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Journal of Asthma and Allergy 2024Severe eosinophilic asthma (SEA) patients often present overlapping inflammatory features rendering them eligible for multiple biologic therapies; switching biologic...
PURPOSE
Severe eosinophilic asthma (SEA) patients often present overlapping inflammatory features rendering them eligible for multiple biologic therapies; switching biologic treatment is a strategy adopted to optimize asthma control when patients show partial or no response to previous biologics.
PATIENTS AND METHODS
ANANKE is a retrospective, multicenter Italian study (NCT04272463). Here, we outline the characteristics and long-term clinical outcomes in naïve-to-biologics and biologics-experienced patients treated with benralizumab for up to 96 weeks. Bio-experienced patients were split into omalizumab and mepolizumab subsets according to the type of biologic previously used.
RESULTS
A total of 124 (76.5%) naïve and 38 (23.5%) bio-experienced patients were evaluated at index date; 13 patients (34.2%) switched from mepolizumab, 21 patients (55.3%) switched from omalizumab, and four patients (10.5%) received both biologics. The mepolizumab subset was characterized by the longest SEA duration (median of 4.6 years), the highest prevalence of chronic rhinosinusitis with nasal polyposis (CRSwNP) (76.5%), and the greatest oral corticosteroid (OCS) daily dosage (median of 25 mg prednisone equivalent). The omalizumab group showed the highest severe annual exacerbation rate (AER) (1.70). At 96 weeks, treatment with benralizumab reduced any and severe AER by more than 87% and 94%, respectively, across all groups. Lung function was overall preserved, with major improvements observed in the mepolizumab group, which also revealed a 100% drop of the median OCS dose. Asthma Control Test (ACT) score improved in the naïve group while its increment was more variable in bio-experienced patients; among these, a marked difference was noticed between omalizumab and mepolizumab subsets (median ACT score of 23.5 and 18, respectively).
CONCLUSION
Benralizumab promotes durable and profound clinical benefits in naïve and bio-experienced groups, indicating that a nearly complete depletion of eosinophils is highly beneficial in the control of SEA, independently of previous biologic use.
PubMed: 38562251
DOI: 10.2147/JAA.S438981 -
Open Forum Infectious Diseases Apr 2024Omalizumab is an anti-immunoglobulin E monoclonal antibody used to treat moderate to severe chronic idiopathic urticaria, asthma, and nasal polyps. Recent research... (Clinical Trial)
Clinical Trial
BACKGROUND
Omalizumab is an anti-immunoglobulin E monoclonal antibody used to treat moderate to severe chronic idiopathic urticaria, asthma, and nasal polyps. Recent research suggested that omalizumab may enhance the innate antiviral response and have anti-inflammatory properties.
OBJECTIVE
We aimed to investigate the efficacy and safety of omalizumab in adults hospitalized for coronavirus disease 2019 (COVID-19) pneumonia.
METHODS
This was a phase II randomized, double blind, placebo-controlled trial comparing omalizumab with placebo (in addition to standard of care) in hospitalized patients with COVID-19. The primary endpoint was the composite of mechanical ventilation and/or death at day 14. Secondary endpoints included all-cause mortality at day 28, time to clinical improvement, and duration of hospitalization.
RESULTS
Of 41 patients recruited, 40 were randomized (20 received the study drug and 20 placebo). The median age of the patients was 74 years and 55.0% were male. Omalizumab was associated with a 92.6% posterior probability of a reduction in mechanical ventilation and death on day 14 with an adjusted odds ratio of 0.11 (95% credible interval 0.002-2.05). Omalizumab was also associated with a 75.9% posterior probability of reduced all-cause mortality on day 28 with an adjusted odds ratio of 0.49 (95% credible interval, 0.06-3.90). No statistically significant differences were found for the time to clinical improvement and duration of hospitalization. Numerically fewer adverse events were reported in the omalizumab group and there were no drug-related serious adverse events.
CONCLUSIONS
These results suggest that omalizumab could prove protective against death and mechanical ventilation in hospitalized patients with COVID-19. This study could also support the development of a phase III trial program investigating the antiviral and anti-inflammatory effect of omalizumab for severe respiratory viral illnesses requiring hospital admission. ClinicalTrials.gov ID: NCT04720612.
PubMed: 38560604
DOI: 10.1093/ofid/ofae102 -
Journal of Clinical Medicine Mar 2024Kounis syndrome is a condition where inflammatory cells (mostly mast cells with the contribution of macrophages and T-lymphocytes) cause an acute coronary syndrome.... (Review)
Review
Kounis syndrome is a condition where inflammatory cells (mostly mast cells with the contribution of macrophages and T-lymphocytes) cause an acute coronary syndrome. Kounis syndrome comes in four variants: type I in patients with normal coronary arteries; type II in patients with inactive pre-existing atheromatous disease; type III in patients with pre-existing coronary artery stenting; type IV in patients with a pre-existing coronary artery bypass. Recently, we came across a case of recurrent type I Kounis syndrome in our clinical practice. The purpose of the paper is to present our case and conduct a review using the Pubmed scientific database about the most relevant cases of recurrent Kounis syndrome. This review shows that recurrent Kounis syndrome is a rare condition and is mostly associated with Kounis syndrome type III. Recurrent Kounis syndrome may be also triggered by vaccination and it could be associated with chronic spontaneous urticaria. In the last condition, therapy is represented by second-generation anti-histamines and corticosteroids, but also by an anti-IgE monoclonal antibody (omalizumab) in the recalcitrant cases.
PubMed: 38541873
DOI: 10.3390/jcm13061647 -
Life (Basel, Switzerland) Mar 2024This is a multicentric investigation involving two Italian centers that examined the clinical course of COVID-19 in patients receiving biological therapy targeting type...
This is a multicentric investigation involving two Italian centers that examined the clinical course of COVID-19 in patients receiving biological therapy targeting type 2 inflammation and those not receiving biologicals. Since the beginning of the COVID-19 pandemic, the management of respiratory and allergic disorders and the potential impact of biological therapy in the most severe forms has been a point of uncertainty. Our multicentric investigation aimed to compare the clinical course of COVID-19 and the impact of vaccination in an Italian cohort of patients with atopic disorders caused by a type 2 inflammation, such as eosinophilic asthma, chronic rhinosinusitis with nasal polyposis (CRSwNP), atopic dermatitis (AD), and chronic spontaneous urticaria (CSU). A questionnaire was given to patients coming to our outpatient clinic for the first evaluation or follow-up visit, asking for the clinical characteristics of the infection, the ongoing therapy during the infection, any relevant change, and the patient's vaccination status. We enrolled 132 atopic patients from two Italian centers; 62 patients were on biological therapy at the time of infection (omalizumab 31%, mepolizumab 26%, benralizumab 19%, and dupilumab 24%). The median age was 56 (IQR 22.8) for patients on biologicals and 48 (IQR 26.5) for those not on biologicals ( = 0.028). The two groups were comparable in terms of sex, body mass index (BMI), smoking history, and systemic oral corticosteroid use (OCS). There were no significant differences in non-biological therapy and comorbidity between the two groups. The patients not on biological therapy had a prevalence of 87% for asthma, 52% for CRSwNP, 10% for CSU, and 6% for AD. The patients on biologicals had a prevalence of 93% for asthma, 17% for CRSwNP, and 10% for CSU. In our work, we observed that mAbs targeting type 2 inflammation in patients with COVID-19 appeared to be safe, with no worsening of symptoms, prolongation of infection, or increase in hospitalizations. Between the two groups, there were no significant differences in the duration of swab positivity ( = 0.45) and duration of symptoms ( = 0.38). During COVID-19, patients on biologicals experienced a significant increase in common cold-like symptoms ( = 0.038), dyspnea ( = 0.016), and more, but not significant, asthma exacerbations, with no significant differences between the different biologicals. Regarding the vaccination status, we observed that there was an increased number of hospitalizations among unvaccinated patients in both groups, although the difference did not reach statistical significance. No patients on biologicals reported safety issues or adverse effects associated with the use of biological treatments during COVID-19. Our investigation showed that mAbs against type 2 inflammation given during Coronavirus Disease 2019 are safe and do not impact the clinical course or main outcomes. Therefore, we found no signals suggesting that anti-Th2 biological therapy should be discontinued during SARS-CoV-2 infection. Controlled studies and analysis, including data from registries and real-life studies, are required to draw firm conclusions regarding the safety or possible advantages that anti-type 2 mAbs could offer in particular clinical contexts, such as infections.
PubMed: 38541703
DOI: 10.3390/life14030378 -
Medicina (Kaunas, Lithuania) Mar 2024: Real-life data on the efficacy of biologic agents (BAs) on asthma-comorbid CRSwNP are needed. Our primary goal is to investigate the effects of BAs on CRSwNP symptoms,...
: Real-life data on the efficacy of biologic agents (BAs) on asthma-comorbid CRSwNP are needed. Our primary goal is to investigate the effects of BAs on CRSwNP symptoms, as well as endoscopic and tomography scores. Our secondary goal is to show a reduction in the frequency of acute sinusitis exacerbations and the need for surgery. : We conducted a multicenter, retrospective, real-life study. We screened the patients with asthma-comorbid CRSwNP treated with omalizumab or mepolizumab. A total of 69 patients (40 F/29 M; omalizumab n = 55, mepolizumab n = 14) were enrolled. We compared the visual analog scale (VAS), sinonasal outcome test-22 (SNOT-22), nasal congestion score (NCS), Lund-Mackay computed tomography score (LMS), and total endoscopic polyp scores (TPS) before and after BAs. We evaluated the endoscopic sinus surgery (ESS) and acute exacerbations of chronic rhinosinusitis (AECRS) frequencies separately, according to the BAs. The overall median (min-max) age was 43 (21-69) years. The median (min-max) of biologic therapy duration was 35 (4-113) months for omalizumab and 13.5 (6-32) for mepolizumab. Significant improvements were seen in VAS, SNOT-22, and NCS with omalizumab and mepolizumab. A significant decrease was observed in TPS with omalizumab [95% CI: 0-4] ( < 0.001), but not with mepolizumab [95% CI: -0.5-2] ( = 0.335). The frequency of ESS and AECRS were significantly reduced with omalizumab [95% CI: 2-3] ( < 0.001) and [95% CI: 2-5] ( < 0.001); and mepolizumab [95% CI: 0-2] ( = 0.002) and [95% CI: 2-8.5] ( < 0.001), respectively. There was no significant difference in LMS with either of the BAs. Omalizumab and mepolizumab can provide a significant improvement in the sinonasal symptom scores. BAs are promising agents for CRSwNP patients with frequent exacerbations and multiple surgeries.
Topics: Adult; Aged; Humans; Middle Aged; Asthma; Chronic Disease; Nasal Polyps; Omalizumab; Retrospective Studies; Rhinosinusitis; Sinusitis; Turkey; Male; Female; Young Adult
PubMed: 38541174
DOI: 10.3390/medicina60030448 -
The Journal of Dermatological Treatment Dec 2024There is a lack of real-life safety data on treatment options for chronic urticaria in the presence of comedication and comorbidities.
BACKGROUND
There is a lack of real-life safety data on treatment options for chronic urticaria in the presence of comedication and comorbidities.
METHODS
We present a single-center UCARE pilot study of 212 outpatients with chronic urticaria. Patients were divided into three groups according to different CU therapies according to international guidelines.
RESULTS
Of 212 patients, 108 (mean age 48.9 years, 71.3% female) had 59 comorbidities, including cardiovascular, autoimmune and malignant diseases. Patients were followed for a mean of 24.6 months (SD ± 21.3). Urticaria therapies were divided into three groups: A: 105 (97.2%) with omalizumab and 2nd generation antihistamines), B: 16 patients (14.8%): dual therapy with antihistamines and cyclosporine in 10 (9.3%), montelukast in five (4. 6%), dapsone in four (3.7%), hydroxychloroquine in one patient (0.9%), C: 12 (11.1%) patients received a third drug for 4.9 months (SD ± 3.2) and one quadruple therapy (2.1 months). 10 out of 12 (83.3%) patients received montelukast, two (16.7%) cyclosporine, two (16.7%) dapsone and one (8.3%) hydroxychloroquine as a third drug for chronic urticaria.
CONCLUSIONS
Combining treatment modalities for chronic urticaria and comorbidities are available and feasible with a good safety profile.
Topics: Humans; Female; Middle Aged; Male; Hydroxychloroquine; Pilot Projects; Chronic Disease; Chronic Urticaria; Urticaria; Omalizumab; Histamine H1 Antagonists; Cyclosporine; Dapsone; Anti-Allergic Agents; Acetates; Cyclopropanes; Quinolines; Sulfides
PubMed: 38508226
DOI: 10.1080/09546634.2024.2329784 -
American Journal of Clinical and... 2024The aim of this study was to explore the laboratory results in severe as asthma patients with omalizumab therapy and provide evidence for estimating omalizumab efficacy.
OBJECTIVE
The aim of this study was to explore the laboratory results in severe as asthma patients with omalizumab therapy and provide evidence for estimating omalizumab efficacy.
METHODS
Retrospective study of 18 patients with severe asthma received omalizumab therapy in Shanghai General Hospital from 2020 to 2022 was performed. The basic data of patients were collected. The absolute number and the percentage of basophil and eosinophil in peripheral blood, total IgE level in serum, and as pulmonary function were detected at the beginning of treatment and 4 months after treatment. Differences between two groups were analyzed using Paired T test.
RESULTS
The most common allergens collected from patients with moderate to severe asthma were dust mite (positive ratio 55.56%), mixed mold (16.67%), cat and dog dander, and Aspergillus fumigatus (11.11%). There was no significant difference in eosinophil and basophil counts in peripheral blood between the two groups. However, serum total IgE levels increased from (437.55±279.35) KU/L to (1071.42±721.28) KU/L (P=0.004), and FEV1/FVC ratio increased from (65.53±14.15)% to (73.91±13.63)% (P=0.005) after 4 months of treatment.
CONCLUSIONS
The existing laboratory indicators for evaluation of omalizumab efficacy are still very limited, and new biomarkers need to be further developed. Elevated serum IgE levels at four weeks of treatment and FEV1/FVC may be potential indicators for omalizumab monitoring.
PubMed: 38496353
DOI: 10.62347/KDXJ2007 -
BioDrugs : Clinical Immunotherapeutics,... May 2024The management of uncontrolled severe asthma has greatly improved since the advent of novel biologic therapies. Up to August 2022, five biologics have been approved for...
BACKGROUND
The management of uncontrolled severe asthma has greatly improved since the advent of novel biologic therapies. Up to August 2022, five biologics have been approved for the type 2 asthma phenotype: anti-IgE (omalizumab), anti-IL5 (mepolizumab, reslizumab, benralizumab), and anti-IL4 (dupilumab) monoclonal antibodies. These drugs are usually well tolerated, although long-term safety information is limited, and some adverse events have not yet been fully characterized. Spontaneous reporting systems represent the cornerstone for the detection of potential signals and evaluation of the real-world safety of all marketed drugs.
OBJECTIVE
The aim of this study was to provide an overview of safety data of biologics for severe asthma using VigiBase, the World Health Organization global pharmacovigilance database.
METHODS
We selected all de-duplicated individual case safety reports (ICSRs) attributed to five approved biologics for severe asthma in VigiBase, up to 31st August 2022 (omalizumab, mepolizumab, reslizumab, benralizumab and dupilumab). Descriptive frequency analyses of ICSRs were carried out both as a whole class and as individual products. Reporting odds ratios (ROR) with 95% confidence intervals (CIs) were used as the measure of disproportionality for suspected adverse drug reactions (ADRs) associated with the study drugs compared with either all other suspected drugs (Reference Group 1, RG1) or inhaled corticosteroids plus long-acting β-agonists (ICSs/LABAs) (Reference Group 2, RG2) or with oral corticosteroids (OCSs) (Reference Group 3, RG3).
RESULTS
Overall, 31,724,381 ICSRs were identified in VigiBase and 167,282 (0.5%) were related to study drugs; the remaining reports were considered as RG1. Stratifying all biologic-related ICSRs by therapeutic indication, around 29.4% (n = 48,440) concerned asthma use; omalizumab was mainly indicated as the suspected drug (n = 20,501), followed by dupilumab, mepolizumab, benralizumab and reslizumab. Most asthma ICSRs concerned adults (57%) and women (64.1%). Asthma biologics showed a higher frequency of serious suspected ADR reporting than RG1 (41.3% vs 32.3%). The most reported suspected ADRs included asthma, dyspnea, product use issue, drug ineffective, cough, headache, fatigue and wheezing. Asthma biologics were disproportionally associated with several unknown or less documented adverse events, such as malignancies, pulmonary embolism and deep vein thrombosis with omalizumab; alopecia and lichen planus with dupilumab; alopecia and herpes infections with mepolizumab; alopecia, herpes zoster and eosinophilic granulomatosis with polyangiitis related to benralizumab; and alopecia with reslizumab.
CONCLUSIONS
The most frequently reported suspected ADRs of asthma biologics in VigiBase confirmed the presence of well-known adverse effects such as general disorders, injection-site reactions, nasopharyngitis, headache and hypersensitivity, while some others (e.g. asthma reactivation or therapeutic failure) could be ascribed to the indication of use. Moreover, the analysis of signals of disproportionate reporting suggests the presence of malignancies, effects on the cardiovascular system, alopecia and autoimmune conditions, requiring further assessment and investigation.
Topics: Humans; Asthma; Pharmacovigilance; World Health Organization; Anti-Asthmatic Agents; Female; Male; Antibodies, Monoclonal, Humanized; Adverse Drug Reaction Reporting Systems; Databases, Factual; Adult; Biological Therapy; Middle Aged; Aged; Omalizumab; Biological Products
PubMed: 38489062
DOI: 10.1007/s40259-024-00653-6 -
European Annals of Allergy and Clinical... Mar 2024Chronic spontaneous urticaria (CSU), characterized by recurrent itchy wheals and angioedema for > 6 weeks, is a quite common disease that may heavily impair the quality...
Chronic spontaneous urticaria (CSU), characterized by recurrent itchy wheals and angioedema for > 6 weeks, is a quite common disease that may heavily impair the quality of life. Omalizumab, an anti-IgE mAb, has much improved the management of CSU but patients' response to the drug may vary and predictive markers are still largely missing. We investigated the predictive value of the autologous serum skin test (ASST) on omalizumab response. 15 patients with severe CSU eligible for omalizumab treatment were prospectively studied submitting them to ASST and to complete blood count, D-dimer, anti-thyroid peroxidase antibodies, and total IgE measurement before the start of the treatment. 14/15 (93%) responded brilliantly to omalizumab at 3 months assessment. 7 responded in less than 1 month ("early responders") and 7 only after multiple administrations ("late responders"). Of 9 patients scoring positive on ASST, 7 (78%) were late, and 2 (22%) early responders to omalizumab (p = 0.021). Of 6 patients scoring negative on ASST, 5 were early omalizumab responders and 1 did not respond. The PPV and NPV of the ASST for a "late" response to omalizumab were 78% and 100%, respectively. Total IgE were significantly higher in early responders. Although larger prospective studies are needed to confirm these results, this study confirms previous retrospective investigations that the positive ASST appears to predict a slow response to omalizumab in CSU patients.
PubMed: 38482859
DOI: 10.23822/EurAnnACI.1764-1489.337 -
Asia Pacific Allergy Mar 2024
PubMed: 38482458
DOI: 10.5415/apallergy.0000000000000137