High-dose Corticosteroid Treatment Research Articles

Utility of C4d Immunohistochemistry in the Diagnosis of Esophageal Pemphigus Vulgaris.

Aims. To assess the utility of C4d immunohistochemistry for esophageal pemphigus vulgaris. Methods and results. We searched for patients with a history of esophageal pemphigus vulgaris who had esophageal biopsies for routine hematoxylin and eosin (H&E) staining. A total of 8 biopsies from 7 patients were available. We also identified 18 non-pemphigus esophageal biopsies for controls. C4d immunohistochemistry was performed on each biopsy. Five of 6 (83%) biopsies with classic pemphigus vulgaris histologic findings were positive for intercellular staining at the basal layer. The negative biopsy was in a patient that had recently received high-dose corticosteroid treatment for a flare. Two biopsies with atypical histologic features for pemphigus vulgaris had negative C4d staining but positive direct immunofluorescence (DIF) studies. Various nonspecific C4d staining patterns were observed in the controls, but none showed the intercellular staining pattern that was observed in pemphigus vulgaris. Conclusions. Suprabasal clefting with acantholysis and "tombstone effect" are described histologic features of pemphigus vulgaris on H&E. However, procedural artifact may mimic these findings. Currently, the gold standard for pemphigus vulgaris is DIF, which is not always available because it cannot routinely be performed on formalin-fixed paraffin embedded tissue. Our study shows that C4d immunohistochemistry may be a useful adjunct in evaluating esophageal pemphigus vulgaris.

Clinical and Economic Burden of Severe Asthma With Low Blood Eosinophil Counts

BackgroundType 2 (T2) low severe asthma phenotype is often a result of corticosteroid-overtreated T2-disease due to persistent symptoms, often not related to asthma, and unlikely to respond to high-dose corticosteroid treatment. ObjectiveThis study aimed to characterise severe asthma patients with low eosinophil counts (<300 cells/μl) and describe their disease burden and treatment across healthcare settings in the UK. MethodsA retrospective cohort study of severe asthma patients using linked Clinical Practice Research Datalink (CPRD) Aurum-Hospital Episode Statistics (HES) and UK Severe Asthma Registry (UKSAR) data indexed patients on latest blood eosinophil count (BEC). Clinical characteristics, treatment patterns, outcomes, and healthcare resource use (HCRU) were described by baseline BEC (≤150 and >150 to <300 cells/μl). ResultsAnalysis included 701 (CPRD-HES) and 1,546 (UKSAR) patients; with 60.5% and 59.4% having BECs ≤150 cells/μl at baseline, respectively. Across BEC groups, the proportion with uncontrolled asthma (≥2 exacerbations) at follow-up (12-months post-index) was 5.4% in CPRD-HES and 45.2% in UKSAR. Maintenance OCS use remained high across BEC groups (CPRD-HES: 29.4%; UKSAR: 51.7%), symptom control remained poor (>200 μg SABA or >500 μg terbutaline/day in CPRD-HES: 48.8%; median ACQ-6 score in UKSAR: 2.0 [1.0-3.3]). HCRU were similar across BEC groups. ConclusionMost patients managed in primary care were infrequent exacerbators, whilst UKSAR patients exacerbated frequently. Large proportions of both patient groups had poor symptom control and continued to receive high levels of maintenance OCS, increasing risk of corticosteroid-induced morbidity. These data highlight the need for rigorous assessment of underlying disease pathology to guide appropriate treatment.

Prior herpes zoster occurrence and high-dose corticosteroids increase herpes zoster risk in rheumatoid arthritis patients receiving janus kinase inhibitors in a retrospective and observational study.

Herpes zoster (HZ) risk is increased in rheumatoid arthritis (RA) patients receiving Janus kinase inhibitors (JAKi) therapy. Identifying and evaluating the risk factors of HZ development in patients receiving JAKi therapy would be clinically helpful. We investigated HZ's incidence rates (IR), identified the risk factors, and further assessed their influence on HZ development in RA patients undergoing JAKi therapy. We retrospectively evaluated 249 RA patients who received JAKi therapy between 2015 and 2023. Data regarding clinical characteristics, HZ reactivation, HZ vaccination status, and concomitant medication use were collected. Among 249 JAKi-treated patients, 44 developed new-onset HZ (tofacitinib, 28/142; baricitinib, 6/35; upadacitinib,10/72), with an IR of 5.11/100patient-years. Multivariate analysis revealed significant predictors of HZ development: a long JAKi exposure period, prior HZ or COVID-19 history, and concomitant high-dose corticosteroids use. The interval between JAKi initiation and HZ development was significantly shorter in patients with prior HZ history than in those without (median, 6.5months versus 33.5months, p < 0.001), suggesting "biphasic" emergence of HZ. Only one patient who had experienced an HZ episode while receiving JAKi developed recurrent HZ. None of the seventeen patients immunized with the non-live recombinant zoster vaccine developed HZ. Our JAKi-treated patients had elevated HZ risks, a class effect across different JAKi. A long exposure period, prior history of HZ or COVID-19, and concomitant high-dose corticosteroid treatment may further increase the risk. The emergence of HZ shows a biphasic pattern: early HZ development in patients with prior HZ and late development in those without. Key Points • An increased risk of HZ was observed in Taiwanese RA patients treated with JAKi, presenting as a class effect. • Patients with a long JAKi exposure period, prior history of HZ or COVID-19, and concomitant use of high-dose corticosteroids were at high risk of HZ while receiving JAKi therapy. • The interval between JAKi initiation and HZ occurrence was shorter in patients with prior HZ than in those without, showing "biphasic" emergence.

Early clinical response and complications of therapeutic plasma exchange in central nervous system demyelinating diseases.

Appropriate treatment reduces the severity and duration of relapses in demyelinating diseases of Central Nervous System (CNS). If high-dose corticosteroids treatment fails, therapeutic plasma exchange (TPE) is considered as a rescue treatment. This study aimed to investigate early clinical response and complications of TPE and prognostic factors in CNS demyelinating relapses. This prospective observational study was designed in a tertiary center during one year. All adult patients diagnosed corticosteroid-resistant Multiple Sclerosis (MS), NeuroMyelitis Optica Spectrum Disorder (NMOSD), idiotypic Transverse Myelitis or Clinical Isolated Syndrome relapses, were eligible. Clinical response is defined based on Expanded Disability Status Scale (EDSS) at discharge. Clinical and laboratory complications recorded. Seventy-two patients were analyzed which 58.3% patients were female. MS was diagnosed for 61.1% of cases. Thirty-five patients (48.6%) responded and the mean differences of EDSS significantly decreased 0.60 score (CI95%:0.44-.77). Electrolyte imbalances and thrombocytopenia occurred in 80.6% and 55.6% of cases respectively and 40.3% of patients had systemic reactions. However, 26.4% patients experienced moderate to severe complications. In patients with moderate to severe disability, responders were younger (MD: 8.42years, CI95%: 1.67-15.17) and had lower EDSS score at admission (median:6, IQR: 5.5-6 against 7.5 IQR: 6.5-8). The risk of failure was higher in active progressive MS patients compared with RRMS patients (OR: 6.06, CI 95%:1.37-26.76). Patients with thrombocytopenia were hospitalized more than others (MD: 1.5 days, CI 95%: 0-3). Females were more prone to hypokalemia and systemic reactions (OR: 3.11, CI 95%:1.17-8.24 and OR: 6.67, CI 95%:2.14-20.81 respectively). The most common indication of TPE was corticosteroid-resistant severe MS relapses. About half of the patients presented an early clinical response. Lower disability, younger age and RRMS diagnosis are prognostic factors of better response. One out of four patients experienced moderate to severe complications, mainly electrolyte imbalances and systemic reactions. Appropriate interventions against these complications should be considered during TPE, especially in females.

In-hospital survival of critically ill COVID-19 patients treated with glucocorticoids: a multicenter real-world data study

The COVID-19 pandemic has posed a major challenge to healthcare systems globally. Millions of people have been infected, and millions of deaths have been reported worldwide. Glucocorticoids have attracted worldwide attention for their potential efficacy in the treatment of COVID-19. Various glucocorticoids with different dosages and treatment durations have been studied in patients with different severities, with a suitable dosage and treatment duration not yet defined. This study aimed to investigate whether in-hospital survival differs between critically ill patients treated with low-dose glucocorticoids, high-dose glucocorticoids or no glucocorticoids. All critically ill patients admitted to the intensive care unit of the Charité Hospital—Universitätsmedizin Berlin between February 2020 and December 2021 with COVID-19 pneumonia receiving supplemental oxygen were eligible to participate in this multicenter real-world data study. Patients were retrospectively assigned to one of three groups: the high corticosteroid dose (HighC) group (receiving 6 mg parenteral dexamethasone or an equivalent corticosteroid dosage for ten days), the low corticosteroid dose (LowC) group (receiving less than 6 mg parenteral dexamethasone or an equivalent corticosteroid dosage for ten days), or the no corticosteroid (NoC) group. Overall survival and risk effects were compared among groups within the total observation period, as well as at 35 days after the onset of COVID-19 symptoms. Adjusted multivariable Cox proportional hazard regression analysis was performed to compare the risk of death between the treatment groups. Out of 1561 critically ill COVID-19 patients, 1014 were included in the baseline analysis. In the survival study, 1009 patients were assigned to the NoC (n = 346), HighC (n = 552), or LowC group (n = 111). The baseline characteristics were balanced between groups, except for age, BMI, APACHE II score, SOFA and SAPS II. While the 35-day survival did not show any differences, a landmark analysis of the patients surviving beyond 35 days revealed differences between groups. The restricted mean survival time was 112 days in the LowC group [95% CI: 97 – 128], 133 days in the HighC group [95% CI: 124 – 141] and 144 days in the NoC group [95% CI: 121 – 167]. The multivariable-adjusted Cox proportional hazard analysis indicated that, regardless of age, sex, health status or invasive oxygenation, a low-dose treatment increased the hazard of death of critically ill COVID-19 patients by a factor of 2.09 ([95% CI: 0.99, 4.4], p = 0.05) and a high-dose corticosteroid treatment increased the risk by a factor of 1.07 ([95% CI: 0.53, 2.15], p = 0.85) compared to no treatment with glucocorticoids. The analysis reveals that corticosteroid treatment does not influence the survival of critically ill COVID-19 patients in the intensive care unit within 35 days. Our evaluations further suggest that regardless of ventilation status, the decision-making process for administering corticosteroid therapy should account for the individual severity of the illness.

A novel syndrome of silent rhinovirus-associated bronchoalveolitis in children with recurrent wheeze

BackgroundRhinovirus (RV) infections trigger wheeze episodes in children. Thus, understanding of the lung inflammatory response to RV in children with wheeze is important. ObjectiveTo examine the associations of RV on lung lavage (BAL) granulocyte patterns and biomarkers of inflammation with age in children with treatment-refractory, recurrent wheeze (n=616). MethodsChildren underwent BAL to examine viral nucleic acid sequences, bacterial cultures, granulocyte counts, and phlebotomy for both general and type-2 inflammatory markers. ResultsDespite the absence of cold symptoms, RV was the most common pathogen detected (30%), and when present, was accompanied by BAL granulocytosis in 75% of children. Compared to children with no BAL pathogens (n=341), those with RV alone (n=127) had greater (p < 0.05) isolated neutrophilia (43% versus 16%), mixed eosinophils and neutrophils (26% versus 11%), and less pauci-granulocytic (27% versus 61%) BAL. Children with RV alone furthermore had biomarkers of active infection with higher total blood neutrophils and serum c-reactive protein (CRP), but no differences in blood eosinophils or total IgE. With advancing age, the log odds of BAL RV alone were lower, 0.82 [0.76-0.88, p < 0.001], but higher, 1.58 [1.01-2.51, p = 0.04], with high-dose daily corticosteroid treatment. ConclusionsChildren with severe recurrent wheeze often (22%) have a silent syndrome of lung RV infection with granulocytic bronchoalveolitis and elevated systemic markers of inflammation. The syndrome is less prevalent by school age, and not informed by markers of type-2 inflammation. We speculate that dysregulated mucosal innate antiviral immunity is a responsible mechanism.

New-Onset, Treatment-Resistant Inflammatory Bowel Disease after Administration of Secukinumab for Plaque Psoriasis: A Case Report and Review of the Existing Literature.

Aberrant activation of the IL-23/IL-17 axis leads to inflammatory phenotypes with overlapping clinical characteristics. Inhibition of IL-17 has mostly an anti-inflammatory effect, but sporadic cases of new-onset IBD have been reported. We present the case of a 65-year-old male patient with new-onset Crohn's-like disease after treatment with secukinumab for skin psoriasis. Discontinuation of the IL-17 inhibitor and high-dose corticosteroid treatment were efficient initially, but a relapse was noted during corticosteroid tapering. Administration of certolizumab pegol did partially relieve the patient, but disease remission was only achieved with subcutaneous risankizumab therapy. Clinical trials and real-world data indicate sporadic cases of new-onset IBD in patients receiving IL-17 inhibitors. Interestingly, our case is a "treatment-resistant" one since treatment with a biologic disease-modifying drug (bDMARD) usually leads to disease remission. As such, it is crucial to investigate the special characteristics of this clinical entity.

Corticosteroid treatment for acute hydrocephalus in neurosarcoidosis: a case report

BackgroundNeurosarcoidosis occurs symptomatically in 5–10% of patients with sarcoidosis, and hydrocephalus is a rare complication of neurosarcoidosis, with either acute or subacute onset and presenting symptoms related to increased intracranial pressure. It represents a potentially fatal manifestation with a mortality rate of 22% (increased to 75% in case of coexistence of seizures) that requires a prompt initiation of treatment. High-dose intravenous corticosteroid treatment and neurosurgical treatment must be considered in all cases of neurosarcoidosis hydrocephalus.Case presentationHere we present a case of hydrocephalus in neurosarcoidosis, complicated by generalized seizures, in a 29-year-old Caucasian male patient treated with medical treatment only, with optimal response.ConclusionSince neurosurgery treatment can lead to severe complications, this case report underlines the possibility to undergo only medical treatment in selected cases. Further studies are needed to stratify patients and better identify those eligible for only medical approach.

IgA nephropathy

IgA nephropathy (IgAN) is the most frequent primary form of glomerulonephritis. The origin of IgAN is only partially understood and appears to involve the occurrence of IgA1, which is normally secreted by mucous membranes, in the circulation followed by its glomerular deposition and inflammatory changes. Clinically, IgAN mostly follows an inapparent course and the disease is often only first diagnosed by kidney biopsy when kidney function disorders are already manifested. Key prognostic indicators include the extent of proteinuria and the already manifested evidence of irreversible kidney damage. Treatment includes supportive measures. The effectiveness of high-dose systemic corticosteroid treatment in European patients is uncertain and controversial due to the adverse side effects. Nefecon (encapsulated budesonide) is the first specific drug licensed for treatment of high risk IgAN patients. Anumber of further approaches are currently in clinical trials.

A High-Dose Corticosteroid Treatment Increases Coronavirus Disease of 2019 Mortality in Intensive Care Units.

The study is aimed to investigate the association between different corticosteroid treatment regimens and clinical status, complications, mechanical ventilation requirement, and intensive care unit (ICU) mortality in individuals diagnosed with Coronavirus Disease of 2019 (COVID-19). This is a descriptive retrospective study. Patients admitted to the ICU for COVID-19 and treated with low- or medium-dose corticosteroid therapy (methylprednisolone at a dose of 0.5-1 mg/kg for 7-10 days) were compared with patients treated with high-dose pulse corticosteroid therapy (methylprednisolone at varying doses of 250 mg, 500 mg or 1000 mg for 3-7 days) in addition to standard therapy because of increased pulmonary infiltrate and elevated inflammatory markers during clinical monitoring. All demographic and clinical data, including age, sex, clinical course, laboratory findings, discharge status, 28-day mortality, intubation status, acute physiological assessment and chronic health evaluation II score, Charlson Comorbidity Index, and sequential organ failure assessment score, were recorded. Corticosteroid treatment was administered to 689 (88.3%) of 780 COVID-19 ICU patients between April 2020 and October 2021. The overall mortality rate was 45.1% (n= 352). When the mortality rates of patients were compared according to the corticosteroid dose, the mortality rate in the low-to-medium-dose group (40%) was significantly lower than that in the high-dose group (76%). In addition, significant deterioration in laboratory and clinical parameters was observed in the high-dose corticosteroid group. High mortality, adverse effects, and complications were significantly increased when high-dose corticosteroids were administered. Corticosteroid therapy should be used cautiously according to the patient's clinical condition, disease stage, comorbidities, and systemic or organ reserves.

Recurrence and long-term outcomes of Tolosa-Hunt syndrome.

Tolosa-Hunt Syndrome (THS) is a rare disorder, and detailed clinical information and treatment outcomes have yet to be fully elucidated. This study aims to investigate the clinical features and factors associated with the treatment outcomes of THS, as defined by the established diagnostic criteria. This study retrospectively recruited 91 patients with a diagnosis of THS from 2003 to 2020. We analyzed the clinical features and outcomes, the initial treatment response, recurrences, and the final treatment response. Isolated ocular motor nerve palsy was the most common (82.4%) finding of ophthalmoplegia, involving the oculomotor nerve in more than half of the cases (52.0%). The MRI lesions were mostly observed in the cavernous sinus (94.5%) with an extracavernous extension in about one-third of them. Five patients showed only extracavernous lesions. A total of 25 (27.5%) patients experienced recurrence. Recurrence occurred during steroid tapering as part of the initial treatment in seven, while in 18 patients, it happened after the successful termination of the initial treatment. However, all patients achieved complete remission at the final. Age was associated with a decrease in initial symptom duration (HR = 1.023, CI = 1.004-1.044) as well as an increase in recurrence-free duration (HR = 0.944, CI = 0.911-0.978). High-dose corticosteroid treatment was associated with a decrease in initial symptom duration (HR = 1.642, CI = 1.001-2.695) and total treatment duration (HR = 2.203 CI = 1.302-3.730). THS can recur frequently especially in younger but have a favorable prognosis. High-dose corticosteroids can be an effective initial treatment and reduce the total treatment duration.

Bowel perforation and peritonitis caused by a jejunal leiomyoma. A rare complication of jejunal leiomyoma

Small-bowel leiomyomas are rare, usually indolent, benign neoplasms, sporadically associated with complications, mainly including bleeding and obstruction. Herein we report a case of a 78-year-old female patient under high-dose corticosteroid treatment for systemic disease, presenting with clinical signs suggestive of peritonitis. Urgent exploratory laparotomy revealed an intraluminal jejunal mass complicated by bowel perforation and multiple enlarged mesenteric lymph nodes. Microscopic examination of the surgical specimen suggested the presence of a jejunal leiomyoma as the cause of perforation and lymph nodes’ infiltration by Hodgkin lymphoma. The patient died on the 15th post-operative day due to pulmonary complications. To our knowledge, this is the first reported case of a jejunal leiomyoma complicated by bowel perforation and peritonitis. A high index of suspicion for the presence of underlying neoplastic disease should be maintained in cases of non-traumatic small-bowel perforation. Additionally, the potentially detrimental effect of comorbidities on a patient’s outcome should be considered even in the context of successful management of primary disease.

IgA nephropathy

IgA nephropathy (IgAN) is the most frequent primary form of glomerulonephritis. The origin of IgAN is only partially understood and appears to involve the occurrence of IgA1, which is normally secreted by mucous membranes, in the circulation followed by its glomerular deposition and inflammatory changes. Clinically, IgAN mostly follows an inapparent course and the disease is often only first diagnosed by kidney biopsy when kidney function disorders are already manifested. Key prognostic indicators include the extent of proteinuria and the already manifested evidence of irreversible kidney damage. Treatment includes supportive measures. The effectiveness of high-dose systemic corticosteroid treatment in European patients is uncertain and controversial due to the adverse side effects. Nefecon (encapsulated budesonide) is the first specific drug licensed for treatment of high risk IgAN patients. Anumber of further approaches are currently in clinical trials.

KNEE OSTEONECROSIS AFTER SARS-COV 2 VIRUS INFECTION.

Osteonecrosis after COVID-19 infection is a complex pathology with multifactorial origin. Factors such as infection itself with associated coagulopathy, as well as genetic mechanisms, and medications used for its treatment such as corticosteroids, may also be involved. The variability in the presentation makes diagnosis difficult, which, if done soon, can help delay progression and reduce morbidity and the need for surgery.This report presents a case of knee osteonecrosis in a female patient who did not have previous knee pathology on imaging tests. She was diagnosed by magnetic resonance imaging months after hospital admission for SARS-COV 2 pneumonia, which required high-dose corticosteroid treatment.

CD4 T cells and toxicity from immune checkpoint blockade.

Immune-related toxicities, otherwise known as immune-related adverse events (irAEs), occur in a substantial fraction of cancer patients treated with immune checkpoint inhibitors (ICIs). Ranging from asymptomatic to life-threatening, ICI-induced irAEs can result in hospital admission, high-dose corticosteroid treatment, ICI discontinuation, and in some cases, death. A deeper understanding of the factors underpinning severe irAE development will be essential for improved irAE prediction and prevention, toward maximizing the benefits and safety profiles of ICIs. In recent work, we applied mass cytometry, single-cell RNA sequencing, single-cell V(D)J sequencing, bulk RNA sequencing, and bulk T-cell receptor (TCR) sequencing to identify pretreatment determinants of severe irAE development in patients with advanced melanoma. Across 71 patients separated into three cohorts, we found that two baseline features in circulation-elevated activated CD4 effector memory T-cell abundance and TCR diversity-are associated with severe irAE development, independent of the affected organ system within 3 months of ICI treatment initiation. Here, we provide an extended perspective on this work, synthesize and discuss related literature, and summarize practical considerations for clinical translation. Collectively, these findings lay a foundation for data-driven and mechanistic insights into irAE development, with the potential to reduce ICI morbidity and mortality in the future.

Collaborative cross strain CC011/UncJ as a novel mouse model of T2-high, severe asthma

Among asthmatics, there is significant heterogeneity in the clinical presentation and underlying pathophysiological mechanisms, leading to the recognition of multiple disease endotypes (e.g., T2-high vs. T2-low). This heterogeneity extends to severe asthmatics, who may struggle to control symptoms even with high-dose corticosteroid treatment and other therapies. However, there are limited mouse models available to model the spectrum of severe asthma endotypes. We sought to identify a new mouse model of severe asthma by first examining responses to chronic allergen exposure among strains from the Collaborative Cross (CC) mouse genetics reference population, which contains greater genetic diversity than other inbred strain panels previously used for models of asthma. Mice from five CC strains and the often-used classical inbred strain BALB/cJ were chronically exposed to house dust mite (HDM) allergen for five weeks followed by measurements of airway inflammation. CC strain CC011/UncJ (CC011) exhibited extreme responses to HDM including high levels of airway eosinophilia, elevated lung resistance, and extensive airway wall remodeling, and even fatalities among ~ 50% of mice prior to study completion. Compared to BALB/cJ mice, CC011 mice had stronger Th2-mediated airway responses demonstrated by significantly elevated total and HDM-specific IgE and increased Th2 cytokines during tests of antigen recall, but not enhanced ILC2 activation. Airway eosinophilia in CC011 mice was completely dependent upon CD4+ T-cells. Notably, we also found that airway eosinophilia in CC011 mice was resistant to dexamethasone steroid treatment. Thus, the CC011 strain provides a new mouse model of T2-high, severe asthma driven by natural genetic variation likely acting through CD4+ T-cells. Future studies aimed at determining the genetic basis of this phenotype will provide new insights into mechanisms underlying severe asthma.

Prolonged oral corticosteroid treatment in patients with systemic lupus erythematosus: An evaluation of 12-month economic and clinical burden.

BACKGROUND: Prolonged, high-dose corticosteroid treatment for systemic lupus erythematosus (SLE) is associated with substantial health care costs, health care resource utilization (HCRU), and adverse events (AEs). OBJECTIVE: To compare all-cause health care costs, HCRU, and oral corticosteroid (OCS)-related AEs among patients with prevalent OCS use and patients without OCS use. METHODS: This retrospective, longitudinal cohort study (GSK study 214100) used claims data from the IQVIA Real-World Data Adjudicated Claims - US, IQVIA, Inc, database between January 1, 2006, and July 31, 2019, to identify patients with SLE. Patients with at least 1 OCS pharmacy claim during the study period and continuous OCS use during the 6-month pre-index (baseline) period (index date is the date of the first OCS claim following 6 months' continuous use) formed the "prevalent OCS use cohort." This cohort was subdivided based on the level of OCS exposure during the 12-month observation period, ie, the number of 6-month periods of greater than 5 mg/day OCS use (0, 1, or 2). Patients without OCS claims formed the "no OCS use cohort." All patients had continuous enrollment during the baseline and observation periods, had at least 1 inpatient or at least 2 outpatient SLE diagnosis codes during baseline, and were aged at least 5 years at index. A 2-part model, a generalized linear regression model with a negative binomial distribution, and a multivariate logistic regression model were used to compare health care costs, HCRU, and the odds of developing an OCS-related AE between cohorts, respectively. RESULTS: The no OCS use and prevalent OCS use cohorts included 21,517 and 16,209 patients, respectively. Adjusted health care cost differences (95% CI) were significantly lower for the no OCS use cohort vs all prevalent OCS use exposure categories ($5,439 [$4,537-$6,371] vs $17,856 [$16,368-$19,498]), driven by inpatient stays and outpatient visits; HCRU was also significantly lower (adjusted incidence rate ratios vs no OCS use cohort [95% CI]: 1.20 [1.16-1.23] vs 1.47 [1.41-1.52]). Health care costs and HCRU increased with increasing length of OCS exposure. OCS-related AEs occurred more frequently for all prevalent OCS use exposure categories vs the no OCS use cohort (odds ratio [95% CI]: 1.39 [1.25-1.55] vs 2.32 [2.02-2.68]), driven by hematologic/oncologic and immune system-related AEs. The mean (SD) average daily dose of OCS increased with increasing periods of prevalent OCS use (2.5 [1.3], 6.9 [31.1], and 34.6 [1,717.3] mg/day, respectively, for patients with 0, 1, and 2 periods of OCS use). CONCLUSIONS: Prevalent OCS use incurs a substantial clinical and economic burden, highlighting the need for restricted OCS doses and durations. DISCLOSURES: This study (GSK Study 214100) was funded by GSK. GSK was involved in designing the study, contributing to the collection, analysis, and interpretation of the data, supporting the authors in the development of the manuscript, and funding the medical writing assistance. All authors, including those employed by GSK, approved the content of the submitted manuscript and were involved in the decision to submit the manuscript for publication. Dr DerSarkissian, Dr Duh, and Mr Benson are employees of Analysis Group, which received research funding from GSK to conduct this study. Dr Wang, Ms Gu, and Mr Vu are former employees of Analysis Group. Mr Bell is an employee of GSK and holds stocks and shares in the company. Ms Averell and Dr Huang are former employees of GSK and held stocks and shares in the company at the time of the study.

The Acute Optic Neuritis Network (ACON): Study protocol of a non-interventional prospective multicenter study on diagnosis and treatment of acute optic neuritis.

ClinicalTrials.gov, identifier: NCT05605951.

Impact of Corticosteroids for IrAEs on the Clinical Outcome of Immunotherapy in Patients With NSCLC.

The impact of corticosteroids for the treatment of immune-related adverse events (irAEs) on the antitumor effect of programmed cell death-1 (PD-1) inhibitor is unclear. A total of 172 patients with non-small cell lung cancer (NSCLC) treated with PD-1 inhibitors were retrospectively reviewed. Patients were divided into four groups: those who did not develop irAEs [1] and those who developed irAE and were either not treated with corticosteroids [2] or treated with low [3] or high doses [4], and overall survival (OS) was analyzed by the time of corticosteroid treatment. Landmark analysis was performed using Cox proportional hazard model with time-dependent covariates. A high-dose steroid treatment within 60 days correlated with a significantly worse OS than that of the group with irAEs without steroids (p=0.004). Moreover, there was no significant difference in OS between the irAE without steroid and low-dose steroid groups. Early severe irAEs and high-dose corticosteroid treatment were poor prognostic factors in patients with NSCLC treated with PD-1 inhibitors.

Corticosteroid effectiveness among hospitalised COVID-19 patients in Malaysia.

Using steroids to manage hospitalised coronavirus disease 2019 (COVID-19) patients caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection has been shown to reduce the need for mechanical ventilation and mortality. To date, low-dose dexamethasone and methylprednisolone corticosteroids have been effective in reducing the infection's progress in hospitalised patients. However, it is unknown if high dosages of corticosteroids can achieve a better clinical outcome. This study aims to compare the clinical outcomes of hospitalised COVID-19 patients who are given a 10-day low-dose corticosteroid treatment (IV 2 mg/kg/day methylprednisolone loading dose (LD) then 0.25 mg/kg four times a day (q.i.d.)) with patients given a 10-day high-dose corticosteroid treatment (IV 20 mg dexamethasone once daily (o.d.) or a 1.5 mg/kg prednisolone tablet o.d.). Retrospective data on hospitalised COVID-19 patients were collected for this study, and the primary outcome measure was the patients' clinical status based on the World Health Organization's (WHO) Ordinal Scale for Clinical Improvement (OSCI) on Day-5 and Day-10 post-steroid. The results demonstrated that using steroids significantly improved patients' clinical outcomes from a WHO OSCI level of 4 (0.1) on Day-1 to 2.6 (2.5) on Day-5 (p < 0.001). There was no significant difference in clinical outcome between low-dose and high-dose corticosteroid treatment on Day-5 (H = 2.15; p = 0.34) and Day-10 (H = 1.12; p = 0.58). This study concludes that using low-dose corticosteroids is recommended for hospitalised COVID-19 patients to ensure clinical outcomes are optimised.