Systemic Corticosteroids In Patients Research Articles

Pharmacokinetics and Pharmacodynamics of Systemic Corticosteroids in Autoimmune and Inflammatory Diseases: A Review of Current Evidence.

Systemic corticosteroids have a long history of use in the treatment of autoimmune and inflammatory diseases. Both efficacy and safety show large interindividual variability (IIV), suggesting that corticosteroids may have the potential for individualised dosing strategies to optimise therapy. This systematic review aims to provide an overview of current evidence on the pharmacokinetic (PK) and pharmacodynamic (PD) relationships of systemic corticosteroids in patients with autoimmune and inflammatory diseases. A systematic literature search was conducted in PubMed and Embase for PK/PD studies of systemic corticosteroids in autoimmune and inflammatory diseases in humans published until December 2023. Studies were scored from 1 to 5 according to criteria for the levels of evidence, as inspired by the Oxford Centre for Evidence-Based Medicine. Twelve studies (1981-2016) were included. The majority of these studies had a small sample size. The corticosteroids involved were prednisone, prednisolone, methylprednisolone and budesonide. Substantial IIV of corticosteroid PK was described in all studies. Evidence for a relationship between the PK of corticosteroids and efficacy was inconclusive and limited. However, there was some evidence for a relationship between the PK of prednisolone and the severity of Cushingoid features. There is insufficient evidence to draw firm conclusions on the potential associations between PK and clinical outcome of systemic corticosteroid treatment in autoimmune and inflammatory diseases. This is remarkable given the many decades that steroid drugs have been used in clinical care. Prospective research is recommended with robust and well-defined cohorts to fully quantify the PK/PD associations of corticosteroids.

Corticosteroid treatment for persistent pulmonary infiltrates following COVID-19 infection: Clearing the fog?

Systemic corticosteroids have been shown to improve outcomes in severe coronavirus disease 2019 (COVID-19) pneumonia; however, their role in post-COVID-19 persistent lung abnormalities is not well defined. Here, we describe our experience with corticosteroids in patients with persistent lung infiltrates following COVID-19 infection. What is the efficacy of systemic corticosteroids in improving lung function and radiological abnormalities in patients following COVID-19 pneumonia? This is a single-center retrospective study evaluating patients with persistent respiratory symptoms and abnormal chest computed tomography findings. Patients were divided into two groups based on treatment with corticosteroids: "steroid group" and "nonsteroid group." Clinical data were collected from the electronic medical records. Between March 2020 and December 2021, 227 patients were seen in the post-COVID-19 pulmonary clinic, of which 75 were included in this study. The mean age was 56 years, 63% were female, and 75% were white. The main physiologic deficit was reduced Diffusing capacity of the Lungs for Carbon Monoxide (DLCO) at 72% (±22). On chest imaging, the most common findings were ground-glass opacities (91%) and consolidation (29%). Thirty patients received corticosteroid (steroid group) and 45 did not (nonsteroid group). Patients treated with corticosteroids had lower DLCO (DLCO [%]: steroid group 63 ± 17, nonsteroid group 78 ± 23; P = 0.005) and all had ground-glass opacities on imaging compared to 84% in the nonsteroid group (P = 0.04). At follow-up, patients in the steroid group (n = 16) had a significant improvement in spirometry and DLCO. In addition, there was a significant improvement with resolution of ground-glass opacities in both the groups (P < 0.05). The use of systemic corticosteroids in patients with persistent respiratory symptoms and radiological abnormalities post-COVID-19 was associated with significant improvement in pulmonary function testing and imaging. Prospective studies are needed to confirm whether these findings are the effect of corticosteroid therapy or disease evolution over time.

Expanding options of supportive care in IgA nephropathy.

Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis worldwide, with a potentially serious prognosis. At present, management of IgAN is primarily based on therapeutic lifestyle changes, and excellent blood pressure control and maximized supportive treatment with the combination of inhibition of the renin-angiotensin-aldosterone system with either inhibitors of angiotensin-converting enzyme or angiotensin II receptor blockers and inhibitors of sodium-glucose cotransporter-2, and possibly in the future also with endothelin antagonists. Supportive care currently represents the cornerstone of treatment of IgAN. Targeted-release formulation of budesonide should replace systemic corticosteroids in patients with higher proteinuria and active histological lesions. New treatment options are aimed at immunopathogenesis of IgAN including depletion or modulation of Galactose-deficient-Immunoglobulin A1-producing B cells, plasma cells, and the alternate and/or lectin pathway of complement. The exact place of monoclonal antibodies and complement inhibitors will need to be determined. This article reviews potential supportive therapies currently available for patients with IgAN.

Economic evaluation and budgetary burden of mepolizumab in severe refractory eosinophilic asthma

ObjectiveMepolizumab is indicated as an additional treatment of severe refractory eosinophilic asthma. The observed differences in population subgroups according to plasma eosinophil count, the existence of patients with high levels of immunoglobulin E who are candidates of omalizumab and mepolizumab, as well as mepolizumab's economic impact, lead to make efficient economic studies for clinical decision making. The aim was to analyze mepolizumab's cost-efficacy and budget impact. MethodCost comparison and the use of mepolizumab's budgetary impact was performed, from the Spanish National Health System's perspective. Among the assessed alternatives, inhaled systemic corticosteroids, plus long acting beta agonist (β2) and/or oral systemic corticosteroids in patients with non immunoglobulin E-mediated severe allergic asthma, and said treatment along with omalizumab in patients with immunoglobulin E mediated eosinophilic allergic asthma were included. Its efficacy was evaluated through avoided clinically relevant exacerbations. The direct costs associated with exacerbation were assessed. ResultsMepolizumab's long run average incremental cost regarding omalizumab's is 797 euros per patient a year. Considering omalizumab's alternative discounted price, including mepolizumab for patients with immunoglobulin E mediated eosinophilic allergic asthma would increase public spending from 2.3 to 4.6 million euros. Given omalizumab's notified price, the gradual introduction of mepolizumab in the Spanish National Health System would save 3.6 million euros in three years. For non immunoglobulin E-mediated severe asthma patients, the avoided cost/exacerbation by introducing mepolizumab is 15,085 euros, assuming a gradual market penetration of mepolizumab. In patients with ≥ 500 eosinophils/µL, this cost decreases to 7,767 euros per avoided exacerbation with a budgetary impact of 183.2 million euros in three years with a progressive penetration of mepolizumab. ConclusionsThe cost comparison between mepolizumab and omalizumab in immunoglobulin E mediated eosinophilic asthma patients suggests a use of the lower cost drug, promoting price competition. Additionally, prioritizing its use among non immunoglobulin E-mediated severe refractory eosinophilic asthma patients and ≥ 500 eosinophils/µL plasma level patients, would improve its efficiency as well as reducing its budgetary impact.

Is there a difference in treatment outcomes between short (seven days or less) and long (greater than seven days) courses of systemic corticosteroids in patients with an acute exacerbation of COPD?

Tripler Army Medical Center, Honolulu, HI The corresponding author is Savannah Smith; [email protected]. The authors declare no conflicts of interest. The opinions and assertions contained herein are those of the authors and are not to be construed as official or as reflecting the views of the US Army Medical Department, the Army at large, or the Department of Defense.

DIAGNOSTIC AND THERAPEUTIC CHALLENGE IN USUAL INTERSTITIAL PNEUMONITIS DUE TO CHEMOTHERAPEUTICS

The Recognition of drug-induced lung disease is difcult because the clinical, radiological, and histological ndings are nonspecic. The development of inammatory damage and toxicities by the drugs are hard to recognize which poses challenge in early recognition and management of the patients. Drugs have been associated with various pulmonary complications like interstitial inammation ,brosis, bronchospasm, pulmonary edema and pleural effusions. Main treatment is the avoidance of further exposure of drugs and administering systemic corticosteroids in patients with progressive or disabling disease.

No Specific Factors Associated with Risk of Readmission for Rebound Pain in Children with Sickle Cell Disease and Asthma Treated with Systemic Corticosteroids

Introduction: Asthma occurs in up to 28% of patients with sickle cell disease (SCD) and is associated with increased incidence of vaso-occlusive pain, acute chest syndrome (ACS), and mortality. Systemic steroids are the standard treatment for acute asthma and are often used in patients with SCD, especially as clinical symptoms of acute asthma exacerbations may often overlap with those of ACS. The risk of rebound pain following treatment with corticosteroids has been reported in other studies. However, the temporal association and the factors associated with the risk of rebound vaso-occlusive pain, specifically in those with co-morbid asthma diagnosis, have not been well described. Objective: To evaluate the temporal association between the use of systemic corticosteroids in patients with SCD and asthma and the factors associated with the risk of rebound vaso-occlusive pain. Methods: Patients with confirmed SCD and asthma, between ages 4-18 years of age, and admitted between 2006 and 2009, were eligible. Based on their associations with SCD and asthma, the co-variables of interest evaluated included hydroxyurea (HU) usage, age, sex, atopy, indication for hospitalization, and length of hospital admission. Participants were included if they received systemic glucocorticoids (dexamethasone, methylprednisolone, prednisone, prednisolone) during admission. Participants were excluded if they were receiving chronic blood transfusion therapies or participating in clinical trials involving blood transfusions. Our primary end-point was readmission for rebound vaso-occlusive pain within 14 days of the index admission. Continuous variables were analyzed with the mean (std. deviation) or median (inter-quartile range), based on the distribution, and compared by group with a t test or Somers'd statistic. Categorical variables were analyzed with counts (percent) and compared with a Chi-square statistic. All tests were adjusted for clustering by patients. Results: Fifteen distinct patients, 9 (60%) females, with a total of seventy-six admissions with administration of corticosteroids were included in the analysis (Table). Fifty-seven (75%) of admissions occurred in female patients with a median length of hospitalization of 3.0 days (IQR 2.0 - 4.8). Of the 76 episodes of corticosteroid use, 65 (85.5%) were due to a primary respiratory illness. There were twenty-eight (36.8%) readmissions for rebound vaso-occlusive pain with a median time to readmission of 3.0 (IQR 2.0 - 6.0) days. Amongst all patients, neither sex, history of atopy (>=2 positive skin sensitization tests), indication for hospitalization, or length of hospitalization were associated with the risk of readmission for rebound pain (p=0.425, p=0.540, p=0.721 respectively). Only 2 patients with 5 admissions were documented to be on HU and so we could not assess the relationship to rebound with HU usage. There was a trend for an association of history of early ACS and risk of rebound vaso-occlusive pain. Patients with ACS before the age of 4 were less likely to experience rebound vaso-occlusive pain compared to those without early ACS (P=0.051). Discussion: Our data shows that patients with sickle cell disease and asthma treated with corticosteroids are at risk for readmission due to rebound vaso-occlusive pain in more than one third of episodes (36.8%) following initial corticosteroid exposure. Our study did not identify any specific factors associated with risk of readmission for rebound pain following corticosteroid use. While corticosteroids are life-saving in status asthmaticus, the risk for rebound pain is significant and clinicians should work to optimize chronic asthma therapy to prevent the need for systemic corticosteroids in asthma exacerbations in patients with SCD. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Prevalence and management of chronic hepatitis B in pemphigus and pemphigoid patients: New evidence for the safety of rituximab.

Although the treatments of pemphigus and pemphigoid patients have tended toward safer options, patients with chronic infections seem to be still at the risk of infection reactivation when they are exposed to any of immunosuppressive treatments. A retrospective study on 1646 registered pemphigus and pemphigoid patients was conducted between January 2017 and February 2019 and the prevalence of HBV, the association between the treatments, mainly prednisolone and rituximab with HBV reactivation as well as outcomes of patients after management with antiviral therapies were evaluated. From 1646 reviewed patients, 10 (0.60%) patients with chronic HBV were identified. We found a negative correlation between the ALT (p-value<0.001), AST (p-value=0.090), and Pemphigus Disease Area Index (PDAI) (p-value=0.034) and age of patients. At the time points that prednisolone dosage was higher, higher levels of ALT, but no difference in AST levels was noted. The portion of patients with normal ALT was significantly higher (p-value=0.036; OR=2.22) in those who had received rituximab within the previous 6 months (38 of 49; 77.6%) as compared to those who did not (81 of 133; 60.9%). We concluded that avoidance (high dose) systemic corticosteroids in patients with chronic HBV, and using rituximab instead in severe cases benefit this group of patients.

Use of systemic corticosteroids in patients newly registered at a claims database with a diagnosis of non-infectious uveitis: results from a real-world claims database analysis.

To investigate the real-world dose of systemic corticosteroids in the treatment of non-infectious uveitis (NIU) in Japan. A retrospective, observational study. Patients newly registered at the Japan Medical Data Center health insurance claims database with a diagnosis of NIU who received systemic corticosteroids were identified, and their systemic corticosteroid dose (prednisolone equivalent) was assessed over 12 months of treatment (data extraction period: January 2008 to May 2017). The mean cumulative systemic corticosteroid dose in 12 months in 1641 new patients with NIU who received systemic corticosteroids was 593.7mg. The mean systemic corticosteroid dose was highest at month 1 (10.7, 218.1, 16.7, and 23.0mg/day in Behçet's disease [BD]-associated NIU [n = 19], Vogt-Koyanagi-Harada [VKH] disease-associated NIU [n = 49], sarcoidosis-associated NIU [n = 27], and "undifferentiated NIU" [NIU without specific primary disease information, n = 1545], respectively) and decreased over time. Systemic corticosteroids were prescribed at month 12 to 68.4%, 22.4%, 44.4%, and 5.6% of patients with BD-associated NIU, VKH disease-associated NIU, sarcoidosis-associated NIU, and undifferentiated NIU, respectively (mean dose, 6.0-14.3mg/day). Multivariate regression analysis identified female sex, middle age (30 to < 40 years), VKH disease, and immunosuppressive agent use as background factors associated with higher systemic corticosteroid dose. The systemic corticosteroid dose was highest at month 1 and decreased over time in all disease categories. This database research revealed that some patients with NIU continued being prescribed systemic corticosteroids for at least 1 year.

Survey on Use of Local and Systemic Corticosteroids in the Management of Chronic Rhinosinusitis with Nasal Polyps: Identification of Unmet Clinical Needs.

Background: Local and systemic corticosteroids have long been the workhorse in management of chronic rhinosinusitis with nasal polyps (CRSwNP), although there is no universally accepted modality of prescription. We carried out a survey in Italy to capture current trends in the use of topical and systemic corticosteroids in patients with CRSwNP. Methods: A survey was set up on Survey Monkey®. Each author distributed the link to the survey in an ad hoc manner and a total of 437 participants filled out the survey. Results: Mometasone furoate (79.3%) was the most frequently prescribed, administered daily by 61.9% of participants; the remaining preferred to discontinue treatment for brief periods to reduce side effects or to modulate the therapy in mild cases. The majority believe that a short cycle of systemic steroids should be prescribed for re-exacerbation of symptoms and that the number of cycles in the previous year should be evaluated to define control of the disease even if international guidelines do not provide clear indications on this topic. A certain degree of divergence emerged from responses regarding how long and the maximal dose of systemic steroids which place patients at high risk for adverse events. Finally, systemic corticosteroids seem to offer only temporary benefit on recovery of smell without guaranteeing long-term control even if the patient is adherent to topical corticosteroids. Conclusions: Our results highlight the need for clear guidelines on oral steroids, which could help supporting the use of a precision medicine approach, including indications for new biological agents.

Risk of vaso-occlusive episode after exposure to corticosteroids in patients with sickle cell disease

AbstractVaso-occlusive episodes (VOEs) are a major concern in patients with sickle cell disease (SCD). Exposure to systemic corticosteroids has been suspected to increase the occurrence of VOEs in case reports or series. No comparative study has been conducted to investigate this risk, which is still debated. Several clinical trials demonstrated the effectiveness of corticosteroids for the treatment of VOEs, but with increased rates of readmission. The aim of the study was to assess the risk of hospitalization for VOE associated with exposure to systemic corticosteroids in patients with SCD. We used a case-case-time-control design in a nationwide population-based cohort built in the French national health insurance database between 2010 and 2018. The population included all patients with SCD with at least 1 hospitalization for VOE. Corticosteroids were identified using out-of-hospital dispensing data. The outcome was the first hospitalization for VOE. The case-case-time-control design induces self-adjustment for time-invariant confounders, including genotype. Analyses were adjusted for time-dependent confounders (infections, red blood transfusions) and stratified by exposure to hydroxyurea. Overall, 5151 patients were included in the main analysis. Corticosteroid exposure was significantly associated with the occurrence of hospitalizations for VOEs: adjusted odds ratio, 3.8; 95% confidence interval [CI], 2.4-5.6). In patients exposed to hydroxyurea, the adjusted odds ratio was 2.6 (95% CI, 1.1-6.4); it was 4.0 (95% CI, 2.5-6.3) in unexposed patients. These results were consistent in children and adults. In conclusion, systemic corticosteroids were associated to an increased risk of hospitalization for VOEs and should be limited in patients with SCD.

Interleukin-37: A Link Between COVID-19, Diabetes, and the Black Fungus.

The COVID-19 pandemic involved millions of people and diabetes was identified as an associated comorbidity. Initiation of systemic corticosteroids in patients suffering from severe COVID-19 was associated with lower mortality. A surge of invasive fungal infections of the maxillofacial region, namely mucormycosis, was linked to a deadly infection known as black fungus. Black fungus, diabetes, corticosteroids, and coronavirus disease 2019 (COVID-19) all have a dysregulated immune response in common, which partly could also be attributed to interleukin 37 (IL-37). IL-37, a new cytokine of the IL-1 family, known for broadly reducing innate inflammation as well as acquired immune responses. The use of corticosteroids in diabetic COVID-19 patients, crowded hospitals, and lack of medical oxygen should be carefully considered to reduce COVID-associated secondary infections.

COVID-19 Infections and Asthma

The severe acute respiratory syndrome coronavirus 2, which causes coronavirus disease 2019 (COVID-19), has infected more than 200 million and led to the deaths of more than 4.3 million people. Although there are known risk factors for severe disease, asthma was initially hypothesized to be a risk factor for severe disease given the association between asthma exacerbations and respiratory viral illnesses in general. Fortunately, clinical outcomes for patients with asthma overall are similar to those for patients without asthma, without convincing evidence that asthma is a risk factor for severe disease. This may be explained in part by the decreasing gradient of angiotensin-converting enzyme-2 receptor from the upper to lower respiratory epithelium and that aeroallergen-sensitized patients with asthma can have up to 50% reduction in angiotensin-converting enzyme-2 receptor expression. Vaccination for patients with asthma is recommended for all without clear contraindications. COVID-19–specific treatment options are available depending on the severity of disease. We caution the use of systemic corticosteroids in patients with asthma not requiring supplemental oxygen given an association with worse outcomes. Postacute COVID-19 syndrome or long-haul COVID does not appear to be more prevalent in the population with asthma, and a multidisciplinary approach to care is a reasonable option.

New Perspectives on the Immunopathogenesis and Treatment of Uveitis Associated With Vogt-Koyanagi-Harada Disease.

Uveitis associated with Vogt-Koyanagi-Harada (VKH) disease is a bilateral, chronic, granulomatous autoimmune disease associated with vitiligo, poliosis, alopecia, and meningeal and auditory manifestations. The disease affects pigmented races with a predisposing genetic background. Evidence has been provided that the clinical manifestations are caused by a T-lymphocyte-mediated autoimmune response directed against antigens associated with melanocytes in the target organs. Alongside of T lymphocytes, autoreactive B cells play a central role in the development and propagation of several autoimmune diseases. The potential role of B lymphocytes in the pathogenesis of granulomatous uveitis associated with VKH disease is exemplified within several studies. The early initial-onset acute uveitic phase typically exhibits granulomatous choroiditis with secondary exudative retinal detachment and optic disc hyperemia and swelling, subsequently involving the anterior segment if not adequately treated. The disease eventually progresses to chronic recurrent granulomatous anterior uveitis with progressive posterior segment depigmentation resulting in “sunset glow fundus” appearance and chorioretinal atrophy if not properly controlled. Chronically evolving disease is more refractory to treatment and, consequently, vision-threatening complications have been recognized to occur in the chronic recurrent phase of the disease. Conventional treatment with early high-dose systemic corticosteroids is not sufficient to prevent chronic evolution. Addition of immunomodulatory therapy with mycophenolate mofetil as first-line therapy combined with systemic corticosteroids in patients with acute initial-onset disease prevents progression to chronic evolution, late complications, vitiligo, and poliosis. Furthermore, patients under such combined therapy were able to discontinue treatment without relapse of inflammation. These findings suggest that there is a therapeutic window of opportunity for highly successful treatment during the early initial-onset acute uveitic phases, likely because the underlying disease process is not fully matured. It is hypothesized that early and aggressive immunosuppressive therapy will prevent remnant epitope generation in the initiation of the autoimmune process, the so-called primary response. B cell depleting therapy with the anti-CD20 monoclonal antibody rituximab is effective in patients with refractory chronic recurrent granulomatous uveitis. The good response after rituximab therapy reinforces the idea of an important role of B cells in the pathogenesis or progression of chronic recurrent uveitis associated with VKH disease.

Systemic Corticosteroids in Patients With Bronchial Asthma: A Real-Life Study.

The objective of the present study was to determine the use of systemic corticosteroids (SCs) in patients with bronchial asthma using big data analysis. We performed an observational, retrospective, noninterventional study based on secondary data captured from free text in the electronic health records. This study was performed based on data from the regional health service of Castille-La Mancha (SESCAM), Spain. We performed the analysis using big data and artificial intelligence via Savana® Manager version 3.0. During the study period, 103 667 patients were diagnosed with and treated for asthma at different care levels. The search was restricted to patients aged 10 to 90 years (mean age, 43.5 [95%CI, 43.4-43.7] years). Of these, 59.8% were women. SCs were taken for treatment of asthma by 58 745 patients at some point during the study period. These patients were older, with a higher prevalence of hypertension, dyslipidemia, diabetes, obesity, depression, and hiatus hernia. SCs are used frequently in the general population with asthma (31.4% in 2015 and 39.6% in 2019). SCs were prescribed mainly in primary care (59%), allergy (13%), and pulmonology (20%). The frequency of prescription of SCs had a direct impact on the main associated adverse effects. In clinical practice, SCs are frequently prescribed to patients with asthma, especially in primary care. Use of SCs is associated with a greater number of adverse events. It is necessary to implement measures to reduce prescription of SCs to patients with asthma, especially in primary care.

Risk of Hospitalization for Vaso-Occlusive Episode in Patients with Sickle Cell Disease after out-Patient Exposure to Systemic Corticosteroids

▪Introduction : Sickle cell disease (SCD) is an inherited disorder which affects 300,000 newborns per year. Vaso-occlusive episodes (VOEs) cause an important morbi-mortality and a decreased quality of life in patients with SCD. Some risk factors of VOE are well known, like infection, cold exposure, stress, pulmonary diseases and dehydration. Exposure to systemic corticosteroids has been suspected to increase the occurrence of VOEs in few case reports or series. However, no comparative study has been conducted to demonstrate this risk which is still debated, resulting in discrepancies among guidelines on SCD management. This study aimed to assess the risk of hospitalization for VOE associated with out-hospital exposure to systemic corticosteroids in patients with SCD in France.Methods : Data source was the French national health insurance system database, named SNDS (Système National des Données de Santé) between 2010 and 2018. The SNDS links sociodemographic, out- and in-hospital data for the entire French population (>66 million inhabitants). The study population consisted in all patients with SCD with at least one hospitalization for VOE during the study period, identified with a primary discharge diagnosis of VOE (D57.0 code of the international classification of disease, 10 th version; positive predictive value: 98.6%). All genotypes (homozygous SS-SCD and double-heterozygous SCD) were included. Because we assessed out-hospital exposure to corticosteroids, patients hospitalized during the three months before the first VOE were excluded. We performed a case-case-time-control study (Figure 1). This self-controlled design results in self-adjustment for time-independent confounders, including genotype. The outcome was the first hospitalization for VOE. The exposure to oral and injectable corticosteroids, identified using out-hospital reimbursement data, was assessed during a case period (28 days before the outcome) compared to the exposure during a control period (28 days, starting 84 days before the outcome). The same comparison was made among future cases (matched patients hospitalized for VOE the year after the given case), in order to adjust for the trend of exposure to corticosteroids (calendar variations of corticosteroid exposure).Results : Overall, 5,151 cases of VOEs were included in the main analysis. Median age at first VOE was 16.9 years; 317 (6.2%) patients were exposed to corticosteroids during the case period. In the main analysis, corticosteroid exposure was significantly associated with the occurrence of hospitalizations for VOEs: adjusted Odds Ratio (aOR): 3.81, 95% confidence interval (95% CI): 2.44 to 5.61. In patients exposed to hydroxyurea, the aOR was 2.61, 95% CI: 1.07 to 6.39, compared with an aOR of 4.00, 95% CI: 2.53 to 6.30 in unexposed patients. In the subgroup analysis by age, the aOR was 2.81, 95% CI: 1.49 to 5.30 in children, and 4.45, 95% CI: 2.37 to 8.37 in adults. The results were consistent in all sensitivity analyses.Conclusion : This study showed an association between outpatient exposure to systemic corticosteroids with an increased risk of hospitalization for VOE, in both adults and children. Hydroxyurea may reduce this risk in adults. [Display omitted] DisclosuresBartolucci: GBT: Consultancy; Emmaus: Consultancy; Fabre Foundation: Research Funding; AGIOS: Consultancy; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Lecture fees, Steering committee, Research Funding; Jazz Pharma: Other: Lecture fees; INNOVHEM: Other: Co-founder; Bluebird: Consultancy, Research Funding; F. Hoffmann-La Roche Ltd: Consultancy; Hemanext: Consultancy; Addmedica: Consultancy, Other: Lecture fees, Research Funding. Moulis: Argenx: Membership on an entity's Board of Directors or advisory committees; Sobi: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Grifols: Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees, Research Funding.

Impact of Immune-Related Adverse Events on Efficacy of Immune Checkpoint Inhibitors in Patients with Advanced Hepatocellular Carcinoma

Introduction: Development of immune-related adverse events (irAEs) has been associated with enhanced efficacy with the use of immune checkpoint inhibitors (ICIs). It remains unknown whether such an association exists in advanced hepatocellular carcinoma (aHCC). This study aims to evaluate the association between irAEs and ICI efficacy in patients with aHCC. Methods: We performed a retrospective cohort study on patients with aHCC who received at least one dose of an ICI between May 2015 and November 2019 at the National Cancer Centre Singapore. The primary study objectives were to compare the overall survival (OS) and progression-free survival (PFS) between patients with and without irAEs. Complementary multivariable landmark analyses were performed at the 6-week and 12-week landmarks. Data cutoff was December 31, 2020. Results: One hundred and sixty-eight patients were included. Median age was 69 years, 85.7% were male, 57.7% had hepatitis B infection, 60.7% had ECOG 0, and 78.0% had Child-Pugh A liver cirrhosis. 82.7% received ICI monotherapy, while 17.3% received ICI in combination. Development and severity of irAE were correlated with survival. The median PFS for grade ≥3 irAE versus grades 1–2 irAE versus no irAE was 8.5 versus 3.6 versus 1.3 mths (p < 0.001). The median OS for grade ≥3 irAE versus grades 1–2 irAE versus no irAE was 26.9 versus 14.0 versus 4.6 mths (p < 0.001). Patients with ≥2 irAEs had a significantly longer OS on multivariable analysis (adjusted hazard ratio [aHR]0.35, p < 0.001). The presence of grade ≥3 irAEs was associated with a significantly longer OS on the multivariable analysis at the 6-week landmark (aHR0.34, p = 0.030) and 12-week landmark (aHR0.28, p = 0.011). The use of systemic corticosteroids in patients with irAE was associated with a trend toward a longer OS (20.7 vs. 14.3 mths, p = 0.064). Conclusion: Our study suggests that the presence of all-grade irAEs may be a potential prognostic biomarker in patients with aHCC treated with ICI. Patients with more severe irAEs and multisystem involvement have better prognosis. The prompt use of systemic corticosteroids to treat patients with irAEs is key to ensure the best long-term outcomes for these patients.

The Benefit of Benralizumab Monoclonal Antibody Treatment for Severe Eosinophilic Asthma in a Case Series (Pulmonology Clinic Târgu Mureș, Romania)

Abstract Background: Monoclonal antibody therapy is currently an additional treatment option to reduce exacerbations and improve symptom control in patients with severe eosinophilic asthma (SEA) that is uncontrolled despite treatment with high-dose inhaled corticosteroids and long-acting beta-2 agonists. Benralizumab, a monoclonal antibody that binds to the interleukin-5 receptor (IL-5), significantly reduces symptoms and annual exacerbations, as well as the use of systemic corticosteroids in patients with SEA. However, few studies are available on the effectiveness of this biological treatment in real life. The aim of this case series was to evaluate the efficacy of benralizumab by analyzing changes in clinical parameters and blood eosinophils in patients with SEA. Methods: We analyzed four patients with SEA who started treatment with benralizumab. The history of symptoms and exacerbations, eosinophil counts, data regarding the oral corticosteroid dose, need for rescue treatment, spirometry measurements and asthma control questionnaires (ACT) regarding the level of asthma control were recorded. A positive response to treatment was defined by a significant reduction in eosinophil counts, increased ACT scores, and lower rates of exacerbations. Results and conclusions: Benralizumab monoclonal antibody was effective in all four patients. This was shown by a reduction in exacerbation rates, symptom severity, and lower dose of oral corticosteroids and rescue medication. This novel treatment was well tolerated by the analyzed patients, thus indicating that benralizumab is an attractive choice for patients due to eosinophilic count reduction as well as the less frequent dosing schedule. However, further studies are required, on larger populations.

Management of hospitalised adults with coronavirus disease 2019 (COVID-19): a European Respiratory Society living guideline.

IntroductionHospitalised patients with coronavirus disease 2019 (COVID-19) as a result of SARS-CoV-2 infection have a high mortality rate and frequently require noninvasive respiratory support or invasive ventilation. Optimising and standardising management through evidence-based guidelines may improve quality of care and therefore patient outcomes.MethodsA task force from the European Respiratory Society and endorsed by the Chinese Thoracic Society identified priority interventions (pharmacological and non-pharmacological) for the initial version of this “living guideline” using the PICO (population, intervention, comparator, outcome) format. The GRADE approach was used for assessing the quality of evidence and strength of recommendations. Systematic literature reviews were performed, and data pooled by meta-analysis where possible. Evidence tables were presented and evidence to decision frameworks were used to formulate recommendations.ResultsBased on the available evidence at the time of guideline development (20 February, 2021), the panel makes a strong recommendation in favour of the use of systemic corticosteroids in patients requiring supplementary oxygen or ventilatory support, and for the use of anticoagulation in hospitalised patients. The panel makes a conditional recommendation for interleukin (IL)-6 receptor antagonist monoclonal antibody treatment and high-flow nasal oxygen or continuous positive airway pressure in patients with hypoxaemic respiratory failure. The panel make strong recommendations against the use of hydroxychloroquine and lopinavir–ritonavir. Conditional recommendations are made against the use of azithromycin, hydroxychloroquine combined with azithromycin, colchicine, and remdesivir, in the latter case specifically in patients requiring invasive mechanical ventilation. No recommendation was made for remdesivir in patients requiring supplemental oxygen. Further recommendations for research are made.ConclusionThe evidence base for management of COVID-19 now supports strong recommendations in favour and against specific interventions. These guidelines will be regularly updated as further evidence becomes available.

Effect of corticosteroid therapy in patients with an acute exacerbation of chronic obstructive pulmonary disease receiving ventilatory support

Background Chronic obstructive pulmonary disease (COPD) is a common, preventable, and treatable disease characterized by persistent respiratory symptoms and airflow limitation that is due to airway and/or alveolar abnormalities, usually caused by significant exposure to noxious particles or gases. The chronic airflow limitation that characterizes COPD is caused by a mixture of small airway disease (e.g. obstructive bronchiolitis) and parenchymal destruction (emphysema), the relative contributions of which vary from person to person. Aim The aim of the study was to determine the effect of systemic corticosteroids in patients with severe acute exacerbations of COPD admitted to the ICU receiving ventilatory support. Patients and methods A total of 100 patients with acute exacerbations of COPD leading to hypoxemia and respiratory acidosis with pH less than 7.35 and PaCO2 more than 45 mmHg admitted to the ICU who were receiving ventilator support (invasive or noninvasive mechanical ventilation) were included. Results It was noticed that steroid group had significantly lower duration of mechanical ventilation (4.67±2.76 vs. 2.76±1.11 days; P=0.01), ICU stay (5.33±2.87 vs. 7.89±3.36 days; P=0.04), and hospital stay (11.65±3.89 vs. 16.67±4.44 days; P=0.03). Conclusion Corticosteroid therapy was associated with significantly lower duration of mechanical ventilation, ICU stay, and hospital stay.