4Tuberculosis and other infections in the anti-tumour necrosis factor-alpha (anti-TNF-α) era
Section snippets
Most frequent infections in different therapies
A number of bacterial, viral and fungal infections occurred in patients with rheumatic diseases treated with anti-TNF-α [11], [12], [13]. the risk of infection is higher early after initiating treatment [14] and decreases with prolonged exposure to anti-TNF-α treatment [15].
Listing et al. [16] followed up for 3 years about 1000 RA patients and 601 control patients treated with TNF-α (512 patients receiving etanercept and 346 patients receiving infliximab) and anakinra (70 patients). The total
Data from registries
Clinical trials and post-marketing analysis are fundamental to monitor the safety profile of biologic therapies. Other good instruments are the national or local registries. The data are extrapolated from the real-world setting and are not biased on inclusion/exclusion criteria, mandatory for the clinical trials.
The ‘RA observation of Biologic Therapies’ (RABBIT) German registry evidenced a significant difference between patients treated with infliximab or etanercept and patients with only
TB
Even in the 21st century, TB kills more people than any other infective agent [48]. Mycobacterium tuberculosis can persist within the human host for years or even for life without causing disease, in a syndrome known as latent tuberculosis infection (LTBI) [49]. In 2008, World Health Organization (WHO) reported that about one-third of the world’s population is believed to harbour LTBI [50] and approximately 10% of immunocompetent persons with LTBI will develop active TB [50], eluding immune
Recommendations
Several recommendations for detecting LTBI have been proposed in different countries [64], [65].
In 2002, the RATIO study group established new recommendations in France [66], [67]. Patients were considered to have LTBI when chest X-rays showed present residual nodular lesions larger than 1 cm3 or old lesions, or when a skin reaction larger than 10 mm induration at tuberculin skin test (TST) is found. Treatment lasting at least 6 months, including at least 2 months with combination
Other opportunistic infections (OIs)
Many infectious adverse events have been reported and the most common pathogens were granulomatous infection [2], aspergillosis [1], Listeria monocitogenes [91] and Salmonella [2].
Other opportunistic infections (OIs), such as hystoplasmosis [92], coccidiomycosis [93] pneumocystosis and other fungal or viral infections have been described in patients on anti-TNF-α blockers.
Significant differences in the rate of serious bacterial infections (which required intravenous antibiotic therapy) were
Viral
Viral disease could be differentiated in three patterns of infectivity (Calabrese). The first one is typical of acute infections such as influenza, which is self-limited. Herpes simplex, Epstein–Barr virus (EBV) and varicella zoster are characterised by a period of acute primary infections, followed by a period of latency. After specific stimuli they may be reactivated, often with different clinical manifestations. Few viral pathogens have the capacity to cause a primary infection and then
Conclusions
Anti-TNF-α therapy has dramatically improved the management of many rheumatic diseases and conditions with altered immunoreactivity.
Conversely, an increased risk of TB and opportunistic infections is reported in clinical trials in post-marketing observations and in national and local registries.
Screening for LTBI and for hepatitis infection is mandatory to reduce the risk of reactivation.
Moreover, a close and careful safety monitoring during treatment is strongly recommended to exclude
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2013, Journal of Crohn's and ColitisCitation Excerpt :The increased clinical use of TNF-α antagonists dramatically improved the management of immunomediated diseases, but has led to a higher incidence of infections with intracellular agents.1–8 Keane et al. were the first to describe an increased incidence of tuberculosis (TB) in patients with rheumatoid arthritis (RA) treated with TNF-α blockers,9 and a relatively large proportion of extra-pulmonary and disseminated forms has been diagnosed, despite the previous latent TB screening and treatment.10,11 There is no gold standard method to define latent TB, and its treatment before anti-TNF-α drugs institution may not be sufficient to protect from the disease.
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