scholarly journals Health outcomes after stopping long-term mepolizumab in severe eosinophilic asthma: COMET

2021 ◽  
pp. 00419-2021
Author(s):  
Mark C Liu ◽  
Elisabeth H Bel ◽  
Oliver Kornmann ◽  
Wendy C Moore ◽  
Norihiro Kaneko ◽  
...  
Keyword(s):  
Health Outcomes ◽  
Healthcare Resource ◽  
Asthma Severity ◽  
Response To Therapy ◽  
Open Label ◽  
Eosinophilic Asthma ◽  
Severe Eosinophilic Asthma ◽  
Link Type ◽  
Increased Risk

AbstractAsthma worsening and symptom control are clinically important health outcomes in patients with severe eosinophilic asthma. This analysis of COMET evaluated whether stopping versus continuing long-term mepolizumab therapy impacted these outcomes.Patients with severe eosinophilic asthma with ≥3 years continuous mepolizumab treatment (via COLUMBA [NCT01691859] or COSMEX [NCT02135692] open label studies) were eligible to enter COMET (NCT02555371), a randomised, double-blind, placebo-controlled study. Patients were randomised 1:1 to continue mepolizumab 100 mg subcutaneous every four weeks or stop mepolizumab, plus standard of care asthma treatment. Patients could switch to open label mepolizumab following an exacerbation. Health outcome endpoints included time to first asthma worsening (composite endpoint: rescue use, symptoms, awakening at night and morning PEF), patient and clinician assessed global rating of asthma severity and overall perception of response to therapy, and unscheduled healthcare resource utilisation.Patients who stopped mepolizumab showed increased risk of and shorter time to first asthma worsening compared with those who continued mepolizumab (Hazard Ratio [HR]:1.71 [95% CI: 1.17 2.52] p=0.006), including reduced asthma control (increased risk of first worsening in rescue use [HR:1.36 (95% CI 1.00 1.84) p=0.047] and morning PEF [HR:1.77 (95% CI 1.21 2.59) p=0.003]). There was a higher probability of any unscheduled healthcare resource use (HR:1.81 [95% CI: 1.31 2.49]; p<0.001) and patients and clinicians reported greater asthma severity and less favourable perceived response to therapy for patients who stopped versus continued mepolizumab.These data suggest that patients with severe eosinophilic asthma continuing long-term mepolizumab treatment sustain clinically important improvements in health outcomes.

scholarly journals Stopping versus continuing long-term mepolizumab treatment in severe eosinophilic asthma (COMET study)

2021 ◽  
pp. 2100396
Author(s):  
Wendy C. Moore ◽  
Oliver Kornmann ◽  
Marc Humbert ◽  
Claude Poirier ◽  
Elisabeth H. Bel ◽  
...  
Keyword(s):  
Emergency Department ◽  
Asthma Control ◽  
Emergency Department Visit ◽  
Hazard Ratio ◽  
Blood Eosinophil ◽  
Eosinophilic Asthma ◽  
Severe Eosinophilic Asthma ◽  
Link Type ◽  
Clinically Significant

The long-term efficacy and safety of mepolizumab for treatment of severe eosinophilic asthma are well established. Here, we examine the clinical impact of stopping mepolizumab after long-term use.COMET (NCT02555371) was a randomised, double-blind, placebo-controlled, parallel-group, multicenter study. Patients who had completed COLUMBA (NCT01691859) or COSMEX (NCT02135692) and received continuous mepolizumab treatment for ≥3 years were randomised 1:1 to stop (switch to placebo) or continue subcutaneous mepolizumab 100 mg every 4 weeks for 52 weeks. Primary endpoint: time to first clinically significant exacerbation; secondary endpoints: time to first exacerbation requiring hospitalisation/emergency department visit, time to decrease in asthma control (≥0.5-point increase in Asthma Control Questionnaire-5 score from COMET baseline), and blood eosinophil count ratio to COMET baseline. Safety was assessed.Patients stopping (n=151) versus continuing (n=144) mepolizumab had significantly shorter times to first clinically significant exacerbation (hazard ratio: 1.61 [95% confidence interval: 1.17,2.22]; p=0.004) and decrease in asthma control (hazard ratio: 1.52 [1.13,2.02]; p=0.005), and higher blood eosinophil counts at Week 52 (270 versus 40 cells·µL−1; ratio [stopping versus continuing]: 6.19 [4.89, 7.83]; p<0.001). Differences in efficacy outcomes between groups were observed when assessed from Week 12 (16 weeks after last mepolizumab dose). Exacerbations requiring hospitalisation/emergency department visit were rare. Adverse events in patients continuing mepolizumab were consistent with previous studies. For patients who stopped mepolizumab, the safety profile was consistent with other eosinophilic asthma populations.Patients who stopped mepolizumab had an increase in exacerbations and reduced asthma control versus those who continued.

scholarly journals Long-term Efficacy and Safety of Mepolizumab in Patients With Severe Eosinophilic Asthma: A Multi-center, Open-label, Phase IIIb Study

2016 ◽  
Vol 38 (9) ◽  
pp. 2058-2070.e1 ◽  
Author(s):  
Njira Lugogo ◽  
Christian Domingo ◽  
Pascal Chanez ◽  
Richard Leigh ◽  
Martyn J. Gilson ◽  
...  
Keyword(s):  
Efficacy And Safety ◽  
Open Label ◽  
Eosinophilic Asthma ◽  
Severe Eosinophilic Asthma ◽  
Term Efficacy ◽  
Phase Iiib ◽  
Open Label Phase

scholarly journals The effectiveness of Reslizumab in severe asthma treatment: a real-world experience

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
H. Ibrahim ◽  
R. O’Sullivan ◽  
D. Casey ◽  
J. Murphy ◽  
J. MacSharry ◽  
...  
Keyword(s):  
Severe Asthma ◽  
Asthma Severity ◽  
Oral Steroid ◽  
Eosinophilic Asthma ◽  
Interleukin 5 ◽  
Severe Eosinophilic Asthma ◽  
Prednisolone Dose ◽  
Exacerbation Frequency ◽  
Efficacy Parameters

Abstract Background Increased numbers of blood and sputum eosinophils are associated with higher exacerbation frequency and increased asthma severity. In clinical trials, targeting Interleukin-5 has been shown to be a useful therapeutic strategy for patients with severe eosinophilic asthma. Methods Twenty-six patients have been commenced on Reslizumab in our institution since early 2017. Safety and clinical efficacy parameters were recorded at regular intervals. Results Mean ACQ-6 score at the start of treatment was 3.5. The average number of exacerbations in the year preceding treatment was 8.3 per person. 30% of patients had been admitted to hospital at least once over the 12 months preceding therapy. 54% of our patients were on long term oral steroid. Our data showed sustained improvement of Asthma control (Mean improvement in ACQ-6 was 1.7 at 1 year, and 2.0 at 2 years, P = 0.0001). Of the patients who were on long term systemic steroids, 35.7% discontinued steroids completely, with a mean reduction of prednisolone dose of 5.2 mg at 1 year. There was a 79% reduction in the annual exacerbation frequency at 1 year, and 88% at 2 years (P = < 0.0001). Modest, albeit statistically significant increases in creatine kinase which seemed to plateau by 1 year were noted. Conclusions Overall, Reslizumab was well tolerated with discontinuation of treatment due to side effects recorded in only one patient. Our data confirm the utility of anti-IL5 therapy in a carefully selected phenotype of severe asthma with evidence of eosinophilic airway inflammation.

scholarly journals Long-Term Physical Health Outcomes of Resettled Refugee Populations in the United States: A Scoping Review

2021 ◽  
Author(s):  
Gayathri S. Kumar ◽  
Jenna A. Beeler ◽  
Emma E. Seagle ◽  
Emily S. Jentes
Keyword(s):  
Health Outcomes ◽  
Physical Health ◽  
Public Health Practice ◽  
The United States ◽  
Inclusion Criteria ◽  
Physical Health Outcomes ◽  
Increased Risk ◽  
The Us ◽  
Bhutanese Refugee

AbstractSeveral studies describe the health of recently resettled refugee populations in the US beyond the first 8 months after arrival. This review summarizes the results of these studies. Scientific articles from five databases published from January 2008 to March 2019 were reviewed. Articles were included if study subjects included any of the top five US resettlement populations during 2008–2018 and if data described long-term physical health outcomes beyond the first 8 months after arrival in the US. Thirty-three studies met the inclusion criteria (1.5%). Refugee adults had higher odds of having a chronic disease compared with non-refugee immigrant adults, and an increased risk for diabetes compared with US-born controls. The most commonly reported chronic diseases among Iraqi, Somali, and Bhutanese refugee adults included diabetes and hypertension. Clinicians should consider screening and evaluating for chronic conditions in the early resettlement period. Further evaluations can build a more comprehensive, long-term health profile of resettled refugees to inform public health practice.

Biologics for oral corticosteroid-dependent asthma

2020 ◽  
Vol 41 (3) ◽  
pp. 151-157
Author(s):  
İnsu Yılmaz
Keyword(s):  
Severe Asthma ◽  
Oral Corticosteroid ◽  
Real Life ◽  
Severe Atopic Dermatitis ◽  
Double Blind ◽  
Eosinophilic Asthma ◽  
Asthma Phenotype ◽  
Severe Eosinophilic Asthma ◽  
Term Administration

Background: Oral corticosteroid (OCS) dependent asthma is one of the severe asthma phenotypes that requires personalized treatment. Objective: To review the role of biologic treatments in OCS-dependent asthma. Methods: A nonsystematic review was performed of emerging multiple novel biologics for potential treatment of OCS-dependent asthma. Results: The serious adverse effects of OCS can be seen as a result of their regular long-term administration. Anti‐interleukin (IL) 5 (mepolizumab), anti‐IL-5R (benralizumab), and anti‐IL-4Rα (dupilumab) are the therapies of choice for OCS-dependent severe asthma. Results of studies showed the efficacy of mepolizumab, benralizumab, and dupilumab, especially in patients with the OCS-dependent severe eosinophilic asthma phenotype and with nasal polyps. Dupilumab may be the therapy of choice of monoclonal antibodies in cases of moderate-severe atopic dermatitis accompanied by OCS-dependent severe asthma. For reslizumab and omalizumab, placebo controlled double-blind studies conducted with OCS-dependent patient populations are needed. Conclusion: Biologics are effective in the “OCS-dependent asthma” phenotype as add-on therapy. It seems that chronic OCS use in OCS-dependent asthma will be replaced by biologic agents that specifically target type 2 inflammation, along with a much better safety profile. However, real-life studies that compare these biologics in OCS-dependent severe asthma are urgently needed.

scholarly journals Corticosteroid tapering with benralizumab treatment for eosinophilic asthma: PONENTE Trial

2019 ◽  
Vol 5 (3) ◽  
pp. 00009-2019 ◽  
Author(s):  
Andrew Menzies-Gow ◽  
Jonathan Corren ◽  
Elisabeth H. Bel ◽  
Jorge Maspero ◽  
Liam G. Heaney ◽  
...  
Keyword(s):  
Adrenal Insufficiency ◽  
Asthma Control ◽  
Severe Asthma ◽  
Maintenance Phase ◽  
Phase Iii ◽  
Eosinophilic Asthma ◽  
Interleukin 5 ◽  
Severe Eosinophilic Asthma ◽  
Link Type ◽  
Related Quality

Benralizumab is an interleukin-5 receptor α-directed cytolytic monoclonal antibody approved in several countries for the add-on maintenance treatment of patients with severe eosinophilic asthma aged 12 years and older. In the 28-week Phase III ZONDA trial (ClinicalTrials.gov identifier: NCT02075255), benralizumab produced a median 75% reduction from baseline in oral corticosteroid (OCS) dosage (versus 25% for placebo) while maintaining asthma control for patients with OCS-dependent severe asthma. This manuscript presents the detailed protocol for the Phase IIIb PONENTE (ClinicalTrials.gov identifier: NCT03557307), a study that will build on the findings from ZONDA.As the largest steroid-sparing study undertaken in severe asthma, PONENTE has a faster steroid tapering schedule for prednisone dosages ≥7.5 mg·day−1 than previous studies, and it includes an evaluation of adrenal insufficiency and an algorithm to taper OCS dosage when prednisone dosage is ≤5 mg·day−1. It also has a longer maintenance phase to assess asthma control for up to 6 months after completion of OCS tapering.The two primary endpoints are whether patients achieve 100% reduction in daily OCS use and whether patients achieve 100% reduction in daily OCS or achieve OCS dosage ≤5 mg·day−1, if adrenal insufficiency prevented further reduction, both sustained over ≥4 weeks without worsening of asthma. Safety and change from baseline in health-related quality of life will also be assessed.PONENTE should provide valuable guidance for clinicians on tapering OCS dosage, including the management of adrenal insufficiency, following benralizumab initiation for the treatment of patients who are OCS-dependent with severe, uncontrolled eosinophilic asthma.

scholarly journals Pharmacist-guided pre-emptive pharmacogenetic testing in antidepressant therapy (PrePGx): study protocol for an open-label, randomized controlled trial

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Céline K. Stäuble ◽  
Markus L. Lampert ◽  
Samuel Allemann ◽  
Martin Hatzinger ◽  
Kurt E. Hersberger ◽  
...  
Keyword(s):  
Randomized Controlled Trial ◽  
Antidepressant Treatment ◽  
Controlled Trial ◽  
Response Rates ◽  
Control Group ◽  
Open Label ◽  
Randomized Controlled ◽  
Link Type ◽  
Increased Risk ◽  
Antidepressant Pharmacotherapy

Abstract Background It is known that only 50% of patients diagnosed with major depressive disorders (MDD) respond to the first-line antidepressant treatment. Accordingly, there is a need to improve response rates to reduce healthcare costs and patient suffering. One approach to increase rates of treatment response might be the integration of pharmacogenetic (PGx) testing to stratify antidepressant drug selection. The goal of PGx assessments is to identify patients who have an increased risk to experience adverse drug reactions or non-response to specific drugs. Especially for antidepressants, there is compiling evidence on PGx influencing drug exposure as well as response. Methods This study is an open-label, randomized controlled trial conducted in two study centers in Switzerland: (1) the Psychiatric Clinic of Solothurn and (2) the Private Clinic Wyss in Münchenbuchsee. Adult inpatients diagnosed with a unipolar moderate or severe depressive episode are recruited at clinic admission and are included in the study. If the adjustment to a new antidepressant pharmacotherapy is necessary, the participants are randomized to either Arm A (intervention group) or Arm B (control group). If no new antidepressant pharmacotherapy is introduced the participants will be followed up in an observational arm. The intervention is the service of pharmacist-guided pre-emptive PGx testing to support clinical decision making on antidepressant selection and dosing. As a comparison, in the control group, the antidepressant pharmacotherapy is selected by the treating physician according to current treatment guidelines (standard of care) without the knowledge of PGx test results and support of clinical pharmacists. The primary outcome of this study compares the response rates under antidepressant treatment after 4 weeks between intervention and control arm. Discussion The findings from this clinical trial are expected to have a direct impact on inter-professional collaborations for the handling and use of PGx data in psychiatric practice. Trial registration ClinicalTrials.govNCT04507555. Registered on August 11, 2020. Swiss National Clinical Trials Portal SNCTP000004015. Registered August 18, 2020.

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