Use Of Corticosteroids In Patients Research Articles

Corticosteroids for CAP, influenza and COVID-19: when, how and benefits or harm?

PurposeCorticosteroids have been considered in medicine for a long time, and they are broadly prescribed. In infectious diseases, corticosteroids have been regarded as a thread due to their immunosuppressive effects and therefore their anti-inflammatory properties.MainIn recent years, there have been several studies published that aimed to determine the role of corticosteroids in patients with community-acquired pneumonia (CAP), because, despite significant advances in new antibiotics and supportive care, deaths of patients with CAP remain unacceptably high. While the 2007 Infectious Disease Society of America (IDSA)/American Thoracic Society (ATS) CAP guidelines did not mention the use of corticosteroids in the management of CAP, the recently published 2019 IDSA/ATS guidelines recommended their use in patients with septic shock refractory to vasopressors and fluid resuscitation. Regarding viral infection, the use of corticosteroids in patients with influenza has shown to be associated with significantly higher mortality and higher incidence of nosocomial infection, while in patients with coronavirus disease 2019 (COVID-19) there is a good body of evidence of the benefit of corticosteroids in terms of mortality.ConclusionsThe use of corticosteroids has been considered as a potential alternative co-adjuvant treatment in patients with pneumonia. In patients with COVID-19, the evidence is quite strong and there is a clear benefit of the use of corticosteroids in those patients presenting severe forms of disease.

Risk Factors of Viral RNAaemia and Its Association With Clinical Prognosis Among Patients With Severe COVID-19

Risk Factors of Viral RNAaemia and Its Association With Clinical Prognosis Among Patients With Severe COVID-19

Consequences of Insurance Denials Among U.S. Patients Prescribed Repository Corticotropin Injection for Acute Exacerbations of Multiple Sclerosis.

IntroductionRepository corticotropin injection (RCI; Acthar® Gel) is indicated for the treatment of acute exacerbations of multiple sclerosis (MS) in adults. Despite the well-documented clinical and economic benefits of RCI, many patients are denied use of the therapy by third-party payers. This study aims to understand the demographic and clinical characteristics of MS relapse patients who received a prescription for RCI from their physicians and then were either approved or denied treatment by their insurers. The study compares measurable clinical outcomes and healthcare resource utilization (HCRU) between approved and denied cohorts.MethodsA retrospective analysis of adults experiencing MS relapse from January 2015 to December 2018 was conducted using a de-identified open-source claims database [Symphony Health Integrated Dataverse® (IDV)]. Patients were identified using ICD codes for MS and considered to have relapsing/remitting type according to established claims-based methodology. Clinical characteristics and HCRU were analyzed during the year preceding (“baseline”) and the year following (“follow-up”) each patient’s index date, defined as the date of a patient’s first approved RCI claim (for patients with ≥ 1 approved claim) or first denied RCI claim (for patients with only denied claims). Baseline characteristics were reported with unadjusted differences and p values indicating the significance of characteristics between the two cohorts. For outcomes, match-adjusted results were reported using propensity matching to account for underlying differences between cohorts.ResultsThe study sample included 1902 MS relapse patients with at least one claim for RCI. At baseline, approved patients were slightly older compared to denied patients (mean age 48.0 vs. 47.2), had higher rates of hemiplegia/paraplegia (6.7% vs. 3.3%), greater mobility impairment (17% vs. 11.5%), more exacerbation episodes (66.2% vs. 59.9%), and a higher number of physical therapy/rehab claims (23.5 vs. 14.0), respectively. Outcomes among the matched sample show an increased use of corticosteroids for patients denied access to RCI compared to approved patients (51.1% vs. 42.4%), more exacerbation episodes (36.6% vs. 28.2%), and an increased number of physical therapy/rehab claims (11.5% vs. 9.9%), respectively.ConclusionThe results of this study may aid providers and payers in evaluating scenarios where RCI may be beneficial and improve quality of care for patients experiencing MS relapse.

Association of Dexamethasone with Shunt Requirement, Early Disability, and Medical Complications in Aneurysmal Subarachnoid Hemorrhage.

Current guidelines do not support the routine use of corticosteroids in patients with aneurysmal subarachnoid hemorrhage (aSAH). However, corticosteroids use in aSAH has been practiced at some centers by convention. The aim of the study was to determine the incidence of hydrocephalus requiring ventriculoperitoneal shunt (VPS) placement as well as functional outcome on discharge and adverse events attributed to corticosteroids in patients with aSAH treated with different dexamethasone (DXM) treatment schemes. We retrospectively analyzed 206 patients with aSAH stratified to three groups based on the DXM treatment scheme: no corticosteroids, short course of DXM (S-DXM; 4mg every 6h for 1day followed by a daily total dose reduction by 25% and then by 50% on last day), and long course of DXM (L-DXM; 4mg every 6h for 5-7days followed by reduction by 50% every other day). The primary outcome measure was the placement of a VPS, and the secondary outcome was a good functional outcome [modified Rankin Scale (mRS) 0-3] at hospital discharge. Safety measures were the incidence of infection (pneumonia, urinary tract infection, ventriculitis, meningitis), presence of delirium, and hyperglycemia. There was no difference in the rate of external ventricular drain (EVD) (p = 0.164) and VPS placement (p = 0.792), nor in the rate of good outcome (p = 0.928) among three defined treatment regimens. Moreover, the median duration of treatment with EVD did not differ between subjects treated with no corticosteroids, S-DXM, and L-DXM (p = 0.905), and the probability of EVD removal was similar when stratified according to treatment regimens (log-rank; p = 0.256). Patients who received L-DXM had significantly more complications as compared to patients, who received no corticosteroids or S-DXM (78.4% vs. 58.6%; p = 0.005). After adjustment, L-DXM remained independently associated with increased risk of combined adverse events (OR = 2.72; 95%CI, 1.30-5.72; p = 0.008), infection (OR = 3.45; 95%CI, 1.63-7.30; p = 0.001) and hyperglycemia (OR = 2.05; 95%CI, 1.04-4.04; p = 0.039). DXM use among patients with aSAH did not relate to the rate of EVD and VPS placement, duration of EVD treatment, and functional disability at discharge but increased the risk of medical complications.

Treatment with corticosteroids is associated with an increase in ventricular arrhythmia burden in patients with clinically manifest cardiac sarcoidosis: Insights from implantable cardioverter-defibrillator diagnostics.

We sought to explore the relationship between ventricular tachycardia (VT) and premature ventricular complex (PVC) burden (from implantable cardioverter-defibrillator diagnostics), before and during corticosteroid use in patients with newly diagnosed clinically manifest cardiac sarcoidosis (CS). A single-centre, prospective cohort study was performed in consecutive patients who met all of the following criteria: (1)presentation with clinically manifest CS, (2)abnormal myocardial fluoro-deoxyglucose (FDG) uptake on positron emission tomography scan, (3)plan for implantation with implantable cardioverter-defibrillatordevice that reports accurate PVC count, (4)plan to initiate corticosteroids after the device healing period. Data were collected during each device interrogation visit for all patients in the study. For each inter-visit period the total number of episodes of VT-sustained and nonsustained, and the number of PVCs was obtained. Each inter-visit period was classified into one of the following three periods: (1)New diagnosis of treatment-naive active disease without corticosteroids during the period. (2)Known treatment-naive active disease with corticosteroids initiated during the inter-visit period. (3)On corticosteroid therapy during the entire period. A total of 20 patients with a mean age of 59.7 ± 7.7 years were recruited and 82 inter-visit periods were analyzed. All patients were corticosteroid responders based on FDG uptake. The maximum left ventricular standardized uptake value was 11.14 ± 5.19 before corticosteroid initiation and 4.07 ± 0.88 after (p < .001). Patients with active untreated CS had an average of 496.4 ± 879.1 PVCs per day. After treatment with corticosteroids, the average PVC count increased to 1332.4 ± 1865.7/day during Period 2 (p = .036) and to 1590.1 ± 2362.2 per day during Period 3 (p = .008). There was also a statistically significant increase in episodes of nonsustained ventricular tachycardia (NSVT) before and after treatment with corticosteroids (p = .017). There were too few episodes of sustained ventricular arrhythmia to analyze. Overall, 18 out of 20 patients (90%) had an increase in PVC burden after corticosteroid initiation. This study demonstrated, on average, a threefold increase in daily PVC count in clinically manifest CS patients during treatment with corticosteroids compared to pretreatment. There was also a significant increase in episodes of NSVT. Clinicians and patients with active manifest CS should be aware that corticosteroids are unlikely to lead to a reduction in the burdens of PVC and NSVT.

High-Dose Prednisone for Treatment of Autoimmune Pancreatitis in a Patient with Coronavirus Disease 2019 (COVID-19) due to Infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)

Patient: Male, 53-year-oldFinal Diagnosis: Autoimmune pancreatitis type 1 • COVID-19Symptoms: Abdominal and/or epigastric pain • feverMedication: —Clinical Procedure: —Specialty: Gastroenterology and Hepatology • Infectious DiseasesObjective:Unusual clinical courseBackground:Autoimmune pancreatitis (AIP) is a rare, steroid-responsive disease of the pancreas. Concurrent treatment with immunosuppressants, including corticosteroids, increases the risk of developing a severe form of coronavirus disease 2019 (COVID-19) due to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The World Health Organization (WHO) advises against the use of corticosteroids in patients with SARS-CoV-2 due to their poor outcomes in patients with SARS-CoV and Middle East respiratory syndrome (MERS-CoV), unless these patients require steroid treatment for a coexisting disease.Case Report:A 53-year old patient was admitted with symptoms and diagnostic findings consistent with AIP. Thorough etiological workup revealed an elevated IgG4 level of 361 mg/dL and significant clinical response to corticosteroid treatment, leading to a diagnosis of AIP. After finishing steroid treatment at home, the patient was readmitted with another episode of AIP complicated by development of acute necrotic collection and COVID-19 while taking a second course of high dose prednisone. The patient was continued on high dose prednisone, started on azathioprine and intravenous meropenem, and underwent CT guided percutaneous drainage. He also received supportive care for COVID-19. After significant clinical improvement, the patient was discharged to quarantine at home, which he completed uneventfully.Conclusions:Despite the use of corticosteroids due to AIP, this high risk patient recovered from COVID-19 without complications. These findings support the use of corticosteroids when necessary for treatment of coexisting conditions in COVID-19 patients.

Efficacy and safety of corticosteroids in COVID-19 based on evidence for COVID-19, other coronavirus infections, influenza, community-acquired pneumonia and acute respiratory distress syndrome: a systematic review and meta-analysis

Very little direct evidence exists on use of corticosteroids in patients with coronavirus disease 2019 (COVID-19). Indirect evidence from related conditions must therefore inform inferences regarding benefits and harms. To support a guideline for managing COVID-19, we conducted systematic reviews examining the impact of corticosteroids in COVID-19 and related severe acute respiratory illnesses. We searched standard international and Chinese biomedical literature databases and prepublication sources for randomized controlled trials (RCTs) and observational studies comparing corticosteroids versus no corticosteroids in patients with COVID-19, severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS). For acute respiratory distress syndrome (ARDS), influenza and community-acquired pneumonia (CAP), we updated the most recent rigorous systematic review. We conducted random-effects meta-analyses to pool relative risks and then used baseline risk in patients with COVID-19 to generate absolute effects. In ARDS, according to 1 small cohort study in patients with COVID-19 and 7 RCTs in non-COVID-19 populations (risk ratio [RR] 0.72, 95% confidence interval [CI] 0.55 to 0.93, mean difference 17.3% fewer; low-quality evidence), corticosteroids may reduce mortality. In patients with severe COVID-19 but without ARDS, direct evidence from 2 observational studies provided very low-quality evidence of an increase in mortality with corticosteroids (hazard ratio [HR] 2.30, 95% CI 1.00 to 5.29, mean difference 11.9% more), as did observational data from influenza studies. Observational data from SARS and MERS studies provided very low-quality evidence of a small or no reduction in mortality. Randomized controlled trials in CAP suggest that corticosteroids may reduce mortality (RR 0.70, 95% CI 0.50 to 0.98, 3.1% lower; very low-quality evidence), and may increase hyperglycemia. Corticosteroids may reduce mortality for patients with COVID-19 and ARDS. For patients with severe COVID-19 but without ARDS, evidence regarding benefit from different bodies of evidence is inconsistent and of very low quality.

SARS-CoV-2 infection and glucose homeostasis in pregnancy. What about antenatal corticosteroids?

Background and aimsAdministration of corticosteroids is common in obstetric practice. In this concise review we queried on the effects of corticosteroids in pregnancies complicated by SARS-CoV-2. MethodsWe performed a literature search on PubMed, regarding the use of corticosteroids in patients with SARS-CoV-2 infection, in pregnancies complicated by SARS-CoV-2, as well as their impact on glycemia in pregnant women with or without diabetes. Furthermore, we searched for effects of SARS-CoV-2 and of other coronaviridae on insulin secretion and glycemia. ResultsSARS-CoV-2 infection appears to be a risk factor for complications in pregnancy. Corticosteroids may not be recommended for treating SARS-CoV-2 pneumonia but they may be needed for at-risk pregnancies. Corticosteroids in pregnancy have a diabetogenic potential. SARS-CoV-2 and other coronaviridae may have effects on glycemia. ConclusionsCaution should be exercised while using corticosteroids in pregnant women with COVID-19 requiring preterm delivery.

PRS10 COST-UTILITY ANALYSIS OF MEPOLIZUMAB VERSUS BENRALIZUMAB FOR SEVERE EOSINOPHILIC ASTHMA IN THE COLOMBIAN HEALTHCARE SYSTEM

BACKGROUND: Adding mepolizumab to standard treatment with inhaled corticosteroids and controller medications decreases asthma exacerbations and long-term oral corticosteroid use in patients with severe eosinophilic asthma. However, since new biological therapies are available in the Colombian healthcare system, it is necessary to establish their cost-effectiveness to inform local payers and decision-makers. To evaluate the cost-effectiveness of new biologics, mepolizumab and benralizumab, to treat adults with severe eosinophilic asthma in Colombia. A Markovian model was used to determine the incremental cost per quality-adjusted life year (QALY) of mepolizumab plus standard of care (SoC) versus benralizumab plus SoC from the payer’s perspective. In a monthly cycle, patients could transition between five health states (three asthma treatment states, asthma related death, and all-cause mortality) and three types of exacerbation events (exacerbations requiring either OCS burst, emergency department visit or hospitalization). Lifetime horizon was used. A network metanalysis (Busse 2019) was used for efficacy data, and local life tables for death probabilities. Costs were estimated following the methods recommended by the local health technology assessment agency. Costs and benefits were discounted at 5% and expressed in 2018 USD (1 USD = 2,956 COP). At the end of the simulation, mean cost of prevention of exacerbations and long-term oral steroid were $69.22 less per patient in mepolizumab, and mean therapy cost was $6,990.0 less per patient in mepolizumab. Treatment with mepolizumab plus SoC and benralizumab plus SoC resulted in 8.97 and 8.73 QALYs respectively. Findings were consistent in the probabilistic sensitivity analysis. Mepolizumab is a dominating alternative compared with benralizumab in the treatment of adults with severe eosinophilic asthma in Colombia from the payer’s perspective. Funding: GSK (PRJ2813).

Expert consensus on the use of corticosteroid in patients with 2019-nCoV pneumonia

Expert consensus on the use of corticosteroid in patients with 2019-nCoV pneumonia

Effect of corticosteroid therapy in the early phase of acute respiratory distress syndrome: a propensity-matched cohort study.

Background/AimsIt is unclear whether corticosteroid use in patients with acute respiratory distress syndrome (ARDS) improves survival. This study aimed to investigate whether the administration of corticosteroids to patients in the early phase of moderate to severe ARDS is associated with improved outcomes.MethodsWe analyzed the data of patients who received corticosteroids within 7 days of the onset of ARDS between June 2006 and December 2015 at a single tertiary teaching hospital. A total of 565 patients admitted with moderate to severe ARDS were eligible. The outcomes of patients treated with methylprednisolone 40 to 180 mg/day or equivalent (n = 404) were compared to those who did not receive steroids (n = 161). The primary and secondary outcomes were 28- and 90-day mortality rates, respectively. Propensity scores were used to adjust for baseline covariates.ResultsThe overall mortality at 28 days was not significantly different between the corticosteroid-treated and control groups (43.8% vs. 41%, p = 0.541). At 90 days, the overall mortality rate was higher in the corticosteroid-treated group than in the control group (59.2% vs. 48.4%, p = 0.021). However, on propensity score matching, corticosteroid therapy was not associated with a higher 28-day mortality rate (odds ratio, 1.031; 95% confidence interval, 0.657 to 1.618; p = 0.895) and 90 days (odds ratio, 1.435; 95% confidence interval, 0.877 to 2.348; p = 0.151).ConclusionsCorticosteroid therapy was not associated with 28- or 90-day mortality in the early phase of moderate to severe ARDS on propensity score matching analysis.

Use of corticosteroids in influenza-associated acute respiratory distress syndrome and severe pneumonia: a systemic review and meta-analysis

Influenza-related severe pneumonia and acute respiratory distress syndrome (ARDS) are severe threats to human health. The objective of this study was to assess the effects of systematic corticosteroid therapy in patients with pneumonia or ARDS. The PubMed, EMBASE, Web of Science and SCOPUS databases were searched up to July, 2019. Nineteen studies including 6637 individuals were identified, and fifteen studies (6427 patients) were included in the meta-analysis of mortality. Eighteen were observational studies and one was a randomized controlled trial (RCT). The meta-analysis results showed that corticosteroid therapy was associated with significantly higher mortality (OR 1.53, 95% CI [1.16, 2.01]) and incidence of nosocomial infection (OR 3.15, 95% CI [1.54, 6.45]). Subgroup analysis showed that among patients with unadjusted estimates, the odds of mortality were higher in patients receiving corticosteroid treatment (OR 1.98, 95% CI [1.23, 3.17]), however, among patients with adjusted estimates, the result showed no statistically significant difference between corticosteroid group and control group (OR 1.31, 95% CI [0.95, 1.80]). Current data do not support the routine use of corticosteroids in patients with influenza severe pneumonia or ARDS. RCTs are needed to provide more robust evidence.

Abstract P2-15-09: Systemic corticosteroid use in patients with metastatic triple-negative breast cancer treated with first-line therapy in the United States

Abstract Background: Corticosteroids (CS) have immunosuppressive properties that may diminish the efficacy of cancer immunotherapy (CIT). In retrospective analyses of clinical trial data, the use of CS for immune-mediated adverse events after starting CIT does not clearly appear to adversely affect outcomes; however, patients (pts) receiving CS at the start of CIT may have shorter overall and progression-free survival (Arbour, J Clin Oncol, 2018). With the increasing use of CIT for pts with metastatic triple-negative breast cancer (mTNBC) following the approval of atezolizumab in combination with nab-paclitaxel, it is important to understand the landscape of CS use as part of first-line (1L) treatment. Here we describe patterns of CS use in pts receiving 1L therapy for mTNBC, with a focus on taxanes. Methods: A total of 974 pts with confirmed mTNBC diagnosed from Jan 1, 2011, to Jul 5, 2018, and treated in the 1L setting from the de-identified Flatiron Health electronic health record-derived database were included in the study. Pts were categorized as having no CS use during 1L treatment, CS use at the start of 1L treatment or CS use after the start of 1L treatment. Results: The median age at mTNBC diagnosis was 60 years. The majority of pts were female (99%), treated at community centers (94%), and had recurrent disease (59%). Among the most common regimens in 1L were those containing capecitabine (n=208), paclitaxel (n=204), or nab-paclitaxel (n=131) (Table 1). Capecitabine was administered as monotherapy more frequently than paclitaxel and nab-paclitaxel (86% vs 67% and 52%, respectively). Most pts receiving capecitabine did not receive CS during 1L therapy (79%), whereas the majority of pts receiving paclitaxel and nab-paclitaxel did (&amp;gt;95% and 78%, respectively). However, among pts treated with nab-paclitaxel, CS use during 1L was more common in pts receiving combination regimens (88%) than those receiving monotherapy (67%). In general, pts who were treated with paclitaxel or nab-paclitaxel and initiated CS use at the start of 1L treatment continued it throughout their 1L treatment. CS was given (orally or intravenously) with 92% of paclitaxel administrations, 67% of nab-paclitaxel monotherapy administrations, 77% of nab-paclitaxel combination therapy administrations, and 81% of administrations when agents were given in combination with capecitabine. Among pts who received nab-paclitaxel monotherapy, pts who used CS during 1L tended to be younger and less likely to have visceral metastases or recurrent disease than pts who did not use CS. Conclusions: Overall, CS use was common at 1L initiation of most regimens used for the treatment of mTNBC, with the exception of capecitabine. Among pts who were treated with taxanes, those who initiated CS at 1L treatment tended to continue CS treatment for the duration of 1L. Despite the lack of requirement for the use of CS with nab-paclitaxel, the majority of pts treated with nab-paclitaxel monotherapy still received CS at the start of 1L treatment, suggesting use as premedication. None of the assessed pt characteristics were associated with CS use in pts who were treated with nab-paclitaxel monotherapy; however, due to widespread use of CS in the population and small sample size, definitive conclusions are difficult. Larger data sets with reasons for CS use are needed to further understand the observed patterns. Table 1CapecitabinePaclitaxelNab-Paclitaxel Othera(n=208)(n=204)(n=431)MonotherapyCombination(n=63)(n=68)Key baseline characteristicsAge at mBC diagnosis, median (IQR), years63 (53, 74)62 (53, 71)63 (57, 72)60 (52, 67)58 (61, 67)White, non-Hispanic, n (%)133 (64)115 (56)35 (56)41 (60)260 (60)De novo mBC, n (%)35 (17)106 (52)22 (35)23 (34)142 (33)mBC diagnosis later than 2015, n (%)112 (54)111 (54)42 (33)38 (56)261 (61)Bone-only mets at diagnosis, n (%)44 (21)38 (19)&amp;lt;5 (&amp;lt;8)11 (16)62 (14)Visceral mets at diagnosis, n (%)118 (57)121 (59)45 (71)37 (54)266 (62)Time from initial to mBC diagnosis (recurrent), median (IQR), months33 (20, 68)40 (23, 83)47 (24, 86)44 (27, 86)30 (17, 57)1L regimen typeMonotherapy, n (%)179 (86)68 (33)63 (100)0 (0)159 (37)Combination therapy, n (%)29 (14)136 (67)068 (100)272 (63)Duration, median (IQR), months3.9 (2.1, 7.0)3.2 (2.0, 4.8)3.2 (1.8, 5.0)5.0 (3.1, 7.3)2.8 (1.6, 4.4)CS use, n (%)No use during 1L164 (79)&amp;lt;6 (&amp;lt;3)21 (33)8 (12)88 (20)Use during 1L44 (21)&amp;gt;198 (&amp;gt;97)42 (67)60 (88)343 (80)Chemotherapy administrations with CS given on the same day, n (%)No39 (19)b177 (8)285 (33)231 (23)820 (27)Yes163 (81)b2104 (92)587 (67)780 (77)2236 (73)a Top 5 other regimens were carboplatin + gemcitabine (n=77), cyclophosphamide + doxorubicin (n=56), eribulin (n=25), carboplatin + docetaxel (n=23), and docetaxel (n=19).b These numbers comprise capecitabine combination regimens only, as chemotherapy administrations did not capture oral capecitabine monotherapy.1L, first-line; CS, corticosteroid; IQR, interquartile range; IV, intravenous injection administration; mBC, metastatic breast cancer; met, metastasis. Citation Format: MK Downer, Patricia Luhn, David Miles, Matthew Kent, Kenneth Russell, Joyce O’Shaughnessy. Systemic corticosteroid use in patients with metastatic triple-negative breast cancer treated with first-line therapy in the United States [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-15-09.

Expert consensus on the use of corticosteroid in patients with 2019-nCoV pneumonia

Expert consensus on the use of corticosteroid in patients with 2019-nCoV pneumonia

DOP76 Corticosteroid sparing effects of ustekinumab therapy for ulcerative colitis through 2 years: UNIFI long-term extension

Abstract Background Ustekinumab (UST) is an IL12/23 blocker approved for Crohn’s disease and ulcerative colitis (UC). In the UNIFI maintenance study of patients with moderate–severe UC, &amp;gt;90% of the patients who achieved clinical response or remission at week 44 were able to eliminate corticosteroids, an important goal of therapy. In this analysis, we describe the corticosteroid (CS) sparing effects of UST treatment through week 92 among patients who were treated in the UNIFI long-term extension (LTE). Methods Responders to UST 8 weeks after IV induction entered the maintenance study and were randomised to UST 90mg SC (q12wks or q8wks) or PBO. Patients who did not respond to UST IV induction received a dose of UST 90mg SC at week 8 and were evaluated at week 16. Those in clinical response at week 16 (delayed responders), were not randomised on entry into the maintenance study and received UST 90mg q8wk. All patients who completed week 44 of the maintenance study were eligible to enter the LTE and continue to receive the same dose. Patients could receive UST dose adjustment during the LTE (q12wk to q8wk or q8wk to q8wk [sham dose adjustment]) from week 56 onward. Patients who remained on PBO were discontinued from the LTE after maintenance study unblinding. During the maintenance study, CS tapering was recommended for all patients receiving CS at maintenance baseline. At week 92 of the LTE, CS-free symptomatic remission rates and CS use were calculated using intention-to-treat analyses with a dose adjustment considered to be a treatment failure and with a dose adjustment not considered to be a treatment failure. Results Of the 284 patients in the randomised population who were treated with UST in the LTE, 139 were receiving CS at maintenance baseline. Of these, 92.8% (n = 129) were CS-free at week 92. CS-free symptomatic remission rates at week 92 are summarised in Table 1. Results were similar for the q8wk and q12wk maintenance doses. Of the UST-treated patients who were in symptomatic remission at week 92, 98.4% (182/185) were CS-free; similar results were seen when dose adjustment was not considered to be a treatment failure. Of the 116 delayed responders (non-randomised population) who continued to receive UST in the LTE, 92 patients were in symptomatic remission at week 92; of whom, 94.6% (87/92) were CS-free. Conclusion UST maintenance therapy, with both q8wk and q12wk dosing regimens, was effective in reducing and eliminating the use of CS in patients with UC. Nearly all patients in the LTE who were in symptomatic remission at week 92, were not taking steroids.

Тhe use of corticosteroids in patients with severe burn injuries

Modern treatment of burns has led to a significant reduction in mortality in patients with burns whose injuries were fatal several years ago. However, along with improved survival, new problems arose in the treatment of burn patients. Systemic inflammatory response, capillary leak, sepsis top the list of the most common problems in both adults and children with severe thermal injury. Currently, new strategies are being developed and studied in the treatment of this category of patients. One of the ways to improve the results of treatment of patients with severe burn injury is to prescribe corticosteroids, both in the stage of burn shock and in the development of septic complications. Do corticosteroids reduce mortality and improve recovery in burn patients? The discussion about this has been going on for many years, but the opinion about their effectiveness remains controversial. An analysis of the literature shows that corticosteroids can play a significant role in the treatment of patients with severe burn injury and can be successfully used at any stage of a burn disease. The effect of reducing capillary leakage, increasing myocardial contractility, antiemetic, membrane-stabilizing effect of corticosteroids will be useful in the stage of burn shock. The anti-inflammatory, immunomodulatory effect of corticosteroids will play a role in any stage of a burn disease. With the aim of preventing and treating sepsis, corticosteroids may be useful in the stage of toxemia, septicotoxemia. It is also necessary to remember about adrenal insufficiency, which develops in burn patients. The article analyzes the literature, substantiates the use of corticosteroids in patients with severe burn injury in different periods of a burn disease.

Effect of different doses and time-courses of corticosteroid treatment in patients with acute respiratory distress syndrome: A meta-analysis.

While previous trials have indicated that the use of corticosteroids for patients with acute respiratory distress syndrome (ARDS) is effective, the dosage and time-course for the use of corticosteroids remain a subject of controversy. The present study aimed to address and resolve these problems. PubMed, Embase and the Cochrane Library databases were searched from inception to March 2017 for randomized controlled trials (RCTs), which included patients with ARDS using corticosteroids. Related data were extracted independently by two investigators. The Mantel-Haenszel method was used with random-effects modeling to calculate the pooled odds ratio (OR) and 95% confidence interval (CI) for the mortality of patients with ARDS, and the risk of new infection arising from the use of glucocorticoids. The inverse variance method was used to calculate the mean difference (MD) and 95% CI for the duration of mechanical-free ventilation and the ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FIO2 ratio). The use of low-dose corticosteroids significantly reduced the mortality rate of patients with ARDS (OR: 0.43; 95% CI: 0.24–0.79; P=0.006) while the use of high-dose corticosteroids provided no significant benefit to reducing the mortality rate (OR: 1.33; 95% CI: 0.86–2.04; P=0.20). The present study identified that glucocorticoids reduced the mortality rate of patients during the early stages of ARDS (OR: 0.61; 95% CI: 0.43–0.86; P=0.005). Glucocorticoids significantly reduced the duration of mechanical ventilation (MD: 3.08; 95% CI: 1.49–4.68; P<0.05) and significantly improved the PaO2/FiO2 ratio (MD: 66.39; 95% CI: 57.79–74.98; P<0.05). The use of corticosteroids did not significantly increase the rate of infectious complications (OR: 0.60; 95% CI: 0.32–1.12; P>0.05). The use of low-dose corticosteroids may significantly reduce the mortality rate, particularly in the early stages of ARD, shorten the duration of mechanical ventilation and improve the PaO2/FiO2 ratio without increasing the risk of a new infection.

Adverse Events Associated with Cumulative Corticosteroid Use in Patients with Castration-Resistant Prostate Cancer: An Administrative Claims Analysis.

Corticosteroids are a mainstay treatment for castration-resistant prostate cancer (CRPC). Although corticosteroids have been associated with adverse events, long-term outcomes related to their sustained use have not been assessed in men with CRPC. This study evaluated the impact of cumulative corticosteroid exposure on the risk of developing specific adverse events in men with CRPC. Data were obtained from administrative claims databases. Adult chemotherapy-naïve men who initiated CRPC treatment following surgical or medical castration were selected. Patients were grouped into four cohorts based on cumulative corticosteroid dose: no exposure, low exposure (< 0.5g), medium exposure (0.5-2.0g), and high exposure (> 2.0g). Time to each adverse event was assessed using Kaplan-Meier analyses and time-dependent Cox proportional hazard models, adjusting for baseline characteristics. Overall, 9425 patients were included (no exposure, N = 6765; low exposure, N = 1660; medium exposure, N = 655; high exposure, N = 345). The mean age was 71-76years across cohorts. During the study period, cumulative corticosteroid exposure was associated with a significantly higher risk of developing an infection [high vs. no exposure, adjusted hazard ratio (HR) 2.55; 95% confidence interval (CI) 2.27-2.85; p < 0.001 for trend], peptic ulcer (HR 1.91; 95% CI 1.39-2.64; p < 0.001), acute cardiovascular events (HR 1.62; 95% CI 1.43-1.83; p < 0.001), endocrine disorder (HR 1.61; 95% CI 1.34-1.94; p < 0.001), fracture (HR 1.59; 95% CI 1.37-1.86; p < 0.001), or mental health condition (HR 1.28; 95% CI 1.06-1.55; p = 0.014). Exposure to corticosteroids was associated with a more rapid onset of adverse events. Patients with CRPC receiving corticosteroids had a higher risk of developing a wide range of adverse events than those not receiving them. The increased adverse event risk was observed after accounting, to the extent possible, for patients' overall disease severity.

715 Corticosteroid Sparing Effects of Ustekinumab Therapy in UC Patients: Results From the UNIFI Program

INTRODUCTION: Ustekinumab (UST), an IL12/23 blocker approved for Crohn's disease, was effective in Phase 3 induction and maintenance studies of patients with moderate-severe ulcerative colitis (UC). Since discontinuation of corticosteroids (CS) is an important goal of therapy in UC, this analysis aims to further describe the CS sparing effects of ustekinumab treatment through Week 44 of the UNIFI trial. METHODS: Responders to UST IV induction entered maintenance and were randomized to UST 90 mg SC (q12wks or q8wks), or PBO. During the induction and maintenance studies, oral CS were not to be initiated or increased beyond baseline. At Week 0 of the maintenance study, a scheduled taper was recommended for all patients receiving CS. CS-free Clinical Response (CSR) and remission (CSRem) rates (at Week 44, and for &gt;90 days prior to Week 44) were calculated for the overall population and for the subset of patients on CS at maintenance baseline. Among the subset of patients on CS at maintenance baseline, the mean prednisone-equivalent (P.Eq) CS dose (mg/day) through Week 44 were calculated as were the rates of subjects who were CS-free at Week 44 and for &gt;90 days prior to Week 44. RESULTS: Overall 50.6% (265/523) of patients in the primary analysis population were receiving CS at maintenance baseline. The proportions of patients who were receiving concomitant CS at maintenance baseline were 52.3%, 47.7%, and 52.3% in the UST q8w, UST q12w and PBO groups, respectively. As detailed in Table 1, in the overall population, CSR and CSRem rates were significantly higher for patients who continued on UST therapy during maintenance compared with placebo. Among the patients who achieved CSR or CSRem at Week 44, the majority achieved these endpoints and eliminated CS use at or up to 90 days prior to Week 44. Similar results were observed in the subset of patients on concomitant CS at maintenance BL. In this group, the mean daily P.Eq CS dose at maintenance BL was approximately 15.0 mg/day for all treatment groups. Mean decrease in average daily P.Eq dose at Wk 44 was more pronounced and the proportion of patients who were CS-free was greater in the UST maintenance arms. CONCLUSION: UST maintenance therapy, with both q8w and q12w dosing regimens, is effective in reducing and eliminating the use of CS in patients with UC; the majority of patients (&gt;90%) who achieved clinical response or clinical remission were able to eliminate corticosteroids.

Health Care Resource Utilization and Costs Associated with Corticosteroid Use in Patients with Castration-Resistant Prostate Cancer: An Administrative Claims Analysis.

Corticosteroids are used in the management of castration-resistant prostate cancer (CRPC) to reduce tumor-related symptoms because of CRPC therapies. Since corticosteroids have been associated with a range of toxicities, their use may increase the economic burden sustained by patients with CRPC. However, the economic impact of using corticosteroids in patients with CRPC has not been well characterized. To assess the effect of previous corticosteroid use on health care resource utilization (HRU) and health care costs among men with CRPC. Using administrative claims data (2007-2016), adult chemotherapy-naive patients who initiated CRPC treatment following surgical or medical castration were identified. Based on the cumulative corticosteroid dose during the 12 months before CRPC treatment initiation, patients were grouped into 4 cohorts: no corticosteroid (0 gm), low corticosteroid (< 0.5 gm), medium corticosteroid (0.5-2.0 gm), and high corticosteroid (> 2.0 gm). All-cause HRU and costs (2017 U.S. dollars) were compared between cohorts during the 1-year study period following CRPC treatment initiation using the no corticosteroid cohort as reference. Multivariable regression models were used to adjust for baseline covariates, including age, region, index year, Charlson Comorbidity Index score, presence of bone metastases, baseline all-cause HRU, and corticosteroid-related clinical events during baseline. 9,425 patients were included (no corticosteroid = 6,765, low corticosteroid = 1,660, medium corticosteroid = 655, and high corticosteroid = 345). On average, patients in the no corticosteroid cohort were older and had a lower baseline HRU and comorbidity burden than patients in the other 3 cohorts. During the study period, patients with corticosteroid exposure (across all corticosteroid cohorts) had significantly more inpatient admissions (high corticosteroid vs. no corticosteroid adjusted incidence rate ratio [IRR] = 1.56; P < 0.001), emergency department visits (high corticosteroid vs. no corticosteroid adjusted IRR = 1.30; P = 0.001), and outpatient visits (high corticosteroid vs. no corticosteroid adjusted IRR = 1.11; P < 0.001). In addition, compared with the no corticosteroid cohort, patients with corticosteroid exposure had significantly higher monthly total costs (high corticosteroid vs. no corticosteroid adjusted difference = $2,600; P < 0.001), including medical service costs (high corticosteroid vs. no corticosteroid adjusted difference = $1,564; P < 0.001) and pharmacy costs (high corticosteroid vs. no corticosteroid adjusted difference = $825; P < 0.001). Cumulative corticosteroid exposure before CRPC treatment initiation was associated with significantly higher HRU and costs. This increase in economic burden was more prominent among patients with annual cumulative corticosteroid doses of more than 2.0 gm. These results suggest that previous corticosteroid use may result in a higher economic burden among patients with CRPC. This study was funded by Astellas Pharma (Northbrook, IL) and Medivation, a Pfizer Company (San Francisco, CA), the codevelopers of enzalutamide. The study sponsor was involved in the study design, data interpretation, and review. All authors contributed to the development of the manuscript and maintained control over the final content. Schultz and Wilson are employed by Astellas Pharma. Schultz owns stock in Gilead Sciences and Shire. Song and Yang are employed by Analysis Group, which received consultancy fees from Astellas Pharma. Ramaswamy is employed by Pfizer, and Lowentritt is employed by Chesapeake Urology and has served as a speaker and consultant for Astellas Pharma, Pfizer, Bayer, Dendreon, and Janssen. A synopsis of the current research was presented in poster format at the AMCP Managed Care & Specialty Pharmacy Annual Meeting 2019, which took place in San Diego, CA, on March 25-28, 2019.