Prescription Of Systemic Corticosteroids Research Articles

Real-world effectiveness of dupilumab versus benralizumab and mepolizumab.

In the United States, this real-world study compared the effectiveness of dupilumab, benralizumab, andmepolizumab in reducing exacerbations and systemic corticosteroid (SCS) prescriptions among patients with asthma. Patients (12 years old) who initiated dupilumab, benralizumab, or mepolizumab (index) between November 2018 and September 2020 were identified by using electronic medical record data. Subjects were included if they had greater than or equal to 12 months of data before and after the index date and two or more severe asthma-related exacerbations before the index date. Differences in baseline characteristics were addressed by using inverse probability treatment weighting (IPTW). Pairwisecomparisons between dupilumab and benralizumab, or mepolizumab were conducted by using negative binomial regression, adjusting for baseline rates and unbalance characteristics (greater than or equal to 10% standardized differences) after IPTW. Overall, a total of 1737 subjects met all criteria: 825 dupilumab, 461 benralizumab, and 451 mepolizumab initiators.In the postindex period, dupilumab was associated with a 24% and 28% significant reduction in the risk of severe asthmaexacerbations versus benralizumab (incidence rate ratio [IRR] 0.76 [95% confidence interval {CI}, 0.67-0.86)] and mepolizumab(IRR 0.72 [95% CI, 0.63-0.82]), respectively. In addition, dupilumab treatment significantly reduced SCS prescriptionsby 16% and 25% versus benralizumab and mepolizumab, respectively (p < 0.05). This study represents one of the largest real-world comparisons of biologics (dupilumab, benralizumab, and mepolizumab) for asthma in the United States to date. This analysis shows that the use of dupilumab was associated with a significantly greater reduction in both severe asthma exacerbations and SCS prescriptions compared with benralizumab and mepolizumab.

Real-world effectiveness of dupilumab in patients with asthma: Findings from the US ADVANTAGE study

BackgroundDupilumab is approved as an add-on maintenance therapy for patients (≥6 years) with moderate-to-severe asthma. Better understanding of real-world effectiveness is needed. ObjectiveTo characterize the real-world effectiveness of dupilumab in asthma management. MethodsThis retrospective study included patients (≥12 years of age) diagnosed with asthma, initiating dupilumab between November 2018 and September 2020. The study used a US electronic medical record database (TriNetX Dataworks, Cambridge, Massachusetts). Asthma exacerbation rates before and after the initiation of dupilumab were analyzed using generalized estimating equations models with Poisson probabilistic link to estimate incidence rate ratios (IRRs). Sensitivity analyses were conducted based on previous exacerbation data, eosinophil levels, history of atopic dermatitis or chronic rhinosinusitis with nasal polyps, previous use of biologics, and presence of SARS-CoV-2 (COVID-19). ResultsA total of 2400 patients initiating dupilumab met all study criteria. After initiation of dupilumab, risk of asthma exacerbation was reduced by 44% (IRR, 0.56; 95% CI, 0.47-0.57; P = <0.0001) and systemic corticosteroid prescriptions by 48% (IRR, 0.52; 95% CI, 0.48, 0.56; P = <0.0001) compared with those before initiation of dupilumab. Adjustment for COVID-19 showed a greater reduction in asthma exacerbations (IRR, 0.50; 95% CI, 0.45-0.55; P = <0.0001). ConclusionCurrent real-world efficacy evidence indicates that dupilumab reduces asthma exacerbations and total systemic corticosteroid prescriptions in clinical practice. The effectiveness of dupilumab was observed independent of exacerbation history, eosinophil levels, or COVID-19 impact.

Esophageal Lichen Planus as a Cause of Dysphagia: Literature Review and Clinical Observation

Aim: to analyze the literature data, and to raise awareness of doctors of various specialties about the methods of diagnosis and treatment of esophageal lichen planus (ELP).Key points. In a 67-year-old female patient with complaints of difficulty swallowing solid food and weight loss, esophagogastroduodenoscopy revealed subcompensated stenosis of the middle third of the esophagus and signs of fibrinous esophagitis. Based on the characteristics of the endoscopic picture and the detection of apoptotic Ciwatt bodies in esophageal biopsies, a diagnosis of ELP was established. Treatment with glucocorticosteroids led to relief of symptoms and positive endoscopic dynamics. ELP is rare and the least studied, data on this disease in the literature are presented mainly in the form of clinical observations and analysis of series of cases. Typical clinical manifestations include dysphagia and odynophagia. Despite the low prevalence, ELP can be associated with serious complications: stenosis and esophageal squamous cell carcinoma. Endoscopic examination reveals characteristic signs in the esophagus: swelling, thickening and increased vulnerability of the mucosa, often with fibrin, formation of membranes and strictures. The histological picture is represented by epithelial dyskeratosis with exfoliation, lichenoid lymphocytic infiltration. The most specific histological sign is the presence of apoptotic Civatte bodies. Recommendations for the treatment of ELP are limited to the results of a series of clinical observations and include the prescription of systemic corticosteroids. The issue of supportive therapy is the least studied.Conclusion. Analysis of the literature data and the clinical case demonstrate that lichen planus of the esophagus is one of the rare causes of dysphagia. Characteristic endoscopic and histological signs are key for the diagnosis. The management of patients with esophageal lichen planus is insufficiently defined and today includes taking of glucocorticosteroids, endoscopic dilation of stricture and dynamic endoscopic observation, given the high risk of squamous cell carcinoma in this category of patients.

Prevalence of asthma in Catalonia (Spain): a retrospective, large-scale population-based study.

Asthma epidemiology reports an estimated global prevalence of about 4.3-8.6% in adults, with last differences among geographical regions. This study analyses a more significant population of asthma patients (473,737 individuals).To study the prevalence of medical diagnosis of asthma, overall and by age, gender, and disease severity, as well as comorbidities and type 2 biomarkers, and undergo medical treatments of a retrospective population-based asthma cohort from Catalonia (Spain). Individuals with a diagnosis of asthma established by medical records at different healthcare levels (primary, hospital, and emergency) from the Catalan Health System (CHS) were included. Socio-demographic characteristics, prevalence, overall and by age and gender, disease severity, comorbidities, and biomarkers of type-2 inflammation were evaluated, together with appropriate medical treatment. The overall diagnosed asthma prevalence in the population of Catalonia was 6.3%, where patients mainly had mild asthma (5.3%) and were significantly higher in females (6.8%) than males (5.7%). By age groups, asthma was more prevalent in boys and young men adults; however, being more prevalent in females above the age of 30y. The prevalence of severe asthma was 0.4%, 42.6% had uncontrolled asthma, and a high proportion (84.2%) were under systemic corticosteroid prescription. As expected, SABAs were the most prescribed drug (62.6%), followed by systemic corticosteroids (43.3%). More than half (53.8%) of patients showed type 2 inflammation. Asthma prevalence in Catalonia is similar to other areas studied in Spain, with a high prevalence in women and of T2 asthma.

Risk of osteoporosis in patients with atrial fibrillation with and without oral anticoagulant therapy

Background We aimed to compare the risk of developing osteoporosis in patients prescribed warfarin or direct-acting oral anticoagulants (DOACs) with those with no therapy. Research design and methods We included 37,632 patients aged between 18 and 111 years with a recorded diagnosis of AF between 1 Jan 2013 and 31 Dec 2017. Patients were followed until the diagnosis of osteoporosis, switch or discontinuation of the OAC, last clinical visit, or end of the study period (31 Dec 2018), whichever occurred first. The incidences of new-onset osteoporosis were calculated using the Cox proportional hazards model. Results Of total, 16,995 (45.2%) had no recorded OAC prescription, and 20,637 had a recorded prescription of warfarin (6,609) or DOAC (14,028). Compared with those not prescribed an OAC, the risk of being diagnosed with new-onset osteoporosis increased in patients prescribed warfarin (HR 2.22, 95% CI 2.00-2.47, p<0.001) and DOACs (HR 1.42, 95% CI 1.29-1.58, p<0.001). However, the effect of DOACs was not statistically significant (HR 1.07, 95% CI 0.86-1.33, p<0.535) after excluding patients with at least one recorded prescription of systemic corticosteroids, antiepileptics, or proton pump inhibitors. Conclusions Use of warfarin or DOACs was associated with a significantly increased risk of developing osteoporosis compared with no OAC treatment.

Factors Associated with Unscheduled Emergency Department Revisits in Children with Acute Lower Respiratory Tract Diseases.

PurposeTo identify factors associated with unscheduled emergency department (ED) revisits within 72 hours in children with acute dyspnea from lower respiratory tract diseases.Patients and MethodsThis retrospective cohort study included pediatric patients (age group: one month to 15 years old) who visited the ED with acute lower respiratory tract diseases between January 1st, 2017 and February 28th, 2019. The medical records were reviewed and discharged patients were dichotomized into revisit and non-revisit groups, based on whether the patients needed a revisit or not. Baseline characteristics, vital signs, diagnosis, treatment, pediatrician consultation, ED length of stay, and primary doctor of both groups were compared. Univariate and multivariate analyses by logistic regression were used to determine the significant factors associated with the revisits.ResultsMedical records of 918 eligible pediatric patients (1417 visits) were reviewed. Factors significantly associated with the revisits were history of asthma or current controller use (odds ratio [OR]: 3.08: 95% confidence interval [CI]: 1.86–5.1). Not prescribing systemic corticosteroids (P < 0.001), or prescribing them upon discharge without first dose in the ED (P = 0.022) were significantly associated with revisits.ConclusionNo prescription of systemic corticosteroids or prescription upon discharge, without an immediate dose at the ED, in children with history of asthma or current controller use were associated with revisits.

Artificial intelligence processing electronic health records to identify commonalities and comorbidities cluster at Immuno Center Humanitas.

BackgroundComorbidities are common in chronic inflammatory conditions, requiring multidisciplinary treatment approach. Understanding the link between a single disease and its comorbidities is important for appropriate treatment and management. We evaluate the ability of an NLP‐based process for knowledge discovery to detect information about pathologies, patients' phenotype, doctors' prescriptions and commonalities in electronic medical records, by extracting information from free narrative text written by clinicians during medical visits, resulting in the extraction of valuable information and enriching real world evidence data from a multidisciplinary setting.MethodsWe collected clinical notes from the Allergy Department of Humanitas Research Hospital written in the last 3 years and used it to look for diseases that cluster together as comorbidities associated to the main pathology of our patients, and for the extent of prescription of systemic corticosteroids, thus evaluating the ability of NLP‐based tools for knowledge discovery to extract structured information from free text.ResultsWe found that the 3 most frequent comorbidities to appear in our clusters were asthma, rhinitis, and urticaria, and that 991 (of 2057) patients suffered from at least one of these comorbidities. The clusters which co‐occur particularly often are oral allergy syndrome and urticaria (131 patients), angioedema and urticaria (105 patients), rhinitis and asthma (227 patients). With regards to systemic corticosteroid prescription volume by our clinicians, we found it was lower when compared to the therapy the patients followed before coming to our attention, with the exception of two diseases: Chronic obstructive pulmonary disease and Angioedema.ConclusionsThis analysis seems to be valid and is confirmed by the data from the literature. This means that NLP tools could have significant role in many other research fields of medicine, as it may help identify other important, and possibly previously neglected clusters of patients with comorbidities and commonalities. Another potential benefit of this approach lies in its potential ability to foster a multidisciplinary approach, using the same drugs to treat pathologies normally treated by physicians in different branches of medicine, thus saving resources and improving the pharmacological management of patients.

Therapeutic management of chronic spontaneous urticaria in clinical practice: results from a pilot survey.

The therapeutic approaches to patients with chronic spontaneous urticaria (CSU) differ among health care professionals and may be influenced by many factors. This cross-sectional survey was aimed at evaluating physicians' attitudes regarding therapeutic management of CSU in clinical practice. A study-specific questionnaire was administered to a group of physicians (N.=21) with a specialist interest in CSU from different areas of Italy (group A) and also to other physicians (N.=25) who manage CSU only occasionally in their clinical activity (group B). In case of ineffectiveness of second-generation antihistamines at standard doses, higher doses of the same drug were always or frequently prescribed by most physicians in both groups, and 64% in group B and one third in group A usually increased the dose up to twice. Old-generation antihistamines were never used in clinical practice by 14% of survey participants in group A and 24% in group B, with the remaining physicians reporting rare or occasional uses. The prescription of systemic corticosteroids appeared to be more common among physicians in group B. The question concerning the use of alternative drugs in refractory CSU produced different answers between the two groups. Costs and access to specialist reference centers were indicated as the most important barriers to the use of medications different from antihistamines. These preliminary results suggest that therapeutic approaches to CSU seem to be heterogeneous in clinical practice and could be at least in part conditioned by the different medical settings where physicians usually work.

P361 PREPARE-IBD: Physician Responses to disease Flares and Patient Adaptation in Relation to Events in Inflammatory Bowel Disease during the COVID-19 pandemic: A multicentre cohort analysis

BackgroundThe COVID-19 pandemic continues to pose complex problems across Europe and the world, with rising numbers of infections and the ongoing need for drastic public health interventions. This is difficult for patients with immune-mediated disorders like Inflammatory Bowel Disease (IBD), where immunosuppressive medications may affect susceptibility to serious infection. It was particularly challenging for physicians and patients during the first wave of the pandemic, when it was unclear whether anti-inflammatory flare treatment should be adapted to reduce infection risk, whilst trying to ensure symptomatic control and avoid admission to overwhelmed hospitals. Despite the development of various IBD / COVID-19 databases, the treatment adaptations and outcomes of patients experiencing IBD flares during the COVID-19 pandemic remain undefined. We aimed to compare IBD management and outcomes between pandemic and pre-pandemic cohorts.MethodsAn observational cohort study was performed, comprising patients who contacted IBD teams for a symptom flare between March – June, 2020 in, 60 National Health Service trusts in the United Kingdom. Data were compared to a pre-pandemic cohort after propensity-matching for age and disease severity. Statistical analyses were performed using R (version, 4.1.0, Vienna, Austria).ResultsIn total, 3728 patients in the pandemic (n=1864) and pre-pandemic (n=1864) cohorts were included. The principal findings were reduced systemic corticosteroid prescription during the pandemic in both Crohn’s disease (prednisolone: pandemic, 199/752, 26.5% vs, 263/708, 37.1%; p<0.001) and ulcerative colitis (UC) (prednisolone: pandemic, 372/1112, 33.5% vs, 470/1156, 40.7%, p<0.001), with increases in poorly bioavailable oral corticosteroids in Crohn’s (pandemic, 117/752, 15.6% vs, 48/708, 6.8%; p<0.001) and UC (pandemic, 131/1112, 11.8% vs, 60/1156, 5.2%; p<0.001). Ustekinumab (Crohn’s and UC) and vedolizumab (UC) treatment also significantly increased during the pandemic. Three-month steroid-free remission was similar in both Crohn’s (pandemic, 175/616, 28.4% vs, 195/608, 32.1%; p=0.17) and UC (pandemic, 312/858, 36.4% vs, 404/1006, 40.2%; p=0.095). The, 65 patients experiencing a flare and COVID-19 were more likely to have moderate-to-severely active disease at three months compared to those with a flare alone.ConclusionDespite several treatment adaptations during the pandemic, steroid-free outcomes were comparable to pre-pandemic levels, though patients with a flare and COVID-19 experienced worse outcomes. These findings have implications for IBD management during future waves or pandemics

Association of clinical and social factors with risk of fracture in children with atopic dermatitis.

Children with atopic dermatitis (AD) have multiple risk factors for accidental fractures, injuries that can lead to significant morbidity and mortality. However, little is known about the factors that mediate the relationship between AD and fracture in children. Our purpose was to examine the association of AD with fracture and to identify potential mediating factors. This retrospective cohort study examined children with and without AD from a longitudinal matched cohort database of 353,040 children registered in the national health insurance service and participated in the national health-screening program of Korea. We defined AD using medical claims and medication prescription records. We investigated accidental fracture events between the index date and the end of follow-up in a propensity score-matched cohort. Pre-specified subgroup analyses considered fractures in four different regions of the body. The mediating effects of 10 possible clinical factors (including the use of antihistamines and systemic corticosteroids) and social factors (including nutritional status and parental safety awareness) were determined. There were 145,704 participating children, 20% with AD and 49% girls. Fractures occurred in 6,652 of the children with AD (23%, mean age: 64.6±29.2months) and in 24,698 of the control group (21%, mean age 65.0±28.9months). Children with AD had an 8% greater risk of fracture events overall (adjusted relative risk [aRR]: 1.08, 95% CI: 1.05-1.10). In subgroup analysis, AD was related to increased rates of skull and facial bone fracture (aRR: 1.09, 95% CI: 1.04-1.14), for trunk including vertebrae (aRR: 1.58, 95% CI: 1.22- 2.05), and for distal limbs (aRR: 1.11, 95% CI: 1.07-1.15). However, the relationship with proximal limb fracture was insignificant. Duration of systemic corticosteroid prescription was the largest mediating factor, followed by duration of antihistamine prescription, and infant feeding practices. In particular, the duration of systemic corticosteroid prescription was significantly associated with fracture events (incidence: 20.1% at the 25th percentile and 23.6% at the 75th percentile; difference: 3.4% [95% CI: 2.8-4.0%]). Children with AD were related to increased fracture events. The key factors with mediating effects were systemic use of corticosteroid and antihistamine. Infant feeding practices had weaker mediating effects.

Corticosteroid Use and Risk of Herpes Zoster in a Population-Based Cohort

ObjectiveTo examine the relationship between corticosteroid use and herpes zoster risk. MethodsWith data from a large cohort of adults (the 45 and Up Study) recruited between 2006 and 2009 and linked to health data sets, the effect of corticosteroid use on zoster risk was analyzed by Cox proportional hazards models, adjusting for age, sex, and other characteristics. ResultsDuring 602,152 person-years (median, 7.36 years) of follow-up, there were 20,048 new systemic corticosteroid users and 6294 incident herpes zoster events among 94,677 participants (zoster incidence, 11.0 per 1000 person-years). Compared with nonusers, the risk of zoster was 59% higher in those using systemic corticosteroids (adjusted hazard ratio [aHR], 1.59; 95% CI, 1.48 to 1.71) and greater with higher cumulative doses: aHR of 1.32 (95% CI, 1.17 to 1.48), 1.74 (95% CI, 1.55 to 1.95), and 1.80 (95% CI, 1.61 to 2.02) for use of less than 500 mg, 500 mg to less than 1000 mg, and 1000 mg or more prednisolone equivalents, respectively (P value for trend, <.001). Compared with nonusers, zoster risk increased significantly (aHR, 6.00; 95% CI, 4.85 to 7.42) in the month after a single prescription of systemic corticosteroids and returned to levels similar to those in nonusers by the third month after dispensing (aHR, 0.91; 95% CI, 0.49 to 1.69). ConclusionPractitioners should be alert to the increased risk of zoster among patients taking systemic corticosteroids. Given the significant morbidity from zoster, particularly in older adults, these findings support judicious prescribing of corticosteroids, including using as low a dose and as short a course as possible.

Impact of Guidelines Publication on Acute Bronchiolitis Management: 10-Year Experience from a Tertiary Care Center in Italy.

Bronchiolitis is the most common lower respiratory tract infection in infants. According to evidence-based guidelines, diagnosis is clinical, there is no need for routine use of laboratory or instrumental tests and therapy is primarily supportive, based on oxygen and adequate fluid supplementation. Nevertheless, unnecessary diagnostic tests and pharmacological treatments are still very common. The aim of this retrospective cohort study was to evaluate how the management of bronchiolitis has changed in the last ten years in a Tertiary Care Center in Italy, assessing adherence to national guidelines. Considering the publication of the Italian inter-society consensus document in 2014, we compared patients admitted in the prior four epidemic seasons with patients admitted in the latter six epidemic seasons. The comparison between the two groups showed a significant reduction in the prescription of systemic corticosteroids (58.9% vs. 41.8%, p < 0.001), nebulized epinephrine (73.8% vs. 38.3%, p < 0.001) and antibiotics (59.5% vs. 42.3%, p < 0.001), together with a drastic decrease in the use of chest X-ray (92.2% vs. 54.4%, p < 0.001). On the contrary, the use of inhaled salbutamol remained substantially stable over time (39.4% vs. 37.6%, p = 0.505). Despite the encouraging results, further efforts are needed to limit the prescription of ineffective therapies like antibiotics and inhaled salbutamol.

Metformin Use and Risk of Asthma Exacerbation Among Asthma Patients with Glycemic Dysfunction

Diabetes is associated with worse asthma morbidity. Metformin, which treats diabetes, may have a role among patients with asthma and glycemic dysfunction. To determine the association between metformin use and asthma exacerbations among patients with diabetes. We queried the Johns Hopkins electronic health record from April 1, 2013, to May 31, 2018. Adults with asthma and diabetes were followed from first hemoglobin A1c (HbA1c) test to an asthma-related systemic corticosteroid prescription, emergency department (ED) visit, or hospitalization. Multivariable Cox models estimated time to each outcome associated with metformin use, modeled as either time-invariant (status at HbA1c testing) or time-dependent (based on fill data). Mediation of results by HbA1c was assessed. Sensitivity analysis was performed by propensity score matching. The cohort comprised 1749 adults with asthma and diabetes. Metformin use at entry was associated with a lower hazard of asthma-related ED visits (adjusted hazard ratio [aHR], 0.40; 95% CI, 0.22-0.75) but not steroid prescription (aHR, 0.89; 95% CI, 0.70-1.13) or hospitalization (aHR, 0.38; 95% CI, 0.13-1.12). HbA1c did not mediate the association with ED visits. With metformin exposure modeled as time-dependent, metformin use was additionally associated with lower hazard of asthma-related hospitalization (aHR, 0.30; 95% CI, 0.09-0.93). Results were consistent within a subcohort of 698 metformin users matched 1:1 to nonusers by propensity score. Metformin use, independent of glycemic control and obesity, was associated with lower hazard of asthma-related ED visits and hospitalizations. Metformin may have benefit in patients with asthma and glycemic dysfunction.

Systemic glucocorticoid at discharge after hospitalization for pediatric asthma: a prospective pilot study

Objective: We examined asthma control in children hospitalized for status asthmaticus 7–10 days after discharge with or without an additional prescription for systemic corticosteroids. Methods: This was a prospective observational study of patients aged 5–17 years with a documented history of asthma or β-agonist responsive wheezing admitted to the hospital for an acute asthma exacerbation. We compared patients who had any systemic corticosteroid prescribed at discharge with those who were not prescribed systemic corticosteroids at discharge. The primary outcomes were asthma control after discharge, as defined by the Asthma Control Test (ACT), and missed school days, which we modeled with multivariable linear and Poisson regression, respectively. Results: A total of 56 patients were included in the study, 29 (52%) received dexamethasone inpatient and then were discharged without additional prescribed systemic corticosteroids. Those without a corticosteroid prescription at discharge were less likely to have received noninvasive ventilation (p = 0.02), pulmonology consultation (p = 0.02), and continuous albuterol (p = 0.01) during hospitalization. These patients also tended toward shorter length of stay (p = 0.07) compared to those receiving systemic corticosteroid prescription at discharge. In multivariable models, being discharged without systemic corticosteroid prescription was associated with poorer asthma control after discharge [beta (95% CI), –2.21 (–2.65 to –1.77)] and more missed school days [coefficient estimate (95% CI), 0.87 (0.07–1.68)]. Conclusions After hospitalization for an asthma exacerbation, patients not given systemic corticosteroids at discharge tended to have worse asthma control following discharge despite having less severe disease and requiring less aggressive inpatient management. Supplemental data for this article can be accessed at publisher’s website.

Montelukast and Neuropsychiatric Events in Children With Asthma: A Nested Case-Control Study

SD Glockler-Lauf, Y Finkelstein, J Zhu, LY Feldman, T To. J Pediatr. 2019;209:176–182.e4 To assess the association between montelukast prescription and neuropsychiatric events in children with asthma. Ontario children aged 5–18 years with an index neuropsychiatric event between April 1, 2004, and March 31, 2016, were identified as cases within a study cohort of children with physician-diagnosed asthma prescribed an asthma maintenance medication. Patients with pre-existing mental health conditions or a dispensed prescription for zafirlukast were excluded. Each case was matched based on sex, asthma diagnosis date, and birthdate to a maximum of four control patients without a neuropsychiatric event from the same study cohort. …

Systemic Corticosteroid Use after Central Serous Chorioretinopathy Diagnosis

To analyze the frequency of systemic corticosteroid prescriptions before and after central serous chorioretinopathy (CSC) diagnosis. Retrospective claims-based analysis. A nationally representative sample of commercial insurance beneficiaries who received care between 2007 and2015. We limited the study population to beneficiaries with incident CSC diagnosed by an eye care provider, excluding those with other major ophthalmologic comorbidities. We developed a non-CSC comparison cohort matched to CSC patients by age, sex, general health (Charlson Comorbidity Index), and geographic region. We compared systemic corticosteroid prescriptions before and after CSC diagnosis and by diagnosing provider (optometrist vs. ophthalmologist) and evaluated likelihood of steroids treatment among CSC versus matched control patients using logistic and Cox proportional hazard regression models. Systemic corticosteroid prescription frequency among CSC patients within 12 months pre-diagnosis and at 6, 12, and 24 months post-diagnosis, median time to steroid initiation and discontinuation, and odds of receiving steroids post-diagnosis among CSC and control patients. We identified 3418 CSC patients. Nearly 39% (n= 1326) were prescribed systemic steroids at some point during the analysis period, versus 23% of controls (4033 of 17 178 patients). Over 12% of CSC patients (n= 430) within 1 year pre-diagnosis, and nearly 12% (n=404) within 1 year post-diagnosis. Most patients who received steroids after diagnosis were steroid naive (n= 231). Among those receiving steroids, CSC patients demonstrated longer median time to first post-diagnosis steroid prescription (1.82 years vs. 0.50 years for non-CSC patients) and longer time to last steroid prescription (1.62 years vs. 0.35 years for non-CSC patients). Although CSC patients were significantly less likely to receive steroids within 6 months post-diagnosis compared with non-CSC patients (odds ratio, 0.72; 95% confidence interval, 0.59-0.89), they were significantly more likely to receive steroids by 2 years post-diagnosis. Prescribing patterns were similar for patients diagnosed by an ophthalmologist versus optometrist. Despite evidence showing that steroids contribute to CSC development, many patients continue to be prescribed systemic corticosteroids after CSC diagnosis. Our results suggest a need for greater communication and collaboration among providers to ensure that clinical practice reflects evidence-based recommendations.

Clinical and economic analysis of Reslizumab use in the treatment of patients with severe allergic eosinophilic asthma

Comparative clinical and economic analysis of reslizumab use in patients with allergic asthma and eosinophilia. Omalizumab was chosen as a reference drug, because until now it was the only MAb for the treatment of severe asthma in Russia. The study population included patients with allergic asthma with both high levels of IgE and high eosinophil counts in peripheral blood, i.e. individuals eligible for both omalizumab and reslizumab treatment. A decrease in the number of exacerbations requiring prescription of systemic corticosteroids and an increase in QALY index was used as efficacy criteria. An indirect comparative study was used, because no direct comparison has been conducted to date. As a result, reslizumab demonstrated a statistically significant reduction in the frequency of clinically significant asthma exacerbations compared with omalizumab. The utility of the both asthma treatment strategies was compared using Markov models, taking into account the frequency of exacerbations, their severity, as well as decrease in QALYs due to exacerbations. The time horizon was 12 months. Reslizumab treatment was 37.2% less expensive compared with omalizumab for the patients who are equally eligible for the both drugs. The calculated cost - effectiveness and cost - utility ratios were in favor of reslizumab. Budget impact analysis showed a significant effect of reslizumab on reducing budget costs. If reslizumab is used in 4250 patients (an estimated number of patients with severe allergic asthma and eosinophilia in Russia), this would reduce the costs for their treatment by up to 4896 million rubles per year. For patients with severe allergic eosinophilic asthma who are equally eligible for the both drugs, reslizumab can be considered a more reasonable medical technology in terms of pharmacoeconomics when compared with omalizumab.

Association of Metformin Initiation and Risk of Asthma Exacerbation. A Claims-based Cohort Study.

Rationale: Diabetes and metabolic syndrome have been associated with worsened asthma control. Metformin improves insulin resistance and metabolic function. Experimental studies suggest that metformin may improve pathologic features of asthma, but evidence of clinical benefit is limited.Objectives: To determine if treatment with metformin in a cohort of individuals with asthma and diabetes is associated with lower risk of asthma exacerbation.Methods: A 6-year retrospective cohort of individuals over age 18 with asthma and diabetes was assembled from a national administrative claims database. New users of metformin were matched to nonusers by propensity score on the basis of demographic, comorbidity, and medication-use characteristics. An exacerbation was defined as an asthma-related hospitalization, emergency department visit, or filling of a systemic corticosteroid prescription within 14 days of an asthma-related ambulatory visit. Cox proportional hazards estimated the change in hazard of asthma exacerbation associated with metformin initiation.Results: In a cohort of 23,920 individuals with asthma and diabetes, metformin initiation was associated with lower hazard of asthma exacerbation (hazard ratio [HR], 0.92; 95% confidence interval [CI], 0.86-0.98), driven by lower hazards of asthma-related emergency department visits (HR, 0.81; 95% CI, 0.74-0.88) and hospitalization (HR, 0.67; 95% CI, 0.50-0.91), without differences in corticosteroid use (HR, 0.96; 95% CI, 0.86-1.03).Conclusions: In an administrative cohort of individuals with asthma and diabetes, metformin initiation was associated with a lower hazard of asthma-related emergency department visits and hospitalizations. These findings suggest a possible benefit of metformin in more severe asthma exacerbations. Investigation within cohorts with more detailed participant characterization is necessary.

Efficacy of Intravenous Reslizumab in Oral Corticosteroid–Dependent Asthma

Reslizumab displays efficacy in patients with inadequately controlled eosinophilic asthma; previous reports in oral corticosteroid-dependent asthma are limited. To assess efficacy of reslizumab in oral corticosteroid-dependent patients and benefits on oral corticosteroid burden. We report post hoc analyses of pooled data from duplicate, placebo-controlled phase 3 trials. Patients aged 12 to 75 years with inadequately controlled, moderate-to-severe asthma were randomized 1:1 to receive intravenous reslizumab 3.0 mg/kg or placebo every 4 weeks for 52 weeks, stratified by oral corticosteroid use at enrollment and by region. Assessments included efficacy and predictors of clinical asthma exacerbation response in oral corticosteroid-dependent patients, and systemic corticosteroids burden in the overall population. Patients were randomized to reslizumab (n= 477) or placebo (n= 476); 73 (15%) patients in each group were taking oral corticosteroids at baseline. Reslizumab was favored over placebo for all efficacy end points in oral corticosteroid-dependent patients, with numerically greater improvements in oral corticosteroid-dependent patients than the overall population. Having 2 or more versus 1 clinical asthma exacerbation in the previous 12 months was the strongest positive predictor of reduced exacerbation risk with reslizumab (risk reduction, 77.5% vs 15.2%; P ≤ .02). Significantly fewer new systemic corticosteroid prescriptions were issued per patient receiving reslizumab versus placebo (mean ± SD, 0.5 ± 1.07 vs 1.0 ± 1.52; P < .0001). Total and per-patient systemic corticosteroid burdens were lower: 121,135 versus 290,977 mg and 254 versus 611 mg/patient, respectively (both P < .0001). Oral corticosteroid-dependent patients benefited from reslizumab across asthma efficacy outcome measures. Reslizumab-treated patients required fewer new systemic corticosteroid prescriptions and had a lower systemic corticosteroid burden compared with placebo.

Adverse outcomes from initiation of systemic corticosteroids for asthma: long-term observational study.

PurposePrior work suggests a threshold of four courses/year of systemic corticosteroid (SCS) therapy is associated with adverse consequences. The objective of this study was to investigate the onset of adverse outcomes beginning at SCS initiation in a broad asthma population.Patients and methodsThis historical matched cohort study utilized anonymized, longitudinal medical record data (1984–2017) of patients (≥18 years) with active asthma. Matched patients with first SCS prescription (SCS arm) and no SCS exposure (non-SCS arm) were followed until first outcome event. Associations between time-varying exposure measures and onset of 17 SCS-associated adverse outcomes were estimated using Cox proportional hazard regression, adjusting for confounders, in separate models.ResultsWe matched 24,117 pairs of patients with median record availability before SCS initiation of 9.9 and 8.7 years and median follow-up 7.4 and 6.4 years in SCS and non-SCS arms, respectively. Compared with patients in the non-SCS arm, patients prescribed SCS had significantly increased risk of osteoporosis/osteoporotic fracture (adjusted hazard ratio 3.11; 95% CI 1.87–5.19), pneumonia (2.68; 2.30–3.11), cardio-/cerebrovascular diseases (1.53; 1.36–1.72), cataract (1.50; 1.31–1.73), sleep apnea (1.40; 1.04–1.86), renal impairment (1.36; 1.26–1.47), depression/anxiety (1.31; 1.21–1.41), type 2 diabetes (1.26; 1.15–1.37), and weight gain (1.14; 1.10–1.18). A dose-response relationship for cumulative SCS exposure with most adverse outcomes began at cumulative exposures of 1.0–<2.5 g and for some outcomes at cumulative exposures of only 0.5–<1 g (vs >0–<0.5 g reference), equivalent to four lifetime SCS courses.ConclusionOur findings suggest urgent need for reappraisal of when patients need specialist care and consideration of nonsteroid therapy.