Real-world association between systemic corticosteroid exposure and complications in US patients with severe asthma
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SUBMITTER: Casale T
PROVIDER: S-EPMC10964513 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
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Project description:BackgroundStudies have shown the efficacy of asthma biologics in real-world settings, confirming the generalizability of randomized controlled trial (RCT) results, but studies on more than one biologic are scarce. Accordingly, little is known about the different background characteristics in users of asthma biologics. This study aimed to describe the backgrounds of asthma patients using biologics (omalizumab, mepolizumab, benralizumab, and dupilumab) and examine the effectiveness of these biologics for reducing asthma exacerbations and total systemic corticosteroid doses.MethodsWe conducted a retrospective cohort study using self-controlled methods to evaluate the association between the use of biologics and reduction in exacerbations and hospitalizations using a large-scale health insurance claims database in Japan.ResultsOf 355 continuously treated asthma patients using biologics, 119, 82, 69, and 85 patients were assigned to the omalizumab, mepolizumab, benralizumab, and dupilumab groups, respectively. The baseline characteristics differed among users of biologics. The incidence ratios of exacerbations and hospitalizations during biologics use were 0.68 (95% confidence interval, 0.62-0.74) and 0.65 (0.55-0.77) compared with the period before biologics use. The total systemic corticosteroid dose equivalent to prednisolone per person-year was reduced from a median of 600 [interquartile range, 90-1713] mg to 164 [0-1010] mg (P < .001). Similar results were obtained for individual biologics with a few exceptions.ConclusionsThe background characteristics of biologics users differed in a real-world setting. Our results confirmed findings from RCTs demonstrating that each biologic (omalizumab, mepolizumab, benralizumab, and dupilumab) is associated with decreased exacerbation numbers and corticosteroid-sparing effects, even outside of the controlled settings of RCTs.
| S-EPMC8585664 | biostudies-literature
Project description:Severe asthma constitutes a serious health burden with significant morbidity and socioeconomic costs. The development and introduction of new biologics targeting type 2 inflammation changed the paradigm for management of severe asthma and initiated a biological era. These changes impose a challenge to clinicians in managing difficult-to-treat and severe asthma. To understand the characteristics and heterogeneity of severe asthma and to develop a better strategy to manage it, the Korean Academy of Asthma, Allergy and Clinical Immunology, Working Group on Severe Asthma, has organized the Korean Severe Asthma Registry (KoSAR). In this review, we describe the challenges of severe asthma management regarding diagnosis, disease burden, heterogeneity, guidelines, and organization of severe asthma clinics. This review also examines the current global activities of national and regional registries and study groups. In addition, we present the KoSAR vision and organization and describe the findings of KoSAR in comparison with those of other countries.
| S-EPMC8925953 | biostudies-literature
Project description:Oral corticosteroids (OCS) have long been a mainstay of treatment for asthma exacerbations and chronic severe asthma. However, it is increasingly recognized that both long-term and short-term OCS use are directly associated with a wide range of serious adverse effects, and as such OCS-sparing treatment alternatives are now widely recommended for patients with severe asthma. While several international guidelines recommend these treatments, guidance on OCS tapering, and which patients are most likely to tolerate OCS reduction and/or discontinuation, is still lacking. Several biologics have demonstrated efficacy in patients with OCS-dependent asthma. One OCS-sparing treatment is the anti-interleukin-5 monoclonal antibody mepolizumab, which is approved for the treatment of severe eosinophilic asthma. In addition to improved exacerbation rates, asthma control, quality of life, and lung function among patients with severe eosinophilic asthma, mepolizumab also has an OCS-sparing effect, which has been demonstrated in randomized controlled trials and real-world studies. Both physicians and patients express concerns about the adverse effects of OCS, and additional data from the randomized, controlled SIRIUS trial (NCT01691508) highlight the high level of concern among patients regarding OCS-related burden. In this article, we discuss current guidance on OCS-sparing strategies for patients with severe asthma, provide a summary of the available evidence of the OCS-sparing effect of mepolizumab, and highlight patient and physician perspectives on the use of OCS and OCS-sparing treatments in severe asthma.
| S-EPMC9386863 | biostudies-literature
Project description:BackgroundSevere asthma in children is a heterogeneous disorder associated with variable responses to corticosteroid treatment. Criterion standards for corticosteroid responsiveness assessment in children are lacking.ObjectiveThis study sought to characterize systemic corticosteroid responses in children with severe asthma after treatment with intramuscular triamcinolone and to identify phenotypic and molecular predictors of an intramuscular triamcinolone response.MethodsAsthma-related quality of life, exhaled nitric oxide, blood eosinophils, lung function, and inflammatory cytokine and chemokine mRNA gene expression in peripheral blood mononuclear cells were assessed in 56 children with severe asthma at baseline and 14 days after intramuscular triamcinolone injection. The Asthma Control Questionnaire was used to classify children with severe asthma into corticosteroid response groups.ResultsThree groups of children with severe asthma were identified: controlled severe asthma, children who achieved control after triamcinolone, and children who did not achieve control. At baseline, these groups were phenotypically similar. After triamcinolone, discordance between symptoms, lung function, exhaled nitric oxide, and blood eosinophils was noted. Clinical phenotypic predictors were of limited utility in predicting the triamcinolone response, whereas systemic mRNA expression of inflammatory cytokines and chemokines related to IL-2, IL-10, and TNF signaling pathways, namely, AIMP1, CCR2, IL10RB, and IL5, strongly differentiated children who failed to achieve control with triamcinolone administration.ConclusionsSystemic corticosteroid responsiveness in children with severe asthma is heterogeneous. Alternative prediction models that include molecular endotypic as well as clinical phenotypic features are needed to identify which children derive the most clinical benefit from systemic corticosteroid step-up therapy given the potential side effects.
| S-EPMC5346343 | biostudies-literature
Project description:BackgroundCommunity-acquired pneumonia (CAP) is a leading cause of morbidity and mortality worldwide despite correct antibiotic use. Corticosteroids have long been evaluated as a treatment option, but heterogeneous effects on survival have precluded their widespread implementation. We aimed to evaluate whether corticosteroids might improve clinical outcomes in patients with severe CAP and high inflammatory responses.Study design and methodsWe analyzed two prospective observational cohorts of patients with CAP in Barcelona and Rome who were admitted to intensive care with a high inflammatory response. Propensity score (PS) matching was used to obtain balance among the baseline variables in both groups, and we excluded patients with viral pneumonia or who received hydrocortisone.ResultsOf the 610 patients admitted with severe CAP, 198 (32%) received corticosteroids and 387 had major criteria for severe CAP. All patients had a baseline serum C-reactive protein above 15 mg/dL. Patients who received corticosteroids were more commonly male, had more comorbidities (e.g., cancer or chronic obstructive pulmonary disease), and presented with significantly higher sequential organ failure assessment scores. Eighty-nine patients met major severity criteria (invasive mechanical ventilation and/or septic shock) and were matched per group. Twenty-eight-day mortality was lower among patients receiving corticosteroids (16 patients, 18%) than among those not receiving them (28 patients, 31%; p = 0.037). After PS matching, corticosteroid therapy reduced the 28-day mortality risk in patients who met major severity criteria (hazard ratio (HR) 0.53, 95% confidence interval (CI) 0.29-0.98) (p = 0.043). In patients who did not meet major severity criteria, no benefits were observed with corticosteroid use (HR 0.88 (95%CI 0.32-2.36).ConclusionsCorticosteroid treatment may be of benefit for patients with CAP who have septic shock and/or a high inflammatory response and requirement for invasive mechanical ventilation. Corticosteroids appear to have no impact on mortality when these features are not present.
| S-EPMC8674860 | biostudies-literature
Project description:BackgroundAlthough systemic corticosteroid (SCS) treatment, irrespective of duration or dosage, is associated with adverse outcomes for patients with asthma, the longitudinal effects of this treatment on adverse outcomes, healthcare resource utilization (HCRU), and healthcare costs are unknown.MethodsWe identified patients initiating intermittent or long-term SCS who were diagnosed with active asthma from UK general practice with linked secondary care data. Control (non-SCS) patients were matched by sex and index date with those initiating SCS. Minimum baseline period was 1 year prior to index date; minimum follow-up duration was 2 years post-index date. Cumulative incidence of SCS-associated adverse outcomes and associated HCRU and costs were compared between SCS and non-SCS patient groups and among average SCS daily exposure categories. Associations between exposure and annualized HCRU and costs were assessed, adjusted for confounders.ResultsAnalyses included 9413 matched pairs. Median (interquartile range) follow up was as follows: SCS group: 7.1 (4.1-11.8) years; control group: 6.4 (3.8-10.0) years. Greater SCS dosages were correlated with greater cumulative incidence. For example, patients with type 2 diabetes receiving an average daily dosage of ≥7.5 mg had a 15-year cumulative incidence (37.5%) that was 1.5-5 times greater than those receiving lower dosages. HCRU and costs increased annually for SCS patients but not for non-SCS patients. Increases in all-cause adverse outcome (excluding asthma)-associated HCRU and costs were dose-dependent.ConclusionsOver the long term, adverse outcomes associated with SCS initiation were relatively frequent and costly, with a positive dosage-response relationship with SCS exposure.
| S-EPMC6587525 | biostudies-literature
Project description:There is an ongoing debate about the benefit-risk balance of systemic corticosteroids (SCS) in asthma treatment. We investigated the associations between SCS use and disease burden in a database cohort of asthmatics, categorized into SCS and non-SCS prescription at baseline and quartiles (Q) by cumulative SCS dosage. Of the 10,579 patients, the SCS cohort comprised 3103 patients (29.3%). Mean SCS dosages at baseline were 0.08, 0.29, 0.79, and 4.58 mg/day in Q1, Q2, Q3, and Q4, respectively. Similar SCS dosages were used within each quartile throughout the study period. No remarkable changes in asthma severity or control status were observed. All SCS cohorts had a higher risk of intermittent SCS exposure during the observation period. SCS use was associated with osteoporosis, diabetes, anxiety/neurosis, and depression. SCS-dependent treatment does not necessarily lead to the future improvement of asthma control; rather, it may negatively impact systemic health, even at mean dosages <5 mg/day.
| S-EPMC7403577 | biostudies-literature
Project description:BackgroundThe additive benefit of inhaled corticosteroid when used with systemic corticosteroid in acute asthma is still unclear. The objective of this study was to assess the effect of high and repeated doses of inhaled budesonide when combined with the standard treatment of adult acute asthma.MethodsIt was a prospective double-blind randomized controlled study performed in the emergency department (ED) from May 1, 2010 to February 28, 2011 (ClinicalTrials.gov, NCT04016220). Fifty patients were included and were randomized to receive intravenous hydrocortisone hemisuccinate in association with nebulized budesonide (n = 23, budesonide group) or normal saline (n = 27, control group). Nebulization of budesonide or saline was done in combination with 5 mg of terbutaline every 20 min the first hour, then at 2 h (H2), and 3 h (H3). All patients received standard treatment. Efficacy and safety of inhaled budesonide were evaluated every 30 min for 180 min.ResultsA significant increase in peak expiratory flow (PEF) was observed in both treatment groups at evaluation times. The increase in PEF persisted significantly compared to the previous measurement in both groups. There was no significant difference in the PEF between the two groups at evaluation times. There was no significant difference between the two groups in the evolution in the respiratory rate and heart rate. There was also no statistically significant difference between the two groups in the rate of hospitalization, the discharge criteria before the end of the protocol.ConclusionsConsidering its limited power, our study suggests that the association of nebulized budesonide with hydrocortisone hemisuccinate has no additional effect over the use of hydrocortisone alone in adults' acute asthma managed in the ED.
| S-EPMC9308286 | biostudies-literature
Project description:PurposeThe oral corticosteroid (OCS)-sparing effect of several biologics (BIOs) has been shown in clinical trials. To date, no study has evaluated differences in OCS dose reduction between BIO-initiated and BIO-non-initiated patients in real-world clinical practice. We compared dose reductions in maintenance OCS between BIO-initiated and BIO-non-initiated severe asthma patients in a real-world setting.Patients and methodsThis retrospective cohort study used the data from the Diagnosis Procedure Combination database of Medical Data Vision in Japan. Severe asthma patients with continuous use of OCS were selected from December 2015 to February 2020. The primary endpoint was the proportion reduction in daily maintenance OCS dose from Week 0 to Week 24. Analyses were performed using inverse probability treatment weighting.ResultsIn total, 2927 patients were included (BIO-initiated: 239 patients, BIO-non-initiated: 2688 patients). Adjusted median (quartile [Q] 1-Q3) proportion reduction in daily maintenance OCS dose at Week 24 from the index date was 25.0% (0.0-100.0%) and 0.0% (0.0-83.3%) in the BIO-initiated and BIO-non-initiated groups, respectively (Hodges-Lehmann estimate [95% confidence interval], 0.0000% [0.0000-0.3365%]). Respective proportions of patients in the BIO-initiated and BIO-non-initiated groups achieving dose reductions from the index date in the daily maintenance OCS dose at Week 24 were >0% reduction, 56.6% and 44.1% (odds ratio [OR] 1.6554); ≥25% reduction, 50.5% and 40.6% (OR 1.4888); ≥50% reduction, 42.8% and 33.7% (OR 1.4714); and 100% reduction, 26.2% and 24.4% (OR 1.1005).ConclusionAmong severe asthma patients, the daily dose of maintenance OCS was reduced with BIO treatment. Although a higher percentage of patients in the BIO-initiated group had an OCS reduction of ≤75% than the BIO-non-initiated group, we found no clear difference in OCS reduction. Our findings will be justified by further research that incorporates a longer observation period and variables excluded from this study.Trial registrationClinicalTrials.gov (NCT05136547).
| S-EPMC10438425 | biostudies-literature
Project description:ImportanceDaily use of inhaled corticosteroids is a widely recommended treatment for mild persistent asthma in children. There is concern that, similar to systemic corticosteroids, inhaled corticosteroids may have adverse effects on bone health.ObjectiveTo determine whether there is an increased risk of bone fracture associated with inhaled corticosteroid use in children with asthma.Design, setting, and participantsIn this population-based nested case-control study, we used health administrative databases to identify a cohort of children aged 2 to 18 years with a physician diagnosis of asthma between April 1, 2003, and March 31, 2014, who were eligible for public drug coverage through the Ontario Drug Benefit Program (Ontario, Canada). We matched cases of first fracture after asthma diagnosis to fracture-free controls (ratio of 1 to 4) based on date of birth (within 1 year), sex, and age at asthma diagnosis (within 2 years). We used a 1-year lookback period to ascertain history of inhaled corticosteroid use. Multivariable conditional logistic regression was used to obtain an odds ratio (OR) with 95% confidence interval for fracture, comparing no inhaled corticosteroid use vs current, recent, and past use.ExposuresInhaled corticosteroid use during the child's 1-year lookback period, measured as current user if the prescription was filled less than 90 days prior to the index date, recent user (91-180 days), past user (181-365 days), or no use.Main outcomes and measuresFirst emergency department visit for fracture after asthma diagnosis, identified using International Statistical Classification of Diseases and Related Health Problems, 10th Revision codes.ResultsThis study included 19 420 children (61.0% male; largest proportion of children, 31.5%, were aged 6-9 years at their index date). The multivariable regression results did not show a significant association between first fracture after asthma diagnosis and current use (OR, 1.07; 95% CI, 0.97-1.17), recent use (OR, 0.96; 95% CI, 0.86-1.07), or past use (OR, 1.00; 95% CI, 0.91-1.11) of inhaled corticosteroids, compared with no use, while adjusting for sociodemographic factors and other medication use. However, use of systemic corticosteroids in the 1-year lookback period resulted in greater odds of fracture (OR, 1.17; 95% CI, 1.04-1.33).Conclusions and relevanceSystemic corticosteroids, but not inhaled corticosteroids, were significantly associated with increased odds of fracture in the pediatric asthma population.
| S-EPMC5833516 | biostudies-literature