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Annals of Allergy, Asthma & Immunology... Aug 2021The anti-immunoglobulin E therapy, omalizumab, improves asthma control and reduces exacerbations in patients with moderate-to-severe allergic asthma. However, it has...
BACKGROUND
The anti-immunoglobulin E therapy, omalizumab, improves asthma control and reduces exacerbations in patients with moderate-to-severe allergic asthma. However, it has been suggested that omalizumab should be reserved for highly allergic patients with multiple allergen sensitivities or perennial-only sensitivities.
OBJECTIVE
To examine impact of allergy burden, including number and type of allergen sensitivities, on omalizumab response in a real-world setting.
METHODS
This post hoc analysis evaluated a subset of omalizumab-treated patients from the Prospective Observational Study to Evaluate Predictors of Clinical Effectiveness in Response to Omalizumab (NCT01922037) who had completed 13 allergen assessments (N=478). Patients were classified by allergen burden (nonsensitized, 1, 2-4, or ≥5 allergen sensitivities) and type of allergen (nonsensitized, seasonal, perennial, or both). Outcome measures included exacerbation rate vs previous year and improvements in lung function and Asthma Quality of Life Questionnaire (AQLQ).
RESULTS
Comparable adjusted exacerbation rates were observed after omalizumab initiation, regardless of number or type of allergen sensitizations (0.56-0.85/y). Improvements in forced expiratory volume in 1 second from baseline at months 6 (0.03-0.09 L) and 12 (-0.08 to 0.08 L) were also similar across subgroups. Least squares mean change in AQLQ from baseline at months 6 (1.0-1.2) and 12 (1.1-1.4) was comparable across patient subgroups, and similar percentages of patients achieved AQLQ minimal clinically important difference of at least a 0.5-point improvement at month 6 (71%-75%), which was maintained or improved to month 12 (71%-89%). In all analyses, 95% confidence intervals overlapped.
CONCLUSION
Overall findings suggest that patients with allergic asthma achieved comparable improvements across distinct outcome measures after omalizumab therapy in a real-world setting, regardless of number and type of allergen sensitizations.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT01922037.
Topics: Adult; Anti-Asthmatic Agents; Antibodies, Anti-Idiotypic; Asthma; Female; Forced Expiratory Volume; Humans; Immunoglobulin E; Male; Middle Aged; Omalizumab; Prospective Studies; Quality of Life
PubMed: 33838339
DOI: 10.1016/j.anai.2021.04.002 -
Acta Medica Academica Aug 2020This review will outline an evidence-based approach for diagnosing and managing children with problematic severe asthma (PSA). Children with PSA have uncontrolled asthma... (Review)
Review
This review will outline an evidence-based approach for diagnosing and managing children with problematic severe asthma (PSA). Children with PSA have uncontrolled asthma symptoms, despite maximal prescribed asthma treatment. These children have high morbidity and mortality and should be referred for specialist respiratory assessment and management. The first step in the assessment of a child with PSA is confirming the diagnosis of asthma using objective evidence. Following this, an assessment of inhaled corticosteroid adherence and a multi-disciplinary team approach is essential for separating difficult asthma (DA) from severe therapy resistant asthma (STRA). The majority of children have DA which entails uncontrolled asthma symptoms due to underlying modifiable factors including poor treatment adherence, poor inhaler technique, exposure to environmental allergens, co-morbid conditions and psycho-social factors. Approximately 20% of children with PSA have STRA, and have persistent asthma symptoms despite good treatment adherence and correction of modifiable factors. Children with STRA typically have multiple and severe aeroallergen sensitization, eosinophilic airway inflammation and high fraction exhaled nitric oxide (FeNO). Further investigation of children with STRA includes an assessment of systemic steroid responsiveness, this is important for confirming the diagnosis of STRA and guiding the choice of additional treatment. Biologics are an add on (immune targeted) therapy for STRA. The current biologics used in children target the T2 helper (Th2) pathway mediating eosinophilic, allergic asthma. CONCLUSION: Future clinical trials of biologics in children will be essential to help identify childhood specific biomarkers and to decide which biologic is best for which individual child.
Topics: Administration, Inhalation; Adolescent; Allergens; Anti-Asthmatic Agents; Antibodies, Monoclonal, Humanized; Anxiety; Asthma; Breath Tests; Child; Comorbidity; Depression; Environmental Exposure; Eosinophilia; Glucocorticoids; Humans; Medication Adherence; Muscarinic Antagonists; Nitric Oxide; Omalizumab; Patient Care Team; Psychology; Respiratory Function Tests; Severity of Illness Index
PubMed: 33189118
DOI: 10.5644/ama2006-124.291 -
International Archives of Allergy and... 2023Chronic urticaria (CU) is a common skin condition that can be divided into chronic spontaneous urticaria (CSU) and chronic inducible urticaria (CIndU). Omalizumab is one...
INTRODUCTION
Chronic urticaria (CU) is a common skin condition that can be divided into chronic spontaneous urticaria (CSU) and chronic inducible urticaria (CIndU). Omalizumab is one treatment option for CU, but currently there are limited clinical studies of omalizumab's efficacy for treating CU in Chinese patients. This study sought to investigate the efficacy and safety of omalizumab treatment for CU patients in a Chinese patient population. Specifically, we aimed to compare the differential efficacy of omalizumab for CSU and CIndU patients and predict risk factors for recurrence.
METHODS
We completed a retrospective clinical data review of 130 CU patients who received omalizumab treatment from August 2020 to May 2022, with a maximum follow-up period of 18 months.
RESULTS
A total of 108 CSU patients and 22 CIndU patients were included in the study. After treatment with omalizumab, the response rate in the CSU group was higher than that in the CIndU group (93.5% vs. 68.2%), and CSU patients accounted for a higher proportion of responders and early responders (responders: 87.1% vs. 12.9%, p < 0.001; early responders: 95.7% vs. 4.3%, p = 0.001). Nonresponders had lower total immunoglobulin E (IgE) levels (75.0 vs. 167.5 IU/mL, p = 0.046) and a relatively shorter duration of treatment (1.0 vs. 3.0 months, p = 0.009) compared to responders. Early responders had shorter disease duration (1.0 vs. 3.0 years, p = 0.028), higher baseline UCT (4.0 vs. 2.0, p = 0.034), lower baseline DLQI (18.0 vs. 18.5, p = 0.026), and shorter total treatment time (2.0 vs. 4.0 months, p < 0.001) compared to late responders. All adverse events reported during treatment were mild. Seventy-four patients with CU discontinued the drug after achieving complete disease control, of which 26 (35.1%) relapsed for 2.0 months (interquartile range: 1.0-3.0 months). Compared with nonrelapsed patients, relapsed patients often had other allergic diseases (42.3% vs. 18.8%, p = 0.029), higher basal levels of total IgE (263.0 vs. 140.0 IU/mL, p = 0.033), and longer disease duration (4.2 vs. 1.0 years, p = 0.002). Relapsed patients could still achieve good disease control after restarting omalizumab therapy.
CONCLUSION
Omalizumab was effective and safe for CSU and CIndU patients. Patients with CSU responded more quickly to omalizumab and showed a relatively better treatment effect. However, there was a possibility of relapse after discontinuation of omalizumab after complete control of CU, and in these cases, restarting omalizumab treatment after relapse was effective.
Topics: Humans; Omalizumab; Anti-Allergic Agents; Chronic Inducible Urticaria; Retrospective Studies; Urticaria; Chronic Urticaria; Chronic Disease; Recurrence; Immunoglobulin E; Treatment Outcome
PubMed: 36996780
DOI: 10.1159/000529250 -
The World Allergy Organization Journal Sep 2022Food allergy (FA) is a growing healthcare problem worldwide and the rising prevalence in many countries can be attributed to lifestyle, environmental, and nutritional... (Review)
Review
Food allergy (FA) is a growing healthcare problem worldwide and the rising prevalence in many countries can be attributed to lifestyle, environmental, and nutritional changes. Immunoglobulin E (IgE)-mediated FA is the most common form of FA affecting approximately 3%-10% of adults and 8% of children across the globe. Food allergen-induced immediate hypersensitivity reactions mediated by IgE and high-affinity IgE receptor (FcεRI) complexes on mast cells and basophils are a major hallmark of the disease. FA can affect several aspects of health-related quality of life and impose a substantial financial burden on patients and healthcare systems. Although currently there is one United States Food and Drug Administration (FDA) and European Medicines Agency (EMA)-approved treatment for peanut allergy (Palforzia), the main treatment approaches are based on allergen avoidance and symptom management. Thus, there is an urgent need for more effective and ideally disease-modifying strategies. Given the crucial role of IgE in FA, anti-IgE monoclonal antibodies are considered promising therapeutic agents. Talizumab was the first humanized anti-IgE antibody to demonstrate substantial protection against allergic reactions from accidental peanut exposure by substantially increasing the peanut reactivity threshold on oral food challenge. However, development of talizumab was discontinued and further trials were performed using omalizumab. In double-blind, Phase 2, placebo-controlled trials in patients with multi-FAs, sustained dosing with omalizumab, or omalizumab in combination with oral immunotherapy, enabled rapid desensitization to multiple trigger foods. In this review, we describe the development of ligelizumab (a derivative of talizumab), a next generation, humanized monoclonal anti-IgE antibody, its existing clinical evidence, and its potential in the management of FA. When compared with omalizumab, ligelizumab binds with ∼88-fold higher affinity for human IgE and recognizes a different epitope that substantially overlaps with the binding site of FcεRI. These properties translate into a high potency to block IgE/FcεRI signaling in both and studies. Given its efficient suppression of IgE levels, good safety and pharmacokinetic/pharmacodynamic profile, ligelizumab clearly warrants further studies for the potential management of FA.
PubMed: 36185545
DOI: 10.1016/j.waojou.2022.100690 -
Pulmonary Pharmacology & Therapeutics Dec 2021The anti-immunoglobulin E (IgE) antibody, omalizumab (Xolair), is approved in the United States for the treatment of allergic asthma and chronic spontaneous urticaria,...
The anti-immunoglobulin E (IgE) antibody, omalizumab (Xolair), is approved in the United States for the treatment of allergic asthma and chronic spontaneous urticaria, and has recently been studied for the treatment of nasal polyposis following completion of the two replicate phase 3 studies (POLYP 1 and POLYP 2). The dosing of omalizumab used in the phase 3 studies is based on a combination of patients' pre-treatment IgE level and body weight, similar to the approach used in allergic asthma. The objectives of the current analyses were to evaluate whether the pharmacokinetics (PK) of omalizumab and its pharmacodynamic (PD) effect on free and total IgE level in chronic rhinosinusitis with nasal polyps (CRSwNP) are consistent with those in allergic asthma via population PK/PD modeling and simulation, and to graphically explore exposure-response relationships and free IgE-response relationships in CRSwNP. Omalizumab PK and PD effect of total and free IgE in CRSwNP are generally consistent with those in asthma. Observed post-treatment free IgE suppressions were generally within the target range of the baseline IgE- and body weight-based omalizumab dosing table, with 74.2% and 93.0% of patients achieving a serum free IgE level below 25 ng/mL and 50 ng/mL, respectively at Week 24. Exposure-response analyses indicated that there was no clear correlation between omalizumab or free IgE concentration and key efficacy endpoints within the POLYP studies. Overall, these results indicate that the body weight and IgE-based dosing regimen of omalizumab was appropriate for use in CRSwNP patients.
Topics: Asthma; Chronic Disease; Humans; Nasal Polyps; Omalizumab; Sinusitis
PubMed: 34592476
DOI: 10.1016/j.pupt.2021.102080 -
Respiratory Research Dec 2023Biomarkers are needed to inform the choice of biologic therapy in patients with asthma given the increasing number of biologics. We aimed to identify proteins associated...
INTRODUCTION
Biomarkers are needed to inform the choice of biologic therapy in patients with asthma given the increasing number of biologics. We aimed to identify proteins associated with response to omalizumab and mepolizumab.
METHODS
Aptamer-based proteomic profiling (SomaScan) was used to assess 1437 proteins from 51 patients with moderate to severe asthma who received omalizumab (n = 29) or mepolizumab (n = 22). Response was defined as the change in asthma-related exacerbations in the 12 months following therapy initiation. All models were adjusted for age, sex, and pre-treatment exacerbation rate. Additionally, body mass index was included in the omalizumab model and eosinophil count in the mepolizumab model. We evaluated the association between molecular signatures and response using negative binomial regression correcting for the false discovery rate (FDR) and gene set enrichment analyses (GSEA) to identify associated pathways.
RESULTS
Over two-thirds of patients were female. The average age for omalizumab patients was 42 years and 57 years for mepolizumab. At baseline, the average exacerbation rate was 1.5/year for omalizumab and 2.4/year for mepolizumab. Lower levels of LOXL2 (unadjusted p: 1.93 × 10E-05, FDR-corrected: 0.028) and myostatin (unadjusted: 3.87 × 10E-05, FDR-corrected: 0.028) were associated with better response to mepolizumab. Higher levels of CD9 antigen (unadjusted: 5.30 × 10E-07, FDR-corrected: 0.0006) and MUC1 (unadjusted: 1.15 × 10E-06, FDR-corrected: 0.0006) were associated with better response to omalizumab, and LTB4R (unadjusted: 1.12 × 10E-06, FDR-corrected: 0.0006) with worse response. Protein-protein interaction network modeling showed an enrichment of the TNF- and NF-kB signaling pathways for patients treated with mepolizumab and multiple pathways involving MAPK, including the FcER1 pathway, for patients treated with omalizumab.
CONCLUSIONS
This study provides novel fundamental data on proteins associated with response to mepolizumab or omalizumab in severe asthma and warrants further validation as potential biomarkers for therapy selection.
Topics: Humans; Female; Adult; Male; Omalizumab; Anti-Asthmatic Agents; Myostatin; Proteomics; Asthma; Biomarkers; Mucin-1
PubMed: 38057814
DOI: 10.1186/s12931-023-02620-1 -
Life (Basel, Switzerland) Jan 2022Management of patients with asthma during the coronavirus disease 2019 (COVID-19) pandemic is a concern, especially since asthma predisposes patients to respiratory... (Review)
Review
Management of patients with asthma during the coronavirus disease 2019 (COVID-19) pandemic is a concern, especially since asthma predisposes patients to respiratory problems. Interestingly, asthma characterized by type 2 inflammation, also known as T-helper type 2-high endotype, displays a cellular and molecular profile that may confer protective effects against COVID-19. The results of experimental and clinical studies have established the actions of immunoglobulin E (IgE) in inducing airway hyperreactivity and weakening an interferon-mediated antiviral response following respiratory viral infection. Robust evidence supports the beneficial effect of the anti-IgE biologic treatment omalizumab on reducing respiratory virus-induced asthma exacerbations and reducing the frequency, duration, and severity of respiratory viral illness in patients with asthma. Indeed, accumulating reports of patients with severe asthma treated with omalizumab during the pandemic have reassuringly shown that continuing omalizumab treatment during COVID-19 is safe, and in fact may help prevent the severe course of COVID-19. Accordingly, guidance issued by the Global Initiative for Asthma recommends that all patients with asthma continue taking their prescribed asthma medications, including biologic therapy, during the COVID-19 pandemic. The impact of biologic treatments on patients with asthma and COVID-19 will be better understood as more evidence emerges.
PubMed: 35207441
DOI: 10.3390/life12020153 -
Annals of Allergy, Asthma & Immunology... Nov 2023Patient adherence to biologic therapies is crucial for clinical benefits. Previous assessments of US patient adherence to severe asthma (SA) biologic therapies have...
BACKGROUND
Patient adherence to biologic therapies is crucial for clinical benefits. Previous assessments of US patient adherence to severe asthma (SA) biologic therapies have relied on health care insurance claims data that have limitations.
OBJECTIVE
To describe real-world, specialist-reported, biologic administration and adherence among US adults with SA.
METHODS
CHRONICLE (ClinicalTrials.gov identifier: NCT03373045) is an ongoing real-world, noninterventional study of patients with SA treated by US subspecialists. Sites report date and location for all biologic administrations. We evaluated biologic (benralizumab, dupilumab, mepolizumab, omalizumab, reslizumab) adherence as the proportion of days covered (PDC) during the first 52 weeks and the mean number of days until patients received the expected number of doses for 13, 26, and 52 weeks of treatment.
RESULTS
A total of 2117 patients received biologic administrations between February 2018 and February 2022. Most patients (84%) received biologic administrations at a subspecialist site. Over time, administrations at specialist sites decreased, whereas at-home administrations increased. The median PDC was 87%; the mean number of days to receive a 52-week (364-day) equivalent number of doses was 423 for all biologics (average delay of 58 days). Dupilumab had the lowest PDC and highest mean delays in dosing across all intervals; better adherence was observed among commercially insured patients.
CONCLUSION
Patients with SA are mostly adherent to biologic therapies. Biologics with shorter dosing intervals and at-home administration had worse adherence, likely because of greater opportunities for delays. Specialist-reported administration data provide a unique perspective on biologic adherence, which may be overestimated for at-home administrations by insurance claims data.
CLINICAL TRIAL REGISTRATION
ClinicalTrials.gov: NCT03373045.
Topics: Adult; Humans; Asthma; Omalizumab; Biological Products; Anti-Asthmatic Agents
PubMed: 37506846
DOI: 10.1016/j.anai.2023.07.017 -
The World Allergy Organization Journal Feb 2020Adherence to medications is crucial in patients with severe asthma in light of the negative clinical impact and costs of non-adherence. Adherence to omalizumab has not...
BACKGROUND
Adherence to medications is crucial in patients with severe asthma in light of the negative clinical impact and costs of non-adherence. Adherence to omalizumab has not been well studied in real-world settings. The aim of this study was to assess adherence to omalizumab and evaluate treatment effectiveness in relation to adherence.
METHODS
This was a retrospective, observational, and multicenter real-world study. Omalizumab dose, timing of administration, and duration of treatment (<2 years; 2-4 years; > 4 years) were analyzed. Adherence was evaluated by examining rates of expected and missing doses. Good adherence (<10% of doses missed) and poor adherence (>10% doses missed) were determined. For effectiveness in relation to adherence of omalizumab we considered asthma exacerbations, hospitalizations, asthma control test (ACT), and Forced Expiratory Volume in 1 s (FEV).
RESULTS
A total of 196 patients were evaluated, and 161 were suitable for data analyses. Good adherence was shown in 90.7% of patients and poor adherence in 9.3%. Considering adherence in relation to treatment duration: <2 years, 87.8% of patients were adherent (expected doses, 1186; missed doses, 53); 2-4 years, 85.9% were adherent (expected doses, 2985; missed doses, 127); >4 years, 100% were adherent (expected doses, 6120; missed doses, none). Indices of efficacy between pre- and post-treatment showed significant improvement (p < 0.001). The effectiveness indices between pre- and post-treatment, among adherent and non-adherent patients, ACT, and asthma exacerbations both showed significant differences (p = 0.043 and p = 0.049, respectively). Binomial logistic regression analysis showed that increasing age, better ACT score, and 14-day timing were significantly associated with increased adherence to therapy.
CONCLUSIONS
High adherence to omalizumab was demonstrated in a real-world setting, which was associated with better outcomes and control of asthma.
PubMed: 32082464
DOI: 10.1016/j.waojou.2020.100103 -
The World Allergy Organization Journal Aug 2022Chronic rhinosinusitis with nasal polyposis (CRSwNP) can be recalcitrant in some patients despite medical therapies and surgery and has higher morbidity. Omalizumab is a...
BACKGROUND
Chronic rhinosinusitis with nasal polyposis (CRSwNP) can be recalcitrant in some patients despite medical therapies and surgery and has higher morbidity. Omalizumab is a new treatment option for patients with CRSwNP. The aim of this study is to evaluate the efficacy and safety of omalizumab (anti-IgE antibody) in patients with CRSwNP.
METHODS
The efficiency and adverse effects of omalizumab were evaluated based on the data extracted from medical records of patients with CRSwNP. Patients were evaluated monthly for efficacy and adverse reactions. Treatment efficacy was evaluated by visual analog scale (VAS) for rhinorrhea, postnasal drip, sneeze, smell, and nasal stuffiness complaints, sinonasal outcome test-22 (SNOT-22), and nose obstruction symptom evaluation (NOSE) score.
RESULTS
17 patients with CRSwNP formed our cohort. The mean (SD) age, weight, and total IgE level were 41.9 (9.4) years, 78.6 (15) kg, and 198.8 (169.2) IU/mL, respectively. 3 patients had mild, 6 had moderate and 1 had severe asthma as comorbidity. The mean (SD) duration of omalizumab treatment and polypectomy numbers were 9.2 (13.3) months and 2.9 (1.5), respectively. All patients had at least one polyp surgery. All sinonasal outcome parameters were significantly improved by the omalizumab treatment, also in subgroups with and without asthma. The median changes from baseline at the last visit date for omalizumab treatment were as follows: SNOT-22 score decreased from 98 to 19, NOSE score decreased from 100 to 20, the VAS for postnasal drip, rhinorrhea, nasal stuffiness, smell and sneeze decreased from 8 to 2, 8 to 2, 10 to 3, 10 to 2, 6 to 1, respectively (P < 0.001). Patients experienced no adverse reaction with omalizumab treatment.
CONCLUSION
Omalizumab was an effective treatment in patients with recalcitrant CRSwNP with or without asthma.
PubMed: 36017064
DOI: 10.1016/j.waojou.2022.100670