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1.
American Journal of Respiratory and Critical Care Medicine ; 205(1), 2022.
Article in English | EMBASE | ID: covidwho-1927860

ABSTRACT

RATIONALE: Around 4.6 million people in the United Kingdom (UK) have asthma, with an estimated 5.7% treated for severe asthma. Benralizumab is indicated for the treatment of severe eosinophilic asthma (SEA) in adults inadequately controlled despite appropriate maintenance therapy. The Connect 360 Patient Support Programme (PSP) for patients on benralizumab includes options for home-based drug administration, education and adherence support by trained nurses - of particular relevance during the COVID-19 pandemic. Limited evidence exists on the benefit of PSPs for asthma patients or those administering biological therapies at home. This study aims to describe patient characteristics, key outcomes and experience with the PSP using UK data from Connect 360. METHODS: A non-interventional, retrospective cohort study of patients, enrolled in the PSP (Oct-2019 onwards) and consenting to the use of personal data for research purposes (“study cohort”). Patients opting for additional support services with at least one nurse interaction within described study timeframes formed the clinical cohort. Patients were observed up to 48 weeks post-PSP enrolment (interim data taken on 31-Mar-2021;data collection ongoing) with study endpoints assessed at baseline (0-4 weeks), 24 (±4) weeks and 48 (±8) weeks post-PSP enrolment. Characteristics at enrolment are described for the study cohort. Patient-reported clinical outcomes (hospitalisations, maintenance oral corticosteroid [mOCS] use, Asthma Control Questionnaire [ACQ-6] scores) and service satisfaction (1-5 point scale, 5 being most satisfied) were analysed where available from routine PSP nurse calls/visits. Analysis was descriptive;Kaplan-Meier estimators were used to estimate PSP discontinuation rates. RESULTS: The study cohort was 611 patients (mean enrolment age: 54.1 years, 63.2% female [N=323]). Most (98.9%) were benralizumab users on maintenance dosing (8-weekly) at enrolment. The clinical cohort consisted of 149 (baseline), 175 (24 weeks) and 195 (48 weeks) patients. PSP discontinuation rates were 4.4% and 11.6% at 24 and 48 weeks. Proportion of patients reporting mOCS use was 49.7%, 44.0% and 32.8% at each timepoint and hospitalizations were 10.9% and 4.1% at 24 and 48 weeks. Mean ACQ-6 scores decreased over time. Mean (SD) satisfaction scores were 4.6 (0.7) and 4.8 (0.5) at 24 and 48 weeks, respectively. (Table 1). CONCLUSIONS: Overall patients' experience with the PSP was positive, evidenced by high satisfaction with and persistence to the PSP. Where data were available, proportion of patients reporting mOCS and hospitalizations at 48 weeks were numerically lower than previous timepoints and mean ACQ-6 scores improved, suggesting a positive impact of benralizumab treatment within the PSP.

2.
American Journal of Respiratory and Critical Care Medicine ; 205(1), 2022.
Article in English | EMBASE | ID: covidwho-1927846

ABSTRACT

Introduction:Dupilumab is an anti-IL4R monoclonal antibody (mAb) with proven efficacy in severe eosinophilic asthma (SEA). We have previously identified that a suboptimal response to the eosinophil targeting anti-IL5/5R mAbs mepolizumab and benralizumab is seen in 27% and 14% of patients with SEA respectively1,2. The mechanism of this is not well-understood. It is unknown whether such patients respond in a clinically meaningful way following a switch to dupilumab. Methods:We performed a retrospective analysis of the clinical effectiveness of dupilumab (minimum 6 months treatment) in patients with SEA at our tertiary severe asthma centre who had failed to adequately respond to at least one of the anti-IL-5/5R mAbs. Change in the annualised exacerbation rate (AER), maintenance oral corticosteroids (mOCS) requirements, ACQ-6 and mAQLQ was recorded. Results:Thirty-two patients (mean age 41.2, 68.8% female, 71.9% atopic) were included in the analysis. 13/32(40.6%) had co-morbid nasal polyposis and 5/32(15.6%) had eczema. The baseline FeNO was 60ppb(IQR 39.6-87.5) and peak eosinophil count prior to any mAb was 0.6(IQR 0.5-0.9). 23/32(71.8%) were switched from benralizumab, of whom, 12/23(52.2%) had also failed to respond to at least one other anti-IL5 mAb previously. At six months, the daily median mOCS dose in those requiring mOCS at baseline (n=18) fell from 10mg(IQR 5-25mg) to 3mg(IQR 0-5mg), p≤0.001. 4/18(22%) were able to stop mOCS completely. Mean(SD) AER improved from 2.34(1.89) to 0.44(0.95), p≤0.001. There were also significant improvements in ACQ6 and mAQLQ that exceeded twice the MCID for both measures: mean (SD) ACQ6 improved from 3.04(1.26) to 1.82(1.28), p≤0.001;mAQLQ improved from 3.90(SD 1.40) to 5.36(SD 1.05), p≤0.001. Due to the COVID-19 pandemic, FEV1 data was only available for 8 patients. However, there was nonetheless a significant rise in FEV1 (%predicted) from 55.6% (9.78) to 68.5%(16.9), p=0.011. One patient discontinued dupilumab during the follow-up period. Conclusion: A minority of individuals with SEA have a suboptimal response to eosinophil targeted therapy with an anti-IL5/5R mAb. In these patients, we report significant clinical improvements following initiation with dupilumab suggesting an important role for the IL-4/-13 pathway in these patients. Further research is required to understand whether these patients represent a distinct subphenotype of T2-high asthma.

3.
J Asthma Allergy ; 15: 623-632, 2022.
Article in English | MEDLINE | ID: covidwho-1869275

ABSTRACT

Introduction: The increase in drugs available for severe uncontrolled asthma and the lifestyle of these patients make it necessary to implement self-administration programs of these therapies at home. Benralizumab, a monoclonal antibody targeting IL5R, was authorized in Spain for poorly controlled severe eosinophilic asthma. The possibility of administration at home was approved in March 2020 in Spain. The aim of the Auto-Benra study was to evaluate the usability and satisfaction of the benralizumab prefilled syringe and autoinjector and assessing the effectivity of these devices in uncontrolled severe eosinophilic asthma (SEA) in home-self administration. Methods: This is a retrospective, observational multicenter study uncontrolled SEA patients treated with benralizumab at least with 3 doses self-administered at home before April 30, 2021. Reliability and satisfaction with benralizumab at home were evaluated with subcutaneous administration assessment questionnaire (SQAAQ) and visual analogic scales (VAS). Effectiveness was evaluated in all patients with asthma control test (ACT), Mini Asthma Quality of Life Questionnaire (MiniAQLQ), annual exacerbation rate, oral corticosteroid treatment (OCS) and asthma-related hospitalizations and emergency visits. Results: Fifty-four patients across 9 hospitals in Spain were included. The mean SQAAQ score was 6.89 (±0.16) points. Patients and their caregivers and doctors report excellent satisfaction by VAS, with no differences between benralizumab devices used (prefilled syringe and autoinjector). Severe exacerbation rate decreased by 65% (p = 0.0007) after benralizumab treatment. ACT score improved on average 6.27 ± 5.35 points (p < 0.0001) and the mean MiniAQLQ increased up to 1.58 ± 1.47 points (p < 0.0001). Twenty-four patients were OCS-dependent and at the end of study 14 patients get complete OCS withdrawal. Conclusion: AUTO-BENRA study supports the use of benralizumab at home given the excellent results of satisfaction and usability by patients and their caregivers.

4.
Cureus ; 13(12): e20364, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1579848

ABSTRACT

We report a case of a patient affected by severe eosinophilic asthma with nasal polyps (SEA+NP) who developed coronavirus disease 2019 (COVID-19) six months after starting benralizumab as add-on therapy. Both SEA and NP were under control with no exacerbations at the time of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The patient was hospitalized for four months, during which the treatment with benralizumab was interrupted. Despite the onset of bilateral interstitial pneumonia, developed as a consequence of the SARS-CoV-2 infection, the patient was discharged without complications, with a significant improvement in the chest CT scan following the administration of systemic corticosteroids (SCS) and low-flow oxygen therapy. The treatment with benralizumab was reintroduced at the regular dosing regimen immediately after his discharge. Lung function was assessed three months after the discharge and showed normal levels as before the development of COVID-19 symptoms. A long-term follow-up after 26 months from the introduction of benralizumab showed a normal lung function and well-controlled asthma, without exacerbations or the need for corticosteroid bursts.

5.
Allergologie ; 44(1):54-80, 2021.
Article in German | Web of Science | ID: covidwho-1572877

ABSTRACT

With the advent of biologicals, more and more therapeutics are available that specifically address specific switch points in the pathomechanism of immunologically dominated diseases. Thus, the focus of diagnostics and therapy (precision medicine) is more on the individual disease characteristics of the individual patient. Regarding the different phenotypes of atopic diseases, severe asthma was the first entity for which biologicals were approved, followed by urticaria, and finally atopic dermatitis and chronic rhinosinusitis with nasal polyps. Experience in the treatment of severe bronchial asthma has shown that the intensity of the response to biological therapy depends on the quality of clinical and immunological phenotyping of the patients. This also applies to different diseases of the atopic form, as patients can suffer from several atopic diseases at the same time, each with different characteristics. Biologics are already emerging that may represent a suitable therapy for allergic bronchial asthma, which often occurs together with severe neurodennatitis. and chronic rhinosinusitis with nasal polyps. In practice, however, the question of possible combinations of biologicals for the therapy of complex clinical pictures of individual patients is increasingly arising. In doing so, the side effect profile must be taken into account, including hypersensitivity reactions, whose diagnostic and logistical management must aim at a safe and efficient therapy of the underlying disease. Increased attention must also be paid to biological therapy in pregnancy and planned (predictable) vaccinations as well as existing infections, such as SARS-CoV-2 infection. Before starting a biological therapy, the immune status should be checked with regard to chronic vi- ral and bacterial infections and, if necessary. the vaccination status should be refreshed or missing vaccinations should be made up for before starting therapy. Currently, reliable data on the effect of biologicals on the immunological situation of SARS-CoV-2 infection and COVID-19 are not available. Therefore, research and development of suitable diagnostic methods for detection of immunologically caused side effects as well as detection of potential therapy responders and non-responders is of great importance.

6.
Allergy: European Journal of Allergy and Clinical Immunology ; 76(SUPPL 110):466, 2021.
Article in English | EMBASE | ID: covidwho-1570403

ABSTRACT

Benralizumab is a humanized, afucosylated IgG1k monoclonal antibody directed against the α subunit of IL-5R. It inhibits IL-5, the main regulator of the biology of eosinophils, from binding to its specific receptor. Moreover, it directly targets and depletes eosinophils and other IL-5R + cells by inducing antibody-dependent cell-mediated cytotoxicity, differentiating it from the other IL-5 ligand targeted therapies. We report a case of a 61-year-old woman with severe eosinophilic asthma and rhinosinusitis, referred to our department in 2014. Blood eosinophilia (560 cells/μL) and normal total IgE levels (57 kU/L) were present. She was on GINA step-5 treatment with additional aminophylline 225mg twice daily. Control was not achieved despite good compliance with frequent asthma exacerbations requiring emergency department visits, multiple systemic corticosteroid courses and hospitalizations. Maintenance therapy with prednisolone 5mg daily was attempted with only a slight improvement. Although no more hospitalizations were required, she continued to have several asthma exacerbations. Treatment with subcutaneous Benralizumab 30mg was started in October 2020. The subsequent administration was skipped because the patient had COVID-19. An interval of approximately 3 months (82 days) separated the first 2 administrations. Regardless of our recommendation, the patient decided to discontinue systemic corticosteroids and aminophiline. Evaluation before the 2nd administration showed that blood eosinophils decreased to 0 cells/μL and clinical improvement that was established by disease control and health-related quality of life questionnaires (see table I) Although maintained eosinopenia after an isolated intravenous administration of Benralizumab has been reported, to our knowledge this is the first case related to a single subcutaneous administration in a previously eosinophilic patient. Additionally, clinical improvement was sustained in spite of stepping down her maintenance therapy. This case raises questions regarding the possibility and success of patient-oriented scheduling of Benralizumab administration as an alternative to the current treatment regimen. (Table Presented).

7.
Allergy: European Journal of Allergy and Clinical Immunology ; 76(SUPPL 110):455, 2021.
Article in English | EMBASE | ID: covidwho-1570397

ABSTRACT

Background: Under the restriction of direct access to specialized health care, COVID-19 pandemic, has created an “iceberg” regarding disease control data in severe Bronchial Asthma (BA). We aimed to evaluate indicators of asthma control, in severe persistent BA, consequences of pandemic and in-person visits limitations among this patient population. Method: A cross-sectional study, obtained data from 86 patients with yearly pre-pandemic hospitalizations, at the only tertiary hospital center for severe persistent BA in Albania. Descriptive data analysis was performed through anamnestic and clinical records. Standardized and validated questionnaires for inhalers adherence and asthma control, have been performed though phone interview during January 2021. Patients under treatment with biologic drugs (anti-IgE) and allergen specific immunotherapy have been excluded. Results: 64% were classified as high TH2 phenotype, predominating late-onset eosinophilic asthma (30.2%), and in low TH2 phenotype, with predominance of obesity associated asthma (18.6 %). 66,3 % were females with mean age of 49.3 ± 13.9. Overall Asthma Control Test (ACT= 19.5 ± 3.8), 43% controlled (20-25 points), with no statistically significant differences, between sex and phenotypes. Among early onset allergic asthma phenotype (25,6%), lower ACT score (18.5 ± 1.5) resulted in outdoor + indoor allergen polysensitization, compared to monosensitization (p < 0.05). Seasonal influenza vaccination rate was 16.2%, ACT score between vaccinated and unvaccinated groups, with significant difference (p = 0.03). Prevalence of confirmed COVID-19 was 15.1%, only 1,2% severe. ATC score, between confirmed or suspected post COVID-19 severe ABs and COVID-19 negative, was not statistically significant. Coexistence of sporadic and intentional nonadherence affected ACT score (p = 0.01), between controlled (ACT, 20-25) and uncontrolled group (ACT<20 points). Conclusion: Asthma control in severe persistent BA population was <50%, affected by sensitization profile, seasonal flu vaccination and type of non-adherence to inhalers. Differences of disease control in ACT score, were not statistically related with phenotype, sex or post COVID-19 infection condition. Particularly, Severe Persistent Bronchial Asthma needs a periodic specialist care to reach disease control and to lower the burden of indirect pandemic effects on disease progression.

8.
Allergy: European Journal of Allergy and Clinical Immunology ; 76(SUPPL 110):468-469, 2021.
Article in English | EMBASE | ID: covidwho-1570395

ABSTRACT

In 2012 a 25-year-old man presented to our outpatient clinic for severe atopic dermatitis (AD) and severe allergic eosinophilic asthma in polisensitivity (house dust mite, cat, gramineous plants, birch, milk protein and, in particular, Alternaria). His clinical history was also characterized by gastro-esophageal reflux disease and chronic rhinitis without polyposis, with septal deviation and turbinate hypertrophy, worthy of surgical intervention. History taking revealed egg and cow milk protein allergy and severe asthma since the first months of life, with frequent hospital admissions due to exacerbations. AD was severe and diffuse, involving especially face, neck, back and superior limbs, often complicated by impetigo. The esthetic, social and psychological impact led him to quit his job as a barman. At presentation, the Eczema Area and Severity Index (EASI) score was 72/72. Laboratory tests showed eosinophilic count ranging between 1.060 and 2.140/mm3, and high serum levels of total Immunoglobulin E (5.939 kUI/L). Tryptase levels were normal and autoantibody analysis was negative. Parasite stool examination was negative. Nasal swab tested positive for Staphylococcus aureus, which was treated with Sulfamethoxazole-Trimethoprim. Asthma Control Test was 15/25, pulmonary function tests (PFTs) showed mild obstruction (FEV1 4.43 L, 103%, FEV1/FVC 69%), with positive bronchodilator testing (FEV1 5.12 L, + 670 mL, + 16%). Firstly, he was treated with topical steroids and sometimes with oral corticosteroids, with poor response. Then, in July 2019, he initiated therapy with cyclosporine 3-5 mg/kg. Soon, the drug had to be discontinued due to adverse effects (gastrointestinal symptoms and infections). In November 2019, at the age of 32 years, he started therapy with monoclonal antibody anti-IL-5 receptor alpha (benralizumab 30 mg 1 subcutaneous vial every 4 weeks for the first three administrations and then every 8 weeks), with a terrific clinical improvement of AD since the first administrations and with benefit on asthma control (ACT after the first administration increased up to 25/25;PFTs could not be performed, due to SARS-CoV-2 pandemic). This therapy has always been well tolerated. The eosinophilic count decreased to 0/mm3 after the first administration. At the moment, after one year of therapy, AD is almost fully disappeared (EASI SCORE 4/72), despite being in free diet, and the quality of life of the patient has definitely improved.

9.
Allergy: European Journal of Allergy and Clinical Immunology ; 76(SUPPL 110):171-172, 2021.
Article in English | EMBASE | ID: covidwho-1570339

ABSTRACT

Background: Mepolizumab, a humanized monoclonal antibody against IL-5, is a therapeutic option in patients with severe eosinophilic asthma. Its efficacy has been shown in clinical trials. Our aim is to present data from our center to corroborate this evidence in the complexity of real-life patients. Method: A retrospective study of patients with severe eosinophilic asthma treated with mepolizumab in our center was performed. We collected data regarding demographics, eosinophilic blood count, FEV 1 , fractional exhaled nitric oxide (FeNO), clinically significant exacerbations [need to start or increase oral corticosteroids (OCS), emergency department visit and/or hospitalization], OCS and safety profile, before and after patients started mepolizumab. Results: A total of 12 patients were included (9 female, mean age 53.7 ± 8.9 years old);10 patients had concomitant chronic rhinosinusitis with nasal polyps. Mepolizumab was administered in a dose of 100 mg every 4 weeks, except for 2 patients diagnosed with eosinophilic granulomatosis with polyangiitis (EGPA) (300 mg every 4 weeks). The mean duration of treatment was 13.75 months [3 - 28 months]. Due to COVID-19 pandemics restriction it was not possible to assess absolute eosinophilic count in 2 patients, as well as FeNO and FEV 1 in 2 different patients after treatment. The mean value before and after treatment for each outcome were the following: absolute eosinophilic blood count, from 537.5/μl to 116/μl ( p = 0.005);FEV 1 , from 1.44L to 1.84L ( p = 0.036);FeNO, from 62.27ppm to 41.8ppm ( p = 0.260);clinically significant exacerbations, from 2.83 in the previous year to 0.25 ( p = 0.007). Prior to treatment, 8 patients were treated with daily OCS, and after starting mepolizumab 3 of them were able to stop OCS and the others reduced daily dose (mean dose reduction 64.7%, ranging from 25% to 98.5%). The only side effect reported was sporadic headache, and no one discontinued treatment. Conclusion: In our sample, we observed a significant reduction in eosinophilic blood count, clinically significant exacerbations and OCS use, as well as improvements in FEV 1 , in patients with severe eosinophilic asthma treated with mepolizumab, with a good safety profile. This information supports data from clinical trials and early real-life experience in other populations.

10.
Respirol Case Rep ; 9(8): e00780, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1328615

ABSTRACT

Severe asthma can be associated with eosinophilic or allergic phenotypes or both. Eosinophilic inflammation is associated with exacerbations and disease severity due to biological activity of interleukin-5 (IL-5). Patients with severe asthma have reported reduced lung function and poor health-related quality of life (HRQoL) and may require systemic corticosteroids for its management. Thus, treatment targeting IL-5 can help improve quality of life and reduce the use of systemic corticosteroids in severe asthma. Mepolizumab is approved for treating severe eosinophilic asthma as it helps reduce exacerbations, improve lung function and asthma control, and reduce the use of systemic glucocorticoids. This further helps in enhancing HRQoL of these patients. This case series includes four adult patients suffering from severe eosinophilic asthma who were treated with mepolizumab.

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