Biologic Therapies and Risk of Infection and Malignancy in Patients With Inflammatory Bowel Disease: A Systematic Review and Network Meta-analysis

Bonovas, Stefanos; Fiorino, Gionata; Allocca, Mariangela; Lytras, Theodore; Nikolopoulos, Georgios K.; Peyrin–Biroulet, Laurent; Danese, Silvio

doi:10.1016/j.cgh.2016.04.039

Cited by 324 publications

(266 citation statements)

References 70 publications

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“…Data were excluded from our analysis if both comparison sides reported zero-event (death) [14]. I 2 and X-square were used to evaluate the statistical heterogeneity among studies.…”

Section: Methodsmentioning

confidence: 99%

Comparison Between Carbapenems and β-Lactam/β-Lactamase Inhibitors in the Treatment for Bloodstream Infections Caused by Extended-Spectrum β-Lactamase-Producing Enterobacteriaceae: A Systematic Review and Meta-Analysis

Muhammed

Flokas

Detsis

et al. 2017

Open Forum Infectious Diseases

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Background.Carbapenems are widely used for the management of bloodstream infections (BSIs) caused by extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-PE). However, the wide use of carbapenems has been associated with carbapenem-resistant Enterobacteriaceae development.Methods.We searched the PubMed and Scopus databases (last search date was on June 1, 2016) looking for studies that reported mortality in adult patients with ESBL-PE BSIs that were treated with carbapenems or β-lactam/β-lactamase inhibitors (BL/BLIs).Results.Fourteen studies reported mortality data in adult patients with ESBL-PE BSI that were treated with carbapenems or BL/BLIs. Among them, 13 studies reported extractable data on empiric therapy, with no statistically significant difference in mortality of patients with ESBL-PE BSI that were treated empirically with carbapenems (22.1%; 121 of 547), compared with those that received empiric BL/BLIs (20.5%; 109 of 531; relative risk [RR], 1.05; 95% confidence interval [CI], 0.83–1.37; I2 = 20.7%; P = .241). In addition, 7 studies reported data on definitive therapy. In total, 767 patients (79.3%) received carbapenems and 199 patients (20.6%) received BL/BLIs as definitive therapy, and there was again no statistically significant difference (RR, 0.62; 95% CI, 0.25–1.52; I2 = 84.6%; P < .001). Regarding specific pathogens, the use of empiric BL/BLIs in patients with BSI due to ESBL-Escherichia coli was not associated with a statistically significant difference in mortality (RR, 1.014; 95% CI, 0.491–2.095; I2 = 62.5%; P = .046), compared with the use of empiric carbapenems.Conclusions.These data do not support the wide use of carbapenems as empiric therapy, and BL/BLIs might be effective agents for initial/empiric therapy for patients with BSI caused by likely ESBL-PE, and especially ESBL-E coli.

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“…Data were excluded from our analysis if both comparison sides reported zero-event (death) [14]. I 2 and X-square were used to evaluate the statistical heterogeneity among studies.…”

Section: Methodsmentioning

confidence: 99%

Comparison Between Carbapenems and β-Lactam/β-Lactamase Inhibitors in the Treatment for Bloodstream Infections Caused by Extended-Spectrum β-Lactamase-Producing Enterobacteriaceae: A Systematic Review and Meta-Analysis

Muhammed

Flokas

Detsis

et al. 2017

Open Forum Infectious Diseases

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“…An increase in risk of infections in patients with IBD is conferred by a spectrum of disease- and treatment-related factors 1–6, 9 Those pertaining to the patient include co-morbidity, severity of IBD, predisposing behavior such as perianal or internally penetrating CD, and malnutrition 1, 2, 4–6, 10, 11 . Important in the context of IBD, systemic immunosuppression that remains the cornerstone of its management, confers a two-fold increase in risk of opportunistic and other serious infections 2, 6, 9, 12 . In clinical trials and prospective observational cohorts, up to 10% of patients on immunosuppressive therapy may develop a significant infection, with 5% developing serious complications often requiring hospitalization 11–14 .…”

Section: Introductionmentioning

confidence: 99%

“…The use of systemic corticosteroids has been consistently associated with an increase in risk of infections, and such risk may act synergistically over and above that conferred by other immunosuppressive therapy 9 . The literature on the risk associated with conventional immunosuppressive (thiopurine, methotrexate) or anti-tumor necrosis factor-α (anti-TNF) biologic therapy is more mixed but a majority of data support a modest increase in risk, particularly for opportunistic infections 2, 4–6, 9, 12 . Additionally, agent-specific risks may exist with distinct therapeutic classes such as re-activation of tuberculosis or hepatitis B with anti-TNF therapy 15 .…”

Section: Introductionmentioning

confidence: 99%

Genetic risk factors for serious infections in inflammatory bowel diseases

Sasidharan

Yajnik

Khalili

et al. 2017

Scandinavian Journal of Gastroenterology

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Introduction Immunosuppression, the cornerstone of management of Crohn’s disease (CD) and ulcerative colitis (UC) (inflammatory bowel diseases; IBD) is associated with an increased risk of serious infections that is inadequately predicted by clinical risk factors. The role of genetics in determining susceptibility to infections is unknown. Methods From a prospective consented patient registry, we identified IBD patients with serious infections requiring hospitalization. Analysis was performed to identify IBD-related and non-IBD related immune response loci on the Immunochip that were associated with serious infections and a genetic risk score (GRS) representing the cumulative burden of the identified SNPs was calculated. Multivariable logistic regression used to identify effect of clinical and genetic factors. Results The study included 1,333 IBD patients (795 CD, 538 UC) with median disease duration of 13 years. A total of 133 patients (10%) had a serious infection requiring hospitalization. Patients with infections were more likely to have CD and had shorter disease duration. The most common infections were skin and soft-tissue, respiratory, and urinary tract infections. Eight IBD risk loci and 2 other polymorphisms were significantly associations with serious infections. Each 1 point increase in the infection GRS was associated with a 50% increase in risk of infections (OR 1.53, 95% CI 1.37 – 1.70,) (p=1×10−14), confirmed on multivariable analysis. Genetic risk factors improved performance of a model predicting infections over clinical covariates alone (p < 0.001). Conclusions Genetic risk factors may predict susceptibility to infections in patients with IBD.

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“…However, these treatments don't cure the disease and are not fully effective because patients are either non-primary responders or secondarily lose response (Ben-Horin et al, 2014). In addition, these drugs are not devoid of sideeffects (Bonovas et al, 2016) thus explaining that patients are reluctant and not compliant with these treatments (Lenti & Selinger, 2017), and are among the highest users of complementary and alternative medicines (Yanai et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Is-there a place for vagus nerve stimulation in inflammatory bowel diseases?

Bonaz

2018

Bioelectron Med

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The vagus nerve (VN), the longest nerve of the organism that innervates the gastrointestinal tract, is a mixed nerve composed of 80% of afferent and 20% of efferent fibers. The VN has anti-inflammatory properties, in particular an anti-TNFα effect through the cholinergic anti-inflammatory pathway. The VN is a key component of the autonomic nervous system, i.e. the parasympathetic nervous system. An imbalance of the autonomic nervous system, as represented by a low vagal tone, is described in many diseases and has a pro-inflammatory role. Inflammatory bowel diseases (IBD) are chronic disorders of the gastro-intestinal tract where TNFα is a key cytokine. VN stimulation (VNS), classically used for the treatment of drug resistant epilepsy and depression, would be of interest in the treatment of IBD. We have recently reported in a 6 month follow-up pilot study that VNS improves active Crohn's disease. Preliminary data of another pilot study confirm this interest. Similarly, VNS has recently been reported to improve rheumatoid arthritis, another TNFα mediated disease. Bioelectronic Medicine, as represented by VNS, opens new therapeutic avenues in the treatment of such chronic inflammatory disorders. In the present manuscript, we will focus on the interest of VNS in IBD.

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Biologic Therapies and Risk of Infection and Malignancy in Patients With Inflammatory Bowel Disease: A Systematic Review and Network Meta-analysis

Abstract: On the basis of a systematic review and meta-analysis, biologic agents increase the risk of opportunistic infections in patients with IBD, but not the risk of serious infections. It is necessary to continue to monitor the comparative and long-term safety profiles of these drugs.

Cited by 324 publications

References 70 publications

Comparison Between Carbapenems and β-Lactam/β-Lactamase Inhibitors in the Treatment for Bloodstream Infections Caused by Extended-Spectrum β-Lactamase-Producing Enterobacteriaceae: A Systematic Review and Meta-Analysis

Comparison Between Carbapenems and β-Lactam/β-Lactamase Inhibitors in the Treatment for Bloodstream Infections Caused by Extended-Spectrum β-Lactamase-Producing Enterobacteriaceae: A Systematic Review and Meta-Analysis

Genetic risk factors for serious infections in inflammatory bowel diseases

Is-there a place for vagus nerve stimulation in inflammatory bowel diseases?

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