Antirheumatic Drugs and the Risk of Tuberculosis

Brassard, Paul; Kezouh, Abbas; Suissa, Samy

doi:10.1086/506935

Cited by 243 publications

(172 citation statements)

References 18 publications

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“…The reported median time to onset of TB after starting infliximab treatment is uniformly short (12-21 weeks) in all series in which this has been examined (e.g., Figure 1, solid line at infliximab) (10)(11)(12). In contrast, the median time to TB onset for etanercept treatment is 3-5 times longer, nearly equaling the midpoint of the period of data collection in these studies ( Figure 1, solid line at etanercept).…”

Section: Objective Tumor Necrosis Factor (Tnf) Blockade Increases Thmentioning

confidence: 79%

“…The time to TB onset after starting infliximab or etanercept therapy was obtained for 287 cases in the US and Europe reported to the Adverse Events Reporting System (AERS) database of the Food and Drug Administration (248 for infliximab and 39 for etanercept) from January 1998 through March 2003 (Figure 1, solid lines). These distributions appear to be unaffected by region (US versus Europe) or period of data collection (1,(10)(11)(12)19). Additional information regarding median time to TB onset for infliximab and etanercept therapy in these studies is provided in the online supplement (see Supplementary Table 1; available at http:// rswallis.com/manuscripts.aspx).…”

Section: Methodsmentioning

confidence: 99%

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Mathematical modeling of the cause of tuberculosis during tumor necrosis factor blockade

Wallis

2008

Arthritis & Rheumatism

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Objective. Tumor necrosis factor (TNF) blockade increases the risk of tuberculosis (TB). The purpose of this study was to use Markov modeling to examine the contributions of reactivation of latent tuberculous infection (LTBI) and the progression of new infection withMycobacterium tuberculosis to active TB due to TNF blockade. These 2 pathogenic mechanisms cannot otherwise be readily distinguished.Methods. Monte Carlo simulation was used to represent the range of reported values for the incidence of TB associated with infliximab (TNF monoclonal antibody) and etanercept (soluble TNF receptor) therapy. Iterative methods were then used to identify for each pair of incidence rates the Markov model parameters that most accurately represented the distribution of time to onset of TB as reported to the Food and Drug Administration.Results. Modeling revealed an apparent median monthly rate of reactivation of LTBI by infliximab treatment of 20.8%, which was 12.1 times that with etanercept treatment (P < 0.001). In contrast, both drugs appeared to pose a high risk of progression of new M tuberculosis infection to active TB. Progression of new infection appeared to cause nearly half of the etanercept-associated cases; it became the predominant cause of infliximab-associated cases only after the first year.Conclusion. Despite sharing a common therapeutic target, infliximab and etanercept differ markedly in the rates at which they reactivate LTBI. Confirmation of these findings will require the application of molecular epidemiologic tools to studies of TB in future biologics registries. Hidden Markov modeling and Monte Carlo simulation are powerful tools for revealing otherwise hidden aspects of the pathogenesis of TB.

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Section: Objective Tumor Necrosis Factor (Tnf) Blockade Increases Thmentioning

confidence: 79%

Section: Methodsmentioning

confidence: 99%

Mathematical modeling of the cause of tuberculosis during tumor necrosis factor blockade

Wallis

2008

Arthritis & Rheumatism

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“…(9,(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39). The majority of cases were reported in countries where TB is endemic.…”

Section: Discussionmentioning

confidence: 99%

Analysis of Infections and All‐Cause Mortality in Phase II, Phase III, and Long‐Term Extension Studies of Tofacitinib in Patients With Rheumatoid Arthritis

Cohen

Radominski

Gómez-Reino

et al. 2014

Arthritis & Rheumatology

156

104

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Objective. To determine the rate of infection and all-cause mortality across tofacitinib phase II, phase III, and long-term extension (LTE) studies in patients with moderately to severely active rheumatoid arthritis (RA).Methods. Conclusion. The overall risk of infection (including serious infection) and mortality rates in RA patients treated with tofacitinib appear to be similar to those observed in RA patients treated with biologic agents. The rates of serious infection were stable over time. 550) is an oral JAK inhibitor used for the treatment of rheumatoid arthritis (RA) and has a novel mechanism of action. The JAK family of tyrosine kinases includes JAK-1, JAK-2, JAK-3, and Tyk-2. Tofacitinib preferentially inhibits signaling by heterodimeric receptors associated with JAK-3 and/or JAK-1, with functional selectivity over receptors that signal in pairs of JAK-2 (1). Common ␥-chaincontaining receptors using JAK-1 and JAK-3 include

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“…Entre estas drogas, el uso de corticoides sistémicos y los agentes anti-TNF son los que se han asociado en forma más signifi cativa y consistente en numerosos reportes a alto riesgo de reactivación de TBC 16,17 . Es importante, por lo tanto, buscar activamente evidencia de infección tuberculosa latente previo la administración de estos fárma-cos, ya sea mediante test de tuberculina cutáneo (PPD) o los nuevos test de liberación de interferón gamma (IGRA), y administrar quimioprofi laxis tuberculosa si resultan positivos.…”

Section: Discussionunclassified

Perfil clínico y epidemiológico de los casos de tuberculosis atendidos en una red de salud universitaria en Santiago de Chile entre los años 2000-2010

et al. 2012

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Antirheumatic Drugs and the Risk of Tuberculosis

Abstract: We found that the use of biological and traditional DMARDs is associated with an increased risk of developing TB in patients with RA, mainly among noncurrent users of corticosteroids.

Cited by 243 publications

References 18 publications

Mathematical modeling of the cause of tuberculosis during tumor necrosis factor blockade

Mathematical modeling of the cause of tuberculosis during tumor necrosis factor blockade

Analysis of Infections and All‐Cause Mortality in Phase II, Phase III, and Long‐Term Extension Studies of Tofacitinib in Patients With Rheumatoid Arthritis

Perfil clínico y epidemiológico de los casos de tuberculosis atendidos en una red de salud universitaria en Santiago de Chile entre los años 2000-2010

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