Efficacy Of Omalizumab Research Articles

Clinical efficacy and safety of combined house dust mite subcutaneous immunotherapy and omalizumab in five cases of allergic rhinitis and asthma

Allergen immunotherapy (AIT) is a well-recognized treatment for altering the natural course of respiratory allergy which builds immune tolerance and prevents progression of allergic diseases. In our five cases of house dust mite (HDM)-driven allergic rhinitis and asthma, combined HDM Subcutaneous Immunotherapy (HDM-SCIT) for 2 years with omalizumab for more than 12 months has achieved disease remission in four cases and disease control in one case along with long-term effect for 3 years after discontinuation of AIT. We hypothesize that combining HDM-SCIT and omalizumab is a promising strategy as it is effective, safe, and synergistic having immune-modifying activity in cases of HDM-driven Allergic Rhinitis and Asthma.

Real-life, long-term data on efficacy, safety, response and discontinuation patterns of omalizumab in a Greek population with chronic spontaneous urticaria.

Omalizumab is approved for the treatment of chronic spontaneous urticaria (CSU) not responding to antihistamines. Data on omalizumab use in real-world settings and in different populations are lacking. To record our five-year experience of omalizumab use in patients with refractory CSU in a real-world setting. A retrospective analysis of medical records of 80 patients with refractory CSU was performed. Demographic, and clinical characteristics, patterns of response, discontinuation strategies and rate of recurrence were analysed. Eighty individuals were included. UAS7 and DLQI significantly decreased from baseline. Complete response was achieved in 86.3%. Late response was observed at 27.5% of the patients. After discontinuation, 21.7% of patients reinitiated omalizumab due to relapse. The mean number of omalizumab administrations up to first discontinuation was 6.8 (based on an approach to shorten the treatment interval). Only 15.0% of patients experienced adverse events during treatment. Omalizumab, with long-term management, was highly effective and safe in achieving control of refractory CSU, with more favourable responses compared to Phase III clinical trials.

Efficacy predictors of omalizumab in Chinese patients with moderate-to-severe allergic asthma: Findings from a post-hoc analysis of a randomised phase III study

BackgroundOmalizumab has demonstrated efficacy as an add-on therapy in Chinese patients with moderate-to-severe allergic asthma. This post-hoc analysis assessed the potential predictors for the efficacy of omalizumab in these patients. MethodsA post-hoc analysis was performed on a Phase III, randomised, controlled study conducted in Chinese patients with moderate-to-severe persistent allergic asthma (NCT01202903). We evaluated if levels of pre-treatment serum total immunoglobulin-E (IgE) and blood eosinophil (EOS), asthma severity, allergen profile, history of perennial allergic rhinitis (PAR), and free IgE level during omalizumab treatment were predictive of omalizumab's efficacy. ResultsThis analysis included 608 patients (omalizumab, N = 306; placebo, N = 302). Improvements in forced expiratory volume in 1 s (FEV1), standardized Asthma Quality of Life Questionnaire (AQLQ), Asthma Control Questionnaire (ACQ), and Global Evaluation of Treatment Effectiveness (GETE) scores with omalizumab treatment compared with placebo were observed in patients with baseline IgE levels ≥76 IU/mL (irrespective of the EOS count). Relatively greater improvements with omalizumab treatment was also noted in patients with both moderate or severe allergic asthma (regardless of asthma severity), and patients sensitised to >3 allergens and with a history of PAR. All patients who were treated with omalizumab achieved free IgE levels below 50 ng/mL by Week 1. Similar clinical outcomes were observed in the subset of patients who achieved free IgE levels of <25 and ≥ 25 ng/mL. ConclusionsIn Chinese patients with moderate-to-severe allergic asthma, baseline IgE and allergen profile (number/PAR history) are potential predictors of treatment response to omalizumab. Trial registrationNCT01202903 (www.clinicaltrials.gov).

A randomized double-blind, placebo-controlled study of omalizumab for idiopathic anaphylaxis

Idiopathic anaphylaxis (IA) is a diagnosis of exclusion, thus taking away the option of therapeutic management focused on eliminating the inciting agent. Epinephrine and antihistamines followed by systemic corticosteroids are the mainstays of therapy for acute events. There is no prophylactic therapy that reliably prevents anaphylaxis. We sought to determine the efficacy of omalizumab in the management of patients with frequent episodes of IA in a double-blind, placebo-controlled trial. We prospectively enrolled 19 patients with frequent IA (≥6 episodes/y) who then underwent a medical evaluation that included a serum tryptase determination, mutational analysis for KIT D816V, and bone marrow evaluation to rule out a clonal mast cell disorder. Computer-generated random numbers were provided by the study pharmacist. The primary end point was anaphylactic events in the 6 months after baseline. Sixteen patients completed the primary trial. No statistically significant difference was demonstrated between the placebo and treated groups. There was a trend for efficacy in the treatment group, particularly after 60 days. Overall, the safety profile was favorable without long-term side effects. Omalizumab was safely administered to a difficult-to-treat patient population with IA. The efficacy results trended modestly in favor of the treatment group, but no statistically significant differences were detected.

Effect of Omalizumab on Nasal Symptoms in Asthma and Perennial Allergic Rhinitis.

To determine the efficacy of omalizumab on nasal symptoms in patients having allergic asthma with rhinitis symptoms. Cohort study. University of Health Sciences, Izmir Tepecik Training and Research Hospital, İzmir, Turkey, between October and November 2019. This study included patients with perennial allergic rhinitis without nasal polyposis who were followed up in the adult allergy outpatient clinic, had findings consistent with allergic rhinitis upon nasal endoscopic examination. They were given 2-4 weekly subcutaneous omalizumab for more than six months changes in nasal symptoms were noted using nasal symptoms score. Each symptom was individually evaluated. There were 42 patients, consisting of 36 women (85.7%) and six men (14.3%), who received omalizumab treatment. Patient age ranged between 30 and 77 years, mean = 54.21±10.85 years. Median change in nasal symptom score of all cases after treatment was a 3.5 (2-6.25) decrease, which was statistically significant (p <0.001). When we examine the decrease in nasal symptoms after omalizumab compared to pre-omalizumab in all cases, the most prominent change was observed in the symptom of nasal congestion. Two-four weekly subcutaneous omalizumab for six months or more was effective in treating all rhinitis symptoms and had the greatest effect on nasal congestion compared to all other symptoms. Key Words: Allergic rhinitis, Anti-IgE, Omalizumab, Total nasal symptom score (TNSS), Asthma.

Real-life safety and efficacy of omalizumab in Japanese patients with severe allergic asthma who were subjected to dosing table revision or expansion: A post-marketing surveillance

BackgroundOmalizumab is an anti-immunoglobulin E monoclonal antibody approved for patients with severe allergic asthma in Japan. With regard to omalizumab dosage in Japanese adults with severe allergic asthma in clinical practice settings, this post-marketing surveillance evaluated safety and efficacy of the dosing table revision (DTR) based on a dosing regimen of omalizumab administration every 4 weeks dosing regimen and dosing table expansion (DTE) for patients with baseline IgE levels >700 IU/mL. MethodsThis 52-week, multicenter study, conducted from September 2013 to November 2018, evaluated omalizumab safety outcomes including adverse events (AEs), serious AEs (SAEs), adverse drug reactions (ADRs), efficacy outcomes including Global Evaluation of Treatment Effectiveness (GETE), change in oral corticosteroid dose, and asthma exacerbation-related events such as hospitalization, emergency room visits, and worsening of symptoms. ResultsOf the 405 patients registered in the study, safety was evaluated in 392 and efficacy in 390. The mean age of patients was 58.5 years and 58.7% were women. In total, 41.3% of the patients were subjected to DTE and 58.7% to DTR. In the safety dataset, 6.6% experienced an ADR, 32.9% experienced an AE, and 16.1% experienced an SAE. In the efficacy dataset, 63.3% of patients at Week 16 and 63.5% at Week 52 had an ‘effective’ or ‘good’ GETE score. Omalizumab was associated with a reduction in worsening of asthma symptoms requiring systemic corticosteroids and frequency of hospitalization. All outcomes were comparable among the DTE and DTR subgroups. ConclusionThe findings from this study support the safety and efficacy of omalizumab administered based on the revised and expanded dosing table in Japanese patients with severe allergic asthma.

Efficacy and safety of treatment with omalizumab for chronic spontaneous urticaria: A systematic review for the EAACI Biologicals Guidelines.

This systematic review evaluates the efficacy and safety of omalizumab for chronic spontaneous urticaria (CSU). PubMed, Embase, and Cochrane Library were searched for RCTs. Critical and important CSU-related outcomes were considered. The risk of bias and the certainty of the evidence were assessed using GRADE. Ten RCTs including 1620 subjects aged 12 to 75years old treated with omalizumab for 16 to 40weeks were evaluated. Omalizumab 150mg does not result in clinically meaningful improvement (high certainty) of the urticaria activity score (UAS)7 (mean difference (MD) -5; 95%CI -7.75 to -2.25), and the itch severity score (ISS)7 (MD -2.15; 95% CI -3.2 to -1.1) does not increase (moderate certainty) quality of life (QoL) (Dermatology Life Quality Index (DLQI); MD -2.01; 95%CI -3.22 to -0.81) and decreases (moderate certainty) rescue medication use (MD -1.68; 95%CI -2.95 to -0.4). Omalizumab 300mg results in clinically meaningful improvements (moderate certainty) of the UAS7 (MD -11.05; 95%CI -12.87 to -9.24), the ISS7 (MD -4.45; 95%CI -5.39 to -3.51), and QoL (high certainty) (DLQI; MD -4.03; 95% CI -5.56 to -2.5) and decreases (moderate certainty) rescue medication use (MD -2.04; 95%CI -3.19 to -0.88) and drug-related serious AEs (RR 0.77; 95%CI 0.20 to 2.91).

Long-term omalizumab efficacy in allergic rhinitis

BackgroundOmalizumab therapy was found to be safe and effective as an add-on therapy for patients with poorly controlled severe asthma. Although several studies over the last decade have demonstrated its efficacy in other Immunoglobulin E related diseases, its use in such conditions is off-label. ObjectiveThis study aimed to assess the effectiveness of long-term therapy with Omalizumab in patients with persistent severe allergic rhinitis and inadequately controlled severe asthma. MethodsPatients with poorly controlled severe asthma and persistent allergic rhinitis were enrolled and treated with Omalizumab for 36 months with every four-week subcutaneous administration. The efficacy assessment included the severity of AR symptoms every six months using Visual Analogue Scale, Asthma Control Test, nasal endoscopy, spirometry, and biomarkers (blood eosinophils and neutrophils, fractional exhaled nitric oxide, total IgE). ResultsEleven patients aged between 26 and 70 years were enrolled, and 10 completed the study. A significant improvement of allergic rhinitis symptoms, Asthma Control Test, and lung function was observed. There was also a reduction in the status of the biomarkers at the end of the study. ConclusionLong-term therapy with Omalizumab was effective and safe in treating severe persistent allergic rhinitis and concomitant asthma.

Omalizumab: for severe ocular allergy

Identify the efficacy of Omalizumab in severe atopic and vernal ketatoconjunctivitis (AKC e VKC). Four pediatric patients with severe refractory allergic keratoconjunctivits were selected and received Omalizumab 300mg once a month for at least 6 months. Ocular symptoms need for medication and use of topical steroids were analyzed before and after the treatment. −Patient 1: Severe AKC, IgE of > 2000 UI/mL and skin prick test for Dermatophagoides pteronyssinus(Dp) 7x7mm wheal. Improve of pruritus and conjunctival hyperemia after the first dose of Omalizumab; however, after the 2nd dose there was worsening of the pruritus and increased ocular secretion. After the 6thdose the drug was discontinued for treatment failure.−Patient 2: Had increase intraocular pressure due to chronic use of topical steroids; IgE of 488UI/mL and no sensitization to any aeroallergns. The VKC symptoms of pruritus, lacrimation, photophobia and conjuctival hyperemia improved after the first dose, and he remained asymptomatic thereafter up to one year.−Patient 3: Showed significant improvement of symptoms and resolution of corneal ulcers. After 3-month ocular symptoms of AKC returned. The treatment was discontinued after 6 months. Serum IgE of 996 UI/mL and 8x8mm wheal in skin prick test for Dp.−Patient 4: Showed no improvement of AKC after 6 doses of Omalizumab 300mg, and after 6 months, the treatment was discontinued. Serum IgE 171 UI/mL and skin prick test positive for Dp (8x8mm) and Blomia(4x4mm). Omalizumab should be tried as a therapy for severe and refractory conjunctivitis. Of the 4 patients evaluated, one VKC presented complete response to the treatment, two had partial remission of symptoms, and one AKC did not remit with omalizumab. The best patient profile and treatment regimen are yet to be determined. Controlled studies are needed in the future.

Effectiveness of omalizumab in patients with severe allergic asthma with and without chronic rhinosinusitis with nasal polyps: a PROXIMA study post hoc analysis

BackgroundA significant proportion of patients with severe asthma may also suffer from nasal polyposis, which is commonly defined as chronic rhinosinusitis with nasal polyps (CRSwNP), the presence of which may adversely affect asthma treatment outcomes. The biologic agent omalizumab is effective as add-on therapy in patients with severe allergic asthma. The aim of this post hoc analysis of the PROXIMA study was to compare the efficacy of omalizumab between patients with severe allergic asthma, with and without comorbid CRSwNP.MethodsPROXIMA was a prospective observational 2-part study conducted in Italy in adult patients with severe allergic asthma, where, in the second part, patients eligible for add-on omalizumab initiated treatment for 12 months. Patient baseline data such as comorbidities and history of exacerbations were collected. Outcomes were asthma control (Asthma Control Questionnaire [ACQ]), lung function (forced expiratory volume in 1 s [FEV1]) and exacerbation rate. The post hoc analysis compared these outcomes between the cohort with comorbid CRSwNP and the cohort without CRSwNP.ResultsOf 123 patients included in this analysis, 17 (13.8%) were in the CRSwNP cohort. There was no significant difference between cohorts in baseline clinical characteristics or in change from baseline at 12 months in ACQ values, % of predicted FEV1 or annual asthma exacerbation rate, although results were numerically in favor of the CRSwNP cohort versus the non-CRSwNP cohort. The proportion of patients who achieved an improvement in all three outcomes was numerically greater in the CRSwNP cohort (35.7% vs 23.0%).ConclusionsIn an observational real-world setting, add-on omalizumab for severe allergic asthma was effective in improving asthma control, lung function and in reducing exacerbations, including in those patients with CRSwNP.

Long-term follow-up effect of omalizumab in chronic spontaneous urticaria and its association with serum C-reactive protein levels.

This study aims to determine the efficacy of omalizumab, a humanized monoclonal anti-immunoglobulin E antibody, in patients with chronic spontaneous urticaria (CSU) refractory to conventional therapy, together with the evaluation of serum CRP levels. All the patients with a diagnosis of CSU who were continuously treated with omalizumab (300 mg/mo) for at least 3 months between June 2016 and July 2019 were included in this study. Urticaria activity score (UAS-7) was used for assessment of disease activity. Serum CRP levels were also retrospectively analyzed. When UAS-7 scores before the initiation of therapy were compared to the week 4, 12, 24, and 36 scores after the treatment, each were significantly different from the pretreatment results (P < .01). CRP level prior to treatment was found to be strongly correlated with baseline UAS scores of the patients' (P = .00). At the 12th week of treatment, decline of CRP level was positively and strongly correlated with the decline of UAS (P = .037). In this study, mean UAS decreased, mean rescue medication use declined, and overall therapeutic response improved with omalizumab treatment. Additionally, significant correlation between the decline of CRP levels and treatment response was found.

Omalizumab for Aspirin Hypersensitivity and Leukotriene Overproduction in Aspirin-exacerbated Respiratory Disease. A Randomized Controlled Trial

Rationale: Aspirin-exacerbated respiratory disease is characterized by severe asthma, nonsteroidal antiinflammatory drug hypersensitivity, nasal polyposis, and leukotriene overproduction. Systemic corticosteroid therapy does not completely suppress lifelong aspirin hypersensitivity. Omalizumab efficacy against aspirin-exacerbated respiratory disease has not been investigated in a randomized manner.Objectives: To evaluate omalizumab efficacy against aspirin hypersensitivity, leukotriene E4 overproduction, and symptoms during an oral aspirin challenge in patients with aspirin-exacerbated respiratory disease using a randomized design.Methods: We performed a double-blind, randomized, crossover, placebo-controlled, single-center study at Sagamihara National Hospital between August 2015 and December 2016. Atopic patients (20–79 yr old) with aspirin-exacerbated respiratory disease diagnosed by systemic aspirin challenge were randomized (1:1) to a 3-month treatment with omalizumab or placebo, followed by a >18-week washout period (crossover design). The primary endpoint was the difference in area under logarithm level of urinary leukotriene E4 concentration versus time curve in the intent-to-treat population during an oral aspirin challenge.Measurements and Main Results: Sixteen patients completed the study and were included in the analysis. The area under the logarithm level of urinary leukotriene E4 concentration versus time curve during an oral aspirin challenge was significantly lower in the omalizumab phase (median [interquartile range], 51.1 [44.5–59.8]) than in the placebo phase (80.8 [interquartile range, 65.4–87.8]) (P < 0.001). Ten of 16 patients (62.5%) developed oral aspirin tolerance up to cumulative doses of 930 mg in the omalizumab phase (P < 0.001).Conclusions: Omalizumab treatment inhibited urinary leukotriene E4 overproduction and upper/lower respiratory tract symptoms during an oral aspirin challenge, resulting in aspirin tolerance in 62.5% of the patients with aspirin-exacerbated respiratory disease.

Efficacy of omalizumab in chronic spontaneous urticaria associated with chronic inducible urticaria

Efficacy of omalizumab in chronic spontaneous urticaria associated with chronic inducible urticaria

Efficacy and safety of omalizumab in nasal polyposis: 2 randomized phase 3 trials

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. Our aim was to determine omalizumab safety and efficacy in CRSwNP in phase 3 trials (POLYP 1 and POLYP 2). 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. 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. Omalizumab significantly improved endoscopic, clinical, and patient-reported outcomes in severe CRSwNP with inadequate response to intranasal corticosteroids, and it was well tolerated.

Efficacy of Omalizumab in extracutaneous symptoms on CSU

Introduction Omalizumab, an anti-IgE antibody, is an efficient treatment for chronic spontaneous urticaria (CSU) and asthma. Moreover, Omalizumab has demonstrated efficacy in treating allergic rhinitis, atopic dermatitis and, more recently, in nasal polyps. So we could suppose that it could be efficient in other mast cell activating disorders (MCAD) as mast cell activation syndrome (MCAS), indolent systemic mastocytosis (ISM) and extracutaneous signs of CSU (CSU + ). Methodes We retrospectively collected data from all ISM, MCAS or CSU+ patients treated with Omalizumab and followed by the Department of clinical immunology of Grenoble-Alpes University Hospital, France. We report the evolution of extracutaneous symptoms in CSU + MCAS and ISM patients treated with Omalizumab. Since 2014, 23 patients were included in our study: 8 ISM, 2 MCAS and 13 CSU+. Resultats The median age of our cohort was 48 years (17-81). The median age of patients having their first symptoms was 33 years (range: 6-68) and when the diagnosis was made was 45 years (range: 13-77). Before Omalizumab therapy, the major debilitating symptoms are angioedema (70 %), urticaria (83 %), gastro-intestinal (GI) symptoms (70 %) and recurrent anaphylactic reaction (35 %). Among patients, 5 (23 %) were treated with a median dose of 300 mg/3 weeks, 11 (50 %) received a dose of 300 mg/month and 6 a dose of 300 mg/15 days (27 %). For our available data, extracutaneous symptoms were improved for all patients except for one. The improvement appeared 3 months post-treatment (range 1- 12). Patients also noticed an asthenia improvement (31 %). Omalizumab was given during a median period of 17 months (range: 5-62) with no serious adverse events. The most common drug side effects were local swelling at the site of injection (4 %), transient asthenia (30 %), fainting attack (13 %), arthralgia (8 %). Conclusion In conclusion, MCAD are relatively rare and heterogeneous diseases with poor therapeutic option. Omalizumab, an anti-IgE Ab, seems to be safe and efficient in several symptoms. It also seems to be efficient in CSU+ extracutaneous symptoms.

High serum free IL-18 is associated with decreased omalizumab efficacy: findings from a 2-year omalizumab treatment study

Objective Omalizumab is more effective in severe allergic patients with eosinophilic asthma than those with non-eosinophilic asthma. IL-18, a unique cytokine involved in allergic but non-eosinophilic inflammation, might be associated with the latter condition. We aimed to clarify the roles of IL-18 related pathways in insufficient response to omalizumab treatment. Methods Patients with severe allergic asthma who completed 2-year omalizumab treatments at Kyoto University Hospital were included in this study (UMIN000002389). Associations between pretreatment levels of serum free IL-18 in addition to other mediators and asthma phenotypes including responses to omalizumab treatment were analyzed. Changes in serum free IL-18, periostin and total IgE levels during the treatment were also examined. Results Twenty-seven patients (19 females, average age of 55.7 years) were examined. Fifteen incomplete responders who experienced exacerbations in the second year, were significantly and more frequently obese and showed significantly earlier asthma onset, lower blood eosinophils and more exacerbations before omalizumab treatment than complete responders. Significantly more patients showed high baseline serum free IL-18 levels (≥141 pg/mL, a threshold for the highest tertile) among the incomplete responders than complete responders. Patients with high serum free IL-18 levels shared similar characteristics with incomplete responders, showing significant reductions in serum total IgE levels during omalizumab treatment. Finally, serum free IL-18 levels negatively correlated with serum periostin levels at baseline and in change ratios. Conclusions High baseline serum free IL-18 levels may predict reduced omalizumab efficacy in severe allergic patients with type-2 low asthma, regarding reduction of exacerbations.

Efficacy and Safety of Omalizumab for Chronic Spontaneous Urticaria: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Omalizumab has been proposed as a possible effective treatment of chronic spontaneous urticaria (CSU). We aimed to access the efficacy and safety of omalizumab in the treatment of CSU based on qualified, randomized controlled trials (RCTs). PubMed, the Cochrane library, and Embase databases. Computerized search by index words was performed to identify qualified RCTs, and relevant literature sources were also searched. Nine RCTs were included in the meta-analysis with 1612 patients in the omalizumab group and 1251 patients in the placebo group. Compared with the placebo group, omalizumab significantly decreased the weekly itch score after therapy [Weighted Mean Difference (WMD), -3.94; 95% confidence interval (CI), -4.64 to -3.24], the weekly hive score (WMD, -5.27; 95% CI, -6.17 to -4.38), the dermatology life quality index (DLQI; WMD, -3.58; 95% CI, -4.66 to -2.50), and the urticaria activity score over 7 days (UAS7; WMD, -9.51; 95% CI, -10.94 to -8.08). There was no significant difference in the incidence of adverse events (AE) [relative risk (RR), 1.01; 95% CI, 0.91-1.12], serious AE (RR, 0.85; 95% CI, 0.57-1.27), and severe AE (RR, 0.83; 95% CI, 0.60-1.14) between the 2 groups. Compared with the placebo, omalizumab significantly decreased the weekly itch score and weekly hive score after therapy in patients receiving 75, 150, and 300 mg omalizumab, respectively. DLQI was significantly reduced in patients receiving 150 and 300 mg of omalizumab, respectively. In all the subgroup of UAS7, omalizumab significantly decreased the score compared with the placebo. Only patients receiving 600-mg omalizumab had a significantly higher AE incidence versus placebo. There was no significant difference in serious and severe AE between the 2 groups. Omalizumab caused a significantly greater reduction in weekly itch score, weekly hive score, DLQI, and UAS7 in CSU patients than the placebo. However, high-quality, multicenter RCTs with a larger sample size are needed to confirm the safety of omalizumab, and whether AEs are caused by omalizumab or other factors.

Add-On Omalizumab for Inadequately Controlled Severe Pollinosis Despite Standard-of-Care: A Randomized Study

Cedar pollinosis (CP), a common form of seasonal allergic rhinitis (AR), is a substantial medical problem in Japan due to its high prevalence and severe symptoms. Omalizumab (anti-IgE therapy) has previously proven to be effective in CP/AR, but no studies for inadequately controlled severe CP/AR despite standard-of-care (SoC) have been conducted. To determine the efficacy of omalizumab added to SoC in patients with inadequately controlled severe CP in a randomized, double-blinded, placebo-controlled, phase III study. Adult/adolescent patients with severe CP whose symptoms were inadequately controlled despite nasal corticosteroids plus 1 or more oral medications in the previous 2 seasons were randomized to receive omalizumab (n= 162) or placebo (n= 175). All patients received concomitant antihistamines and nasal corticosteroids as SoC. The primary endpoint was the mean nasal symptom score during the severe symptom period. Secondary endpoints included mean ocular symptom score, quality of life (QoL), and safety. The SoC+ omalizumab treatment had statistically significantly and clinically important lower nasal (least squares mean difference,-1.03, P < .001) and ocular (-0.87, P < .001) symptom scores compared with SoC+ placebo, respectively. Differences in scores for individual components of nasal and ocular symptoms were also statistically and clinically significant. SoC+ omalizumab also improved QoL scores as overall and in all domains. No unexpected safety signals were observed. In patients with severe CP, omalizumab added to SoC demonstrated consistent efficacy in improving symptoms and QoL, and was well tolerated. These results indicate that omalizumab could be a promising therapeutic option for severe CP/AR.

Efficacy and safety of treatment with biologicals (benralizumab, dupilumab and omalizumab) for severe allergic asthma: A systematic review for the EAACI Guidelines - recommendations on the use of biologicals in severe asthma.

Allergic asthma is a frequent asthma phenotype. Both IgE and type 2 cytokines are increased, with some degree of overlap with other phenotypes. Systematic reviews assessed the efficacy and safety of benralizumab, dupilumab and omalizumab (alphabetical order) vs standard of care for patients with uncontrolled severe allergic asthma. PubMed, Embase and Cochrane Library were searched to identify RCTs and health economic evaluations, published in English. Critical and important asthma-related outcomes were evaluated. The risk of bias and the certainty of the evidence were assessed using GRADE. All three biologicals reduced with high certainty the annualized asthma exacerbation rate: benralizumab incidence rate ratios (IRR) 0.63 (95% CI 0.50-0.81); dupilumab IRR 0.58 (95%CI 0.47-0.73); and omalizumab IRR 0.56 (95%CI 0.42-0.73). Benralizumab and dupilumab improved asthma control with high certainty and omalizumab with moderate certainty; however, none reached the minimal important difference (MID). Both benralizumab and omalizumab improved QoL with high certainty, but only omalizumab reached the MID. Omalizumab enabled ICS dose reduction with high certainty. Benralizumab and omalizumab showed an increase in drug-related adverse events (AEs) with low to moderate certainty. All three biologicals had moderate certainty for an ICER/QALY value above the willingness to pay threshold. There was high certainty that in children 6-12years old omalizumab decreased the annualized exacerbation rate [IRR 0.57 (95%CI 0.45-0.72)], improved QoL [relative risk 1.43 (95%CI 1.12 -1.83)], reduced ICS [mean difference (MD) -0.45 (95% CI -0.58 to -0.32)] and rescue medication use [ MD -0.41 (95%CI -0.66 to -0.15)].

Protocol for a double-blind, randomized controlled trial on the dose-related efficacy of omalizumab in multi-food oral immunotherapy

BackgroundPrevious proof-of-concept studies have shown that a short course of omalizumab can safely accelerate the oral immunotherapy schedule for multiple allergens simultaneously. Considering the high cost of medication, the dose-related efficacy of omalizumab at decreasing the duration of oral immunotherapy up-dosing phase must be objectively quantified before cost–benefit analyses can be performed. The primary objective of this trial will be to compare the efficacy of 2 omalizumab dosages to placebo at decreasing time-to-maintenance dose during a symptom-driven multi-food OIT protocol.MethodsA total of 90 participants aged 6 to 25 with multiple food allergies (3 or more) will be enrolled at four sites in Canada. Participants will be randomized to: (A) Omalizumab 8 mg/kg per month (n = 36); (B) Omalizumab 16 mg/kg per month (n = 36); or (C) Placebo (n = 18). Study drug will be administered at full dosage for 12 weeks, then progressively tapered at 50% dosage (8 mg/kg vs 4 mg/kg vs placebo) for 4 weeks and at 25% dosage (4 mg/kg vs 2 mg/kg vs placebo) for another 4 weeks. After a pre-treatment period of 8 weeks, participants will undergo an initial food escalation (IFE) to an OIT mix containing 3 allergens and start daily home dosing with biweekly increases until a target daily maintenance of 1500 mg protein is achieved. The amount escalated at each visit will vary based on treatment tolerance according to a standardized up-dosing algorithm. Participants will be followed for at least 12 months following the initial food escalation. The primary endpoint will be time from IFE to the target maintenance dose of 1500 mg protein. Time-to-event analytic methods, including the log-rank test, will be used to compare the 3 arms.DiscussionThis trial uses a novel pragmatic approach to compare OIT with omalizumab to OIT without omalizumab in a blinded manner, which allows to single out the effect of this anti-IgE medication on treatment effectiveness speed without the recourse to predetermined schedules. The innovative patient-centered up-dosing algorithm allows to maximise treatment effectiveness speed without compromising patient safety, regardless of whether the patient is on omalizumab or not. This study will also provide novel prospective data to inform on the optimal and most cost-effective dosage for this indication.Trial registration ClinicalTrials.gov, NCT04045301, Registered 5 August 2019, https://clinicaltrials.gov/ct2/show/NCT04045301