Omalizumab Administration Research Articles

Extracorporeal IgE Immunoadsorption in Allergic Asthma: Safety and Efficacy

BackgroundPrevention of IgE-binding to cellular IgE-receptors by anti-IgE (Omalizumab) is clinically effective in allergic asthma, but limited by IgE threshold-levels. To overcome this limitation, we developed a single-use IgE immunoadsorber column (IgEnio). IgEnio is based on a recombinant, IgE-specific antibody fragment and can be used for the specific extracorporeal desorption of IgE. ObjectiveTo study safety and efficacy of IgEnio regarding the selective depletion of IgE in a randomized, open-label, controlled pilot trial in patients with allergic asthma and to investigate if IgEnio can bind IgE-Omalizumab immune complexes. MethodsFifteen subjects were enrolled and randomly assigned to the treatment group (n=10) or to the control group (n=5). Immunoadsorption was done by veno-venous approach, processing the twofold calculated plasma volume during each treatment. A minimum average IgE-depletion of 50% after the last cycle in the intention-to-treat population was defined as primary endpoint. Safety of the treatment was studied as secondary endpoint. In addition, possible changes in allergen-specific sensitivity were investigated, as well as clinical effects by peak flow measurement and symptom-recording. The depletion of IgE-Omalizumab immune complexes was studied in vitro.The study was registered at clinicaltrials.gov (NCT02096237) and conducted from December 2013 to July 2014. ResultsIgE immunoadsorption with IgEnio selectively depleted 86.2% (±5.1% SD) of IgE until the end of the last cycle (p<0.0001). Removal of pollen allergen-specific IgE was associated with a reduction of allergen-specific basophil-sensitivity and prevented increases of allergen-specific skin-sensitivity and clinical symptoms during pollen seasons. IgEnio also depleted IgE-Omalizumab immune complexes in vitro.The therapy under investigation was safe and well-tolerated. During a total of 81 aphereses, 2 severe adverse events (SAE) were recorded, one of which, an episode of acute dyspnea, possibly was related to the treatment and resolved after administration of antihistamines and corticosteroids. ConclusionsThis pilot study indicates that IgE immunoadsorption with IgEnio may be used to treat patients with pollen-induced allergic asthma. Furthermore, the treatment could render allergic patients with highly elevated IgE-levels eligible for the administration of Omalizumab and facilitate the desorption of IgE-Omalizumab complexes.This study was funded by Fresenius Medical Care Deutschland GmbH, Bad Homburg, Germany.

Anaphylactic reactions associated with omalizumab administration: Analysis of a case-control study

Anaphylactic reactions associated with omalizumab administration: Analysis of a case-control study

Comparison of Costs and Clinical Outcomes Between Hospital and Outpatient Administration of Omalizumab in Patients With Severe Uncontrolled Asthma

ObjectivesTo compare clinical outcomes and costs between two administration strategies of omalizumab treatment. MethodWe evaluated two cohorts of patients with uncontrolled severe asthma over a 1-year period. Patients received the treatment in the primary care center in Hospital A and conventional hospital administration in Hospital B. ResultsWe studied 130 patients, 86 in Hospital A and 44 in Hospital B, 30 men (24%) and 100 women (76%), age 50±15 years, FEV1% 67±22%, body mass index (BMI) 28±6kg/m2, 639±747UIIgE/mL, followed for 24±11 months (12–45), Asthma Control Test (ACT) score 12±4 and Asthma Control Questionnaire (ACQ) 3±2. There were no significant pretreatment differences between the groups in hospital admissions and emergency room visits in the previous year, nor in proportion of patients receiving oral steroids. Evaluations were performed at baseline and after 12 months of treatment, revealing significant differences in ACT (P<.001), ACQ (P<.001), improvement in FEV1% (P<.001), reduction in total admissions (P<.001), days of hospitalization (P<.001), emergency room visits (P<.001), cycles and doses of oral steroids (P<.001) compared to the previous year. Hospitalization costs, emergency room visits, unscheduled visits to primary care and to the pulmonologist were significantly reduced in each hospital and on the whole, but administration and travel costs were 35% lower in the ambulatory strategy adopted in Hospital A. ConclusionThe administration of omalizumab in ambulatory health centers achieved the same clinical results as a hospital administration strategy, but with lower costs.

Lack of basophil CD203c-upregulating activity as an immunological marker to predict response to treatment with omalizumab in patients with symptomatic chronic urticaria

Lack of basophil CD203c-upregulating activity as an immunological marker to predict response to treatment with omalizumab in patients with symptomatic chronic urticaria

Russian experience of refractory chronic urticaria treatment with omalizumab

Background. To study the efficacy and safety of omalizumab in patients with chronic urticaria, refractory to antihistamines in clinical practice. Methods. In this retrospective clinical analysis, we assessed effectiveness, time to relief of symptoms, dose change after omalizumab administration, and safety in 17 CU patients, 16 with chronic spontaneous urticaria (CSU), 1 with different forms of chronic inducible urticaria (CindU) and 4 with both. Results. Treatment with omalizumab showed excellent effect in 70,6%, significant - in 17,7%, no effect - in 11,7% of CU patients. Eight patients marked effect for 24 hours, 2 - within 2-3 days, 2 - during 2 weeks, 1 - 4 weeks, and 2 patients - for 8 weeks. Eleven patients were receiving omalizumab 300 mg once per 4 weeks, one patient - 150 mg, 4 patients 2 injections of 300 mg, followed by 150 mg of 2, one patient had started treatment with a dose of 150 mg, continued treatment with omalizumab 300 mg. Omalizumab was safe. There was no influence of baseline total IgE levels and the results of test with autosera on the efficacy of omalizumab treatment. Conclusion. Our observation of patients with chronic spontaneous urticaria, with the concomitant or separate physical (induced) hives can resume high efficacy and safety of omalizumab treatment which can be recommended for CU patients, torpid to the first and secondline therapy.

Comparación de costes y resultados clínicos entre la administración hospitalaria o ambulatoria de omalizumab, en pacientes con asma grave no controlada

ObjectivesTo compare clinical outcomes and costs between two administration strategies of omalizumab treatment. MethodWe evaluated two cohorts of patients with uncontrolled severe asthma over a 1-year period. Patients received the treatment in the primary care center in Hospital A and conventional hospital administration in Hospital B. ResultsWe studied 130 patients, 86 in Hospital A and 44 in Hospital B, 30 men (24%) and 100 women (76%), age 50±15 years, FEV1% 67±22%, body mass index (BMI) 28±6kg/m2, 639±747 UI IgE/mL, followed for 24±11 months (12-45), Asthma Control Test (ACT) score 12±4 and Asthma Control Questionnaire (ACQ) 3±2. There were no significant pretreatment differences between the groups in hospital admissions and emergency room visits in the previous year, nor in proportion of patients receiving oral steroids. Evaluations were performed at baseline and after 12 months of treatment, revealing significant differences in ACT (P<0.001), ACQ (P<0.001), improvement in FEV1% (P<0.001), reduction in total admissions (P<0.001), days of hospitalization (P<0.001), emergency room visits (P<0.001), cycles and doses of oral steroids (P<0.001) compared to the previous year. Hospitalization costs, emergency room visits, unscheduled visits to primary care and to the pulmonologist were significantly reduced in each hospital and on the whole, but administration and travel costs were 35% lower in the ambulatory strategy adopted in Hospital A. ConclusionThe administration of omalizumab in ambulatory health centers achieved the same clinical results as a hospital administration strategy, but with lower costs.

Omalizumab for Difficult-to-Treat Dermatological Conditions: Clinical and Immunological Features from a Retrospective Real-Life Experience

Omalizumab, a therapeutic monoclonal antibody specific for human IgE, has thus far been used as add-on therapy for moderate-to-severe allergic asthma in adults and children. The objective of this study was to test omalizumab efficacy in other conditions in which the IgE-mast cell axis is supposed to play a role. Nine patients with dermatological manifestations possibly related to activation of the IgE-mast cell axis (six chronic spontaneous urticaria and three atopic dermatitis patients) were administered off-label omalizumab because of refractoriness to standard therapy. All patients were subjected to strict clinical, laboratoristic, and imaging follow-up to monitor for possible adverse effects. In addition, to further assess the role of omalizumab on T cells, mast cells, and eosinophils, T-cell immune polarisation as well as eosinophil cationic protein and tryptase serum levels were determined before and during omalizumab administration. Therapy was effective in seven out of nine patients (six complete responses, one partial response, and two no responses). Interestingly, omalizumab appeared to induce lymphocyte polarisation toward a type 2 immune response and to be able to quench eosinophil-mediated inflammation, particularly in atopic dermatitis patients. Tryptase serum levels were generally low and remained unchanged during omalizumab treatment. Despite treatment spanning over several years in most of the patients, no adverse effects nor new ensuing medical conditions have thus far been observed (median follow-up: 42 months). Off-label omalizumab was safe and effective in our patients. The novel immunologic features recorded in our patients add further complexity to the mechanism of action of omalizumab.

Developing Strategies to Treat Asthma Exacerbations Caused by Rhinovirus

Developing Strategies to Treat Asthma Exacerbations Caused by Rhinovirus

The observed incidence of anaphylaxis and serum sickness in patients receiving omalizumab in a tertiary allergy and asthma clinic in Canada

Conclusion Meticulous care was taken by our omalizumab administration clinic to ensure optimal safety based on the emphasized warnings of anaphylaxis, as well as, the indicated warnings and precautions for serum sickness. Data collected in this analysis observed no cases of anaphylaxis or serum sickness like symptoms in the treatment of over 250 patients, during a period of 15.5 years, who combined received 21,000 injections of omalizumab thus confirming the low incidence of both anaphylaxis and serum sickness. Authors’ details Allergy and Asthma Research Centre, Ottawa, ON, Canada. University of Ottawa Medical School, Ottawa, ON, Canada.

Omalizumab as a Desensitizing Agent and Treatment in Mastocytosis: A Review of the Literature and Case Report

Patients with all forms of mastocytosis can experience urticaria, abdominal cramps, nausea, diarrhea, or hypotension due to release of mediators by mast cells. Patients with mastocytosis and Hymenoptera venom allergy can develop severe adverse reactions to Hymenoptera stings. In addition, patients with mastocytosis and on venom immunotherapy are at high risk for incomplete protection and fatal reactions. Recent literature has reported the use of omalizumab as an adjunctive treatment in patients with mastocytosis, used for both symptom improvement and to dampen adverse effects caused by venom immunotherapy. This article reviews the literature regarding omalizumab use in the treatment of mastocytosis and for protection against the adverse effects during venom immunotherapy. In addition, we report the case of a patient at high risk and with cutaneous mastocytosis, whose symptoms improved with concomitant administration of omalizumab and venom immunotherapy.

Effect of omalizumab on biomarkers in middle ear effusion in patients with eosinophilic otitis media

Conclusions: Eosinophil cationic protein (ECP) concentrations in middle ear effusion (MEE) in patients with eosinophilic otitis media (EOM) were significantly decreased at 3 months after the administration of omalizumab from the baseline level (p < 0.05). This study provides new evidence that omalizumab reduces eosinophilic inflammation in the middle ear and that the reduction of ECP may not be caused by suppression of interleukin (IL)-5 production in the middle ear mucosa. Objective: EOM is an intractable otitis media characterized by a highly viscous effusion containing eosinophils. We recently reported that anti-IgE therapy using omalizumab was efficacious in the treatment of EOM. To clarify the underlying mechanism, we determined changes in biomarkers in MEE related to eosinophilic inflammation after therapy. Methods: Nine patients with EOM received the anti-IgE agent omalizumab for 3 months. Among them, five patients continued anti-IgE therapy for longer than 1 year. Eight EOM patients without administration of omalizumab were also included in the study as controls. The concentrations of eosinophilic inflammatory markers such as ECP, IgE, IL-4, and IL-5 in MEE were measured before and after the administration of omalizumab. Results: After 3 months of omalizumab therapy, the ECP concentration in MEE was significantly reduced from the baseline level (p < 0.05), while no significant change of ECP in the serum was observed. The concentrations of IL-4 and IL-5 in MEE showed no significant change before and after the therapy in EOM patients treated with omalizumab.

Omalizumab is an effective and rapidly acting therapy in difficult-to-treat chronic urticaria: A retrospective clinical analysis

BackgroundOmalizumab (anti-IgE) therapy is effective and safe in chronic urticaria (CU) in placebo-controlled clinical trials but real life clinical data are scarce. ObjectiveTo better understand the effects of omalizumab in CU patients treated outside of clinical trials. MethodsIn this retrospective clinical analysis, we assessed responder rates, optimal dosage, response to up-/downdosing, time to relief of symptoms, rates of return and time of relapse after omalizumab administration, and safety in 51 CU patients, 20 with chronic spontaneous urticaria (CSU) alone, 21 with different forms of chronic inducible urticaria (CindU) and 10 with both. ResultsOmalizumab treatment led to complete remission in 83% of CSU and 70% of CindU patients. When starting with 150mg omalizumab 4 weekly, only 2/15 CSU and 7/17 CindU patients required updosing to achieve complete remission. In CSU, 57% of complete responses occurred within week one, all on the first day. Relapses were 2–8 weeks in all but six patients, where they were <4 months. Omalizumab was safe. Efficacy was not correlated to baseline IgE levels. ConclusionClinical experience from more than 1250 injections in 51 patients over four years indicates that omalizumab is a rapidly acting, highly effective and safe drug in CSU and CindU patients. Our observations in a real life clinical setting support the recommendation of current EAACI/GA2LEN/EDF/WAO guideline for the management of urticaria to use omalizumab to treat urticaria patients.

AB1143 Successful control of churg-strauss syndrome with omalizumab

BackgroundChurg-Strauss syndrome (CSS) is extremely rare in children and is associated with higher cardiopulmonary disease and mortality rates compared to adult patients (1). Treatment consists essentially of corticosteroids (CST), however...

Omalizumab Attenuates Airway Inflammation and Interleukin-5 Production by Mononuclear Cells in Patients with Severe Allergic Asthma

Background: Omalizumab, an anti-immunoglobulin E monoclonal antibody, has shown an inhibitory effect on airway inflammation, which may be associated with clinical improvement of severe asthma. This study evaluated changes in airway inflammation and cytokine release by the peripheral blood mononuclear cells (PBMCs) of Japanese patients with severe asthma after administration of omalizumab. Methods: Sixteen Japanese patients with severe asthma who were allergic to house-dust mites were enrolled in this study. Eight received omalizumab every 2 or 4 weeks for 16 weeks, and 8 control subjects were treated with conventional drug treatment. Changes in clinical scores for sputum eosinophils and levels of fraction of exhaled nitric oxide (FeNO) were measured at the time of enrollment and at week 16. Cytokines from PBMCs stimulated by house-dust mite (Dermatophagoides farinae) or ionomycin/phorbol myristate acetate (PMA) were measured at baseline and at week 16. Results: In the omalizumab-treated group, decreases in sputum eosinophils and FeNO were observed following treatment. Furthermore, the ex vivo production of interleukin (IL)-5 by PBMCs in response to both mite allergen and ionomycin/PMA decreased significantly. In contrast, interferon (IFN)-γ production was unchanged. There were no changes in any of the parameters observed in the control group. Conclusion: Omalizumab exerts inhibitory effects on airway inflammation in Japanese patients with severe allergic asthma. This treatment attenuates production of IL-5 by PBMCs stimulated with both a specific allergen and a nonspecific activator. Reduction of the Th2 inflammatory cascade likely contributes to clinical benefits; however, further studies are required to clarify these results due to the small sample size in this study.

Effectiveness of Omalizumab in a Patient with Severe Asthma, Low Serum IgE Level, and Lack of Sensitized Allergens Induced by Oral Steroid Therapy: The Usefulness of Impulse Oscillation for Assessment of Omalizumab Therapy

Background. Omalizumab is a humanized monoclonal anti-IgE antibody that was recently approved for the treatment of severe allergic asthma. However, omalizumab is not licensed for allergic asthma in patients with a low serum IgE level (<30 IU/mL) or negative results for specific allergen tests. Case history. We present a patient with severe asthma and low serum IgE levels who had negative results for specific allergens induced by oral steroid therapy. Omalizumab administration improved asthma exacerbated forced expiratory volume in 1 s (FEV1) and respiratory resistance measurements based on the impulse oscillation technique (Mostgraph-01). The response to omalizumab therapy was evidenced by a decrease in airway resistance at 1 month. Conclusions. The findings of this case report indicate that omalizumab treatment had beneficial effects in a patient with severe asthma and low total serum IgE levels with negative results for specific IgE, which may have been induced by long-term corticosteroid administration.

Granulomatous foreign-body reaction with facial dermal fillers after omalizumab treatment for severe persistent allergic asthma: a case report

Madam, During the past few decades, an increasing number of soft‐tissue filler substances have been introduced to the beauty market worldwide for treating age wrinkles, correcting atrophic scars or small cutaneous defects, and cosmetically augmenting soft tissue of different parts of the body.1 Although these injectable fillers are considered safe, significant adverse reactions may occur.2 As was reported with interferon alfa, new immunomodulatory therapies used for inflammatory and allergic disease may produce a foreign‐body granulomatous reaction in patients injected with dermal fillers.3 We report on a case of a patient who had received hyaluronic acid (HA) and calcium hydroxylapatite injections and showed foreign‐body granulomatous reaction after omalizumab administration for severe persistent allergic asthma. A 50‐year‐old white woman with facial erythematous nodules was referred to our clinic. She had received treatment for adult‐onset severe allergic asthma with maximal inhaled corticosteroids and montelukast, but the asthma remained poorly controlled, with frequent exacerbations requiring monthly courses of oral steroids. A 16‐week trial treatment with omalizumab (300 mg subcutaneously per month) was started. The last short course of oral steroids for an exacerbation was stopped 10 days before the first administration of omalizumab.

271 Evaluation of Adverse Events Associated to Administration of Omalizumab

BackgroundAnti IgE therapy is the ultimate therapeutic option for severe atopic conditions, not controlled by conventional treatment. Its efficacy and safety was described in several peer reviewed publications. Here we report on the events temporally related to the administration of almost 4 hundred doses of the only monoclonal Anti IgE antibody approved in our country for the treatment of severe asthma.MethodsDescriptive retrospective analysis of clinical charts of patients receiving omalizumab because of Severe Uncontrolled Asthma, considering those events presented in the 72 hours after administration of it, which was not present before the procedure or as a concomitant condition of the patient. Vital signs, respiratory and cardiovascular evaluation, and dermatological inspection were performed in the hour after administration of corresponding doses. Patients having any kind of complaint were evaluated in unscheduled visits.Results384 doses of 150 mg omalizumab were given to from April 2007 to June 2011, to nine severe asthmatic patients. One of them received treatment for over 4 years, and two for over 3 years.ConclusionsOur records from patients receiving omalizumab have not registered severe adverse events in almost four hundred doses given. The moderate adverse events of nausea and tachycardia resulted in discontinuation of treatment in this unique patient. Overall, omalizumab demonstrated a very acceptable safety profile in our patients.

S12 Unscheduled healthcare resource utilisation and health-related quality of life before and after omalizumab initiation in UK clinical practice: the apex study

ObjectivesThe efficacy and safety of omalizumab for the treatment of severe persistent allergic asthma have been demonstrated in randomised controlled clinical trials. However, there are limited “real world” data on...

Plasmapheresis Prior to Omalizumab Administration in a 15-Year-Old Boy with Severe Asthma and Very High IgE Levels: Sustained Effect Over 2 Years

Anti-IgE therapy with omalizumab is an innovative therapy option in patients with severe allergic asthma. However, many patients are excluded from this treatment due to very high serum IgE levels which lie above the weight-dependent cut-off for a reasonable omalizumab administration (700 kU/l). We sought to evaluate whether a preceding plasma exchange is suitable to establish the starting basis for a subsequent anti-IgE therapy in a 15 year-old boy with steroid-resistant unstable allergic asthma whose pretreatment serum IgE levels ranged between 3 000 and 8 000 kU/l. Our aim was to create a period with relatively low IgE serum concentrations, which could be overridden by a high dose of omalizumab. 3 sessions of plasmapheresis were performed and 3×3 000 ml plasma were exchanged against albumin solution. We removed an absolute amount of 8 650 kU total IgE. During plasmapheresis, serum IgE levels markedly declined and fell below 500 kU/l. Immediately after the third plasma exchange, we started omalizumab therapy. As expected, total IgE levels began to rise again upon cessation of plasmapheresis, and after 2 months the pre-treatment values were reached. In contrast, serum concentrations of free IgE remained stable on a level of about 80 kU/l during the whole observation period. During this period, the boy displayed a considerable improvement of asthma control and an increase in quality of life. In addition, his previously poor lung function normalized. Plasmapheresis prior to omalizumab administration is suitable to temporarily reduce grossly elevated serum IgE levels and might facilitate anti-IgE therapy in selected patients previously considered not suitable for this therapy.

Omalizumab in the management of oral corticosteroid-dependent IGE-mediated asthma patients

Background:Several studies have demonstrated the beneficial effects of omalizumab in asthma patients. Here we describe the drug’s tolerance and oral corticosteroid sparing capacity in a long-term observational study.Methods:Thirty-two patients aged ≥18 years with obstructive airway disease and FEV1 reversibility ≥12% and 200 mL, with an oral steroid requirement ≥7.5 mg per day of prednisolone during a period of ≥1 year, a positive prick test or in vitro reactivity (RAST) to at least one perennial aeroallergen and a baseline immunoglobulin E level ranking between 30–700 IU/mL were prospectively followed for 17.2 ± 8.5 months. Patients were visited once or twice a month, depending on their schedule for omalizumab administration. Intervention: blood analysis every six months; spirometry and nitric oxide measurement at every visit.Results:One patient who dropped out early was excluded. Follow-up period: the treatment benefited 83.9% (26/31) of the cohort; oral corticosteroids were reduced from 7.19 ± 11.1 to 3.29 ± 11.03 mg (p < 0.002) and withdrawn in 74.2% of patients. FEV1 (percent predicted) was 64.4 ± 22.7 at the beginning and 62.9 ± 24.3 at the end. IgE at entry was 322.2 ± 334.2 IU/mL and increased 2.34-fold. Respiratory function and NO did not present statistically significant changes. We identified three groups of patients: the first (n = 17) receiving oral steroid at entry in whom the accumulated dose of oral steroids progressively decreased; another (n = 10) including patients who had quit oral steroids before starting omalizumab although they had not been instructed to do so and whose oral steroid dose at the end of follow-up was zero; and a third group (n = 4) that did not benefit from omalizumab treatment. The only relevant side effect was a flu-like syndrome which required discontinuation of treatment in one patient.Conclusion:In our series, a substantial, safe decrease in oral corticosteroid requirements was observed due, at least to some extent, to omalizumab therapy. Oral corticosteroids were withdrawn in three-quarters of the patients. We were unable to identify a factor able to predict which patients would benefit most from omalizumab treatment.