Real-life experience with mepolizumab in the French early access program for severe eosinophilic asthma

Background: Severe eosinophilic asthma decreases lung function and causes worsen symptoms, often forcing recurrent maintenance corticosteroid use. The aim of our real-life study was to evaluate the effectiveness of an add-on treatment with benralizumab in patients with severe eosinophilic asthma, paying particular attention to the impact on their quality of life (QoL).Materials and methods: In this prospective study, 10 outpatients with severe eosinophilic asthma were added-on with benralizumab and followed-up in our severe asthma clinic after 12 and 24 weeks. At each patient visit, pre-bronchodilator FEV1 and inflammatory markers were recorded. Variations in asthma symptoms control and QoL perception was assessed by validated questionnaires.Results: All the subjects experienced a marked reduction of nocturnal and diurnal symptoms over time and were able to stop using OCS, as documented by the improvement in Asthma control test (ACT) and Asthma Control Questionnaire score. Similarly, we recorded a statistically significant increase in patient’s QoL perception in EQ-VAS, EQ-5D-3L and Asthma Quality of Life Questionnaire (AQLQ) assessment (p < 0.05). Simultaneously we recorded a significant reduction in eosinophilic inflammation, an improvement in pre-bronchodilator FEV1. These results appear to be in line with those already obtained in the previous randomized controlled trials (RCTs).Conclusion: Our 24-weeks real life experience supports the effectiveness of an add-on treatment with benralizumab in reducing eosinophilic inflammation and OCS-use, increasing lung function and improving control of nocturnal and diurnal symptoms, as well as restoring severe asthma patients to a better QoL.

Download Full-text

Switch from Omalizumab to Benralizumab in Allergic Patients with Severe Eosinophilic Asthma: A Real-Life Experience from Southern Italy

Biomedicines ◽

10.3390/biomedicines9121822 ◽

2021 ◽

Vol 9 (12) ◽

pp. 1822

Author(s):

Corrado Pelaia ◽

Claudia Crimi ◽

Santi Nolasco ◽

Giovanna Elisiana Carpagnano ◽

Raffaele Brancaccio ◽

...

Keyword(s):

Life Experience ◽

Symptom Control ◽

Real Life ◽

Forced Expiratory Volume ◽

Blood Eosinophil ◽

Asthma Control Test ◽

Biologic Treatment ◽

Eosinophilic Asthma ◽

Exacerbation Rate ◽

Severe Eosinophilic Asthma

Background. The wide availability of monoclonal antibodies for the add-on therapy of severe asthma currently allows for the personalization of biologic treatment by selecting the most appropriate drug for each patient. However, subjects with overlapping allergic and eosinophilic phenotypes can be often eligible to more than one biologic, so that the first pharmacologic choice can be quite challenging for clinicians. Within such a context, the aim of our real-life investigation was to verify whether allergic patients with severe eosinophilic asthma, not adequately controlled by an initial biologic treatment with omalizumab, could experience better therapeutic results from a pharmacologic shift to benralizumab. Patients and methods. Twenty allergic patients with severe eosinophilic asthma, unsuccessfully treated with omalizumab and then switched to benralizumab, were assessed for at least 1 year in order to detect eventual changes in disease exacerbations, symptom control, oral corticosteroid intake, lung function, and blood eosinophils. Results. In comparison to the previous omalizumab therapy, after 1 year of treatment with benralizumab our patients experienced significant improvements in asthma exacerbation rate (p < 0.01), rescue medication need (p < 0.001), asthma control test (ACT) score (p < 0.05), forced expiratory volume in the first second (FEV1) (p < 0.05), and blood eosinophil count (p < 0.0001). Furthermore, with respect to the end of omalizumab treatment, the score of sino-nasal outcome test-22 (SNOT-22) significantly decreased after therapy with benralizumab (p < 0.05). Conclusion. The results of this real-life study suggest that the pharmacologic shift from omalizumab to benralizumab can be a valuable therapeutic approach for allergic patients with severe eosinophilic asthma, not adequately controlled by anti-IgE treatment.

Download Full-text

Change in Patient-Reported Outcomes in Severe Eosinophilic Asthma Patients Treated With Benralizumab Under Real-life Conditions

Case Medical Research ◽

10.31525/ct1-nct04184284 ◽

2019 ◽

Author(s):

Keyword(s):

Patient Reported Outcomes ◽

Real Life ◽

Eosinophilic Asthma ◽

Severe Eosinophilic Asthma ◽

Life Conditions ◽

Patient Reported ◽

Asthma Patients

Download Full-text

Lorlatinib in pretreated ALK- or ROS1-positive lung cancer and impact of TP53 co-mutations: results from the German early access program

Therapeutic Advances in Medical Oncology ◽

10.1177/1758835920980558 ◽

2021 ◽

Vol 13 ◽

pp. 175883592098055 ◽

Cited By ~ 1

Author(s):

Nikolaj Frost ◽

Petros Christopoulos ◽

Diego Kauffmann-Guerrero ◽

Jan Stratmann ◽

Richard Riedel ◽

...

Keyword(s):

Treatment Failure ◽

Survival Rates ◽

Real Life ◽

Progression Free Survival ◽

Leptomeningeal Carcinomatosis ◽

Resistance Mutations ◽

Duration Of Treatment ◽

Tp53 Mutations ◽

Early Access ◽

Access Program

Introduction: We report on the results of the German early access program (EAP) with the third-generation ALK- and ROS1-inhibitor lorlatinib. Patients and Methods: Patients with documented treatment failure of all approved ALK/ROS1-specific therapies or with resistance mutations not covered by approved inhibitors or leptomeningeal carcinomatosis were enrolled and analyzed. Results: In total, 52 patients were included [median age 57 years (range 32–81), 54% female, 62% never smokers, 98% adenocarcinoma]; 71% and 29% were ALK- and ROS1-positive, respectively. G1202R and G2032R resistance mutations prior to treatment with lorlatinib were observed in 10 of 26 evaluable patients (39%), 11 of 39 patients showed TP53 mutations (28%). Thirty-six patients (69%) had active brain metastases (BM) and nine (17%) leptomeningeal carcinomatosis when entering the EAP. Median number of prior specific TKIs was 3 (range 1–4). Median duration of treatment, progression-free survival (PFS), response rate and time to treatment failure were 10.4 months, 8.0 months, 54% and 13.0 months. Calculated 12-, 18- and 24-months survival rates were 65, 54 and 47%, overall survival since primary diagnosis (OS2) reached 79.6 months. TP53 mutations were associated with a substantially reduced PFS (3.7 versus 10.8 month, HR 3.3, p = 0.003) and were also identified as a strong prognostic biomarker (HR for OS2 3.0 p = 0.02). Neither prior treatments with second-generation TKIs nor BM had a significant influence on PFS and OS. Conclusions: Our data from real-life practice demonstrate the efficacy of lorlatinib in mostly heavily pretreated patients, providing a clinically meaningful option for patients with resistance mutations not covered by other targeted therapies and those with BM or leptomeningeal carcinomatosis.

Download Full-text

Results in clinical practice in the treatment of severe eosinophilic asthma with mepolizumab: a real-life study

Journal of Asthma ◽

10.1080/02770903.2021.1897835 ◽

2021 ◽

pp. 1-7

Author(s):

Ana Isabel Enríquez-Rodríguez ◽

Tamara Hermida Valverde ◽

Pedro Romero Álvarez ◽

Francisco Julián López-González ◽

Jose Antonio Gullón Blanco ◽

...

Keyword(s):

Clinical Practice ◽

Real Life ◽

Eosinophilic Asthma ◽

Life Study ◽

Severe Eosinophilic Asthma ◽

Real Life Study

Download Full-text

Real-life evaluation of the clinical, functional, and hematological effects of mepolizumab in patients with severe eosinophilic asthma: Results of a single-centre observational study

Pulmonary Pharmacology & Therapeutics ◽

10.1016/j.pupt.2018.09.006 ◽

2018 ◽

Vol 53 ◽

pp. 1-5 ◽

Cited By ~ 29

Author(s):

Corrado Pelaia ◽

Maria Teresa Busceti ◽

Sabina Solinas ◽

Rosa Terracciano ◽

Girolamo Pelaia

Keyword(s):

Observational Study ◽

Real Life ◽

Single Centre ◽

Eosinophilic Asthma ◽

Severe Eosinophilic Asthma ◽

Life Evaluation ◽

Hematological Effects

Download Full-text

Mepolizumab Is an Effective Option in Severe Eosinophilic Asthma Regardless of Baseline Features: Single-Center Real-Life Data

International Archives of Allergy and Immunology ◽

10.1159/000520725 ◽

2021 ◽

pp. 1-13

Author(s):

Betül Özdel Öztürk ◽

Zeynep Yavuz ◽

Dilek Eraslan ◽

Dilşad Mungan ◽

Yavuz Selim Demirel ◽

...

Keyword(s):

Quality Of Life ◽

Real Life ◽

Blood Eosinophil ◽

Life Questionnaire ◽

Eosinophilic Asthma ◽

Quality Of Life Questionnaire ◽

Severe Eosinophilic Asthma ◽

Median Dosage ◽

Act Score

Background: Mepolizumab has been approved as a treatment option for severe eosinophilic asthma (SEA) patients in our country. We aimed to evaluate the clinical and functional efficacy of mepolizumab in this group of patients in real life as well as the response rates to mepolizumab and the possible factors affecting the response. Methods: The study was a retrospective chart review of patients with SEA treated with mepolizumab. The data were collected at baseline, and at the 6th and 12th month. Results: A total of 62 patients (41F/21M) with a mean age of 44.41 ± 13.24 years were included in the study. They had poor symptom control with a mean asthma control test (ACT) score of 16.61 ± 5.59, frequent exacerbations with a mean of 3.4 ± 3.7 in the previous 12 months, and 80.6% required daily oral corticosteroid (OCS) with a median dosage of 8 mg/day as methylprednisolone. The ACT score increased to 22.47 ± 3.18 and 22.03 ± 4.31, respectively, and blood eosinophil count decreased from 1,146/μL to 89/μL and 85/μL at the 6th and 12th month, respectively. The mean FEV1 at baseline was 2.102 L there was an increase of 0.373 L at 6th month and 0.596 L at 12th month. The percentage of regular users of OCS decreased to 66.0% at 6th month with a median dosage of 4 mg and 52.6% at 12th month with a median dosage of 2 mg. Mepolizumab reduced the rate of exacerbations compared with the previous year from a mean of 3.40 to 0.15 at 6th month and 0.36 at 12th month. There was a significant improvement in Asthma Quality of Life Questionnaire (AQLQ), Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), and Sino-nasal Outcome Test (SNOT-22) scores at both of time points. The rate of responders and super-responders at 6th month was 60% and 28%, respectively, and consequently, the overall response rate was 88%. At the 12th month, the super-responder rate increased to 44.7% as well as the overall response to 89.4%. The only difference between the nonresponders, responders, and super-responders at the 6th and 12th month was whether regular daily OCS was used pre-mepolizumab. All nonresponders at both 6th and 12th month were using OCS regularly, whereas most of super-responder used the OCS only during exacerbations. Conclusion: Mepolizumab effectively reduced asthma exacerbations, steroid requirement, blood eosinophil counts and improved asthma control, pulmonary function, sinonasal symptoms and quality of life. Our data suggest that mepolizumab would be effective in selected patients in real-life settings.

Download Full-text

Biologics for oral corticosteroid-dependent asthma

Allergy and Asthma Proceedings ◽

10.2500/aap.2020.41.200015 ◽

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.

Download Full-text