Quantitative characterization of the relationship between levels of extended corticosteroid use and related adverse events in a US population

Rice, J. Bradford; White, Alan G.; Johnson, Michaela E.; Wagh, Aneesha; Qin, Yimin; Bartels-Peculis, Laura; Ciepielewska, Gosia; Nelson, Winnie W.

doi:10.1080/03007995.2018.1474090

Cited by 23 publications

(19 citation statements)

References 15 publications

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“…Nevertheless, the aHR for developing keratopathies was higher in the study group after adjustment. On the other hand, higher incidences of hypertension, DM, and hyperlipidemia were also found in the study group, which probably results from the systemic administration of corticosteroid and cyclosporine in the uveitic and rheumatologic patients in the study group, [36][37][38][39][40] and DM itself is a risk factor for keratopathies. 41,42 Although the corticosteroid and immunosuppressant would lead to certain types of keratopathy, the effect of uveitis on the development of keratopathies was still significant after adjusting the influence of immunosuppressant and immunosuppressant-induced systemic diseases, which indicates that uveitis is an independent risk factor for keratopathies.…”

Section: Discussionmentioning

confidence: 71%

Effect of Uveitis on the Development of Keratopathy: A Population-Based Cohort Study

Nien

Lee

Chao

et al. 2018

Invest. Ophthalmol. Vis. Sci.

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The purpose of this study was to evaluate the effect of uveitis on the development of various keratopathies via the use of the National Health Insurance Research Database (NHIRD) in Taiwan. METHODS. Approximately 1 million patients were randomly sampled from the registry of the NHIRD. Patients diagnosed with uveitis by ophthalmologists were enrolled in the study group after exclusion. Each individual in the study group was age and sex matched to four nonuveitis individuals who serve as the control group. In addition to keratopathy, other possible risk factors and medications were included in the multivariate model, and the effects of different subtypes of uveitis for developing keratopathies were also analyzed. RESULTS. A total of 4773 uveitis patients (2662 male and 2111 female) and 19,092 non-uveitis patients (10,648 male and 8444 female) were enrolled. There were 406 events of keratopathy in the study group, and another 764 events occurred in the control group. A higher incidence rate was found in the study group after adjustment (adjusted hazard ratio [aHR]: 1.772), with a greater cumulative probability (P < 0.0001). For the subgroup analysis, anterior uveitis (aHR ¼ 1.765) and panuveitis (aHR ¼ 3.386) increased the risk of developing keratopathies. Moreover, male sex was associated with a higher aHR than female sex for developing keratopathies in the study group. CONCLUSIONS. The presence of uveitis significantly elevates the risk for developing keratopathy.

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Section: Discussionmentioning

confidence: 71%

Effect of Uveitis on the Development of Keratopathy: A Population-Based Cohort Study

Nien

Lee

Chao

et al. 2018

Invest. Ophthalmol. Vis. Sci.

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“…The hypertensive effect is attributed to increased sodium retention via stimulation of the mineralocorticoid receptors and increased vascular tone via upregulation of angiotensin-1 receptors. Long term, higher dose (prednisolone equivalent of >15 mg/day for >60 days) glucocorticoid use results in hypertension in a quarter of patients (low dose = 33.9 and high dose = 41.9 cases per 1000 patient-months) [ 122 , 123 , 124 ]. In a retrospective study conducted by Chari et al investigating the incidence and risk of hypertension in patients newly treated for multiple myeloma, they found that 54% of patients with multiple myeloma with co-existing diabetes had hypertension compared to 36% in those without diabetes.…”

Section: Hypertensive Cardiotoxicities Of Cancer Therapiesmentioning

confidence: 99%

Hypertensive Cardiotoxicity in Cancer Treatment—Systematic Analysis of Adjunct, Conventional Chemotherapy, and Novel Therapies—Epidemiology, Incidence, and Pathophysiology

Chung

Tyebally

Chen

et al. 2020

JCM

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Cardiotoxicity is the umbrella term for cardiovascular side effects of cancer therapies. The most widely recognized phenotype is left ventricular dysfunction, but cardiotoxicity can manifest as arrhythmogenic, vascular, myocarditic and hypertensive toxicities. Hypertension has long been regarded as one of the most prevalent and modifiable cardiovascular risk factors in the general population, but its relevance during the cancer treatment journey may be underestimated. Hypertensive cardiotoxicity occurs de novo in a substantial proportion of treated cancer patients. The pathology is incompletely characterized—natriuresis and renin angiotensin system interactions play a role particularly in conventional treatments, but in novel therapies endothelial dysfunction and the interaction between the cancer and cardiac kinome are implicated. There exists a treatment paradox in that a significant hypertensive response not only mandates anti-hypertensive treatment, but in fact, in certain cancer treatment scenarios, hypertension is a predictor of cancer treatment efficacy and response. In this comprehensive review of over 80,000 patients, we explored the epidemiology, incidence, and mechanistic pathophysiology of hypertensive cardiotoxicity in adjunct, conventional chemotherapy, and novel cancer treatments. Conventional chemotherapy, adjunct treatments, and novel targeted therapies collectively caused new onset hypertension in 33–68% of treated patients. The incidence of hypertensive cardiotoxicity across twenty common novel therapies for any grade hypertension ranged from 4% (imatinib) to 68% (lenvatinib), and high grade 3 or 4 hypertension in < 1% (imatinib) to 42% (lenvatinib). The weighted average effect was all-grade hypertension in 24% and grade 3 or 4 hypertension in 8%.

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“…Pharmacodynamic biomarkers could also be correlated with exposure, thereby aiding in dose selection or extrapolation of data between age groups or indications. Chronic glucocorticoid use is associated with extensive safety concerns [1], some of which are already monitored clinically by blood biomarkers: insulin resistance measured by fasting insulin and glucose; adrenal suppression measured by first in morning cortisol; bone morbidities measured by markers of bone turnover. Expanding a panel of pharmacodynamic safety biomarkers could aid in the development of alternative dosing regimens of glucocorticoids in AAV and JDM, and in testing of novel steroidal drugs that may reduce side effects.…”

Section: Introductionmentioning

confidence: 99%

Serum biomarkers of glucocorticoid response and safety in anti-neutrophil cytoplasmic antibody-associated vasculitis and juvenile dermatomyositis

et al. 2018

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Glucocorticoids are standard of care for many chronic inflammatory conditions, including juvenile dermatomyositis (JDM) and anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). We sought to define pharmacodynamic biomarkers of therapeutic efficacy and safety concerns of glucocorticoid treatment for these two disorders. Previous proteomic profiling of patients with Duchenne muscular dystrophy (DMD) and inflammatory bowel disease (IBD) treated with glucocorticoids identified candidate biomarkers for efficacy and safety concerns of glucocorticoids. Serial serum samples from patients with AAV (n = 30) and JDM (n = 12) were obtained during active disease, and after treatment with glucocorticoids. For AAV, 8 of 11 biomarkers of the anti-inflammatory response to glucocorticoids were validated ( P -value ≤0.05; CD23, macrophage-derived cytokine, interleukin-22 binding protein, matrix metalloproteinase-12, T lymphocyte surface antigen Ly9, fibrinogen gamma chain, angiopoietin-2 [all decreased], and protein C [increased]), as were 5 of 7 safety biomarkers ( P -value ≤0.05; afamin, matrix metalloproteinase-3, insulin growth factor binding protein-5, angiotensinogen, leptin [all increased]). For JDM, 10 of 11 efficacy biomarkers were validated ( P -value ≤0.05; all proteins except fibrinogen gamma chain) and 6 of 7 safety biomarkers ( P -value ≤0.05; AAV proteins plus growth hormone binding protein). The identified efficacy biomarkers may be useful as objective outcome measures for early phase proof-of-concept studies when assessing novel anti-inflammatory drugs in JDM and AAV, and likely in other inflammatory disorders. Similarly, safety biomarkers may also be helpful assessing toxicity of alternatives to glucocorticoids.

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Quantitative characterization of the relationship between levels of extended corticosteroid use and related adverse events in a US population

Abstract: Through a rigorous quantitative characterization, extended steroid exposure was associated with increased incidence and earlier onset of AEs among privately insured adults in the US.

Cited by 23 publications

References 15 publications

Effect of Uveitis on the Development of Keratopathy: A Population-Based Cohort Study

Effect of Uveitis on the Development of Keratopathy: A Population-Based Cohort Study

Hypertensive Cardiotoxicity in Cancer Treatment—Systematic Analysis of Adjunct, Conventional Chemotherapy, and Novel Therapies—Epidemiology, Incidence, and Pathophysiology

Serum biomarkers of glucocorticoid response and safety in anti-neutrophil cytoplasmic antibody-associated vasculitis and juvenile dermatomyositis

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