Search

AbstractObjectiveMethodResultConclusionMepolizumab, an anti-IL-5 monoclonal antibody, has shown promise in reducing exacerbations and steroid dependency in severe eosinophilic asthma. This study aims to evaluate the effectiveness of mepolizumab in achieving clinical remission in asthma over 12 months and explore Vitamin D levels as a predictor of response.We assessed Asthma Control Questionnaire (ACQ) scores, spirometry, number of exacerbations, oral corticosteroid (OCS) use, and inhaled corticosteroid (ICS) use in 32 patients, observing significant clinical improvements. Data were collected 1 year prior to starting mepolizumab and one year after starting mepolizumab. Nasal polyps were not seen in all the patients, and computed tomography of para-nasal sinuses are not available for all the patients, so nasal polyps status are not evaluated to avoid any bias.Our results indicate that 12 patients achieved clinical remission after starting mepolizumab, with a strong correlation between higher Vitamin D levels and positive treatment outcomes. This suggests that optimizing Vitamin D levels could enhance the response to mepolizumab in asthma patients, and help in achieving better asthma control.Mepolizumab is an effective treatment for severe eosinophilic asthma, significantly improving clinical outcomes and reducing corticosteroid use. This study highlights the importance of Vitamin D as a predictor of response to mepolizumab, suggesting that higher Vitamin D levels may enhance treatment efficacy. [ABSTRACT FROM AUTHOR]

AbstractObjectiveMethodsResultsConclusionsThis study aimed to compare the clinical characteristics and treatment outcomes of allergic patients (AP) and non-allergic patients (NAP) with severe eosinophilic asthma (SEA) treated with anti-IL5/IL5R biologic agents (mepolizumab, benralizumab, or reslizumab) over one year. Sub-analyses assessed treatment response variations between AP and NAP based on the biological used and compared outcomes among AP with and without fungal allergy.Observational retrospective analysis. Clinical characteristics, laboratory findings, pulmonary function tests, Asthma Control Test (ACT) scores, oral corticosteroid (OCS) usage, and exacerbation frequency were assessed at the initiation of biological treatment and after one year.Sixty-five patients with SEA were included, 41 AP and 24 NAP. 55.4% were treated with mepolizumab, 33.8% with benralizumab, and 10.8% with reslizumab. Before anti-IL5/5R treatment, AP had worse baseline outcomes but there were no differences in pulmonary function. Mean annual exacerbation rate and percentage of patients requiring OCS and dose of prednisone were higher in AP than NAP. AP had significantly higher total IgE values. After one year of treatment, more AP discontinued OCS than NAP (p = 0.025). Both experienced a significant reduction in exacerbation frequency (p = 0.001) and improved respiratory function. 70.7% of AP and 60% of NAP improved ACT ≥3 points. There was no significant difference between AP and NAP using mepolizumab (p = 0.145) or benralizumab (p = 0.174) in reducing OCS.Anti-IL5/IL5R reduced the need for OCS and improved asthma control, regardless of allergic status. Fungal allergy led to lower ACT scores and higher exacerbations than other allergens; both groups improved with anti-IL5/ILR. [ABSTRACT FROM AUTHOR]

The aim of this retrospective multicentre study is to describe the clinical characteristics of patients diagnosed with severe eosinophilic asthma receiving anti-IL-5/anti-IL-5Rα therapies and to compare their effectiveness. We collected and analysed results separately for anti-IL-5 and anti-IL-5Rα therapies from January 2016 until December 2021 in multidisciplinary severe asthma units. We collected demographic and clinical data, treatment with previous anti-IgE and/or anti-IL-5 agents, and comorbidities. We compared the number of exacerbations and admissions to the hospital, daily oral corticosteroid intake, pulmonary function tests, and Asthma Control Test scores before and after 12 months of therapy. 261 patients were included: 176 patients in the anti-IL-5 group and 85 in the anti-IL-5Rα group. Both groups led to statistically significant reductions in asthma exacerbations, hospital admissions, and visits to the Emergency Room. Although both groups showed a significant reduction in blood eosinophiliccount, we found a difference, although not significant, in the magnitude of reduction as benralizumab was able to decrease eosinophil counts to zero. Patients in the anti-IL-5 group achieved higher ACT scores after treatment, although this improvement was seen in both treatment groups. The anti-IL-5 and anti-IL-5Rα biologics have shown similar effectiveness despite having different mechanisms of action. The anti-IL-5 group appeared to be better than benralizumab at improving ACT scores and FEV1/FVC and at reducing the number of inhalers. Although these differences were not statistically significant, it is not clear whether they may have clinical relevance and they might highlight the need for further head-to-head studies comparing these treatments. [ABSTRACT FROM AUTHOR]

Mepolizumab is an anti-interleukin-5 monoclonal antibody shown to reduce asthma exacerbations in adults and adolescents with severe eosinophilic asthma. To assess the impact of mepolizumab on children and adolescents over 12 months by examining steroid usage, asthma-related hospitalizations, Asthma Control Test (ACT) scores, fractional exhaled nitric oxide concentration (FeNO), forced expiratory volume in 1 s (FEV1), mid expiratory flow (FEF25–75%), and blood eosinophil count. Retrospective analysis performed between October 2015 and December 2022. Data was reviewed 12 months before and after commencing mepolizumab. Mepolizumab was offered if the patient had severe eosinophilic asthma and were unresponsive to or ineligible for omalizumab. Sixteen participants (age 7–17, 8 males, 8 females) received subcutaneous mepolizumab monthly with no serious adverse reactions. Incidence of hospital admissions fell significantly (IRR 0.33, p = 0.007). Among the 11 patients receiving daily oral corticosteroids, 3 were weaned off daily oral steroids and 3 patients' daily dose was significantly reduced (mean Δ-0.095 ± 0.071 mg/kg, p = 0.0012). Eosinophil count was decreased (mean Δ-0.85 x 109/L, p < 0.001). There was no significant change in mean overall steroid burden per patient (mean Δ-1445.63 ± 1603.18 mg, p = 0.10), ACT scores (mean Δ2.88 ± 6.71, p = 0.17), FEV1 z-scores (mean Δ-0.99 ± 1.88, p = 0.053), FEF25–75% z-scores (mean Δ-0.65 ± 1.61, p = 0.13), FeNO (mean Δ-20.09 ± 80.86, p = 0.34), or number of courses of oral steroids given for asthma attacks (IRR 0.71, p = 0.09). Among children and adolescents with severe eosinophilic asthma ineligible for or not responsive to omalizumab, mepolizumab therapy exhibited significant reduction in rate of asthma-related hospitalizations and significant decrease in daily steroid dosage. [ABSTRACT FROM AUTHOR]

AbstractBackgroundObjectiveMethodsResultsConclusionSpecific biomarkers, such as eosinophilia in peripheral blood or fractional exhaled nitric oxide (FeNO), can guide us in the choice of biologic therapy, allowing a more personalized approach. Although there are multiple evidences in the literature about the role of FeNO as a predictor of response to different biologic treatments, there are no data on the relationship between FeNO changes and clinical response to the four biologic drugs currently in use.To evaluate and to compare the expression of multiple-flows FeNO parameters in a cohort of patients with severe asthma (SA) before and during the treatment with biologics to evaluate the performance of these biomarkers in predicting the achievement of clinical remission.We prospectively enrolled 50 patients with severe asthma eligible for biologic therapy. Patients underwent clinical and functional monitoring at baseline (T0) and after 1, 6, and 12 months of treatment (T1, T6, T12), including multiple flows FeNO assessment.A statistically significant reduction of FeNO50 values and J’awNO was observed only in benralizumab and dupilumab subgroups. Among biomarkers, the reduction of FeNO 50 values at T1 was associated with a higher probability of achieving clinical remission at T12 (p = 0.003), which was also confirmed by ROC curve analysis (AUC 0.758, p = 0.002; sensitivity 60% and specificity 74% for a reduction of 16 ppb).These data confirm the potential of this biomarker in predicting clinical response to biologic treatment in patients with severe asthma in order to guide clinical decisions and evaluate a shift to other biologic therapy. [ABSTRACT FROM AUTHOR]

Mepolizumab is a therapy for severe asthma. We have little knowledge of the characteristics of people in the US that discontinue mepolizumab in clinical care. To investigate the real-world efficacy and time to clinical discontinuation of mepolizumab, we evaluated individuals with asthma started on mepolizumab at the Cleveland Clinic. We hypothesized that individuals that discontinue mepolizumab have more severe and uncontrolled asthma at baseline. Between 2016 and 2022, patients who started on mepolizumab consented to be assessed over 18 months. At baseline, a questionnaire including demographic and medical history was collected. Laboratory findings such as ACT score, FENO (Fractional Excretion of Nitric Oxide), and spirometry were recorded. At the conclusion of the observation period, the participants were divided into two categories: Group A and Group B. Group B [N = 28] discontinued mepolizumab (p < 0.05) at an average of 5.8 months (SD 4.2 months). Group A [N = 129] stayed on the therapy for at least 1 year. A participant with an ACT score less than 13 has an odds ratio of 6.64 (95% CI, 2.1 − 26.0) of discontinuing mepolizumab therapy. For a male, the odds of discontinuing mepolizumab therapy is 3.39 (95% CI, 1.1–11.2). In this real-world study, we find that high eosinophil count may not be adequate in screening which individuals will benefit from mepolizumab. Up to 17% of patients fail therapy within 6 months, with male sex and low ACT score increasing risk of mepolizumab discontinuation at Cleveland Clinic. [ABSTRACT FROM AUTHOR]

Biologic drugs have been shown to reduce asthma exacerbations, improve lung function and quality of life, reduce oral corticosteroid use in appropriately selected patients. Mepolizumab has been demonstrated to have a safety profile that is similar to placebo, however, when present side effects may lead to treatment discontinuation. Among these, headache is one of the most common. We hereby describe the case of a never-smoking male patient with an eosinophilic corticosteroid-dependent severe asthma. He displayed well controlled comorbidities and good adherence to the inhaled therapy. Mepolizumab was started in 2017 with an initial remarkable clinical improvement. After three doses of biologic therapy, he reported a severe orthostatic headache associated with vomiting, unresponsive to analgesic drugs, that required hospitalization. No other cause than treatment with Mepolizumab was found to be plausibly associated with this new-onset headache. The therapeutic regimen was modified by administering Mepolizumab for two consecutive months alternated with a one-month break. The patient did not experience any further episodes of headache, while maintaining a good and stable control of his asthma. We were able to taper oral corticosteroids, and no flares-ups occurred in the following 5 years. Our experience indicates that a tailored strategy for managing severe asthmatic patients, who have experienced side effects from biologic drugs, can be effective in maintaining drug efficacy while minimizing side effects. Further studies on a larger number of patients are required to demonstrate whether the positive outcomes here described are replicable on a larger scale. [ABSTRACT FROM AUTHOR]

Clinical trials and real world studies demonstrated benefit of mepolizumab treatment in severe asthma but data on its effectiveness beyond 2 years remain limited. Herein, we provide mepolizumab treatment evaluation up to 4 years. we studied all patients initiated on mepolizumab in our center from June 2017 to August 2018. Clinical outcomes data were retrieved from the local dendrite systems registry. Comparison analyses and logistic regression were conducted to explore longevity and predictors of response to mepolizumab treatment. a total of 66 patients initiated on mepolizumab with a median follow-up of 45.8 (42.4,48.1) months were included in the study [mean age 50.3 years (range 18-79), females 50 (73%) ]. At 20.7 months of treatment, 42 patients (63.6%) had positive response, 13 (19.7%) negative response, and 11 (16.7%) discontinued due to other factors. At 45.8 months, 35 (53%) patients were still on mepolizumab, 21 (31.8%) switched to a different biologic, and 10 (15.2%) discontinued biologics. Two deaths were recorded during the study period. The median blood eosinophil was reduced from 0.43x109/L (0.27, 0.75) to 0.04 (0.0, 0.1) (p < 0.00001)]. The median annual exacerbations were reduced from 6.0 (4,8) to 1.0 (0.0,3.0) (p < 0.00001), and mOCS use was reduced from59% to 29%, p = 0.001. The mean asthma control questionnaire-6 (ACQ6) improved from 3.1 ± 1.7 to 2.1 ± 1.3 (p < 0.00001). mepolizumab clinical benefit was sustained over 4 years. However, approximately half of the cohort discontinued the treatment prompting the need for further research into the treatment response longevity. [ABSTRACT FROM AUTHOR]

The data on the use of dual biologics are scant, but a topic of current interest. In this report, the treatment regimen of a patient with two T helper 2 pathway-related comorbidities, severe asthma, and chronic spontaneous urticaria, was presented. Both urticaria and asthma symptoms of the patient could not be controlled entirely with monotherapy while both diseases could be controlled after omalizumab-mepolizumab dual treatment. No adverse events were observed after 6 months of dual biologics use. This report supports other publications in the literature involving the use of dual biologics and provides a summary of the literature. [ABSTRACT FROM AUTHOR]

Background: Asthma has a high healthcare burden globally, with up to 10% of the asthma population suffering from severe disease. Biologic agents are a newer class of asthma treatments for severe asthma, with good evidence for efficacy in clinical trials. Nevertheless, real-world studies of its impact on clinical outcomes are limited. Methods: This is an observational cohort study using administrative claims data. The study population consisted of patients aged ≥18 years who had a diagnosis of asthma and initiated mepolizumab after November 4, 2015 and had continuous medical and drug coverage in both the 365 days prior to and following mepolizumab initiation. In patients treated with mepolizumab, we described clinically significant asthma exacerbations by minimum continuous treatment thresholds following initiation of mepolizumab, medication switching patterns and chronic oral corticosteroid (≥28 days) use. Results: We identified 2,536 adults with asthma who initiated mepolizumab. There was an association toward reduction in severe asthma-related events over the first one year of exposure. We observed associations with reduced dispensings of oral corticosteroids over the first year after mepolizumab initiation. Very few patients switched to other biologics during the study period. Conclusions: Treatment with mepolizumab may be associated with fewer asthma-related events in the first year. Over the first one year after initiating mepolizumab, we found associations with decreased concomitant dispensings of oral corticosteroids and medium to high dose ICS/LABA. Additionally, most patients who initiated mepolizumab did not switch to other biologics. [ABSTRACT FROM AUTHOR]

Introduction: Many studies have reported a poor prognosis for eosinophilic granulomatosis with polyangiitis (EGPA) patients with cardiac involvement. Case study: a woman developed eGpa at 37 years of age, with weight loss, numbness in the right upper and lower extremities, muscle weakness, skin rash, abdominal pain, chest pain, an increased peripheral blood eosinophil count (4165/µL), and necrotizing vasculitis on peroneal nerve biopsy. the patient was treated with prednisolone, immunosuppressants, intravenous immune globulin, and mepolizumab, but she experienced many relapses, with chest pain, abdominal pain, numbness, and paralysis, over a long period. the patient died from aspiration pneumonia at 71 years of age after undergoing left total hip arthroplasty for left hip neck fracture. Results: autopsy showed bronchopneumonia in the lower lung lobes on both sides, as well as infiltration of inflammatory cells, including neutrophils and lymphocytes. there was no evidence of active vasculitis in either the lung or colon. at autopsy the heart showed predominantly subendocardial fibrosis and fatty infiltration, but no active vasculitis or eosinophilic infiltration. Conclusion: to our knowledge, there have been no autopsy reports of EGPA patients who have survived for 34 years with recurrent cardiac lesions. In this case, the cardiac involvement (active vasculitis and eosinophilic infiltration) had improved by the time of death. [ABSTRACT FROM AUTHOR]

NSAID-exacerbated respiratory disease (NERD) is characterized by exacerbation of respiratory symptoms after NSAID intake. While research for specific treatment options continues in patients who cannot tolerate or are unresponsive to aspirin treatment after aspirin desensitization (ATAD), biologicals have emerged as a new therapeutic option in NERD patients. The aim of this study was to compare the quality of life, and the sinonasal and respiratory outcomes of NERD patients treated with ATAD or biologicals. Patients who have been followed up at a tertiary care allergy center and who have been receiving at least one of ATAD, mepolizumab or omalizumab for at least six months were included. Evaluations were made using sinonasal outcome test (SNOT-22), asthma control test (ACT), short form-36 (SF-36), blood eosinophil counts, need for recurrent functional endoscopic sinus surgeries (FESS), and asthma or rhinitis exacerbations requiring oral corticosteroids (OCS). A total of 59 patients comprised of 35 (59%) females and 24 (41%) males with a mean age of 46.1 (min-max, 20–70) years were included. The baseline blood eosinophil count was higher, and a significant decrease in blood eosinophil counts was observed in the mepolizumab group compared to ATAD group (p = 0.001, p < 0.001, respectively). At follow-up, the rate of recurrent FESS was lower in the group that received mepolizumab (p = 0.02). In NERD patients, mepolizumab significantly decreased blood eosinophil counts and recurrent FESS. There was no significant difference between the patients receiving ATAD or mepolizumab regarding other clinical parameters. [ABSTRACT FROM AUTHOR]

Results of biological therapies are often encouraging for severe asthma who are phenotyped as Type 2 inflammation. Unfortunately, some patients do not achieve the desired responses. In this group of patients, there are often switches between anti Ig E and anti-IL-5s and partial improvements are often is deemed sufficient. We planned to start combination therapy with mepolizumab and omalizumab in a 52-year-old patient with uncontrolled allergic asthma whose asthma could not be controlled with omalizumab and mepolizumab treatment, respectively. After complete asthma control was achieved, we aimed to discontinue mepolizumab and continue with omalizumab because it was allergic asthma. The combination of omalizumab 300 mg/month and mepolizumab 100 mg/month was tried and emergency admissions and oral corticosteroids were stopped. At the same time, significant improvement was observed in asthma control test, pulmonary function test and comfort of life. Combined use of Anti-Ig E (omalizumab) and Anti IL 5 (mepolizumab) with a synergistic effect by acting through both pathways, especially in patients with allergic asthma and high levels of both total Ig E and eosinophilia, was found to be effective and no side effects were observed in long-term follow-up. Combination therapy with omalizumab and mepolizumab may become a safe option in patients with severe allergic asthma with a Type 2 inflammatory phenotype who cannot be controlled with each biologic agent. [ABSTRACT FROM AUTHOR]

Mepolizumab, a humanized anti IL-5 monoclonal antibody, has been used off-label for chronic eosinophilic pneumonia (CEP), inducing disease remission and saving systemic corticosteroids. We present a case of CEP, requiring long-term corticosteroids therapy due to relapse upon withdrawal. Mepolizumab was started and maintained for 2 years and 6 months. Corticosteroids could be withdrawn and mepolizumab dose interval was spared up to 10 wk with no disease relapse. Mepolizumab is shown to be useful for chronic eosinophilic pneumonia, allowing corticosteroid withdrawal. Dose interval may be individualized under close monitoring, for a more efficient treatment, reducing medical costs while improving patients' quality of life. [ABSTRACT FROM AUTHOR]

Severe eosinophilic asthma (SEA) is associated with multiple exacerbations. Fractional exhaled nitric oxide (FeNO), a biomarker of airway T2 inflammation, is known to be correlated with the risk of exacerbations. While the use of FeNO is well established to predict the therapeutic response to dupilumab (anti-IL-4/IL-13), it remains uncertain for biologics targeting the IL-5 pathway. We conducted an observational, retrospective, monocentric analysis of adults with SEA who started mepolizumab (anti-IL-5) or benralizumab (anti-IL-5R) between January 1, 2016 and December 31, 2020. Data were collected for 109 patients. All participants reported uncontrolled asthma with a median of 3 annual exacerbations and a median Asthma Control Test score of 12. They all had an initial blood eosinophilia >300/mm3, with a median at 610/mm3 (IQR 420-856). Patients with a baseline FeNO ≥50 ppb reported more exacerbations in the previous year than those with a FeNO <50 ppb (p = 0.02). After initiation of treatment, change in FeNO was not associated with therapeutic response. However, decrease in the annual number of exacerbations was significantly greater in patients with a baseline FeNO ≥50 ppb than in those with a baseline FeNO <50 ppb (-3.3 ± 2.7 vs −0.9 ± 2.4, respectively; p = 0.01). There was no association between baseline FeNO values and subsequent lung function, asthma control or reduction of oral corticosteroids use. In this real-world cohort, adults with SEA who had a baseline FeNO ≥50 ppb experienced a greater decrease in exacerbations after 12 months of anti-IL-5 or IL-5R biologics than those with a FeNO <50 ppb. [ABSTRACT FROM AUTHOR]

Background: Mepolizumab 300 mg is an approved treatment option for patients with eosinophilic granulomatosis with polyangiitis (EGPA), yet, the adequacy of 100 mg of mepolizumab in disease control is controversial. Objective: To evaluate the sinonasal and respiratory outcomes of EGPA patients treated with 100 mg mepolizumab for one year. Methods: Evaluations of 11 patients were made of the sinonasal outcome test (SNOT-22) (nasal, otologic, sleep, and emotional domains), asthma control test (ACT), forced expiratory volume in 1 s (FEV1), blood eosinophil counts and oral steroid doses before mepolizumab treatment (T0) and at the 6th (T6) and 12th (T12) months. Results: A significant decrease was observed in the total SNOT-22 scores in the 6th month, after which the scores continued to be stable until the 12th month. (SNOT-22 median (IQR); T0: 70(53-82); T6: 19(4-35); T12: 11(6-40); T0-T6, p = 0.02; T6-T12, p = 0.85). In the subdomains of SNOT-22, nasal and sleep-related domains improved significantly in the first 6 months, and the otologic and emotional domains only improved from baseline in the 12th month. There was a significant decrease in blood eosinophil counts in the 6th month and oral steroid dose in the 12th month (eosinophils, median(IQR), T0: 1000(700-1800), T6: 100(0-200), p = 0.02; OCS dose, median(IQR), T0: 16(8-16); T6: 4(0-4); T12: 0(0-4); T0-T12, p = 0.002). A significant improvement was observed in ACT values in the 6th month (ACT median (IQR); T0:16(8-18); T6: 22(21-25); p = 0.01). Conclusion: Mepolizumab 100 mg provided a significant decrease in SNOT-22 values, especially in nasal and sleep domains, eosinophil counts and OCS dose in the 6th month. [ABSTRACT FROM AUTHOR]

In order to decrease the use of systemic corticosteroids and prevent asthma exacerbations, EAACI and GINA made recommendations in favor of severe asthma patients continuing the use of biologicals during the pandemic. However, the course of SARS-CoV-2 infection remains uncertain, especially in patients taking biological therapy for severe asthma. The aim of this study was to demonstrate the clinical course of COVID-19 in severe asthmatic patients receiving biological treatment. A total of 75 patients under the care of a tertiary level allergy clinic and receiving omalizumab or mepolizumab, which are the approved biologicals for severe asthma in Turkey, were included in the survey between April 1 and December 31, 2020. A questionnaire was administered via a telephone call by one of the treating physicians. Of the total patients, 46 (61%) were receiving mepolizumab and 29 (39%) omalizumab. Of the patients, 14 (19%) had COVID-19, 9 (64%) had pneumonia, 4 (29%) were hospitalized. A total of 12 (16%) patients interrupted biological treatments because they did not want to attend hospital for injections during the pandemic. The incidence of COVID-19 was higher in patients who have interrupted biological treatment (p < 0.001). In addition, the risk of having COVID-19 was higher in the ones who have interrupted their biological treatment (Relative risk:2.71; 95% Confidence interval:1.21-6.06). Asthma control was better in patients attending regular injections (p = 0.006). Severe asthma itself seems to be a risk factor for COVID-19, whether biological treatment has a role in the disease course needs further research. [ABSTRACT FROM AUTHOR]

Monoclonal antibodies (mABs) have become available to treat more efficiently patients with severe uncontrolled asthma (SUA). However, the use of mABs is lower than expected given the prevalence of SUA, with significant disparities in the use of these treatments. To evaluate the proportion of patients with SUA treated with mABs in Spain, and to analyze some of the factors that could determine these prescription patterns. An analysis was performed on the data provided from the Hospitals National Health System (NHS) 2018 catalogue where Chest Diseases Department and a Hospital Pharmacy were available. Random sampling was performed to determine the sample size, stratifying proportionally by geographic area and hospital level. Characteristics of the participating sites, as well as the prescribing of mABs were collected, which included geographic area, hospital levels, prescribing medical specialities, types of clinics, and mABs prescribed. Data from 90 hospitals were analyzed (Response rate 64.3%). Level 4 hospitals, the Canary Islands geographical area, and the presence of a high complexity Asthma Healthcare Unit (ACU) were associated with a higher probability that the SUA was treated with mABs. The map of the prescribing of mABs for SUA in Spain shows a significant variation by geographic area, hospital level, type of clinic, and the accreditation level of the ACUs. At the current time, there appears to be significant under-prescribing of these treatments. [ABSTRACT FROM AUTHOR]

Add-on therapy with monoclonal antibodies is the recommended therapy for severe asthmatic patients refractory to maintenance treatment. In randomized control trials, mepolizumab reduced the number of exacerbations, the need of oral corticosteroids (OCS), increased asthma control, and lung function in a population of uncontrolled severe eosinophilic asthmatic patients. In this piece of work, we aimed to assess mepolizumab efficacy and safety in a cohort of patients with severe eosinophilic asthma in real-life conditions. A retrospective study was carried out at eight hospitals from Asturias (Spain). The sample included patients treated with mepolizumab from 1 January 2016 to 31 March 2019. Demographic and clinical variables were collected, including OCS use, asthma control, lung function, and exacerbation rate. Sixty-nine patients (72% women) with mean age 56 ± 13 years were included. Annual exacerbation rate decreased from 4.7 (SD 3.7) to 1.3 (SD 2.5) (p < 0.001). The number of patients requiring OCS treatment decreased from 25 patients (36%, mean prednisone dose = 18 mg/day) to 13 patients (19%, mean prednisone dose = 9 mg/day) (p < 0.001). Twelve patients (48%) stopped OCS treatment. Forced expired volume in one second (FEV1) as percentage increased from 68% (SD 20) to 76% (SD 21) (p < 0.001). Fifty-six patients (81%) were considered responders to mepolizumab. No serious adverse events were detected during the study period. Overall, this study demonstrates mepolizumab efficacy and safety in a cohort of patients with uncontrolled severe eosinophilic asthma in routine clinical practice. [ABSTRACT FROM AUTHOR]

To evaluate the cost-effectiveness of mepolizumab added to standard of care (SOC) compared with SOC alone among patients with severe uncontrolled eosinophilic asthma in the Singapore setting. A Markov model with three health states (asthma on mepolizumab and SOC, asthma on SOC alone, and death) was developed from a healthcare system perspective over a lifetime horizon. During each 4-week cycle, patients in the non-death health states could experience asthma exacerbations requiring oral corticosteroid burst, emergency department visit, or hospitalization. Asthma-related mortality following an exacerbation or all-cause mortality could also occur at each cycle. The model was populated using local costs while utilities were derived from international literature. Transition probabilities were obtained from a mixture of Singapore-specific and internationally published data. The base-case analysis comparing mepolizumab plus SOC with SOC alone resulted in an incremental cost-effectiveness ratio (ICER) of SGD335 486 (USD238 195) per quality-adjusted life-year (QALY) gained. Sensitivity analysis demonstrated that the ICER was most sensitive to the price of mepolizumab, followed by the proportion of exacerbations which required hospital intensive care. Despite restricting mepolizumab use to patients with a higher baseline exacerbation rate (3 in the past year) in a scenario analysis, the ICER remained high at SGD238 876 (USD 169 602) per QALY gained. At its current price, mepolizumab is not considered a cost-effective use of healthcare resources in Singapore. Substantial price reductions for mepolizumab are required to improve its cost-effectiveness to an acceptable range. These results will be useful to inform national funding decisions. [ABSTRACT FROM AUTHOR]

Introduction: Severe eosinophilic asthma is an incapacitating disease. Mepolizumab, a humanized anti-interleukin-5 monoclonal antibody, proved to be effective as an add-on therapy in patients with severe eosinophilic asthma. However, only data from randomized controlled trials are available and real world data are lacking. Methods: A retrospective observational longitudinal study was conducted in a real world cohort of patients with severe eosinophilic asthma treated with mepolizumab. The primary objective was to determine response rate, based on a global evaluation of treatment effectiveness by the treating pulmonologist. Secondary objectives were to assess exacerbation frequency, systemic maintenance glucocorticoid usage, Asthma Control Questionnaire (ACQ), lung function, and adverse events. Results: Seventy-eight patients were included. Treatment with mepolizumab was considered beneficial and was therefore continued in 75.6% of patients 12 months from the initiation of mepolizumab. The most common reason for drop-out was insufficient response. Secondary objectives: 12 months from the initiation of mepolizumab there was a decrease of 3.2 (CI 2.5–4.1; p < 0.001) severe asthma exacerbations per year, a decrease of ACQ of 0.80 points (CI 0.49–1.12; p < 0.001), and an increase of 3.7 (CI 0.3–7.2; p = 0.034) percent of predicted FEV1 compared to baseline. At baseline 51.3% of patients were treated with systemic glucocorticoid maintenance therapy, compared to 15.4% (p < 0.001) of patients 12 months from the initiation of mepolizumab. No serious adverse events considered to be related to mepolizumab were reported. Conclusion: This study confirms that mepolizumab add-on therapy is effective and safe in a real world cohort of patients with severe eosinophilic asthma. [ABSTRACT FROM AUTHOR]

The interleukin 5 (IL-5) pathway is an important component in the pathophysiology of severe eosinophilic asthma. Mepolizumab is a monoclonal antibody that targets the IL-5 pathway. Clinical trials showed efficacy of Mepolizumab in patients with severe eosinophilic asthma. However, reports on experience with treatment in a real-world cohort are limited. Evaluation of the efficacy and safety of Mepolizumab for treatment of severe eosinophilic asthma in a real-world cohort of patients. A clinical prospective observational trial included all patients >18 years treated with Mepolizumab between March 2016 to March 2019 at Rabin Medical Center. The composite primary outcome measures evaluated: increase in FEV1 by≥ 200 ml and/or decrease in exacerbation rate of ≥50% and/or cessation of oral corticosteroids (OCS) treatment or ≥50% decrease in dosage. Also evaluated: blood eosinophil count, adverse events and quality of life. Of 61 patients, 50 (82.0%) achieved the primary outcome. The number of patients who suffered from frequent exacerbations decreased from 52 (85.2%) to 8 (13.1%) (p < 0.001). Twenty-two patients (68%) stopped OCS treatment or received >50% reduced dosage (p < 0.001). Mean FEV1 increased from 1.72 ± 0.78 liters to 1.87 ± 0.85 liters (p = 0.043). Response to therapy was seen within six months. Forty-nine patients (80%) reported an improvement in quality of life (p < 0.001). Only minor adverse events were reported. Treatment with mepolizumab was well tolerated and significantly lowered the exacerbation rate and OCS dependence in a real-world cohort of severe eosinophilic asthma patients. Response to therapy was within six months and treatment effect was sustained over time. [ABSTRACT FROM AUTHOR]

Difficult-to-treat or severe persistent asthma accounts for 5–10% of the asthma population worldwide. However, this group of patients creates a higher burden on health systems due to their morbidity and need for long-term and additional treatment. Biological drugs constitute an alternative therapy in the treatment of patients with refractory asthma. In cases where inhalant allergy is part of the pathomechanism, allergen-specific immunotherapy (SIT) is a causative treatment option for allergic asthma. However, SIT is contraindicated for uncontrolled asthma and cannot be administered according to the guidelines. This is due to the risk of further worsening of uncontrolled asthma during treatment. We herein report a case of a 67-year-old male with severe allergic asthma who was successfully treated with SIT after asthma control was achieved by using target treatments. Complete control of asthma was achieved, and SIT with allergens from early flowering trees (birch-alder-hazel) was administered. Further, no asthmatic exacerbations or decrease in respiratory function occurred during the 15 months of treatment with mepoluzimab. He did not need any oral glucocorticosteroids. The case report presented here suggests the effectiveness of an individualized approach and phenotype-specific treatment of patients who cannot receive allergen-specific immunotherapy due to the contraindication uncontrolled asthma and who receive SIT after asthma control is achieved by using target treatments. [ABSTRACT FROM AUTHOR]

Objective: To assess the effect of asthma exacerbations and mepolizumab treatment on health status of patients with severe asthma using the St George's Respiratory Questionnaire (SGRQ). Methods: Post hoc analyses were conducted using data from two randomized controlled trials in patients ≥12 years old with severe eosinophilic asthma randomized to receive placebo or mepolizumab 75 mg intravenously (32-week MENSA study) or 100 mg subcutaneously (MENSA/24-week MUSCA studies), and an observational single-visit study in patients with severe asthma (IDEAL). Linear regression models assessed the impact of historical exacerbations on baseline SGRQ total and domain scores (using data from each of the three studies), and within-study severe exacerbations and mepolizumab treatment on end-of-study SGRQ scores (using data from MENSA/MUSCA). Results: Overall, 1755 patients were included (MENSA, N = 540; MUSCA, N = 551; IDEAL, N = 664). In all studies, higher numbers of historical exacerbations were associated with worse baseline SGRQ total scores. Each additional historical exacerbation (beyond the second [MENSA/MUSCA]) or first [IDEAL] was associated with worsening mean total SGRQ scores of +1.5, +1.1 at baseline and +2.3 within the year prior to study enrollment. During MENSA and MUSCA, each within-study severe exacerbation was associated with a worsening in total SGRQ score of +2.4 and +3.4 points at study end. Independent of exacerbation reduction, mepolizumab accounted for an improvement in total SGRQ score of −5.3 points (MENSA) and −6.2 points (MUSCA). Conclusions: These findings support an association between a higher number of exacerbations and worse health status in patients with severe (eosinophilic) asthma. [ABSTRACT FROM AUTHOR]

The clinical phenotyping of severe asthma could improve treatment outcomes, quality of life, morbidity, and mortality of asthma patients. The growing availability of rich clinical data could provide opportunities to address a broad range of real-world questions regarding clinical phenotyping and effective therapeutic approaches of severe asthma. Accordingly, in this Letter to the Editor, we provide data relevant to constructing the clinical profile of a Greek severe asthma patient cohort who receive biological treatment. [ABSTRACT FROM AUTHOR]

Objectives: Assess the relationship between inhaled corticosteroid use (ICS) and weight (BMI) in pediatric patients with moderate-severe asthma. Assess if the number of emergency department (ED) visits correlates with overall BMI trajectory. Assess the trend of prescribing biologic therapy in pediatric patients with moderate-severe asthma and determine its relationship with weight (BMI). Methods: A retrospective chart review was performed on 93 pediatric patients with moderate-severe asthma to determine the relationship between ICS use and weight (BMI), biologic therapy and BMI, and number of ED visits and BMI trajectory. A mixed effects model was employed with the correlation between repeated measures accounted for through the random effects. Results: There is a statistically significant increase of 0.369 kg/m2 in BMI trajectory per year in subjects on high-dose steroids compared to an increase of 0.195 kg/m2 in the low dose group (p < 0.05). The BMI of subjects initiated on biologic therapy (omalizumab or mepolizumab) had a statistically significant decrease in BMI trajectory of 0.818 kg/m2 per year (p < 0.05). Subjects with ≥5 ED visits due to asthma exacerbations had a significantly higher BMI trajectory (p < 0.05). Conclusions: The potency of ICS use in pediatric patients with moderate-severe asthma affects BMI trajectory; the higher the dose, the greater the projected BMI increase per year. Initiation of biologic therapy decreased BMI trajectory over time. Lastly, those with frequent ED visits had a higher BMI trend. Future prospective studies are warranted that further evaluate the potential metabolic impacts of ICS and assess the effects of biologic therapy on BMI. [ABSTRACT FROM AUTHOR]

Objectives: Severe asthma comprises several distinct phenotypes. Consequently, patients with severe asthma can be eligible for more than one biologic treatment targeting Th2 inflammation, such as anti-interleukin (IL)-5 and anti-immunoglobulin (Ig) E. The objective of this study was to describe treatment eligibility and overlap in treatment eligibility for mepolizumab (anti-IL-5), omalizumab (anti-IgE) and reslizumab (anti-IL-5) in patients with severe asthma, who were recruited from clinical practice.Methods: This cross-sectional, single-visit, observational study in six countries enrolled patients with severe asthma (defined by American Thoracic Society/European Respiratory Society guidelines). Assessable patients were analysed as a total cohort and a sub-cohort, who were not currently receiving omalizumab. Treatment eligibility was defined according to the local prescribing information or protocol-defined inclusion/exclusion criteria. Patients currently receiving omalizumab were automatically categorised as omalizumab-eligible.Results: The total cohort comprised 670 patients who met the analysis criteria, of whom 20% were eligible for mepolizumab, 31–41% were eligible for omalizumab (depending on eligibility criteria used), and 5% were eligible for reslizumab. In patients not currently receiving omalizumab (n= 502), proportions eligible for each biologic were similar (mepolizumab: 20%, reslizumab 6%) or lower (omalizumab 7–21%) than those for the total cohort. Overlap in treatment eligibility varied; in mepolizumab-eligible patients not currently receiving omalizumab (n= 101), 27–37% were omalizumab-eligible and 18% were reslizumab-eligible.Conclusions: Treatment eligibility for mepolizumab and omalizumab was higher than that for reslizumab. Although there was some overlap in treatment eligibility, the patient groups eligible for treatment with anti-IL-5 or anti-IgE therapies were often distinct, emphasising the different phenotypes and endotypes in severe asthma. [ABSTRACT FROM PUBLISHER]

Objective: The purpose of this study is to examine the comparative efficacy of Omalizumab (OMA) and Mepolizumab (Mepo) in the treatment of severe asthma by performing a network meta-analysis. Method: Data Sources: A systematic review of the literature was performed through four databases from their inception to February 2016. Study Selections: Randomized control trials and cohort studies were considered if they addressed the individual efficacy of OMA and Mepo in the treatment of asthma that was not well controlled on inhaled corticosteroids (ICSs) with or without other agents. Results: OMA was significantly better than Mepo in improving the Asthma Quality of Life Questionnaire with a mean difference of 0.38 and a confidence interval of (0.21–0.55), p < 0.0001, without reaching the minimal clinically important difference of 0.5. No significant difference was seen in Asthma Control Questionnaire, forced expiratory volume in second 1 (FEV1), and Peak Expiratory Flow Rate (PEFR) improvement from baseline. Both medications were successful in reducing the calculated annualized rates of asthma exacerbations (AEs) vs placebo by approximately 50%. The heterogeneity score for the different comparisons were elevated except for the PEFR. Conclusion: When compared indirectly via a network meta-analysis, the efficacy of OMA and Mepo was similar in the treatment of asthma that was not well controlled on at least high-dose ICS. The high heterogeneity observed and the different selection criteria for the use of the two drugs do not permit us to make any definitive recommendations for the preferential use of OMA vs Mepo in the patient populations studied. However, the current data do not suggest any major differences in efficacy. [ABSTRACT FROM AUTHOR]

A Combination of Mepolizumab and Omaluzimab injections for severe asthma. Introduction. Patients with severe persistent asthma account for a large proportion of asthma morbidity and health care expenditures. In this case report we describe the use of a combination of omalizumab and mepolizumab in severe asthma with elevated IgE levels and eosinophilic phenotype. Case Study: We are treating a 55 year old woman with severe persistent eosinophilic asthma and elevated IgE levels. Her regimen included salmeterol/fluticasone propionate inhaler 500/50 one puff twice a day, budesonide nebulizer twice a day, tiotropium respimat inhaler two puffs daily, montelukast 10 mg daily, Albuterol as needed, Azithromycin 250 mg three times a week, and also omalizumab injections. She was having recurrent asthma exacerbations requiring the use of oral corticosteroids. Due to frequent exacerbations, we referred her for Bronchial Thermoplasty. This procedure was denied by insurance and therefore the patient was started on 20 mg PO prednisone daily. Mepolizumab was added approximately 4 months after starting chronic PO prednisone. We were able to taper down the steroids and she is currently on 4 mg daily. Results: Since we added the mepolizumab injections along with the omalizumab injections, we have been able to decrease the prednisone steadily and currently the patient is on 4 mg daily. The plan is to taper off the corticosteroids slowly as the clinical status allows. Conclusion: Combination of omalizumab and mepolizumab could become the gold standard for severe asthma patients that have elevated IgE levels and an eosinophilic phenotype. Case Report: A Combination of Mepolizumab and Omaluzimab injections for severe asthma. [ABSTRACT FROM AUTHOR]