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Risk of Cancer Recurrence Among Individuals Exposed to Antitumor Necrosis Factor Therapy: A Systematic Review and Meta-Analysis of Observational Studies.

ABSTRACT: BACKGROUND:Patients with immune-mediated disorders such as ankylosing spondylitis, inflammatory bowel disease, psoriasis and rheumatoid arthritis are increasingly treated with tumor necrosis factor (TNF) inhibitors. The safety of anti-TNF therapy in patients with a history of cancer requires further evaluation. We conducted a systematic review and a meta-analysis of observational studies including patients with a history of cancer exposed to anti-TNF therapy assessing for a risk of new cancer or cancer recurrence. MATERIALS AND METHODS:A computerized literature search of MEDLINE, Google scholar, and Cochrane Database of Systematic Reviews was performed through September 1, 2015. Study characteristics, quality, and risk of bias were assessed. Random-effects model meta-analyses were used to estimate the risk of new cancer development or cancer recurrence. RESULTS:Nine English-language observational studies including patients with a history of cancer and exposed to anti-TNF therapy were idenitifed. The pooled incidence rate ratio of new or recurrent cancer among individuals with a history of cancer exposed to anti-TNF therapy was not significantly different compared with control therapies (incidence rate ratio, 0.90; 95% confidence interval, 0.59-1.37). Subgroup analyses were performed according to disease type, underlying cancer diagnosis, time to initiation of anti-TNF therapy and study quality. Heterogeneity of study populations, heterogeneity of the included cancer subtypes and utilization of observational studies limits the study quality. CONCLUSIONS:The risk of new cancer or cancer recurrence among patients with a history of cancer and use of anti-TNF therapy is similar to the risk with nonbiological disease modifying therapies. These results support the use of anti-TNF medications in select populations despite prior diagnosis of cancer.

SUBMITTER: Micic D

PROVIDER: S-EPMC5776073 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Risk of Cancer Recurrence Among Individuals Exposed to Antitumor Necrosis Factor Therapy: A Systematic Review and Meta-Analysis of Observational Studies.

Micic Dejan D Komaki Yuga Y Alavanja Aleksandar A Rubin David T DT Sakuraba Atsushi A

Journal of clinical gastroenterology 20190101 1

<h4>Background</h4>Patients with immune-mediated disorders such as ankylosing spondylitis, inflammatory bowel disease, psoriasis and rheumatoid arthritis are increasingly treated with tumor necrosis factor (TNF) inhibitors. The safety of anti-TNF therapy in patients with a history of cancer requires further evaluation. We conducted a systematic review and a meta-analysis of observational studies including patients with a history of cancer exposed to anti-TNF therapy assessing for a risk of new c ...[more]

PMID: 28737645

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Project description:Sepsis is a lethal syndrome annually affecting approximately 900,000 patients in the United States alone. Despite their benefit in rheumatoid disease, selective antitumor necrosis factor agents failed to improve outcome in early sepsis trials in the 1990s. However, data from additional sepsis trials testing these agents are now available. We therefore sought to determine the effect on survival of selective antitumor necrosis factor agents in randomized clinical sepsis trials..PubMed, Scopus, Embase, and Web of Science.Randomized human sepsis trials of selective antitumor necrosis factor agents reporting survival rates.Two investigators independently collected relevant data on study characteristics, treatment interventions, and patients from each study.Antitumor necrosis factor agents in 15 sepsis trials (n=8,896 patients) meeting inclusion criteria had similar effects (I=0, p=0.84) and compared with controls (placebo in 14 trials or a lower dose in one trial) overall decreased the relative risk of death (95% CI) (0.93 [0.88-0.98], p=0.01). In subgroup analysis, tumor necrosis factor monoclonal antibodies (10 trials, n=6,818) alone produced a significant survival benefit (0.93 [0.87, 0.99], p=0.02) (I=0, p=0.83). Tumor necrosis factor polyclonal antibodies (two trials, n=151) and low-molecular-weight soluble receptor (two trials, n=1,786) had similar beneficial effects to antitumor necrosis factor agents overall (0.82 [0.49-1.37], p=0.45; 0.93 [0.81-1.08], p=0.33, respectively). The effect of tumor necrosis factor high-molecular-weight soluble receptor (one trial, n=141) was not significantly different from other agents but was on the side of harm (1.50 [0.86-2.61], p=0.16).Antitumor necrosis factor agents produced a modest but significant decrease in the risk of dying with sepsis. Prior individual trials failed to demonstrate benefit, likely because they were underpowered. A definitive trial demonstrating the potential benefit of such agents might require 10,000 or more patients with sepsis.

Project description:ObjectiveObservational data facilitate examination of treatment-effect heterogeneity, but the risk of bias is substantial. The present study was undertaken to highlight methodologic considerations through an analysis of whether smoking affects response to tumor necrosis factor inhibitors (TNFi) in axial spondyloarthritis (SpA).MethodsWe used longitudinal data from the British Society for Rheumatology Biologics Register for Ankylosing Spondylitis. Participants fulfilling the Assessment of SpondyloArthritis international Society criteria for axial SpA who started their first TNFi were eligible for analysis. In comparing the impact of smoking status, weighted generalized estimating equations were used to examine changes in several continuous outcome measures, including the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the Ankylosing Spondylitis Disease Activity Score (ASDAS). Inverse probability weights were used to account for differences in baseline covariates and excluded participants. We separately assessed response in the first 3 months to account for nonrandom dropout.ResultsFor 840 participants who started on TNFi, 1,641 assessments from 627 individuals were analyzed (69% male, mean age 46 years). A total of 33% were current smokers and 30% ex-smokers. Ex-smokers and current smokers had worse disease than never smokers at baseline. Accounting for these differences, response did not differ according to smoking status. Compared to never smokers, ex-smokers (β = -0.6, 95% confidence interval [95% CI] -1.4, 0.3) and current smokers (β = -0.4, 95% CI -1.1, 0.4) had a similar response according to the BASDAI and ASDAS (ex-smokers β = -0.1, 95% CI -0.5, 0.3; current smokers β = -0.01, 95% CI -0.4, 0.4) at 3 months.ConclusionTNFi response did not differ according to baseline smoking status in this UK cohort. Conflicting results from previous studies were likely due to methodologic differences. This analysis highlights potential sources of bias that should be addressed in future studies.

Dataset Information

Risk of Cancer Recurrence Among Individuals Exposed to Antitumor Necrosis Factor Therapy: A Systematic Review and Meta-Analysis of Observational Studies.

Publications

Risk of Cancer Recurrence Among Individuals Exposed to Antitumor Necrosis Factor Therapy: A Systematic Review and Meta-Analysis of Observational Studies.

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