Systemic Corticosteroid Exposure Research Articles

Impact of comorbidities on EQ-5D quality-of-life index in severe asthma

BackgroundSevere asthma pathology encompasses a wide range of pulmonary and extra-pulmonary treatable traits with a high prevalence of comorbidities. Although asthma-specific health related quality of life measures are most sensitive to changes in asthma control, generic measures, such as EQ-5D-5L (EuroQol 5-Dimension 5-Level questionnaire), are potentially better for capturing the impact of comorbidities. ObjectiveTo examine the impact of pulmonary and extra-pulmonary treatable traits on quality of life at initial severe asthma assessment, and to compare the characteristics of those patients whose quality of life does and does not improve during follow-up at severe asthma centres. MethodsPatients characteristics at baseline assessment within the UK Severe Asthma Registry were compared by EQ-5D-5L utility index quartile. Patients with follow-up review data were stratified by change in EQ-5D-5L utility index from baseline to follow-up, and characteristics similarly examined. ResultsPatients in the quartiles with worst dysutility at baseline were observed to exhibit more treatable traits and in particular extra-pulmonary traits associated with cumulative systemic corticosteroids, including obesity, anxiety/depression, and osteoporosis. In those patients whose quality of life improved over follow-up, a reduction in exacerbations, uncontrolled symptoms and requirement for maintenance oral corticosteroids (OCS) was observed. ConclusionBoth pulmonary and extra-pulmonary treatable traits are important determinants of quality of life in severe asthma. Comorbidities associated with cumulative systemic corticosteroid exposure are particularly associated with worse quality of life, emphasising the importance of early identification and management of severe asthma before comorbidities develop.

Real-world association between systemic corticosteroid exposure and complications in US patients with severe asthma

BackgroundSystemic corticosteroid (SCS) use remains widespread among patients with severe asthma, despite associated complications.ObjectiveEvaluate the association between cumulative SCS exposure and SCS-related complications in severe asthma.MethodsThis retrospective, longitudinal study used claims data from the Optum Clinformatics Data Mart database (GSK ID: 214469). Eligible patients (≥ 12 years old) had an asthma diagnosis and were divided into two cohorts: SCS use and non/burst-SCS use. Patients in the SCS use cohort had a claim for a daily prednisone-equivalent dose ≥ 5 mg SCS following ≥ 6 months of continuous SCS use; those in the non/burst-SCS cohort had no evidence of continuous SCS use and had a non-SCS controller/rescue medication initiation claim. For each cohort, the date of the qualifying claim was the index date. SCS users were further stratified by SCS use during each quarter of follow-up: low (≤ 6 mg/day), medium (> 6–12 mg/day), high (> 12 mg/day), and continuous high (≥ 20 mg/day for 90 days). SCS-related complications were evaluated in the quarter following SCS exposure. The adjusted odds ratios (OR) of experiencing SCS-related complications during follow-up in each of the SCS use groups versus the non/burst SCS cohort were calculated using generalized estimating equations models.ResultsSCS and non/burst-SCS use cohorts included 7473 and 89,281 patients (mean follow-up: 24.6 and 24.2 months), respectively. Compared with the non/burst-SCS use cohort, medium, high, and continuous high SCS use was associated with greater odds of any SCS-related complication (adjusted OR [95% confidence interval]: 1.30 [1.21, 1.39], 1.49 [1.35, 1.64] and 1.63 [1.40, 1.89], respectively) including increased acute gastrointestinal, cardiovascular, and immune system-related complications, and chronic cardiovascular, metabolic/endocrine, central nervous system, bone-/muscle-related, ophthalmologic, and hematologic/oncologic complications. Low-dose SCS use was also associated with significantly increased odds of acute gastrointestinal and immune system-related complications, and chronic bone-/muscle-related and hematologic/oncologic complications versus the non/burst-SCS use cohort.ConclusionSCS use, even at low doses, is associated with increased risk of SCS-related complications among patients with severe asthma.

A Fully Decentralized Randomized Controlled Study of As-Needed Albuterol-Budesonide Fixed-Dose Inhaler in Mild Asthma: The BATURA Study Design.

Decentralized clinical trials, where trial-related activities occur at locations other than traditional clinical sites(eg participant homes, local healthcare facilities), have the potential to improve trial access for people for whom time and/or distance constraints may impede participation. Albuterol-budesonide 180/160 µg pressurized metered-dose inhaler (pMDI) is FDA approved for the as-needed treatment or prevention of bronchoconstriction and to reduce the risk of exacerbations in patients with asthma 18 years or older. BATURA (NCT05505734) is a fully decentralized study, investigating as-needed albuterol-budesonide in participants with mild asthma. BATURA is a fully decentralized, phase 3b, randomized, double-blind, event-driven exacerbation study conducted in the United States. Participants aged ≥12 years using as-needed short-acting β2-agonist (SABA), alone or with low-dose inhaled corticosteroid or leukotriene receptor antagonist maintenance, are randomized 1:1 to as-needed albuterol-budesonide 180/160 µg or albuterol 180 µg pMDI for up to 52 weeks (minimum 12 weeks). Participants continue their current maintenance therapy, if applicable. Participants must have used SABA for ≥2 days in the 2 weeks pre-enrollment and have an Asthma Impairment Risk Questionnaire score ≥2 at screening and randomization. All trial-related visits, including screening and consent, are conducted virtually, with study medication shipped directly to each participant's residence. The primary objective is to evaluate the efficacy of as-needed albuterol-budesonide versus albuterol on severe asthma exacerbation risk, measured by time-to-first severe asthma exacerbation (primary endpoint). Secondary endpoints include annualized rate of severe asthma exacerbation and total systemic corticosteroid exposure. Study medication use is captured via a Hailie sensor attached to the study medication pMDI. The intended sample size is 2500 participants. BATURA evaluates as-needed albuterol-budesonide in participants with mild asthma. The decentralized study model enables the trial to move out of research sites into participant homes, reducing participant burden and improving access.

Immunosuppressive Medications and COVID-19 Outcomes in Patients with Noninfectious Uveitis in the Era of COVID-19 Vaccinations

To determine the risk of coronavirus disease 2019 (COVID-19) infection, hospitalization, and death in the era of COVID-19 vaccination among patients with noninfectious uveitis (NIU) taking immunosuppressive therapies. Retrospective cohort study from July 1, 2021, to June 30, 2022, using data from the Optum Labs Data Warehouse (OLDW) de-identified claims database. Patients with a diagnosis of NIU from January 1, 2017, and who had ≥ 1year of continuous enrollment in the OLDW. Incidence rates (IRs) were calculated for each COVID-19 outcome. Unadjusted and adjusted hazard ratios (HRs) were estimated for each variable and COVID-19 outcome using Cox proportional hazards models with time-updated dichotomous indicators for outpatient immunosuppressive medication exposure. To assess the dose-dependent effect of systemic corticosteroid (SC) exposure, the average daily dose of prednisone over the exposed interval was included in the adjusted models. Hazard ratios and IRs for COVID-19 infection, hospitalization, and death. This study included 62 209 patients with NIU. A total of 12 895 (20.7%) were exposed to SCs during the risk period. Incidence rates were increased when exposed to SCs versus unexposed for all COVID-19 outcomes. Incidence rates were also increased for all COVID-19 outcomes when exposed to SCs without COVID-19 vaccination versus exposed to SCs with ≥ 1 vaccination. In adjusted models, SCs were associated with increased risk of COVID-19 infection (HR, 3.57; 95% confidence interval [CI], 3.24-3.93; P<0.0001), hospitalization (HR, 2.75; 95% CI, 2.07-3.65; P<0.0001), and death (HR, 2.49; 95% CI 1.29-4.82; P= 0.007). Incremental increases in SC dose were associated with a greater risk for all outcomes. Disease-modifying anti-rheumatic drugs were associated with a decreased risk of infection (HR, 0.84; 95% CI, 0.74-0.96; P= 0.01), and tumor necrosis factor-α inhibitors were associated with an increased risk of infection (HR, 1.18; 95% CI, 1.01-1.39; P= 0.04). Systemic corticosteroid exposure continues to be associated with greater risk of COVID-19 infection, hospitalization, and death among patients with NIU in an era of widespread COVID-19 vaccination. Unvaccinated individuals who are exposed to immunosuppressive treatments have a greater risk of severe outcomes. Coronavirus disease 2019 vaccination should be strongly encouraged in these patients. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Adverse Outcomes, Healthcare Resource Utilization, and Costs Associated with Systemic Corticosteroid use Among Adults with Systemic Lupus Erythematosus in the UK.

This analysis was conducted to assess the incidence of adverse clinical outcomes, healthcare resource use (HCRU), and the costs associated with systemic corticosteroid (SCS) use in adults with systemic lupus erythematosus (SLE) in the UK. We identified incident SLE cases using the Clinical Practice Research Datalink GOLD, Hospital Episode Statistics-linked healthcare, and Office for National Statistics mortality databases from January 1, 2005, to June 30, 2019. Adverse clinical outcomes, HCRU, and costs were captured for patients with and without prescribed SCS. Of 715 patients, 301 (42%) had initiated SCS use (mean [standard deviation (SD)] 3.2 [6.0] mg/day) and 414 (58%) had no recorded SCS use post-SLE diagnosis. Cumulative incidence of any adverse clinical outcome over 10-year follow-up was 50% (SCS group) and 22% (non-SCS group), with osteoporosis diagnosis/fracture most frequently reported. SCS exposure in the past 90days was associated with an adjusted hazard ratio of 2.41 (95% confidence interval 1.77-3.26) for any adverse clinical outcome, with increased hazard for osteoporosis diagnosis/fracture (5.26, 3.61-7.65) and myocardial infarction (4.52, 1.16-17.71). Compared to low-dose SCS (< 7.5mg/day), patients on high-dose SCS (≥ 7.5mg/day) had increased hazard for myocardial infarction (14.93, 2.71-82.31), heart failure (9.32, 2.45-35.43), osteoporosis diagnosis/fracture (5.14, 2.82-9.37), and type 2 diabetes (4.02 1.13-14.27). Each additional year of SCS use was associated with increased hazard for any adverse clinical outcome (1.15, 1.05-1.27). HCRU and costs were greater for SCS users than non-SCS users. Among patients with SLE, there is a higher burden of adverse clinical outcomes and greater HCRU in SCS versus non-SCS users.

Early Ileocecal Resection for Crohn’s Disease Is Associated With Improved Long-term Outcomes Compared With Anti-Tumor Necrosis Factor Therapy: A Population-Based Cohort Study

Early Crohn's disease (CD) treatment involves anti-tumor necrosis factor (TNF) agents, whereas ileocecal resection (ICR) is reserved for complicated CD or treatment failure. We compared long-term outcomes of primary ICR and anti-TNF therapy for ileocecal CD. Using cross-linked nationwide registers, we identified all individuals diagnosed with ileal or ileocecal CD between 2003 and 2018 and treated with ICR or anti-TNF agents within 1 year of diagnosis. The primary outcome was a composite of ≥1 of the following: CD-related hospitalization, systemic corticosteroid exposure, CD-related surgery, and perianal CD. We conducted adjusted Cox's proportional hazards regression analyses and determined the cumulative risk of different treatments after primary ICR or anti-TNF therapy. Of 16,443 individuals diagnosed with CD, 1279 individuals fulfilled the inclusion criteria. Of these, 45.4% underwent ICR and 54.6% received anti-TNF. The composite outcome occurred in 273 individuals (incidence rate, 110/1000 person-years) in the ICR group and in 318 individuals (incidence rate, 202/1000 person-years) in the anti-TNF group. The risk of the composite outcome was 33% lower with ICR compared with anti-TNF (adjusted hazard ratio, 0.67; 95% confidence interval, 0.54-0.83). ICR was associated with reduced risk of systemic corticosteroid exposure and CD-related surgery, but not other secondary outcomes. The proportion of individuals on immunomodulator, anti-TNF, who underwent subsequent resection, or were on no therapy 5 years post-ICR was 46.3%, 16.8%, 1.8%, and 49.7%, respectively. These data suggest that ICR may have a role as first-line therapy in CD management and challenge the current paradigm of reserving surgery for complicated CD refractory or intolerant to medications. Yet, given inherent biases associated with observational data, our findings should be interpreted and applied cautiously in clinical decision making.

Evaluation of Usage of a Fracture Risk Assessment by FRAX Tool in Adults With Type 2 Diabetes Mellitus.

Fragility fractures are increasingly recognized as a complication of type 2 diabetes mellitus (T2DM). The FRAX-Port® is a calculation tool that assesses the 10-year risk of either major and hip fracture, integrating several clinical risk factors, including T2DM. We aimed to evaluate the fracture risk in adults with T2DM and determine the rate of patients at high risk for fracture under anti-osteoporotic therapy. We developed a cross-sectional study, including a convenience sample of adults with T2DM, followed in our tertiary center between 2019 and 2022. Fracture risk was evaluated according to FRAX-Port®. One hundred adults were included, 54% male, with a mean age of 68.4±9.2 years. Respecting fracture risk factors, 17% had a previous fragility fracture, 12% had a history of hip fracture in their parents, 9% had active alcohol consumption, and 4% had active smoking. Additionally, 17% presented secondary osteoporosis, being the most frequent cause of systemic corticosteroid exposure (10%). Regarding diabetes-specific risk factors, 94% had a diabetes duration longer than five years; HbA1c greater than 7% in 70%; 42% had diabetic retinopathy, 33% had diabetic chronic kidney disease, 18% had peripheral neuropathy, and 7% had autonomic neuropathy; 83% were on insulin, 2% on canagliflozin and 1% on pioglitazone. According to the FRAX-Port®, the median probability of major fracture was 6.8% (IQR 6.9), and hip fracture was 2.4% (IQR 3.9). Fracture risk was high, intermediate, and low at 41%, 15%, and 44%, respectively. Lastly, 56% of participants should undergo bone densitometry and 45% had a formal recommendation to begin an anti-osteoporotic treatment. However, only 6% were under anti-osteoporotic therapy: bisphosphonates (5%) and denosumab (1%). More than a third of T2DM patients evaluated had a high fracture risk. We found that FRAX-Port® is an easy-to-apply tool, which helps in the decision to perform densitometry or to institute anti-osteoporotic therapy. Given the increasing prevalence of T2DM and the associated risk of falls, this study highlights the need to recognize the fracture risk in these patients, usually a forgotten complication during the screening of risk factors for adverse events in adults with T2DM.

Real-World Impact of Systemic Corticosteroid (SCS) Exposure on Healthcare Resource Utilization (HRU) due to SCS-Related Complication among Patients with Asthma in the US

SCS remains overused for asthma management despite the documented risk of complications associated with both long-term and short-term use. This study examined the association between cumulative SCS exposure and HRU due to SCS-related complications among patients with asthma.

Albuterol-budesonide Fixed-dose Combination (FDC) Inhaler As-needed Reduces Progression from Symptomatic Deterioration to Severe Exacerbation in Patients with Moderate-to-severe Asthma: Analysis from MANDALA

Short-acting β2-agonists (SABAs) treat symptoms, but not the underlying inflammation. A “window of opportunity” may exist to prevent severe exacerbations if symptoms and inflammation are treated concomitantly, as advocated by GINA and NAEPP. In the Phase 3 MANDALA study (NCT03769090), as-needed albuterol-budesonide 180/160μg FDC significantly reduced severe exacerbation risk by 27%, annualized severe exacerbation rate by 24%, and annualized total systemic corticosteroid exposure mean was reduced by 33% versus albuterol.

OP11 Ileocecal resection for recently diagnosed ileocecal Crohn’s disease is associated with improved long-term outcomes compared to anti-tumor necrosis factor therapy: a population-based study

Abstract Background Early treatment of Crohn’s disease (CD) often involves biologics such as anti-tumor necrosis factor (anti-TNF) agents. Ileocecal resection (ICR), while a therapeutic option in early CD, is generally reserved for complicated CD or when medical treatment fails. We aimed to compare long-term outcomes of ICR and anti-TNF therapy as index treatment for ileocecal CD, initiated within one year of diagnosis, in the Danish nationwide cohort. Methods Using cross-linked nationwide registers, we identified all individuals who lived in Denmark and were diagnosed with ileal CD between 2003 and 2018. We included individuals who underwent ICR or received anti-TNF drugs as index treatment for ileocecal CD within one year of diagnosis. We excluded patients who did not have pathology information confirming disease in the ileocecal region. The primary outcome was a composite of CD-related hospitalization, systemic corticosteroid exposure, CD-related surgery, and perianal CD diagnosis. We conducted Cox proportional hazards regression analyses to compare outcomes in the two groups after adjusting for potential confounders. We also determined the proportion of individuals initiated on immunomodulator (IMM), anti-TNF, or no therapy at 5 years after ICR. Results Of the 16,443 individuals diagnosed with ileocecal CD between 2003 and 2018, 581 (3.5%) and 698 (4.2%) individuals with confirmed disease in the ileocecal region underwent ICR and received anti-TNF as the index treatment, respectively. The composite outcome occurred in 273 individuals (IR 110.3/100,0 person years (PY)) in the ICR group and in 318 individuals (IR 201.9/100,0 PY) in the anti-TNF group. The risk of the composite outcome was 33% lower in the ICR group compared to the anti-TNF group (aHR 0.67; 95% CI 0.54, 0.83), after adjusting for demographic and clinical variables. On analysis of individual outcomes, ICR was associated with reduced risk of systemic corticosteroid exposure and CD-related surgery, but not CD-related hospitalization or perianal CD diagnosis. Of individuals who underwent ICR, the proportion that was initiated on IMM, anti-TNF treatment or no treatment at 5 years of follow up was 47.5%, 17.1%, and 50.3%, respectively. Conclusion These data support the role of ICR as an index treatment for ileocecal CD and challenge the current paradigm of reserving surgery for complicated CD refractory or intolerant to medications. Further studies will help identify characteristics of individuals who needed no treatment after ICR.

A phase I first-in-man study to investigate the pharmacokinetics and safety of liposomal dexamethasone in patients with progressive multiple myeloma

Despite the introduction of multiple new drugs and combination therapies, conventional dexamethasone remains a cornerstone in the treatment of multiple myeloma (MM). Its application is, however, limited by frequent adverse effects of which the increased infection rate may have the strongest clinical impact. The efficacy-safety ratio of dexamethasone in MM may be increased by encapsulation in long-circulating PEG-liposomes, thereby both enhancing drug delivery to MM lesions and reducing systemic corticosteroid exposure. We evaluated the preliminary safety and feasibility of a single intravenous (i.v.) infusion of pegylated liposomal dexamethasone phosphate (Dex-PL) in heavily pretreated relapsing or progressive symptomatic MM patients within a phase I open-label non-comparative interventional trial at two dose levels. In the 7 patients that were enrolled (prior to having to close the study prematurely due to slow recruitment), Dex-PL was found to be well tolerated and, as compared to conventional dexamethasone, no new or unexpected adverse events were detected. Pharmacokinetic analysis showed high and persisting concentrations of dexamethasone in the circulation for over a week after i.v. administration, likely caused by the long-circulation half-life of the liposomes that retain dexamethasone as the inactive phosphate prodrug form, something which could significantly limit systemic exposure to the active parent drug. Thus, despite the limitations of this small first-in-man trial, Dex-PL seems safe and well tolerated without severe side effects. Follow-up studies are needed to confirm this in a larger patient cohort and to evaluate if i.v. Dex-PL can provide a safer and more efficacious dexamethasone treatment option for MM.Graphical

LB933 Systemic corticosteroid exposure during cutaneous immune related adverse events worsens overall survival

Although immune checkpoint inhibitor(ICI) therapy represents a breakthrough in advanced cancer treatment, further research into immune related adverse events (irAEs) and their management is warranted. Cutaneous irAEs (cirAEs) represent an early irAE for which systemic corticosteroids(SCS) are recommended, depending on their severity and morphology. We sought to investigate the impact of SCS exposure and dose on survival outcomes when administered during cirAE episodes. In this retrospective, single-institution study, we screened patients receiving ICI therapy between 1/1/16-6/29/21 and confirmed cirAE status using previously defined criteria.

S108: A SYSTEMATIC POST-MARKETING (PM) REVIEW OF RARE INFUSION-RELATED REACTIONS (IRRS) PRESENTING AS PAIN EVENTS DURING OR AFTER CRIZANLIZUMAB INFUSION IN PATIENTS WITH SICKLE CELL DISEASE (SCD)

Background: Vaso-occlusive crises (VOCs) are the hallmark of SCD and can lead to complications and premature death. Crizanlizumab, an anti-P-selectin monoclonal antibody (mAb), is authorized to prevent/reduce VOCs in SCD patients aged ≥16 years. IRRs are defined as signs/symptoms experienced by patients during/within 24 hours of infusion of a pharmacologic/biologic agent.1 IRRs are quite common with mAbs (frequency 1.6–99%)2 and can present as pain events, such as back pain, chest pain and myalgia. Pain events are known adverse drug reactions in the crizanlizumab label, however, pain events occurring during/within 24 hours of crizanlizumab infusion in SUSTAIN were not identified as potential IRRs.3 For SCD patients, IRR-related pain events may differ in location, severity and/or nature from their usual SCD/VOC pain. Aims: We reviewed PM data on IRRs presenting as pain events in SCD patients treated with crizanlizumab. Methods: A custom search of the Novartis safety database (comprising PM reports [spontaneous] and managed access/patient orientation program reports) was performed for reports received in November 2019–June 2021, using ~111 MedDRA terms associated with potential signs/symptoms of IRRs presenting as pain events. IRRs must have occurred during/within 24 hours of the most recent crizanlizumab infusion, and pain could differ from a patient’s usual SCD/VOC. As reports were not gathered via a uniform data collection system, potential limitations include underreporting, incompletely documented cases, or bias towards reporting severe events. Results: IRRs presenting as pain events were experienced by 28 patients (Table), and most commonly presented as back pain, pain in extremity, arthralgia, musculoskeletal chest pain and headache. Reporting rate was 1.67 cases per 100 patient-years (95% CI 1.11–2.42). Most patients (n=24) initially experienced IRR at the first or second infusion. IRR recurred on subsequent infusion(s) in six patients. Twenty patients (71%) were hospitalized for treatment, including analgesics, antihistamines, IV fluids and/or steroids. Nine patients (32%) reported known complications of SCD following IRR (Table). Crizanlizumab was discontinued in 23 patients (82%) after their most recent IRR, including all who experienced secondary SCD complications. All patients recovered (the majority within 3 days; one with sequelae), except one who died following SCD complications and refusal of blood transfusions for personal reasons. Resolution time was prolonged for patients who reported SCD complications following IRR. Causal analysis of complications was confounded by the underlying disease and use of steroids to treat IRR (systemic corticosteroid exposure in SCD patients has been associated with pain, complications [including severe VOCs and hemorrhagic stroke] and death). We do not know whether the 28 patients had an active VOC or other SCD complications before receiving crizanlizumab. Summary – Conclusion: Although rare, based on review of PM data, healthcare professionals should be aware of the possibility of IRRs presenting as pain events during/after crizanlizumab infusion. Crizanlizumab labels have been/are being updated by Novartis to provide information on monitoring, management and prevention of IRRs, including a statement recommending caution when using corticosteroids. Given the limited data available regarding IRRs, Novartis is committed to further understanding these events.

Rare Cases of Infusion-Related Reactions (IRRs) Presenting As Pain Events during or after Crizanlizumab Infusion in Patients (Pts) with Sickle Cell Disease (SCD): A Systematic Evaluation of Post-Marketing (PM) Reports

Rare Cases of Infusion-Related Reactions (IRRs) Presenting As Pain Events during or after Crizanlizumab Infusion in Patients (Pts) with Sickle Cell Disease (SCD): A Systematic Evaluation of Post-Marketing (PM) Reports

P064 CONSECUTIVE-YEAR HIGH-RISK SYSTEMIC CORTICOSTEROID EXPOSURES IN CHILDREN AND ADULTS WITH ASTHMA IN THE UNITED STATES

Systemic corticosteroid (SCS)-requiring asthma exacerbations are related to prior-year exacerbations. Cumulative SCS exposure ≥500mg leads to adverse health conditions. To understand long-term SCS morbidity, we examined whether high-risk SCS exposure in one year is accompanied by similar exposure in the preceding year.

P025 A NEW FRONTIER: DO BIOLOGICS REDUCE CUMULATIVE STEROID EXPOSURE IN AERD?

The objective of this study is to assess whether the cumulative systemic corticosteroid exposure in subjects with AERD differs in the 12-month period pre- versus post-initiation of one of the five FDA-approved respiratory biologic therapies.

Use of Systemic Corticosteroids for Reasons Other than Asthma in Subjects with Asthma

Backgrounds: Recent studies have reported increased risks of adverse events from systemic corticosteroids even with only low-dose or short-term use. Some patients with asthma experience complications requiring systemic corticosteroids. However, few studies have examined issues associated with administration of systemic corticosteroids for reasons other than asthma among subjects with asthma. Objectives: We investigated patterns of systemic corticosteroid exposure for reasons other than asthma in subjects with asthma. Method: We retrospectively reviewed the records of adult subjects with asthma followed up for >1 year at Yokohama City University Hospital from January 1, 2010, to December 31, 2019. We investigated patterns and reasons for systemic corticosteroid use during follow-up. In addition, factors related to systemic corticosteroid use for reasons likely other than asthma were investigated. Results: Among the 568 subjects with asthma analyzed, 326 (57.4%) had received systemic corticosteroids for some reason. Among those 326 patients, 120 (36.8%) had received systemic corticosteroids for reasons likely other than asthma. Multivariable analysis revealed rheumatoid arthritis, eosinophilic granulomatosis with polyangiitis, other collagen vascular diseases, chronic rhinosinusitis, and malignancy as positively associated with systemic corticosteroid exposure for reasons likely other than asthma in subjects with asthma. Conclusions: About 40% of systemic corticosteroid use in subjects with asthma was for reasons likely other than asthma. Clinicians should be aware of their asthma patients’ exposures to systemic corticosteroids for nonasthma reasons, to avoid missing adverse events or underestimating the severity of asthma, and to reduce systemic corticosteroid use.

Systemic Corticosteroid Exposure and Atrioventricular Conductance Delays After Transcatheter Aortic Valve Implantation

BackgroundAtrioventricular conduction delays (AVCD) are common after transcatheter aortic valve implantation (TAVI) and frequently require implantation of a permanent pacemaker (PPM). Autopsy studies demonstrated the role of ischemia, inflammation, and oedema in the pathogenesis of AVCD. Corticosteroids (CS) reduce inflammation and oedema and hence might lead to a lower rate of AVCD. MethodsBased on a prospective single-center registry, we performed a propensity score (PS) matched analysis of subjects treated with or without systemic CS (>2.5 mg prednisolone-equivalent per day) at the time of TAVI. The primary endpoint was a composite of PPM-implantation and new-onset left bundle branch block (LBBB) within 30 days after TAVI. ResultsAmong 2213 consecutive patients undergoing TAVI (51.5% female, mean age 82.1 ± 6.1 years) 89 patients were treated with systemic CS, of which 87 were included in the PS matched analysis. At 30 days, rates of the composite of PPM and LBBB were comparable between patients with versus without CS both in the overall cohort (33.7% versus 33.0%, p = 0.89) and the PS matched cohort (34.5% versus 40.2%, p = 0.443). There were no differences in a composite of major or minor vascular complications and major or life-threatening bleeding events between patients with versus without CS in the overall cohort (34.8% versus 26.6%, p = 0.088) or the PS matched cohort (33.3% versus 33.3%, p ≥ 0.999). ConclusionIn this exploratory study, intake of systemic CS among patients undergoing TAVI was not associated with differences in rates of AVCD, vascular complications, or bleeding events after TAVI.

Survival outcomes associated with corticosteroid use before chemoimmunotherapy in patients with advanced lung cancer

BackgroundHow corticosteroid use affects treatment response to chemotherapy and immune-checkpoint inhibitors (CICPIs) remains unknown. We assessed how systemic corticosteroid exposure before CICPI modifies the effect of CICPI on outcomes among patients with metastatic non-small cell lung cancer (mNSCLC) or extensive-stage small-cell lung cancer (ES-SCLC). MethodsWe conducted a retrospective cohort study using electronic health records to examine patients with mNSCLC or ES-SCLC who received chemotherapy (CT) between 1st April 2015 and 31st January 2018 or CICPI between 1st February 2018 and 31st August 2019. We excluded those with an actionable driver mutation. Baseline corticosteroid use was defined as systemic corticosteroids within 28 days before the initiation of CT or CICPI, not including premedications. Coprimary outcomes included overall survival (OS), real-world progression (rwP), and real-world progression-free survival (rwPFS) in CICPI-treated corticosteroid users versus non-users. We used inverse probability of treatment weighting (IPW) to adjust for potential confounding. ResultsThe cohort of 316 patients (median [interquartile range] age, 67 [61–73] years; 156 [49%] male) included 228 CT-treated and 88 CICPI-treated patients. After applying IPW, characteristics were well-balanced between the CT and CICPI groups, and steroid users and non-users. Using CT-treated steroid non-users as a common comparator, CICPI-treated steroid users were as likely as CICPI-treated steroid non-users to die (users IPW hazard ratio [HR] = 0.67, 95% CI = 0.35–1.28 versus non-users IPW-HR = 0.88, 95% C = I0.55–1.42; p = 0.49), have rwP (IPW-HR = 0.35, 95% C = I0.12–0.99 versus IPW-HR = 0.41, 95% C = I0.24–0.70; p = 0.77), or experience rwPFS (IPW-HR = 0.56, 95% C = I0.29–1.09 versus IPW-HR = 0.69, 95% CI0.46–1.03; p = 0.59). ConclusionCorticosteroid use before CICPIs was not associated with worse outcomes, suggesting that corticosteroids should be used with CICPIs when indicated.

Complications and Health Care Resource Utilization Associated with Systemic Corticosteroids in Children and Adolescents with Persistent Asthma

BACKGROUND:Limited comparative data are available on the impact of systemic corticosteroid (SCS) use in children and adolescents.OBJECTIVE:To determine if asthmatic children and adolescents treated with SCS have a higher likelihood of developing complications versus those not receiving SCS and to examine health care resource utilization (HCRU) in this population.METHODS:A retrospective study of data from children and adolescents with persistent asthma retrieved from the MarketScan database, a large US health claims data set, for the period 2000 to 2017 was performed. Propensity score matching was used to pair patients in the SCS and control cohorts. For complications, SCS subgroups (≥4 or 1-3 annual prescriptions) were compared with asthmatic controls without SCS using logistic regression, and for HCRU, cohorts were compared using negative binomial regression.RESULTS:A total of 67,081 patients were included (SCS: 23,898; control: 43,183). The odds of having a complication were 2.9 (95% confidence interval [CI], 2.5-3.2; P < .001) and 1.6 (95% CI, 1.6-1.7; P < .001) times higher in the ≥4 and 1 to 3 SCS groups, respectively, in the first year of follow-up versus controls. For asthma-related hospitalizations, the incidence rate ratio (IRR) was 6.9 (95% CI, 5.6-8.6) and 3.1 (95% CI, 2.8-3.4) times greater in the ≥4 SCS and 1 to 3 SCS groups, respectively, versus controls; for asthma-related emergency department visits, IRR was 5.0 (95% CI, 4.4-5.6) and 2.9 (95% CI, 2.7-3.0) times greater, respectively, versus controls (all P < .01).CONCLUSION:Children and adolescents receiving SCS for persistent asthma have an increased risk of developing complications and have greater HCRU in the first year of follow-up versus those without SCS exposure.