Steroid-related Adverse Events Research Articles

Prevention of esophageal stenosis after large endoscopic submucosal dissection: is there a better way to use steroids?

Prevention of esophageal stenosis after large endoscopic submucosal dissection: is there a better way to use steroids?

Projected worldwide disease burden from giant cell arteritis by 2050.

To estimate and project the number of people affected worldwide by giant cell arteritis (GCA) by 2050. Modeling the number of people visually impaired as a result of this disease will help establish the projected morbidity and resource burden. A systematic literature review up to December 2013 was conducted using PubMed and ISI Web of Science. Studies reporting an incidence rate for GCA were used to model disease incident cases at regional and national levels. United Nations Population Prospect data were used for population projections. Morbidity burden was established through rates of visual impairment. The associated financial implications were calculated for the United States. The number of incident cases of GCA will increase secondary to an aging population. By 2050, more than 3 million people will have been diagnosed with GCA in Europe, North America, and Oceania. About 500,000 people will be visually impaired. By 2050, in the United States alone, the estimated cost from visual impairment due to GCA will exceed US$76 billion. Inpatient care for patients with active GCA will total about US$1 billion. Management of steroid-related adverse events will increase costs further, with steroid-induced fractures estimated to total US$6 billion by 2050. Projecting disease burden for GCA on a global scale allows for optimization of healthcare planning and prioritization of research domains. Additional population-based studies are required to more accurately project worldwide disease burden. Our work highlights the future global disease burden of GCA, and illustrates the associated financial implications.

CN-04 * TREATMENT OF PEDIATRIC CEREBRAL RADIATION NECROSIS: A META-ANALYSIS

BACKGROUND: Cerebral radiation necrosis (CRN) is a well-characterized toxicity of radiation therapy that can result in significant neurologic deficits and be life threatening. Treatment for CRN has included surgical resection, corticosteroids, hyperbaric oxygen therapy (HBOT), and bevacizumab among other modalities, but no consensus approach has been identified. Given the paucity of pediatric CRN data, we sought to codify the approaches to treatment of radiation necrosis in pediatric patients. METHODS: The Cochrane Central Register of Controlled Trials (CENTRAL) and Ovid MEDLINE were searched to identify all relevant pediatric reports. RESULTS: Thirty-one pediatric patients, twenty-six with primary central nervous system tumors and four with arteriovenous malformations developed CRN, diagnosed by characteristic MRI findings, most (n = 28) with accompanying neurologic deficits. Patients received treatment with steroids alone (n = 5) or steroids followed by bevacizumab (n = 11) or HBOT (n = 12). Three asymptomatic patients did not receive intervention. 10/11 patients treated with steroids and bevacizumab, and 11/12 treated with steroids and HBOT improved. In all cases of steroid-resistent CRN, addition of bevacizumab induced improvement except in one case of disease progression. One patient treated with steroids alone died with progressive neurologic deterioration. With the exception of steroid-related adverse events, there were no reported significant side effects. CONCLUSIONS: Due to the small numbers of pediatric patients with CRN, analysis of treatment modalities is confined to limited reports. Furthermore, cases of CRN are likely underreported as we have seen much higher rates of CRN than the 3-5% reported in the literature at our institution in the past five years. The most common treatment following steroid initiation is addition of either bevacizumab or HBOT with good success. However, larger randomized controlled trials are needed to establish a definitive treatment algorithm that can be applied to children affected by CRN.

PIH20 - Incidence and Long-Term Cost of Oral Steroid-Related Adverse Events in Chronic Diseases in Poland

PIH20 - Incidence and Long-Term Cost of Oral Steroid-Related Adverse Events in Chronic Diseases in Poland

Non-neurological, steroid-related adverse events in very low birth weight infants: a prospective audit

To assess the incidence of cardiac and metabolic adverse events in very low birth weight (VLBW) infants receiving systematic steroids. Prospective single centre audit in VLBW infants (<1,500 g) at the neonatal intensive care unit at the University Children's Hospital of Saarland, Germany. A total of 72 VLBW infants (38 female) were included in this report (mean birth weight: 967 ± 338 g; range: 320-1490 g). Birth weight, gestational age and Apgar scores were significantly lower in the steroid group (p <0.01). Mortality rate was 8/72 (7/34 in the steroid treated vs nontreated 1/38; odds ratio [OR]: 9.6; 95% confidence interval [CI]: 1.1-82.6 p = 0.02). In 34/72 infants, steroids were given (22 hydrocortisone alone; 12 combination of hydrocortisone and dexamethasone). The most common indication for use of steroids was respiratory distress syndrome (RDS) and respiratory insufficiency (30/34). Adverse events that occurred more often in the steroid group included hypertrophic cardiomyopathy (14/34 vs 0/38; p <0.001); thrombus formation (8/34 vs 1/38; OR: 11.4; 95% CI: 1.3-96.6; p <0.05), hyperglycaemia (27/34 vs 3/38; OR: 45.0; 95% CI: 10.6-190.4; p <0.01), hypernatraemia (15/34 vs 7/38; OR: 3.5; 95% CI: 1.2-10.1; p <0.05), and sepsis/infections (8/34 vs 1/38; OR: 11.4; 95% CI: 1.3-96.6; p <0.05). No significant differences were seen between hydrocortisone alone and the combination of hydrocortisone with dexamethasone. Birth weight and severity of RDS were predictors of steroid use (p <0.01). The use of steroids was significantly associated with severe short-term adverse events - most importantly hypertrophic cardiomyopathy and thrombus formation. These complications must be taken into consideration when administering steroids to VLBW infants.

FRI0366 Gender differences in health-related quality of life in poymyalgia rheumatica

BackgroundThe limited evidence on gender differences in outcomes in PMR suggests females experience a more severe and protracted course of disease. Females have longer duration of symptoms, higher relapse rate,...

Erythrocytes-mediated Delivery of Dexamethasone 21-phosphate in Steroid-dependent Ulcerative Colitis

Efficacy of erythrocyte-mediated delivery of dexamethasone 21-phosphate in patients with steroid-dependent ulcerative colitis. Thirty-seven patients with steroid-dependent ulcerative colitis were randomized to infusions of dexamethasone 21-phosphate encapsulated into autologous erythrocytes (n = 19) or to sham infusions (n = 18). Each infusion was given monthly for 6 months. The primary endpoint was the proportion of patients able to discontinue oral corticosteroids during treatment while maintaining clinical remission or stable disease. Secondary endpoint was the proportion of patients with disappearance of steroid-related adverse events. At each infusion, a mean of 9.8 ± 4.6 mg dexamethasone 21-phosphate was administered at each infusion, which allowed steady-state plasma levels of 8 ng/mL for the following 28 days. Thirteen patients in the dexamethasone 21-phosphate group and 4 sham-treated patients attained the primary outcome of the study, i.e., maintaining a stable condition despite oral steroids withdrawal (P = 0.008). In the remaining patients (6 and 15 in the 2 experimental groups, respectively), the treatment was prematurely withdrawn because of clinical deterioration while tapering oral steroids. At endoscopy, mucosal healing was ascertained in 4 patients and 1 patient of the 2 experimental groups, respectively (P = 0.339). At inclusion, 14 and 13 patients in the 2 experimental groups complained of steroid-related adverse events; at end of the treatment, events were still present in 5 and 13 patients, respectively (P = 0.008). In patients with steroid-dependent ulcerative colitis, 6-month therapy with low dose of dexamethasone 21-phosphate allowed the withdrawal of oral steroids and the reversal of steroid-related adverse events in most patients while maintaining clinical remission (ClinicalTrials.gov number, NCT01171807).

Baseline central macular thickness predicts the need for retreatment with intravitreal triamcinolone plus laser photocoagulation for diabetic macular edema

PurposeTo identify baseline characteristics that predict the number of treatments with intravitreal triamcinolone acetonide (IVTA) plus laser photocoagulation needed to treat diabetic macular edema over a 2-year period.MethodsIndividual data from 42 eyes of 42 participants treated with IVTA plus laser photocoagulation for diabetic macular edema during a prospective, randomized, double-masked, placebo-controlled trial were used for this post hoc analysis. Baseline characteristics – age, gender, best-corrected visual acuity, glycosylated hemoglobin, phakic status, intraocular pressure, and central macular thickness (CMT) – were correlated with the number of IVTA plus laser treatments received during the 2 years of this study.ResultsThe median number of treatments received over the 2-year period was 2.5 (interquartile range 1.0–3.0), with 21 (50%) eyes needing three or more treatments. Eyes that received more IVTA plus laser treatments had a higher mean baseline CMT and eyes with a higher baseline CMT were more likely to receive three or more treatments (odds ratio 5.13, 95% confidence interval 1.75–15.04, P=0.003 per 100 μm increase in CMT). No significant relationship was found between other baseline characteristics and the number of IVTA plus laser treatments received.ConclusionHigher baseline CMT was strongly linked with receiving more IVTA plus laser treatments. These patients may be at higher risk of developing dose-dependent steroid-related adverse events, cataract progression, and intraocular pressure rise.

Management of Severe Refractory Asthma

Most patients with asthma have mild to moderate disease and are well controlled by regular use of inhaled corticosteroids with or without long-acting β2-agonists. However, about 5-10% patients with severe asthma remain poorly controlled despite optimal treatment, and these patients have greater morbidity and mortality than mild to moderate asthmatics. Patients with severe refractory asthma (SRA) often require regular systemic corticosteroid use, which increase risk of steroid-related adverse events and require more health care support. A systematic approach is necessary to establish a correct diagnosis, identify coexisting disorders, and evaluate aggravating factors. The management of SRA remains extremely challenging, and many clinical studies are currently in progress. Anti-IgE antibody (omalizumab) and bronchial thermoplasty may be alternative treatment for SRA approved by US Food and Drug Administration. SRA is a heterogeneous disease, which is classified in to distinct clinical phenotypes. A better understanding of these subtypes may lead to improved treatment of SRA. (Korean J Med 2012;83:438-443)

Refractory Asthma : An Overview

Patients whose asthma is not adequately controlled despite treatment pose a major clinical challenge and it is an important health care problem. It carries several names; each one points to an aspect of the disease. Chronic severe asthma, steroid-dependent asthma, steroid-resistant asthma, difficult-to-control asthma and refractory asthma are some of these terminologies. Patients with severe refractory disease often require regular oral corticosteroid with an increased risk of steroid-related adverse events. Alternatively, immunomodulatory and biologic therapies may be considered, but they show wide variation in efficacy across studies, thus limiting their generalization. Managing asthma that is refractory to standard treatment requires a systematic approach to evaluate adherence, ensure a correct diagnosis, identify coexisting disorders and trigger factors. In future phenotyping of patients with severe refractory asthma will also become an important element of this systematic approach.&#x0D; TAJ 2011; 24(1): 57-61

Recommendation for optimal management of severe refractory asthma

Patients whose asthma is not adequately controlled despite treatment with a combination of high dose inhaled corticosteroids and long-acting bronchodilators pose a major clinical challenge and an important health care problem. Patients with severe refractory disease often require regular oral corticosteroid use with an increased risk of steroid-related adverse events. Alternatively, immunomodulatory and biologic therapies may be considered, but they show wide variation in efficacy across studies thus limiting their generalizability. Managing asthma that is refractory to standard treatment requires a systematic approach to evaluate adherence, ensure a correct diagnosis, and identify coexisting disorders and trigger factors. In future, phenotyping of patients with severe refractory asthma will also become an important element of this systematic approach, because it could be of help in guiding and tailoring treatments. Here, we propose a pragmatic management approach in diagnosing and treating this challenging subset of asthmatic patients.

A placebo-controlled study investigating the dexamethasone-sparing effects of corticorelin acetate in patients with primary or metastatic brain tumors and peritumoral edema

2078 Background: The standard therapy for patients with peritumoral edema (PTE) associated with cerebral tumors is long-term dexamethasone (dex), which is associated with significant short- and long-term adverse events (AEs). Corticorelin acetate (CrA) is a synthetic peptide of corticotropin-releasing factor that may have the potential to allow such patients to reduce or stop dex therapy. This study investigated the steroid-sparing effect of CrA in patients with cerebral tumors and PTE. Methods: Patients were randomized to CrA 1.0 mg bid SC (n = 100) or placebo (PLA) SC (n = 100) for 12 weeks. The primary endpoint was the percentage of responders, defined as patients able to reduce their daily dex dose by ≥50% by week 2 and maintain this reduction until week 5, without deterioration in neurologic or performance status. Secondary endpoints included maximum percent dex dose reduction from baseline and proximal myopathy (Kendall Myopathy Scale). Steroid-specific treatment-emergent AEs (TEAEs) were also evaluated. Results: The groups were comparable at baseline. There were more responders in the CrA arm vs the PLA arm (62/100 vs. 47/100; p = 0.03). A maximum dex dose reduction of ≥75% was achieved by 42% of CrA patients vs 22% of PLA patients (p = 0.01). 15% of CrA patients were able to stop dex vs. 6% PLA (p = 0.04). At week 12 vs. baseline, proximal myopathy was improved in the CrA group vs the PLA group for upper limbs (p = 0.06) and lower limbs (p = 0.02). AE profiles in both groups were dominated by dex-associated side effects. The overall AE profiles of the treatment groups were generally similar. Emergent cushingoid signs were seen in 13 PLA vs 2 CrA patients (p = 0.01); 14 PLA patients reported skin/subcutaneous tissue disorders as TEAEs vs. 7 CrA patients (p = 0.07). Conclusions: CrA may benefit patients with symptoms of PTE associated with primary or metastatic cerebral tumors by allowing them to reduce/stop their dex treatment, so reducing the incidence of the steroid-related AEs of myopathy, cushingoid symptoms, and skin disorders. [Table: see text]

Treatment of steroid-naive ulcerative colitis

The introduction of steroid therapy by Truelove and Witts in the 1950s revolutionized the treatment of ulcerative colitis. Corticosteroids are potent inhibitors of T-cell activation and proinflammatory cytokines and still represent the mainstay of therapy of patients with ulcerative colitis. About 15% of patients are resistant to steroids, and about a quarter of patients become dependent within 1 year of therapy. Steroid-related adverse events are numerous and occur frequently. So, new steroids with low systemic absorption and better safety profile have been studied, but they show an overall lower efficacy compared with traditional steroids. A new drug-delivery system based on the use of autologous erythrocytes loaded with dexamethasone 21-phosphate has been recently developed. Several studies have demonstrated its efficacy in steroid-dependent patients leading to complete withdrawal of oral steroids and disappearance of the most steroid-related adverse events. In this review we elaborate on the role of steroids in the treatment of ulcerative colitis, focusing on the aspects related to the mechanisms of action and resistance to the steroids, and their secondary effects. Moreover, we analyse the alternatives to traditional systemic steroids such as the new steroids with low bioavailability and the steroids encapsulated into erythrocytes.

Erythrocyte-Mediated Delivery of Dexamethasone in Patients With Mild-to-Moderate Ulcerative Colitis, Refractory to Mesalamine: A Randomized, Controlled Study

Nearly 25% of patients with ulcerative colitis (UC) requiring steroids therapy become steroid-dependent after 1 yr, and virtually all develop steroid-related adverse events. We planned a controlled study to investigate the efficacy and safety of dexamethasone 21-P (Dex 21-P) encapsulated into erythrocytes (DEE). Forty patients with mild-to-moderate UC, refractory to mesalamine, were randomly assigned to one of the following three treatments: two DEE infusions 14 days apart (group A, N = 20), oral prednisolone (0.5 mg/kg for 14 days followed by a 6 mg/weekly tapering (group B, N = 10), and sham infusions (group C, N = 10). The clinical, biochemical, and endoscopic parameters were monitored at inclusion and after 8 wk. In group A, a mean dose of 9.9 +/- 4.1 mg Dex 21-P was loaded into autologous erythrocytes at each infusion. At 8 wk, 15 patients in group A (75%), 8 in group B (80%), and 1 in group C (10%, P < 0.001 vs A and B) were in clinical and endoscopic remission. When compared with the baseline values, C-reactive protein (CRP) dropped in groups A (1.6 mg/dL vs 0.4 mg/dL, P= 0.006) and B (1.0 vs 0.5, P= 0.02), but not in group C. No steroid-related adverse events were apparent in the patient treated with DEE, compared with 8 out of 10 patients on oral steroids (P< or = 0.01). Low doses of Dex (mean total dose +/- 20 mg) loaded into autologous erythrocytes were significantly more effective than sham infusions in terms of symptoms relief, endoscopic, and biochemical improvements in UC patients refractory to mesalamine. In addition, in contrast to oral prednisolone (mean total dose +/- 1 g), no steroid-related adverse events were induced.

The first case of a patient with neutropenia and giant-cell arteritis treated with rituximab

Dear Editor, Giant-cell arteritis (GCA) is the most frequent primary vasculitis of large and medium-sized vessels [1]. Corticosteroids remain the cornerstone of therapy for giant-cell arteritis, but relapse during dose tapering and steroid-related adverse events often complicate management [2]. Methotrexate has been used as a steroid-sparing drug with conflicting results [3, 4]. Because of leukopenia as a possible adverse during a methotrexate therapy, we report the first case of a patient with giant cell arteritis and a coexisting neutropenia, who was treated with rituximab after the first relapse during prednisone tapering. A 67-year-old man had been in a good health until one and a half years ago, when he developed dry cough, shoulder pain, myalgia, stiffness, night sweats, malaise, and neutropenia (2.8 cells per mm). Atypical pneumonia was suspected by a chest physician, and the patient was commenced on a course of macrolides. After he had consulted a rheumatologist because of the reported finger and hip pain, he got prednisone (25 mg per day) for a few days and a nonsteroidal anti-inflammatory drug. The patient reported a reduction of his symptoms. Because of a lack of evidence for a rheumatologic disorder, he tapered the prednisone-medication to a minimum of 5 mg per day. The reported symptoms recurred, especially the neutropenia (1.2 cells per mm), so he was admitted to the fourth department for internal medicine specialized in hematology, oncology, and immunology in Wels (Austria). On physical examination, the patient was pale. The lungs and the heart were normal, and the abdominal examination showed no abnormalities. There was only a slightly swelling at the proximal interphalangeal joints of the hands and on the back of the hands. The medication on admission were a beta-blocker, an angiotensin II receptor blocker, a hydrochlorothiazide, a HMG-CoA reductase inhibitor, and prednisone (5 mg per day). Further investigations (chest radiograph, abdominal ultrasound, abdominal and thoracic CT scan, transthoracic echocardiogram, endoscopy of the stomach, and the bowel and bone marrow aspiration/biopsy) did not show signs of any malignancy or an underlying infectious disease. In particular, there was no evidence of myeloor lymphoproliferative disease. On the third day of admission, a biopsy of the right temporal artery was performed confirming the clinical suspicion. The histologic picture was panarteritis with mixed-cell inflammatory infiltrate without any giant cells. Prednison (25 mg/day) was started again, and symptoms resolved within 24 h. Neutropenia improved subsequently but did not return to normal. After 6 months, we could not taper the corticoid dose down to 18 mg because of relapsing with symptoms and hematological disorders (neutropenia). Therefore, we thought about an additional immunosuppressive therapy. Because of a possible cytopenia, as a side effect during a therapy with methotrexate or tumor necrosis factor inhibitors, we started treatment with rituximab (1,000 mg on days 1 and 15) in addition to the prednisone. Clin Rheumatol (2007) 26:1597–1598 DOI 10.1007/s10067-007-0684-0

Efficacy and safety of oral beclomethasone dipropionate for ileal or ileal-right colon Crohn's disease of mild-to-moderate activity or in remission: Retrospective study

Although conventional glucocorticosteroids are the main treatments for active Crohn's disease, several problems are associated with steroid dependence and steroid-related adverse events. To assess the efficacy and safety of oral beclomethasone dipropionate (BDP) coated tablets in adults with mild-to-moderate Crohn's disease. Thirty-four patients (age 18–70 years) with a diagnosis of Crohn's disease confirmed by conventional criteria (barium enema, clinical criteria, colonoscopy, histology) were retrospectively evaluated in the study. All subjects received a treatment schedule with BDP 5–10 mg/day for 24 weeks. BDP significantly ( p = 0.005) reduced mean Crohn's Disease Activity Index (CDAI) score from 169.6 at baseline to 123.2 after 24 weeks. Clinical success was evident at 24 weeks in 66.7% of patients with initial active disease, and remission was maintained at week 24 in 93.8% of patients with remission at baseline. Overall, female non-smokers had the best response to treatment. BDP was well tolerated and the only adverse events observed were nausea ( n = 1), facial erythema ( n = 1) and one patient with raised fasting blood glucose level. These results clearly suggest that oral BDP coated tablets are effective and safe for treatment of mild-to-moderate Crohn's disease of ileal or ileal-right colonic localisation.