-
The Journal of Allergy and Clinical... Sep 2020Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by IgE hyperproduction and eosinophilic inflammation. The anti-IgE antibody, omalizumab, has... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by IgE hyperproduction and eosinophilic inflammation. The anti-IgE antibody, omalizumab, has demonstrated efficacy in patients with CRSwNP and comorbid asthma previously.
OBJECTIVE
Our aim was to determine omalizumab safety and efficacy in CRSwNP in phase 3 trials (POLYP 1 and POLYP 2).
METHODS
Adults with CRSwNP with inadequate response to intranasal corticosteroids were randomized (1:1) to omalizumab or placebo and intranasal mometasone for 24 weeks. Coprimary end points included change from baseline to week 24 in Nasal Polyp Score (NPS) and Nasal Congestion Score. Secondary end points included change from baseline to week 24 in Sino-Nasal Outcome Test-22 (SNOT-22) score, University of Pennsylvania Smell Identification Test, sense of smell, postnasal drip, runny nose, and adverse events.
RESULTS
Patients in POLYP 1 (n = 138) and POLYP 2 (n = 127) exhibited severe CRSwNP and substantial quality of life impairment evidenced by a mean NPS higher than 6 and SNOT-22 score of approximately 60. Both studies met both the coprimary end points. SNOT-22 score, University of Pennsylvania Smell Identification Test score, sense of smell, postnasal drip, and runny nose were also significantly improved for omalizumab versus placebo. In POLYP 1 and POLYP 2, the mean changes from baseline at week 24 for omalizumab versus placebo were as follows: NPS, -1.08 versus 0.06 (P < .0001) and -0.90 versus -0.31 (P = .0140); Nasal Congestion Score, -0.89 versus -0.35 (P = .0004) and -0.70 versus -0.20 (P = .0017); and SNOT-22 score, -24.7 versus -8.6 (P < .0001) and -21.6 versus -6.6 (P < .0001). Adverse events were similar between groups.
CONCLUSION
Omalizumab significantly improved endoscopic, clinical, and patient-reported outcomes in severe CRSwNP with inadequate response to intranasal corticosteroids, and it was well tolerated.
Topics: Adrenal Cortex Hormones; Adult; Anti-Allergic Agents; Chronic Disease; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Mometasone Furoate; Nasal Polyps; Omalizumab; Rhinitis; Sinusitis; Treatment Outcome
PubMed: 32524991
DOI: 10.1016/j.jaci.2020.05.032 -
The Journal of Allergy and Clinical... May 2023Multiple mAbs are currently approved for the treatment of asthma. However, there is limited evidence on their comparative effectiveness. (Clinical Trial)
Clinical Trial
BACKGROUND
Multiple mAbs are currently approved for the treatment of asthma. However, there is limited evidence on their comparative effectiveness.
OBJECTIVE
Our aim was to compare the effectiveness of omalizumab, mepolizumab, and dupilumab in individuals with moderate-to-severe asthma.
METHODS
We emulated a hypothetical randomized trial using electronic health records from a large US-based academic health care system. Participants aged 18 years or older with baseline IgE levels between 30 and 700 IU/mL and peripheral eosinophil counts of at least 150 cells/μL were eligible for study inclusion. The study period extended from March 2016 to August 2021. Outcomes included the incidence of asthma-related exacerbations and change in baseline FEV value over 12 months of follow-up.
RESULTS
In all, 68 individuals receiving dupilumab, 68 receiving omalizumab, and 65 receiving mepolizumab met the inclusion criteria. Over 12 months of follow-up, 31 exacerbations occurred over 68 person years (0.46 exacerbations per person year) in the dupilumab group, 63 over 68 person years (0.93 per person year) in the omalizumab group, and 86 over 65 person years (1.32 per person year) in the mepolizumab group (adjusted incidence rate ratios: dupilumab vs mepolizumab, 0.28 [95% CI = 0.09-0.84]; dupilumab vs omalizumab, 0.36 [95% CI = 0.12-1.09]; and omalizumab vs mepolizumab, 0.78 [95% CI = 0.32-1.91]). The differences in the change in FEV comparing patients who received the different biologics were as follows: 0.11 L (95% CI = -0.003 to 0.222 L) for dupilumab versus mepolizumab, 0.082 L (95% CI -0.040 to 0.204 L) for dupilumab versus omalizumab, and 0.026 L (95% CI -0.083 to 0.140 L) for omalizumab versus mepolizumab.
CONCLUSIONS
Among patients with asthma and eosinophil counts of at least 150 cells/μL and IgE levels of 30 to 700 kU/L, dupilumab was associated with greater improvements in exacerbation and FEV value than omalizumab and mepolizumab.
Topics: Humans; Anti-Asthmatic Agents; Asthma; Immunoglobulin E; Omalizumab; Comparative Effectiveness Research
PubMed: 36740144
DOI: 10.1016/j.jaci.2023.01.020 -
Allergology International : Official... Jan 2023Biologics have been a key component of severe asthma treatment, and there are currently biologics available that target IgE, IL-5, IL-4/IL-13, and TSLP. Randomized... (Review)
Review
Biologics have been a key component of severe asthma treatment, and there are currently biologics available that target IgE, IL-5, IL-4/IL-13, and TSLP. Randomized controlled trials have established clinical evidence, but a significant portion of patients with severe asthma in real-life settings would have been excluded from those trials. Therefore, real-world research is necessary, and there is a growing body of information about the long-term efficacy and safety of biologics. Multiple clinical phenotypes of severe asthma exist, and it is crucial to choose patients based on their phenotypes. Blood eosinophil count is an important biomarker for anti-IL-5 therapies, and FeNO and eosinophil counts serve as prediction markers for dupilumab. Reliable markers for predicting response, however, have not yet been fully established for omalizumab. Identification of clinical or biological prediction factors is crucial for the path toward clinical remission because the current treatment goal includes clinical remission, which is defined as a realistic goal for remission off treatment. Additionally, since there are now multiple biologic options and overlaps in eligibility for biologics in clinical practice, the evidence regarding the effectiveness of switching the biologics is crucial. Investigations into the clinical trajectory following the cessation of biologics are another important issue. Recent research on omalizumab, mepolizumab, benralizumab and dupilumab's real-world effectiveness, the prediction factor for the efficacy, and the impact of switching or discontinuation will be reviewed and discussed in this review.
Topics: Humans; Omalizumab; Asthma; Eosinophils; Interleukin-5; Interleukin-13; Biological Products; Anti-Asthmatic Agents
PubMed: 36543689
DOI: 10.1016/j.alit.2022.11.008 -
The New England Journal of Medicine Oct 2019In the majority of patients with chronic spontaneous urticaria, most currently available therapies do not result in complete symptom control. Ligelizumab is a... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
In the majority of patients with chronic spontaneous urticaria, most currently available therapies do not result in complete symptom control. Ligelizumab is a next-generation high-affinity humanized monoclonal anti-IgE antibody. Data are limited regarding the dose-response relationship of ligelizumab and the efficacy and safety of ligelizumab as compared with omalizumab and placebo in patients who have moderate-to-severe chronic spontaneous urticaria that is inadequately controlled with H-antihistamines at approved or increased doses, alone or in combination with H-antihistamines or leukotriene-receptor antagonists.
METHODS
In a phase 2b dose-finding trial, we randomly assigned patients to receive ligelizumab at a dose of 24 mg, 72 mg, or 240 mg, omalizumab at a dose of 300 mg, or placebo, administered subcutaneously every 4 weeks for a period of 20 weeks, or a single 120-mg dose of ligelizumab. Disease symptoms of hives, itch, and angioedema were monitored by means of weekly activity scores. The main objective was to determine a dose-response relationship for the complete control of hives (indicated by a weekly hives-severity score of 0, on a scale from 0 to 21, with higher scores indicating greater severity); the primary end point of this response was assessed at week 12. Complete symptom control was indicated by a weekly urticaria activity score of 0 (on a scale from 0 to 42, with higher scores indicating greater severity). Safety was analyzed throughout the trial.
RESULTS
A total of 382 patients underwent randomization. At week 12, a total of 30%, 51%, and 42% of the patients treated with 24 mg, 72 mg, and 240 mg, respectively, of ligelizumab had complete control of hives, as compared with 26% of the patients in the omalizumab group and no patients in the placebo group. A dose-response relationship was established. At week 12, a total of 30%, 44%, and 40% of the patients treated with 24 mg, 72 mg, and 240 mg, respectively, of ligelizumab had complete control of symptoms, as compared with 26% of the patients in the omalizumab group and no patients in the placebo group. In this small and short trial, no safety concerns regarding ligelizumab or omalizumab emerged.
CONCLUSIONS
A higher percentage of patients had complete control of symptoms of chronic spontaneous urticaria with ligelizumab therapy of 72 mg or 240 mg than with omalizumab or placebo. (Funded by Novartis Pharma; ClinicalTrials.gov number, NCT02477332.).
Topics: Adult; Aged; Anti-Allergic Agents; Antibodies, Anti-Idiotypic; Antibodies, Monoclonal, Humanized; Chronic Disease; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Humans; Immunoglobulin E; Male; Middle Aged; Omalizumab; Patient Acuity; Remission Induction; Urticaria; Young Adult
PubMed: 31577874
DOI: 10.1056/NEJMoa1900408 -
Frontiers in Immunology 2022Bullous pemphigoid (BP) is the most common autoimmune subepidermal bullous disease of the skin. First-line treatment of systemic corticosteroids may cause serious...
BACKGROUND
Bullous pemphigoid (BP) is the most common autoimmune subepidermal bullous disease of the skin. First-line treatment of systemic corticosteroids may cause serious adverse events. Rituximab, omalizumab, and dupilumab should be explored as alternative treatment options to improve outcomes.
OBJECTIVE
To systematically review the rituximab, omalizumab, and dupilumab treatment outcomes in bullous pemphigoid.
METHODS
A PubMed, Embase, Web of Science, and Cochrane library search were conducted on March 10, 2022. A total of 75 studies were included using Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines.
RESULTS
Use of rituximab (n=122), omalizumab (n=53) and dupilumab (n=36) were reported in 211 patients with BP. Rituximab led to complete remission in 70.5% (n=86/122) and partial remission in 23.8% (n=29/122) of patients within 5.7 months, with a recurrence rate of 20.5% (n=25/122). 9.0% (n=11/122) of patients died and infection (6.6%, n=8/122) was the most common adverse event. Omalizumab led to complete remission in 67.9% (n=36/53) and partial remission in 20.8% (n=11/53) of patients within 6.6 months, with a recurrence rate of 5.7% (n=3/53). 1.9% (n=1/53) of patients died and thrombocytopenia (1.9%, n=1/53) was observed as the most common adverse event. Dupilumab led to complete remission in 66.7% (n=24/36) and partial remission in 19.4% (n=7/36) of patients within 4.5 months of treatment without any reported adverse events, with a recurrence rate of 5.6% (n=2/36).
CONCLUSIONS
Rituximab, omalizumab, and dupilumab have similar clinical benefits for BP patients. However, rituximab resulted in higher recurrence rates, adverse events, and mortality rates.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022316454.
Topics: Antibodies, Monoclonal, Humanized; Humans; Omalizumab; Pemphigoid, Bullous; Rituximab; Treatment Outcome
PubMed: 35769474
DOI: 10.3389/fimmu.2022.928621 -
The Journal of Allergy and Clinical... Dec 2022The high prevalence of atopic diseases in women of childbearing age reveals the need to determine the safety of biologics during pregnancy. This review summarizes the... (Review)
Review
The high prevalence of atopic diseases in women of childbearing age reveals the need to determine the safety of biologics during pregnancy. This review summarizes the effects of 7 Food and Drug Administration-approved biologics (omalizumab, mepolizumab, reslizumab, benralizumab, dupilumab, tezepelumab, and tralokinumab) on maternal and fetal outcomes. For this purpose, we reviewed English-language publications to investigate whether the use of biologics for atopic diseases during pregnancy increased the risk of preterm delivery, stillbirth, low birth weight, or congenital malformations. Most publications found were case reports, case series, or observational studies reporting outcomes in a total of 313 pregnancies. No randomized controlled studies were identified. We found that biologics do not seem to influence maternal or fetal outcomes. Indeed, worsening of the underlying atopic disease during pregnancy appears to be more detrimental to the viability of the pregnancy. Given the small sample size and scarcity of studies, future research should include prospective studies with comparable control groups without exposure to biologics and multicenter registries for long-term follow-up.
Topics: Pregnancy; Infant, Newborn; Female; Humans; Biological Products; Asthma; Prospective Studies; Omalizumab; Anti-Asthmatic Agents; Multicenter Studies as Topic
PubMed: 35987486
DOI: 10.1016/j.jaip.2022.08.013 -
International Journal of Molecular... May 2023Currently, three classes of monoclonal antibodies targeting type 2 inflammation pathways are available in Italy for the treatment of severe asthma: anti-IgE... (Review)
Review
Currently, three classes of monoclonal antibodies targeting type 2 inflammation pathways are available in Italy for the treatment of severe asthma: anti-IgE (Omalizumab), anti-IL-5/anti-IL-5Rα (Mepolizumab and Benralizumab), and anti-IL-4Rα (Dupilumab). Numerous randomized controlled trials (RCTs) and real-life studies have been conducted to define their efficacy and identify baseline patients' characteristics potentially predictive of favorable outcomes. Switching to another monoclonal antibody is recommended in case of a lack of benefits. The aim of this work is to review the current knowledge on the impact of switching biological therapies in severe asthma as well as on predictors of treatment response or failure. Almost all of the information about switching from a previous monoclonal antibody to another comes from a real-life setting. In the available studies, the most frequent initial biologic was Omalizumab and patients who were switched because of suboptimal control with a previous biologic therapy were more likely to have a higher baseline blood eosinophil count and exacerbation rate despite OCS dependence. The choice of the most suitable treatment may be guided by the patient's clinical history, biomarkers of endotype (mainly blood eosinophils and FeNO), and comorbidities (especially nasal polyposis). Due to overlapping eligibility, larger investigations characterizing the clinical profile of patients benefiting from switching to different monoclonal antibodies are needed.
Topics: Humans; Omalizumab; Asthma; Antibodies, Monoclonal; Biological Therapy; Eosinophils; Anti-Asthmatic Agents
PubMed: 37298514
DOI: 10.3390/ijms24119563 -
The Journal of Allergy and Clinical... Apr 2023A growing number of studies have shown encouraging results with omalizumab (OMA) as monotherapy and as an adjunct to oral immunotherapy (OMA+OIT) in patients with... (Meta-Analysis)
Meta-Analysis
BACKGROUND
A growing number of studies have shown encouraging results with omalizumab (OMA) as monotherapy and as an adjunct to oral immunotherapy (OMA+OIT) in patients with single/multiple food allergies.
OBJECTIVES
To evaluate the efficacy and safety of OMA or OMA+OIT in patients with immunoglobulin E (IgE)-mediated food allergy.
METHODS
An extensive literature search (inception to December 31, 2020) was performed to identify randomized, controlled, and observational studies that assessed OMA as monotherapy or OMA+OIT in patients with IgE-mediated food allergy. The outcomes were an increase in tolerated dose of foods, successful desensitization, sustained unresponsiveness, immunological biomarkers, severity of allergic reactions to food, quality of life (QoL), and safety. A P less than .05 was considered significant.
RESULTS
In total, 36 studies were included. The OMA monotherapy (vs pre-OMA) significantly increased the tolerated dose of multiple foods; increased the threshold of tolerated dose for milk, egg, wheat, and baked milk; improved QoL; and reduced food-induced allergic reactions (all P < .01). The OMA+OIT significantly increased the tolerated dose of multiple foods (vs placebo and pre-OMA), desensitization (vs placebo+OIT and pre-OMA) (all P ≤ .01), and improved QoL (vs pre-OMA) and immunoglobulin G4 levels (both P < .01). No major safety concerns were identified.
CONCLUSIONS
In IgE-mediated food allergy, OMA can help patients consume multiple foods and allow for food dose escalation. As an adjunct to OIT, OMA can also support high-dose desensitization and higher maintenance doses. Further studies are warranted to empirically evaluate the effect of OMA and confirm these findings.
Topics: Humans; Animals; Omalizumab; Quality of Life; Immunoglobulin E; Desensitization, Immunologic; Administration, Oral; Food Hypersensitivity; Allergens; Milk
PubMed: 36529441
DOI: 10.1016/j.jaip.2022.11.036 -
Clinical Reviews in Allergy & Immunology Aug 2020Chronic spontaneous urticaria (CSU) is defined as the spontaneous development of itchy hives and/or angioedema due to known or unknown causes that last for at least... (Review)
Review
Chronic spontaneous urticaria (CSU) is defined as the spontaneous development of itchy hives and/or angioedema due to known or unknown causes that last for at least 6 weeks. At any given time, CSU is believed to affect 0.5-1% of the global population. Omalizumab (a recombinant, humanized anti-immunoglobulin-E antibody) is the only approved treatment for antihistamine refractory CSU. However, ~ 30% of patients remain symptomatic at licensed doses of omalizumab 150 mg and 300 mg, even after a treatment period of over 6 months. In the recent years, there have been several studies on updosing of the drug, suggesting that the individualized approach for urticaria treatment with omalizumab is useful. In this article, we provide an overview of these studies and the real-world data on omalizumab updosing as it became necessary to obtain complete CSU symptom control in a proportion of patients. Published observational studies (from June 2003 to October 2019) on the updosing of omalizumab in CSU were identified using PubMed and Ovid databases. Reports mainly show that updosing/dose adjustment evaluated with the assessment of disease activity (Urticaria Activity Score) and control (Urticaria Control Test) achieves better clinical response to omalizumab with a good safety profile in a pool of patients with CSU. These real-world data will provide an overview of updosing of omalizumab in CSU and aid in setting informed clinical practice treatment expectations.
Topics: Anti-Allergic Agents; Chronic Urticaria; Evidence-Based Medicine; Humans; Immunoglobulin E; Omalizumab; Precision Medicine; Treatment Outcome
PubMed: 32418171
DOI: 10.1007/s12016-020-08794-6