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

Calzada-Hernández, Joan; Antón-López, Jordi; Bou-Torrent, Rosa; Iglesias-Jiménez, Estibaliz; Ricart-Campos, Sílvia; Carpi, Javier Martín de; Torrente-Segarra, Vicenç; Sánchez-Manubens, Judith; Gimenez-Roca, Clara; Rozas-Quesada, Librada; Juncosa-Morros, Maria Teresa; Fortuny, Clàudia; Noguera-Julián, Antoni

doi:10.1186/s12969-015-0054-4

Cited by 34 publications

(19 citation statements)

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“…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).…”

Section: Resultsmentioning

confidence: 99%

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

et al. 2019

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BackgroundJuvenile Idiopathic arthritis (JIA) is the most common chronic rheumatic disease in childhood. The diagnosis is based on the underlying symptoms of arthritis with an exclusion of other diseases Biologic agents are increasingly used on the side of disease-modifying anti-rheumatic drugs (DMARD) in JIA treatment.Main bodyThe aim of this meta-analysis was to investigate the observed infections in JIA children during tumor necrosis factor (TNF)-alpha inhibitor therapy. A systematic search of three databases (Medline via PubMed, Embase, Cochrane Library) was carried out up to May 2018. Published trials that evaluated the infectious adverse events in patients receiving TNF-alpha inhibitor vs. a control group were included in the analysis. Full-text data extraction was carried out independently by the investigators from ten relevant publications. 1434 patients received TNF-alpha inhibitor therapy; the control group consisted of 696 subjects. The analysis presented the risk of infection in the active treatment group (OR = 1.13; 95% CI: 0.76–1.69; p = 0.543). The majority of infections were upper respiratory tract infections (URTIs). Furthermore, the subgroup analysis demonstrated a higher infection rate in the observed localization.ConclusionAnti-TNF therapy slightly but not significantly increases the incidence of infection in JIA children compared to other therapies (GRADE: moderate evidence). The most common infections reported were mild URTIs. Further studies with larger patients number with a strong evidence level are crucially needed to finalize the answer whether anti-TNF therapy elevates and if yes on what extent the incidence of infection in JIA children.Trial registrationProspero: CRD42017067873.Electronic supplementary materialThe online version of this article (10.1186/s12969-019-0305-x) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

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

et al. 2019

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“…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.…”

Section: Bmj Global Healthmentioning

confidence: 99%

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

2021

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Background and objectivesIdentifying and treating children with latent tuberculosis infection (TB infection) is critical to prevent progression to TB disease and to eliminate TB globally. Diagnosis and treatment of TB infection requires completion of a sequence of steps, collectively termed the TB infection care cascade. There has been no systematic attempt to comprehensively summarise literature on the paediatric TB infection care cascade.MethodsWe performed a scoping review of the paediatric TB infection care cascade. We systematically searched PubMed, Cumulative Index to Nursing and Allied Health Literature, Cochrane and Embase databases. We reviewed articles and meeting abstracts that included children and adolescents ≤21 years old who were screened for or diagnosed with TB infection, and which described completion of at least one step of the cascade. We synthesised studies to identify facilitators and barriers to retention, interventions to mitigate attrition and knowledge gaps.ResultsWe identified 146 studies examining steps in the paediatric TB infection care cascade; 31 included children living in low-income and middle-income countries. Most literature described the final cascade step (treatment initiation to completion). Studies identified an array of patient and caregiver-related factors associated with completion of cascade steps. Few health systems factors were evaluated as potential predictors of completion, and few interventions to improve retention were specifically tested.ConclusionsWe identified strengths and gaps in the literature describing the paediatric TB infection care cascade. Future research should examine cascade steps upstream of treatment initiation and focus on identification and testing of at-risk paediatric patients. Additionally, future studies should focus on modifiable health systems factors associated with attrition and may benefit from use of behavioural theory and implementation science methods to improve retention.

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“…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.…”

Section: Introductionmentioning

confidence: 95%

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

Noguera-Julián

Calzada-Hernández

Brinkmann

et al. 2019

Clinical Infectious Diseases

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Background In adults, anti–tumor necrosis factor-α (TNF-α) therapy is associated with progression of latent tuberculosis (TB) infection (LTBI) to TB disease, but pediatric data are limited. Methods Retrospective multicenter study within the Paediatric Tuberculosis Network European Trials Group, capturing patients <18 years who developed TB disease during anti–TNF-α therapy. Results Sixty-six tertiary healthcare institutions providing care for children with TB participated. Nineteen cases were identified: Crohn’s disease (n = 8; 42%) and juvenile idiopathic arthritis (n = 6; 32%) were the commonest underlying conditions. Immune-based TB screening (tuberculin skin test and/or interferon-γ release assay) was performed in 15 patients before commencing anti–TNF-α therapy but only identified 1 LTBI case; 13 patients were already receiving immunosuppressants at the time of screening. The median interval between starting anti–TNF-α therapy and TB diagnosis was 13.1 (IQR, 7.1–20.3) months. All cases presented with severe disease, predominantly miliary TB (n = 14; 78%). One case was diagnosed postmortem. TB was microbiologically confirmed in 15 cases (79%). The median duration of anti-TB treatment was 50 (IQR, 46–66) weeks. Five of 15 (33%) cases who had completed TB treatment had long-term sequelae. Conclusions LTBI screening is frequently false-negative in this patient population, likely due to immunosuppressants impairing test performance. Therefore, patients with immune-mediated diseases should be screened for LTBI at the point of diagnosis, before commencing immunosuppressive medication. Children on anti–TNF-α therapy are prone to severe TB disease and significant long-term morbidity. Those observations underscore the need for robust LTBI screening programs in this high-risk patient population, even in low-TB-prevalence settings.

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

Cited by 34 publications

References 23 publications

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

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

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

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

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