positive TST or QFT-G result, in whom active TB ruled out, were to receive appropriate treatment for latent TB one month prior to the first dose of canakinumab and continue throughout 9 months. Chest radiographs were performed prior to therapy and every 6 months. In case TST was anergic, both chest X-ray and TST were repeated after 3 months. Patients were evaluated for signs and symptoms of active TB by an infectious disease specialist every 3 months while on canakinumab therapy according to the “guidelines of Ministry of Health for use of biologic agents”. The TST conversion was considered as a variation ≥5 mm between the two TSTs performed within an interval at least 3 months. If TB was suspected during the study, repeat TB testing (TST, QFT-G, and chest radiograph) was recommended. Results: 29 Familial Mediterranean fever, 6 systemic juvenile idiopathic arthritis, 1 TRAPS and 1 hyper Ig D syndrome patients were evaluated. The mean age at canakinumab onset was 12.4 ± 4.3 years (min: 2, max: 17 years). The average duration of canakinumab use was 2.3±1.4years (min: 1 max: 6.5 years). Among 37 patients, 5 patients had positive TST and one had positive QFT-G with normal chest X-ray prior to therapy. They were given isoniasid prophylaxis for latent TB. QFT-G was checked in 6 patients prior to canakinumab, 5 were negative. Seven patients had TST conversion during follow-up. Their chest X-rays were normal. None of them had active TB symptoms, such as; cough, fever, night sweats and weight loss. The mycobacterial cultures, mycobacterium tuberculosis PCR of induced sputum (via hypertonic saline nebulization) or morning gastric aspirates were negative in these patients. QFT-G was checked in 10 patients during follow-up and all were negative. None of the patients experienced active TB during follow-up. Conclusion: To the best of our knowledge, this is the first study investigating the frequency of latent tuberculosis infection among patients treated with canakinumab. The results of this study suggest that although frequency of latent TB infection in children treated with canakinumab may not be low in a TB-medium burden country, canakinumab seems to be a safe treatment option in terms of active tuberculosis risk. Close follow-up of children on canakinumab treatment with respect to TB by the pediatric infectious disease department is important to prevent possible complications. Reference: [1] T.C Saglik Bakanligi Turkiye Halk Sagligi Kurumu AntiTNF Kullanan Hastalarda Tuberkuloz Rehberi. Available at: http://www.mhsm.gov.tr/images/diger_haberler/anti_tnf_kullanan_hasta_tb_rehber.pdf. Disclosure of Interests: Balahan Makay Speakers bureau: Enzyvant, Novartis, Roche, Abbvie, ozge altug gucenmez Speakers bureau: Novartis, Abbvie, Ilknur Caglar: None declared, Suleyman Nuri Bayram: None declared, Nesrin Gulez: None declared, Ilker Devrim: None declared