Reduction In Oral Corticosteroid Use Research Articles

Factors Affecting the Ability to Discontinue Oral Corticosteroid Use in Patients with EGPA Treated with Anti-Interleukin-5 Therapy

Introduction: Patients with eosinophilic granulomatosis with polyangiitis (EGPA) and some with severe eosinophilic asthma require continuous long-term oral corticosteroid (OCS) treatment for disease control. The anti-interleukin-5 agent, mepolizumab, has recently become available for the treatment of severe eosinophilic asthma and EGPA, with promising results and safety profiles. The proportion of patients with EGPA who discontinued oral steroids was 18% in the MIRRA trial. To compare patients with EGPA who were able to discontinue steroids with mepolizumab with those who could not. Methods: Twenty patients with EGPA treated with mepolizumab were evaluated at Osaka Habikino Medical Center. The OCS dose, asthma control test score, fractional exhaled nitric oxide levels, peripheral eosinophil count, and spirometric parameters were evaluated before and after treatment. Results: There was a significant reduction in the mean OCS dose from a prednisolone equivalent of 8.88 ± 4.99 mg/day to 3.18 ± 3.47 mg/day (p < 0.001). In this study, 40% of patients discontinued oral steroids. The most common reason for the failure to discontinue steroids in patients was poor asthma control. The percentage of predicted forced expiratory volume in 1 s significantly improved in patients with EGPA who could discontinue steroids after receiving mepolizumab. Conclusion: In this real-world study, treatment with mepolizumab for EGPA was associated with a significant reduction in OCS use; however, poor asthma control was identified as an inhibiting factor for steroid reduction.

CO124 Real-World Reduction of Oral Corticosteroid Use in Patients Treated with Dupilumab and with Moderate-to-Severe Asthma

Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin-4/-13, key and central drivers of type 2 inflammation in asthma. Patients with oral corticosteroid (OCS)-dependent severe asthma are at increased risk of OCS-related adverse events. This real-world analysis investigated the reduction in OCS use in patients treated with dupilumab, both overall cohort and with OCS-dependent severe asthma.

Safety and Efficacy of Mepolizumab in Hypereosinophilic Syndrome: An Open-Label Extension Study

A double-blind, placebo-controlled, phase III study (200622) showed that mepolizumab reduces disease flares for patients with uncontrolled FIP1-like-1-platelet-derived growth factor receptor α-negative hypereosinophilic syndrome (HES) and two or more flares in the previous year. To further characterize the safety, clinical benefit, and pharmacodynamics of mepolizumab. Eligible patients from both treatment arms of the double-blind study could enter an open-label extension study (205203; NCT03306043) to receive 4-weekly mepolizumab (300mg subcutaneously) plus background therapy for 20 weeks. Primary end points were safety-based; other end points included flare rates and changes from baseline in mean daily oral corticosteroid (OCS) dose and blood eosinophil count. Of 104 patients who completed the double-blind study, 98% (previous placebo, n= 52; previous mepolizumab, n= 50) enrolled in the open-label extension. Overall, 66 of patients reported adverse events (AEs) (65%), 15 reported treatment-related AEs (15%), and nine reported serious AEs (9%). No events were fatal. The annualized flare rate (95% confidence interval) in the previous placebo and previous mepolizumab groups was 0.37 (0.16-0.86) and 0.14 (0.04-0.49) events/y, respectively. Of 72 patients receiving OCS during weeks 0 to 4, 20 (28%; previous placebo, n= 14; previous mepolizumab, n= 6) achieved 50% or greater reductions in mean daily dose during weeks 16 to 20. At week 20, blood eosinophil count was reduced by 89% in patients previously receiving placebo and remained reduced for those previously receiving mepolizumab. Extended mepolizumab treatment was associated with a positive benefit-risk profile. Continued control of disease flares and blood eosinophil counts, plus reductions in OCS use, were observed with mepolizumab in patients with FIP1-like-1-platelet-derived growth factor receptor α-negative HES.

Real-World Reductions in Oral Corticosteroid Use in the USA Following Mepolizumab Therapy for Severe Asthma.

BackgroundPatients with severe asthma often require oral corticosteroid (OCS) treatment. Clinical trials have demonstrated that mepolizumab can reduce OCS dependence, but real-world data are limited.ObjectiveTo evaluate the impact of mepolizumab on OCS use, asthma exacerbations, and asthma exacerbation-related costs in a real-world setting.MethodsThis retrospective cohort study (GSK ID: 209642; HO-19-19597) analyzed data from the MarketScan® Commercial database (identification period: November 2015–September 2017). Patients were ≥12 years old at mepolizumab initiation (index date), had a baseline asthma diagnosis, and received ≥2 mepolizumab administrations in the first 6 months of follow-up. OCS use, asthma exacerbation rate, and asthma exacerbation-related costs were assessed in the 12-months before (baseline) and 12-months after (follow-up) mepolizumab initiation.ResultsMepolizumab was associated with a 14.7% reduction in the proportion of patients with ≥1 OCS claim from baseline to follow-up (93.4% vs 79.7%; P<0.001). The mean numbers of OCS claims/patient and OCS bursts (≥20 mg prednisone equivalents for 3‒28 days) between baseline and follow-up were also reduced by 29.1% (P<0.001) and 36.8% (P<0.001), respectively. Reductions in chronic OCS use were demonstrated during follow-up in patients with baseline mean OCS dose ≥5mg and those with a mean OCS dose ≥10mg 90 days before index; the proportion of patients with no OCS use also increased from 6.6% to 20.3% between baseline and follow-up.ConclusionOur findings demonstrate that mepolizumab therapy is associated with reduced OCS use in patients treated in a real-world setting, potentially mitigating adverse health sequelae caused by OCS use in these patients.

Treatment response with mepolizumab in severe eosinophilic asthma patients with previous omalizumab treatment.

BackgroundWe performed post hoc analyses to evaluate the effect of humanized monoclonal antibody mepolizumab in patients with severe eosinophilic asthma previously treated with omalizumab.MethodsData were collected from two randomized double‐blind, placebo‐controlled studies: MENSA (NCT01691521: 32‐week treatment phase) and SIRIUS (NCT01691508: 24‐week treatment phase). Active treatment was 75 mg intravenous mepolizumab (MENSA) or 100 mg subcutaneous mepolizumab (MENSA, SIRIUS). Patients had evidence of eosinophilic inflammation ≥150 cells/μl (at screening) or ≥300 cells/μl (during the previous year). Primary outcomes were the rate of exacerbations (MENSA) and the percentage reduction in oral corticosteroid (OCS) dose (SIRIUS). Other outcomes included lung function (forced expiratory volume in 1 s and morning peak expiratory flow), Asthma Control Questionnaire (ACQ‐5), St George's Respiratory Questionnaire (SGRQ) scores, and safety.ResultsOverall, 576 patients were included from MENSA and 135 from SIRIUS, with 13% and 33% previously receiving omalizumab, respectively. In MENSA, mepolizumab reduced the rate of exacerbations by 57% (prior omalizumab) and 47% (no prior omalizumab) vs placebo. In SIRIUS, reductions in OCS use were comparable regardless of prior omalizumab use. Despite reducing chronic OCS use, mepolizumab also resulted in similar reductions in exacerbation rate relative to placebo in both subgroups. Asthma control and quality of life improved with mepolizumab vs placebo in both studies independent of prior omalizumab use, as shown by ACQ‐5 and SGRQ scores. Adverse events were also comparable irrespective of prior omalizumab use.ConclusionsThese post hoc analyses indicate that patients with severe eosinophilic asthma respond positively to mepolizumab regardless of prior use of omalizumab.

Reduction in oral corticosteroid use in patients receiving omalizumab for allergic asthma in the real-world setting

BackgroundOral corticosteroids (OCS) are commonly administered in patients with severe persistent allergic asthma. Despite their efficacy, they are associated with a wide variety of adverse events. The eXpeRience registry was set up to investigate real-world outcomes among patients receiving omalizumab for the treatment of uncontrolled allergic asthma. Here, we present the effect of omalizumab treatment on OCS use.MethodseXpeRience was a 2-year, multinational, non-interventional, observational registry of patients receiving omalizumab for uncontrolled allergic asthma. OCS use (proportion of patients on maintenance OCS, mean total daily OCS dose and change in status of OCS therapy) was assessed at baseline, 16 weeks, and 8, 12, 18, and 24 months after the initiation of omalizumab. Response to omalizumab was assessed using the physician’s Global Evaluation of Treatment Effectiveness (GETE) at approximately Week 16. Safety data were also recorded.ResultsA total of 943 patients (mean age, 45 years; female, 64.9%) were enrolled in the registry, 263 of whom were receiving maintenance OCS at baseline. The proportion of patients taking maintenance OCS was markedly lower at Months 12 (16.1%) and 24 (14.2%) than at baseline (28.6%; intent-to-treat population). GETE status was determined in 915 patients receiving omalizumab: 64.2% were responders (excellent or good response), 30.7% were non-responders (moderate, poor or worsening response); 5.1% had no assessment. The frequency of serious adverse events was comparable to that seen in controlled trials of omalizumab.ConclusionsOmalizumab use is associated with an OCS-sparing effect in patients with uncontrolled persistent allergic asthma in the real-world setting.

Reduction in oral corticosteroid use in patients with severe allergic (IgE‐mediated) asthma receiving omalizumab in a real‐world setting

Background Patients with severe allergic asthma (SAA) are often inadequately controlled despite available treatments including high-dose inhaled corticosteroids and longacting b2-agonists. Use of oral corticosteroids (OCS) in SAA patients may not achieve full asthma control, and leads to significant long-term side effects. Omalizumab is a recombinant humanized monoclonal anti-immunoglobulin E (IgE) antibody approved in the European Union as an add-on therapy for patients with SAA. In clinical studies, omalizumab has been shown to reduce OCS use. Here we report the effect of omalizumab treatment on OCS maintenance use for up to 24 months in patients with SAA in the real-world eXpeRience registry.

PRS6 Impact of Omalizumab on Emergency-Department Visits, Hospitalizations and Corticosteroid Use in Patients with Uncontrolled Asthma Using High-Dose Inhaled Corticosteroids

This study evaluated the impact of omalizumab on emergency-department (ED) visits, hospitalizations and corticosteroid use among uncontrolled asthma patients using high-dose inhaled corticosteroids (ICS) prior to initiating omalizumab. Health insurance claims from the MarketScan database (2002Q1-2009Q1) were analyzed. Patients with ≥12 months of continuous insurance coverage prior to and after the first omalizumab dispensing, ≥8 weeks of high-dose ICS use, ≥8 weeks of long-acting beta2-agonist (LABA) use, and uncontrolled asthma at baseline were included. A retrospective analysis was conducted to quantify the impact of omalizumab on resource use by comparing ED visits, hospitalizations, and corticosteroid use one year before and after omalizumab initiation. A one-year period was chosen to cover any potential seasonality impacts. A total of 644 patients (mean age: 49.9; female: 59.2%) formed the study population. Omalizumab was associated with a 48.6% reduction in the proportion of patients with ≥1 asthma-related ED visits (pre vs. post-omalizumab period: 21.4% vs. 11.0%, P<0.001) and 40.8% reduction in asthma-related hospitalizations (25.0% vs. 14.8%, respectively, P<0.001). Compared to the pre-omalizumab period, the use of ICS decreased significantly after omalizumab initiation (7.8 vs. 6.5 dispensings, P<0.001; 41.9% of patients had a reduction in ICS use). A similar reduction in oral corticosteroid use was observed (5.0 vs. 3.6 dispensings, P<.001; 53.3% of patients had a reduction in oral corticosteroid use). The results of the current study showed that omalizumab treatment initiation was associated with statistically significant reductions in ED visits, hospitalizations and corticosteroid use.

Impact of omalizumab on emergency-department visits, hospitalizations, and corticosteroid use among patients with uncontrolled asthma

Omalizumab is a monoclonal antibody indicated for moderate to severe allergic asthma patients with inadequately controlled symptoms. To evaluate the impact of omalizumab on emergency department (ED) visits, hospitalizations, and corticosteroid use among patients with uncontrolled asthma using high-dose inhaled corticosteroids (ICS) and long-acting beta2-agonists (LABA). Health insurance claims from the MarketScan database (2002Q1-2009Q1) were analyzed. Patients with 12 months or more of continuous insurance coverage before and after the first omalizumab dispensing, 8 or more weeks of high-dose ICS use, 8 or more weeks of LABA use, and uncontrolled asthma at baseline were included. A retrospective analysis was conducted to quantify the impact of omalizumab on resource use by comparing ED visits, hospitalizations, and corticosteroid use 1 year before and after omalizumab initiation. A 1-year period was chosen to cover any potential seasonality impacts. In total, 644 patients (mean age, 49.9; female, 59.2%) formed the study population. Omalizumab was associated with a 48.6% reduction in the proportion of patients with 1 or more asthma-related ED visits (pre vs post-omalizumab period: 21.4% vs 11.0%; P < .001) and a 40.8% reduction in asthma-related hospitalizations (25.0% vs 14.8%, respectively, P < .001). Compared with the pre-omalizumab period, the use of ICS decreased significantly after omalizumab initiation (7.8 vs 6.5 dispensings, P < .001; 41.9% of patients had a reduction in ICS use). A similar reduction in oral corticosteroid use was observed (5.0 vs 3.6 dispensings, P < .001; 53.3% of patients had a reduction in oral corticosteroid use). The current analysis showed that omalizumab treatment initiation was associated with significant reductions in ED visits, hospitalizations, and corticosteroid use.

Reductions In Oral Corticosteroid Use In Patients With Allergic (IgE- Mediated) Asthma Receiving Omalizumab

Reductions In Oral Corticosteroid Use In Patients With Allergic (IgE- Mediated) Asthma Receiving Omalizumab

Oral corticosteroid-sparing effects of inhaled corticosteroids in the treatment of persistent and acute asthma

To review the efficacy and safety of inhaled corticosteroids (ICSs) when used to reduce daily oral corticosteroid (OCS) requirements in patients with severe persistent asthma and periodic requirements in patients with acute asthma exacerbations. Clinical studies of the OCS-sparing effects of ICSs were located by searching MEDLINE databases from 1966 onward using the terms oral, steroid, and asthma in combination with the generic names for each marketed ICS. Studies reporting on the use of ICSs to reduce OCS requirements in patients with persistent and acute asthma are included. Clinical study results consistently show that ICSs significantly improve asthma control and reduce OCS requirements among adults, children, and infants with persistent asthma. A dose reduction or complete discontinuation of use of OCSs is possible in most patients without loss of asthma control. ICSs also can control asthma during acute asthma exacerbations and reduce the need for short courses of OCSs. With many ICSs, the reductions in OCS use are accompanied by recovery of hypothalamic-pituitary-adrenal axis function, indicating that the safety of asthma therapy is improved when OCS requirements are decreased with ICSs. Of the available ICSs that may reduce OCS needs, budesonide appears to be the most intensively studied. ICSs can reduce OCS requirements in adults and children with persistent asthma and during acute asthma exacerbations. The reduced systemic corticosteroid activity associated with ICS treatment improves the overall safety of asthma therapy.

Reduction in Oral Corticosteroid Use with Mometasone Furoate Dry Powder Inhaler Improves Health-Related Quality of Life in Patients with Severe Persistent Asthma

Severe persistent asthma can have a substantial impact on a patient's health-related quality of life (HRQL), both as a result of symptoms and from side effects of treatment. The HRQL impact of two doses (400 and 800 µg twice daily) of mometasone furoate dry powder inhaler (MF DPI) was compared with placebo in patients with severe persistent asthma previously maintained on oral steroids as a component of a previously published randomized, 12-week, double-blind, placebo-controlled, multicenter trial. A 9-month open-label extension (OLE), with all patients treated with MF DPI, followed. Patients 12 years of age or older completed a generic HRQL measure, the Medical Outcomes Trust Short Form-36 (SF-36), and an asthma-specific measure, the Marks Asthma Quality of Life Questionnaire (AQLQ-M), at baseline, at endpoint (last evaluable visit) of the double-blind phase (EODBP), and after the first 3 months of the OLE. Of 132 patients enrolled in the study, 128 provided HRQL data at baseline and at EODBP. Mean SF-36 scores at baseline showed significant HRQL impairment compared with U.S. general population norms. With treatment, the reduction in oral corticosteroid (OCS) requirements of the MF-DPI–treated groups was accompanied by significant (p < 0.05) improvement over placebo in the physical domain of HRQL (SF-36 physical component summary score and the physical function subscale) at EODBP. MF-DPI–treated patients also showed significant improvements at EODBP in each of the four subscales of the AQLQ-M (p < 0.05). From EODBP to the OLE 3-month endpoint, patients treated with MF DPI twice daily maintained, or improved, SF-36 scores in most domains. Symptomatic improvement and reduction in OCS use with MF DPI were accompanied by significant improvement in HRQL in patients with severe persistent asthma. These improvements were maintained during the 3-month period of the OLE in which HRQL was evaluated.

Asthma therapies and churg-strauss syndrome

The pulmonary vasculitides are a group of rare but serious disorders that require early recognition, accurate diagnosis, and effective therapy. Churg-Strauss syndrome (CSS) is classified as small vessel vasculitis. Four different definitions for the diagnosis of CSS have been developed: (1) the pathologic criteria put forth by Churg and Strauss, (2) the criteria based on clinical grounds from Lanham and colleagues, (3) the criteria based on clinical grounds from the American College of Rheumatology, and (4) the criteria from the Chapel Hill Consensus Conference, which closely concur with the Churg and Strauss definition. It is apparent that cessation, diminution, or even a switch from low-dose systemic to inhaled corticosteroid therapy can precipitate the appearance of CSS. The term forme fruste has been used to indicate that the signs and symptoms of CSS were (inadvertently) suppressed by cortico-steroids. The clinical risk factors for CSS are moderately severe or severe asthma, chronic sinusitis, or reductions in systemic corticosteroid therapy. Differential diagnosis, treatment, and ongoing monitoring of CSS therapeutic responses are reviewed. The introduction of leukotriene modifiers and high-potency inhaled corticosteroids have allowed control of asthma symptoms, which results in avoidance or reduction in oral corticosteroid use. The advent of these agents has been associated with reports of CSS appearing in patients with asthma. The available data regarding the association of CSS and antiasthma agents are most consistent with the unmasking of a previously contained pathologic condition (forme-fruste CSS) or disease that progresses because systemic corticosteroids were avoided. Early recognition and immunosuppressive therapy are the keystones of successful treatment of this rare disorder (J Allergy Clin Immunol 2002;109:S1-20).

Pharmacologic management of asthma

Therapy for asthma has largely been focused on the end-organ effect of bronchoconstriction on airway smooth muscle. Xanthine derivatives such as theophylline were the initial oral bronchodilators used to manage asthma. Recent therapies directed at airway smooth muscle relaxation promote bronchodilation through stimulation of the b-adrenoreceptor. 1 The pharmacologic evolution of b-adrenergic agonists has led to the development of airway smooth muscle receptor‐specific agents, agents that can be administered topically through aerosol inhalation, and agents that are long lasting. Epidemiologic studies have validated the safety of the long-acting b-adrenoreceptor drugs and established that tachyphylaxis, as measured by the direct bronchodilating effect of these agents after repeated use, is inconsequential. More recently, the focus of asthma therapy development has been on modification of the inflammatory component of this disorder. 2 Oral corticosteroids cause substantial improvement in objective measures of lung function, but these agents are associated with considerable toxicity. 3, 4 The development of potent, highly lipidsoluble agents permits twice-daily dosage and may lead to a reduction in oral corticosteroid use in patients with corticosteroid-dependent asthma. Furthermore, inhaled corticosteroids provide an effective means of managing the pathology of inflammation with minimal adverse effects. With the enhanced understanding of asthma pathophysiology, drugs now are being designed to act against different steps in the inflammatory process. Newer agents include those directed at antagonizing the effects of leukotrienes that are secreted from inflammatory cells. These include two classes: 5-lipoxygenase inhibitors and leukotriene receptor antagonists. A number of other therapies are currently in development. Some of these interventions (e.g., monoclonal antibodies) prevent adhesion of inflammatory cells to vascular endothelium in conducting airways. Other mechanisms of action of investigational agents include modification of Thelper (TH2) cell interactions that trigger inflammatory activation, suppression of eosinophil development, and induction of eosinophil apoptosis in the bone marrow. PATHOPHYSIOLOGY