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Diabetes and the risk of infections with immunomodulator therapy in inflammatory bowel diseases.

ABSTRACT: Infections are an important concern in patients using immunosuppressive therapy for their inflammatory bowel disease (IBD). Diabetes affects nearly 10% of Americans. Whether it confers an additional risk with immunosuppression in IBD has not been examined previously.To examine the association between diabetes and infections with immunomodulator use in IBD METHODS: Using a validated, multi-institutional IBD cohort, we identified all patients who received at least one prescription for immunomodulators (thiopurines, methotrexate). Our primary outcome was infection within 1 year of the prescription of the immunomodulator. Multivariable logistic regression adjusting for relevant confounders was used to estimate the independent association with diabetes.Our study included 2766 patients receiving at least one prescription for immunomodulators among whom 210 (8%) developed an infection within 1 year. Patients who developed an infection were likely to be older, have more comorbidities, more likely to have received a prescription for steroids but similar in initiation of anti-TNF therapy within that year. Only 8% of those without an infection had diabetes compared to 19% of those who developed an infection within 1 year [odds ratio (OR) 2.74, 95% confidence interval (CI) 1.88-3.98, P < 0.001]. On multivariate analysis, diabetes was independently associated with a nearly two-fold increase in risk of infections (OR: 1.80, 95% CI: 1.20-2.68). There was no increase in risk of infections with addition of anti-TNF therapy (OR: 1.14, 95% CI: 0.80-1.63).Diabetes is an independent risk factor for infection in IBD patients using immunomodulator therapy.

SUBMITTER: Ananthakrishnan AN

PROVIDER: S-EPMC4420684 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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Diabetes and the risk of infections with immunomodulator therapy in inflammatory bowel diseases.

Ananthakrishnan A N AN Cagan A A Cai T T Gainer V S VS Shaw S Y SY Churchill S S Karlson E W EW Murphy S N SN Kohane I I Liao K P KP

Alimentary pharmacology & therapeutics 20150413 11

<h4>Background</h4>Infections are an important concern in patients using immunosuppressive therapy for their inflammatory bowel disease (IBD). Diabetes affects nearly 10% of Americans. Whether it confers an additional risk with immunosuppression in IBD has not been examined previously.<h4>Aim</h4>To examine the association between diabetes and infections with immunomodulator use in IBD METHODS: Using a validated, multi-institutional IBD cohort, we identified all patients who received at least on ...[more]

PMID: 25864945

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Project description:Background & aimsExposure to hormone contraception has been associated with an increased risk of relapse of inflammatory bowel diseases (IBDs). Little is known about the effects of cancer therapies, specifically hormone therapies, on the course of IBD.MethodsWe conducted a retrospective cohort study, collecting data from 5 medical centers, on patients with IBD who received a subsequent diagnosis of breast or prostate cancer from 1997 through 2018. For patients with quiescent IBD at their cancer diagnosis, the primary outcome was relapse of IBD. For patients with active IBD at their cancer diagnosis, the primary outcome was IBD remission.ResultsOur analysis included 447 patients with IBD (44% with Crohn's disease, 53% with ulcerative colitis, and 3% with IBD unclassified) who had either breast (78%) or prostate (22%) cancer. At their cancer diagnosis, 400 patients (90%) had inactive IBD, and 47 (10%) had active IBD. Among patients with inactive IBD, 112 (28%) developed active IBD. Previous exposure to steroids, immunomodulators, or biologics was associated with IBD relapse after a cancer diagnosis (hazard ratio [HR] for steroids, 1.79; 95% CI, 1.18-2.71; HR for immunomodulators, 2.22; 95% CI, 1.38-3.55; HR for biologics, 1.95; 95% CI, 1.01-5.36). Hormone monotherapy (HR, 2.00; 95% CI, 1.21-3.29) and combination cytotoxic and hormone therapy (HR, 1.86; 95% CI, 1.01-3.43) was associated with IBD relapse. Among 34 patients who received only cytotoxic chemotherapy, 75% remained in remission from IBD at 250 months compared with 42% of those who received hormone monotherapy (log rank, 0.02). Among patients with active IBD at their cancer diagnosis, 14 (30%) entered remission from IBD, but there were no significant factors of achieving IBD remission.ConclusionsIn a multicenter retrospective study, we found that patients with IBD and breast or prostate cancer who receive hormone therapy have an increased risk for relapse of IBD and related adverse outcomes.

Project description:Background & aimsWe performed a systematic review and meta-analysis to evaluate the comparative risk of serious infections with tumor necrosis factor (TNF) antagonists, non-TNF targeted biologics, tofacitinib, and immunosuppressive agents in patients with inflammatory bowel diseases (IBDs).MethodsIn a systematic search of publications, through March 18, 2018, we identified 15 observational studies (>500 person-years) of patients with IBD treated with TNF antagonists, non-TNF targeted biologics, tofacitinib, and/or immunosuppressive agents (thiopurines, methotrexate) that reported risk of serious infections. Only studies with active comparators were included, to allow appropriate comparative synthesis. We performed random-effects meta-analysis and estimated relative risk (RR) and 95% CIs.ResultsCompared with anti-TNF monotherapy, risk of serious infection increased with the combination of anti-TNF and an immunosuppressive agent (in 6 cohorts: RR, 1.19; 95% CI, 1.03-1.37), with anti-TNF and a corticosteroid (in 4 cohorts: RR, 1.64; 95% CI, 1.33-2.03), or with all 3 drugs (in 2 cohorts: RR, 1.35; 95% CI, 1.04-1.77); there was minimal heterogeneity among studies. In contrast, monotherapy with an immunosuppressive agent was associated with a lower risk of serious infections than monotherapy with a TNF antagonist (7 cohorts: RR, 0.61; 95% CI 0.44-0.84) or a TNF antagonist with an immunosuppressive agent (2 cohorts: RR, 0.56; 95% CI, 0.39-0.81). Infliximab-based therapy was associated with a lower risk of serious infections compared with adalimumab-based therapy in patients with ulcerative colitis (4 cohorts: RR, 0.57; 95% CI, 0.33-0.97), but not Crohn's disease (4 cohorts: RR, 0.91; 95% CI, 0.49-1.70). Few data were available on the comparative safety of biologic agents that do not inhibit TNF and tofacitinib.ConclusionsCombination therapies for IBD that include TNF antagonists, especially with corticosteroids, are associated with a higher risk of serious infection, whereas monotherapy with an immunosuppressive agent is associated with a lower risk, compared with monotherapy with a TNF antagonist. Studies are needed to evaluate the comparative safety of non-TNF targeted biologics and small molecules for treatment of IBD.

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Diabetes and the risk of infections with immunomodulator therapy in inflammatory bowel diseases.

Publications

Diabetes and the risk of infections with immunomodulator therapy in inflammatory bowel diseases.

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