Successful pregnancy in the setting of eosinophil depletion by benralizumab.
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ABSTRACT:
SUBMITTER: Manetz S
PROVIDER: S-EPMC8377677 | biostudies-literature | 2021 Mar
REPOSITORIES: biostudies-literature
Publications
Successful pregnancy in the setting of eosinophil depletion by benralizumab.
Manetz Scott S Maric Irina I Brown Thomas T Kuang Fei Li FL Wetzler Lauren L Battisto Elizabeth E Klion Amy D AD
The journal of allergy and clinical immunology. In practice 20201213 3
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Project description: Not available
| S-EPMC7605198 | biostudies-literature
Project description:Eosinophils play a pivotal role in the inflammatory pathology of asthma and have been the target of new biologic treatments for patients with eosinophilic asthma. Given the central role of interleukin (IL)-5 in the eosinophil lifecycle, several therapies directed against the IL-5 pathway have been developed, including the anti-IL-5 antibodies mepolizumab and reslizumab and the IL-5 receptor α (IL-5Rα)-directed cytolytic antibody benralizumab. Eosinophil-depleting therapies represent a relatively new class of asthma treatment, and it is important to understand their long-term efficacy and safety. Eosinophils have been associated with host protection and tumor growth, raising potential concerns about the consequences of long-term therapies that deplete eosinophils. However, evidence for these associations in humans is conflicting and largely indirect or based on mouse models. Substantial prospective clinical trial and postmarketing data have accrued, providing insight into the potential risks associated with eosinophil depletion. In this review, we explore the current safety profile of eosinophil-reducing therapies, with particular attention to the potential risks of malignancies and severe infections and a focus on benralizumab. Benralizumab is an IL-5Rα-directed cytolytic monoclonal antibody that targets and efficiently depletes blood and tissue eosinophils through antibody-dependent cell-mediated cytotoxicity. Benralizumab is intended to treat patients with severe, uncontrolled asthma with eosinophilic inflammation. The integrated analyses of benralizumab safety data from the phase III SIROCCO and CALIMA trials and subsequent BORA extension trial for patients with asthma, and the phase III GALATHEA and TERRANOVA trials for patients with chronic obstructive pulmonary disease, form the principal basis for this review.
| S-EPMC7165132 | biostudies-literature
Project description:Eosinophilic bronchiolitis is a rare allergic disorder caused by eosinophilic inflammation in the bronchioles of the lungs. An effective treatment strategy is needed in cases resistant to steroids. However, its pathophysiology remains unclear owing to the limited number of cases. We herein present the case of a 31-year-old man who experienced eosinophilic bronchiolitis with eosinophil ETosis (EETosis) in the mucus plugs. The patient was diagnosed with asthma. His respiratory symptoms worsened with eosinophilia when treated with the standard asthma regimen, including inhaled corticosteroids, long-acting β2-agonist, long-acting muscarinic antagonist, and leukotriene receptor antagonist. Chest computed tomography revealed bronchial wall thickening and centrilobular nodules in the lower lobes of both lungs. Bronchoscopy showed obstruction of the subsegmental bronchus with mucus plugs. Histological analysis demonstrated abundant eosinophils in the mucus plugs. Cytolytic eosinophils together with Charcot-Leyden crystal formations and deposition of major basic proteins were also observed, indicating the occurrence of EETosis. Introduction of benralizumab, an anti-interleukin-5 receptor α antibody, successfully controlled the patient's condition and reduced the amount of systemic corticosteroids administered. Our findings confirm that this antibody strongly decreases airway eosinophils in patients with severe asthma. Thus, benralizumab might be an optimal therapeutic agent for the treatment of mucus plug-forming and/or EETosis-occurring eosinophilic lung diseases, including eosinophilic bronchiolitis.
| S-EPMC8794752 | biostudies-literature
Project description:BackgroundMepolizumab and benralizumab are biologics approved for severe eosinophilic asthma. Mepolizumab is an anti-interlukin-5 (IL-5) antibody while benralizumab is an anti-interleukin-5 receptor alpha (IL-5Rα) antibody targeting the IL-5 receptor on eosinophils. Both therapies reduce oral corticosteroid requirements and asthma exacerbations. However, no head-to-head studies have been published. The aim of the present study was to compare the efficacy of peripheral eosinophil reduction of mepolizumab and benralizumab.MethodsA retrospective chart review was conducted on patients with severe eosinophilic asthma who were approved for either IL-5 agent. Patients with noted non-adherence or those who were on fluctuating doses of corticosteroids for non-asthma related illnesses were excluded. The last detectable eosinophil count for each patient prior to start of therapy was compared to the highest eosinophil count noted after therapy start with at least 30 days of adherence.ResultsThirty-six patients taking mepolizumab and 19 patients taking benralizumab met the inclusion criteria and had both pre-treatment and post-treatment eosinophil counts. Baseline characteristics were not statistically different between those on mepolizumab and benralizumab therapy. The mean pre-therapy serum eosinophil count did not statistically differ between patients on mepolizumab (597.2 cells/µL) compared to benralizumab (521.6 cells/µL), p = 0.3769. While both therapies resulted in a significant decrease in eosinophil count (p < 0.0001); the mean decrease did not statistically differ between patients taking mepolizumab compared to those on benralizumab, p = 0.9079. Nonetheless, 100% of patients receiving benralizumab had undetectable eosinophil counts post-therapy compared to 31% of patients receiving mepolizumab (p < 0.0001).ConclusionBoth mepolizumab and benralizumab are potent targets of the IL-5 pathway with the ability to significantly reduce peripheral eosinophil counts. While there is there is no statistical difference in the magnitude of eosinophil reduction offered by each agent, benralizumab is able to decrease peripheral eosinophil counts to 0 cells/µL in more patients than mepolizumab.
| S-EPMC7789431 | biostudies-literature
Project description:Uterine serosal pregnancy is an extremely rare form of ectopic pregnancy. This is a report of a 35-year-old primigravida woman who was diagnosed with uterine serosal pregnancy via laparoscopic intervention. A 35-year-old woman (gravida 1, para 0) was referred from a local clinic for a ruptured left tubal pregnancy at amenorrhea 5+0 weeks with elevated serum beta human chorionic gonadotropin (16,618 mIU/mL). A pregnancy on the left posterior wall of the uterine serosa was diagnosed during the operation and successfully treated with laparoscopic surgery as a conservative management strategy to enable fertility preservation. With the advantages of ultrasonography and laparoscopy, an early diagnosis of a primary abdominal pregnancy located on the left posterior wall of the uterine serosa was made, prior to the occurrence of severe intra-abdominal massive hemorrhage, which was then treated laparoscopically as a conservative management strategy enabling the preservation of fertility.
| S-EPMC5547090 | biostudies-other
Project description:Leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5) is expressed in many organs, including female reproductive organs, and is a stem cell marker in the stomach and intestinal epithelium, hair follicles, and ovarian surface epithelium. Despite ongoing studies, the definitive physiological functions of Lgr5 remain unclear. We utilized mice with conditional deletion of Lgr5 (Lgr5(d/d)) in the female reproductive organs by progesterone receptor-Cre (Pgr(Cre)) to determine Lgr5's functions during pregnancy. Only 30% of plugged Lgr5(d/d) females delivered live pups, and their litter sizes were lower. We found that pregnancy failure in Lgr5(d/d) females was due to insufficient ovarian progesterone (P4) secretion that compromised decidualization, terminating pregnancy. The drop in P4 levels was reflected in elevated levels of P4-metabolizing enzyme 20α-hydroxysteroid dehydrogenase in corpora lutea (CL) inactivated of Lgr5. Of interest, P4 supplementation rescued decidualization failure and supported pregnancy to full term in Lgr5(d/d) females. These results provide strong evidence that Lgr5 is critical to normal CL function, unveiling a new role of LGR5 in the ovary.
| S-EPMC3986831 | biostudies-literature
Project description:BackgroundThe ORBE II study aimed to describe the characteristics and clinical outcomes of adult patients with severe eosinophilic asthma (SEA) treated with benralizumab in a real-world setting in Spain.MethodsORBE II (NCT04648839) was an observational, retrospective cohort study in adult SEA patients who had been prescribed benralizumab. Demographic and clinical data of 204 SEA patients were collected 12 months prior to benralizumab initiation (baseline) and at follow-up. Exacerbation rate, asthma symptoms, maintenance oral corticosteroid (OCS) use and lung function were evaluated, among other variables.ResultsA total of 204 SEA patients were evaluated. Mean (standard deviation, SD) age of the study population was 56.4 (12.4) years, 62.3% were women and mean (SD) duration of asthma was 15.1 (12.7) years. Median (Q1-Q3) follow-up duration was 19.5 (14.2-24.2) months. At baseline, 72.6% of the overall population (OP) presented blood eosinophil counts ≥ 300 cells/µL; 36.8% had comorbid chronic rhinosinusitis with nasal polyps (CRSwNP); 84.8% reported at least one severe exacerbation, and 29.1% were OCS-dependent. At 1 year of follow-up, patients receiving benralizumab treatment had a 85.6% mean reduction in exacerbations from baseline, and 81.4% of patients achieved zero exacerbations. We also found a clinically relevant mean (SD) increase in pre-bronchodilator (BD) FEV1 of 331 (413) mL, with 66.7% of patients achieving a pre-BD FEV1 increase ≥ 100 mL, and 46.3% of patients achieving a pre-BD FEV1 ≥ 80% of predicted. Regarding symptom control, 73.8% of the OP obtained an ACT score ≥ 20 points. After 1 year of follow-up, mean reduction in the daily OCS dose was 70.5%, and complete OCS withdrawal was achieved by 52.8% of the OCS-dependent patients. Almost half (43.7%) of the OP on benralizumab met all four criteria for clinical remission. Patients with concomitant CRSwNP obtained similar or enhanced outcomes.ConclusionsThese data support the real-world benefits of benralizumab in SEA patients, and particularly in those with concomitant CRSwNP.Trial registrationNCT04648839.
| S-EPMC10540395 | biostudies-literature
Project description:Eosinophilic chronic rhinosinusitis (ECRS) is characterized by the presence of nasal polyps, dominant ethmoid shadows in computed tomography (CT) scans, and elevated levels of eosinophil infiltration into the nasal polyps and peripheral blood. ECRS is often accompanied by severe asthma. The recent development of monoclonal antibody-based biologics, including benralizumab, has offered new therapeutic approaches for the treatment of asthma and allergic diseases. Asthma and ECRS are closely related; hence, benralizumab could provide clinical benefit in ECRS patients with severe asthma. Herein, we report a case of a 47-year-old female patient with severe asthma that presented with nasal obstruction and hearing impairment. Nasal endoscopic and otoscopic examinations indicated the presence of bilateral nasal polyps in the middle nasal meatus, as well as a bilateral effusion in the tympanic cavity. Sinus and temporal CT images showed dominant ethmoid sinus and tympanic cavity shadows. Biopsy of nasal polyps revealed high numbers of eosinophils, which led to the diagnosis of ECRS; eosinophilic otitis media (EOM) with hypereosinophilia was also suspected. Treatment with benralizumab reduced the number of peripheral blood eosinophils and improved asthma symptoms. Prolonged benralizumab administration also resulted in a remarkable size reduction in bilateral middle nasal polyps and aeration of the tympanic cavity. In conclusion, benralizumab treatment improved the symptoms of severe asthma, ECRS, and EOM. Eosinophil depletion could be an important mechanism by which benralizumab improves ECRS and EOM. The use of benralizumab for the treatment of ECRS and EOM patients with severe asthma merits further investigation in large-cohort studies.
| S-EPMC7322358 | biostudies-literature
Project description:BackgroundData from phase 3 trials have demonstrated the efficacy and safety of benralizumab in patients with severe eosinophilic asthma (SEA). We conducted a real-world study examining the baseline characteristics of a large SEA population treated with benralizumab in clinical practice and assessed therapy effectiveness.MethodsANANKE is an Italian multi-center, retrospective cohort study including consecutive SEA patients who had started benralizumab therapy ≥ 3 months before enrolment (between December 2019 and July 2020), in a real-world setting. Data collection covered (1) key patient features at baseline, including blood eosinophil count (BEC), number and severity of exacerbations and oral corticosteroid (OCS) use; (2) clinical outcomes during benralizumab therapy. We also conducted two post-hoc analyses in patients grouped by body mass index and allergic status. Analyses were descriptive only.ResultsOf 218 patients with SEA enrolled in 21 Centers, 205 were evaluable (mean age, 55.8 ± 13.3 years, 61.5% females). At treatment start, the median BEC was 580 cells/mm3 (interquartile range [IQR]: 400-850); all patients were on high-dose inhaled controller therapy and 25.9% were on chronic OCS (median dose: 10 mg/die prednisone-equivalent [IQR: 5-25]); 92.9% experienced ≥ 1 exacerbation within the past 12 months (annualized exacerbation rate [AER] 4.03) and 40.3% reported ≥ 1 severe exacerbation (AER 1.10). During treatment (median duration: 9.8 months [IQR 6.1-13.9]; ≥ 12 months for 34.2% of patients), complete eosinophil depletion was observed; exacerbation-free patients increased to 81% and only 24.3% reported ≥ 1 severe event. AER decreased markedly to 0.27 for exacerbations of any severity (- 93.3%) and to 0.06 for severe exacerbations (- 94.5%). OCS therapy was interrupted in 43.2% of cases and the dose reduced by 56% (median: 4.4 mg/die prednisone-equivalent [IQR: 0.0-10.0]). Lung function and asthma control also improved. The effectiveness of benralizumab was independent of allergic status and body mass index.ConclusionsWe described the set of characteristics of a large cohort of patients with uncontrolled SEA receiving benralizumab in clinical practice, with a dramatic reduction in exacerbations and significant sparing of OCS. These findings support benralizumab as a key phenotype-specific therapeutic strategy that could help physicians in decision-making when prescribing biologics in patients with SEA. Trial registration ClinicalTrials.gov Identifier: NCT04272463.
| S-EPMC8858449 | biostudies-literature
Project description:Background and aimsFrequent failure of adrenal vein (AV) cannulation is a major obstacle to the universal use of adrenal vein sampling (AVS) for subtyping primary aldosteronism (PA). This study aimed to confirm and modify the value of a previously reported AVS parameter for PA subtyping in the case of cannulation failure on one side.MethodsSuccessfully catheterized AVS studies in 157 patients (121 patients as a derivation cohort and 36 patients as a validation cohort) from two tertiary hospitals were retrospectively reviewed. The AV/inferior vena cava (IVC) index was defined by dividing the aldosterone/cortisol ratio (ACR) of AV by the ACR of the IVC. Cutoff values for lateralized PA were obtained from two methods: scatterplots and the values corresponding to Youden's index in receiver operating characteristic (ROC) curves, on the assumption of catheterization failure on one side.ResultsDue to multiple samplings in a single AVS procedure, 252 left AV/IVC ratios (LIRs) and 272 right AV/IVC ratios (RIRs) were calculated. Scatterplot cutoffs of LIR >5.4 or <0.5 predicted unilateral PA with a sensitivity of 42.1% and a specificity of 98.6%. Scatterplot cutoffs of RIR <0.5 or >7.0 showed a sensitivity of 55.1% and a specificity of 98.6%. ROC curve cutoffs of LIR ⩽0.8 or >3.1 predicted unilateral PA with a sensitivity of 82.5% and a specificity of 69.6%. ROC curve cutoffs of RIR ⩽0.8 or >3.9 resulted in 87.4% sensitivity and 80.7% specificity.ConclusionIn the case of unilateral AVS failure, the AV/IVC index may help in diagnosing PA subtype.
| S-EPMC7887669 | biostudies-literature