Tuberculosis in pediatric patients treated with anti-TNFα drugs: a cohort study

Abstract

BackgroundAdult patients receiving anti-TNFα drugs are at increased risk of tuberculosis (TB), but studies in pediatric populations are limited, and the best strategy for latent tuberculosis infection (LTBI) screening in this population remains controversial. We describe the prevalence of LTBI prior to anti-TNFα therapy and the long-term follow-up after biological treatment initiation in a cohort of children and adolescents.MethodsCohort observational study in children and adolescents receiving anti-TNFα agents in a tertiary-care pediatric hospital. LTBI was ruled out prior to the implementation of anti-TNFα drugs by tuberculin skin test (TST), and, from March 2012 on, QuantiFERON Gold-In Tube® test (QTF-G). During anti-TNFα treatment, patients were evaluated every 6 months for TB with history and physical examination. TST/QTF-G were not repeated unless signs or symptoms consistent with TB arose or there was proven TB contact.ResultsThe final cohort consisted of 221 patients (56.1 % female; 261 treatments), of whom 51.7 %/30.0 %/17.3 % were treated with etanercept/adalimumab/infliximab, respectively, for a variety of rheumatic diseases (75.6 %), inflammatory bowel disease (20.8 %), and inflammatory eye diseases (3.6 %). The median (IQR) age at diagnosis of the primary condition was 6.8 years (2.7–11.0) and the duration of the disease before implementing the anti-TNFα agent was 1.8 years (0.6–4.2). LTBI was diagnosed in 3 adolescent girls (prevalence rate: 1.4 %; 95 % CI: 0.4–4.2) affected with juvenile idiopathic arthritis: TST tested positive in only 1, while QTF-G was positive in all cases (including 2 patients already on etanercept). They all received antiTB chemoprophylaxis and were later (re)treated with etanercept for 24–29 months, without incidences. No incident cases of TB disease were observed during the follow-up period under anti-TNFα treatment of 641 patients-year, with a median (IQR) time per patient of 2.3 years (1.4–4.3).ConclusionsIn our study, the prevalence of LTBI (1.4 %) was similar to that reported in population screening studies in Spain; no incident cases of TB disease were observed. In low-burden TB settings, initial screening for TB in children prior to anti-TNFα treatment should include both TST and an IGRA test, but systematic repetition of LTBI immunodiagnostic tests seems unnecessary in the absence of symptoms or known TB contact.

The effects of TNF-alpha inhibitor therapy on the incidence of infection in JIA children: a meta-analysis

“…TB-screening is one of the preliminary tests before the induction of a biologic agent therapy. One trial that was excluded used a retrospective observational study design to investigate JIA patients with TB [35]. Latent TB infection prior to therapy was diagnosed in 3/221 adolescent girls (prevalence rate: 1.4%; 95% CI: 0.4–4.2).…”

A scoping review of paediatric latent tuberculosis infection care cascades: initial steps are lacking

“…28 Using chest radiograph as a gold standard, authors devised a score based on cough and reduced playfulness that could identify child contacts with high probability of having TB disease, enabling them to differentiate these patients from paediatric patients with TB infection or no TB infection following exposure to infected adults. [87][88][89][90][91][92][93][94][95][96][97][98][99][100] Only one study documented <90% recommendation rate: a study from Australia in which 86% of paediatric patients with TB infection were recommended to start treatment. 101 The primary reason treatment was not recommended in high-income countries and LMIC was because providing treatment was not strictly indicated, for example, because of guidelines not supporting TB infection treatment for select patients with positive tests 37 87 and presumed falsepositive tests in the setting of prior BCG vaccination.…”

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

“…To our knowledge, fewer than 20 cases have been described in detail in the peer-reviewed literature so far [10][11][12][13][14][15][16]. Concerningly, several of those cases had a fatal outcome.…”