Dose Of Omalizumab Research Articles

Position statement for the use of omalizumab in the management of chronic spontaneous urticaria in Indian patients.

Chronic spontaneous urticaria (CSU) affects 1% of the world population and also their quality of life, and 50% of these patients are refractory to H1-antihistamines. Omalizumab is a humanized monoclonal anti-IgE antibody that binds with free IgE antibodies and reduces the circulating levels of free IgE. This reduction in free IgE prevents mast-cell degranulation. The EAACI/GA2LEN/EDF/WAO guidelines recommend omalizumab as the third-line of therapy as an add-on to antihistamines. The recommended dose of omalizumab is 300 mg, 4 weekly in the management of CSU refractory to standard of care with H1-antihistamines in adults and adolescents ≥12 years of age. In some patients, a dose of 150 mg may be acceptable. Omalizumab has a good safety profile. However, due to the biologic nature of the drug, all patients administered omalizumab must be observed for 2 h after administration for anaphylactoid reactions. There have been no studies on the effect of impaired renal or hepatic function on the pharmacokinetics of omalizumab. While no particular dose adjustment is recommended, omalizumab should be administered with caution in these patients.

Treatment of Chronic Spontaneous Urticaria with a Single Dose of Omalizumab: A Study of Four Cases.

Background:Chronic spontaneous urticaria (CSU) has a detrimental effect on patients’ emotional and physical quality of life. Omalizumab, an anti-immunoglobulin E humanized monoclonal antibody, has been shown to be very effective in the treatment of refractory chronic urticaria patients but may not be an economically viable option for all CSU patients. However, we present a case series where a single dose of omalizumab gave sustained relief of symptoms in patients with CSU, which may be an economical option.Aims:The aim of this study is to assess the efficacy of a single dose of omalizumab in the treatment of CSU. Materials and Methods: Four patients of CSU whose disease was not controlled with four times the licensed dose of tablet fexofenadine 180 mg were exhibited one subcutaneous injection of omalizumab and were followed up at 4 weekly intervals for 24 weeks for Weekly Urticaria Activity Score 7 (UAS7) and Dermatology Life Quality Index (DLQI).Results:A sharp decline in UAS7 and DLQI was documented in 7–10 days. The decline was maintained up to 16 weeks in one case and 20 weeks in the other three cases. Both the scores at the end of the follow-up period of 24 weeks were better than the pre-omalizumab scores.Conclusion:The results of this case series indicate the efficacy of a single-dose omalizumab in treating moderate to severe refractory CSU. Further studies are required to identify the minimum frequency of administering omalizumab to effectively control CSU. This would greatly reduce the cost of this novel therapy.

Anti‐IgE for chronic urticaria – are children little adults after all?

Omalizumab is a recombinant monoclonal antibody, targeting the epsilon 3 domain of free serum IgE antibodies, and thus preventing their attachment to the cognate high-affinity receptor on mast cells and reducing the number of cell-bound receptors. It represents the first ‘biological’ that has been studied in allergy and was registered several years ago for the treatment of severe allergic asthma in adults and children by the FDA and the EMA. About one year ago, omalizumab was registered for adult patients with chronic spontaneous urticaria – with or without angioedema – which is insufficiently controlled by standard treatment, including high-dose antihistamines. During the last years, international guidelines have profoundly changed our therapeutic approaches to chronic urticarial patients in which, instead of a previously recommended combination treatment with different histamine receptor antagonists, an increase of non-sedating H-1 receptor antagonists of the second generation up to a quadruple dose of the standard recommended regimen is now the general rule (1,2,3,4). These new recommendations have led to a remarkable improvement of response rates seen in urticarial patients; however, by far not all adult patients with chronic spontaneous urticaria are sufficiently controlled even by high doses of antihistamines. The application of omalizumab as a third-line option has demonstrated an unexpected additional benefit and leads to a complete relief of symptom in almost all treated patients. All three of the pivotal phase III studies in adults have led to a recommended dose of 300 mg omalizumab in 4 weeks, which differs from dose regimens for allergic asthma, where the patient's body weight and the total serum IgE levels determine the omalizumab dose. It seems that with the novel treatment option the vast majority of all adult patients with chronic spontaneous urticaria are adequately controlled without major safety problems, which is a remarkable step forward in the long-term treatment of urticaria. The problems of chronic urticaria in childhood seem to be inadequately perceived, which may be due to its low prevalence compared to adults. Until recently, the natural course of CU has not really been studied in large cohorts of children. A recent prospective study from Thailand suggests that chronic urticaria in children has a more favorable outcome than in adults, with a remission rate of 18.5% after one year and 54% after 3 years 5. Like adults, more than 30% of the children with a chronic spontaneous urticaria were found to have autoantibodies to the alpha subunit of the high-affinity IgE receptor (Fc-epsilon-R 1) and/or anti-IgE antibodies. The presence of these autoantibodies may be screened for by performing the autologous serum skin test (ASST). Up to now, the intervention with the recombinant monoclonal antibody omalizumab has been studied in childhood only for severe asthma as well as in rhinitis. In most parts of the world, it is registered for the treatment of uncontrolled severe asthma after the age of six. A systematic review on the use of omalizumab in children, which appears in this issue, indicates that the addition of omalizumab in patients with uncontrolled allergic asthma can be considered as effective and safe 6. Up to now, there is not a single randomized controlled trial in children with urticaria. Therefore, the different case reports presented in this issue reporting a beneficial effect in refractory solar urticaria, and in spontaneous and physical urticaria are very encouraging and of high interest (7,8,9). Although very severe clinical cases of uncontrollable chronic urticaria compared to adults seem to be rare and the outcome may be more favorable in childhood, the information presented here strongly suggests that the pathophysiologic mechanism leading to chronic urticaria in childhood may be similar. It appears that the time has come to ask for randomized controlled trials with omalizumab and possibly other biologics for an apparently forgotten disorder in childhood which may deserve more attention and consideration than given in the past.

Comparison of different medical treatment options for CRSwNP: doxycycline, methylprednisolone, mepolizumab and omalizumab

Methods In total, 100 patients were randomly assigned to receive doxycycline for 20 days (n=14), methylprednisolone in decreasing doses for 20 days (n=14), mepolizumab 2 single intravenous injections (n=20), omalizumab 2 to 4 subcutaneous doses (n=15) or placebo (n=37) in three separate clinical double-blind, placebo-controlled trials. Participants were followed for 8 weeks. Endoscopic evaluation of nasal polyp score, assessment of symptom score and measurement of markers of inflammation in nasal secretions and serum occurred at baseline, week 4 and week 8. All treatments were completed at week 4, except for 2 patients who received a fourth subcutaneous dose of omalizumab at week 6.

Off-Label Uses of Omalizumab.

The off-label use of medicines is a common and extensive clinical practice. Omalizumab has been licensed for use in severe allergic asthma and chronic urticaria. Omalizumab dosing was based on body weight and baseline serum IgE concentration. All patients are required to have a baseline IgE between 30 and 700 IU/ml and body weight not more than 150 kg. The use of off-label drugs may lead to several problems including adverse effects and an increased risk/benefit balance. In this article, there are summarized off-label uses of omalizumab in the last recent years in diseases in which IgE maybe or certainly has a corner role such as allergic rhinitis, allergic bronchopulmonary aspergillosis, anaphylaxis, keratoconjunctivitis, food allergy, drug allergy, urticaria, angioedema, non-atopic asthma, atopic dermatitis, nasal polyps, Churg-Strauss syndrome, eosinophilic otitis media, chronic rhinosinusitis, bullous pemphigoid, contact dermatitis, and others. Use in pregnancy asthmatic women and pre-co-administration with specific immunotherapy will also be revised.

Omalizumab in the treatment of aspirin-exacerbated respiratory disease

Omalizumab in the treatment of aspirin-exacerbated respiratory disease

Effectiveness of omalizumab in an asthmatic patient with severe airway and blood eosinophilia.

Omalizumab is a monoclonal antibody raised against class E immunoglobulin (IgE), approved for the treatment of chronic severe (in the EU) or moderate-to-severe (in the USA) IgE-mediated asthma. Omalizumab is effective in reducing asthma exacerbations, hospitalizations and emergency visits due to exacerbations as well as in improving patients’ quality of life (QoL) [1–3].

Revision of omalizumab dosing table for dosing every 4 instead of 2 weeks for specific ranges of bodyweight and baseline IgE

The dosing level and frequency of omalizumab are guided by a dosing table based on total serum immunoglobulin E (IgE) and bodyweight. Using a validated, mathematical simulation model (based on concentration data from 8 studies), we evaluated the impact of a revised omalizumab dosing table (every 4weeks dosing regimen) on the pharmacokinetic and pharmacodynamic profiles of free and total IgE. Safety analysis, in patients with high levels of exposure to omalizumab, was done using data from the clinical and post-marketing databases. The model accurately predicted observed omalizumab, free and total IgE concentrations. After reaching steady-state, the average increase in exposure was 10%, even for patients with the highest concentrations at the upper 97.5th percentile. Free IgE suppression slightly increased in the initial phase, and slightly reduced at the trough of the dosing cycle, but average suppression remained similar for both regimens. The safety profile of omalizumab was similar for patients receiving higher or lower doses. Thus, doubling the dose of omalizumab, in a subset of patients receiving 225–300mg of omalizumab (every 2weeks dosing regimen) can efficiently suppress free IgE without compromising safety or efficacy.

The Xolair Pregnancy Registry (EXPECT): The safety of omalizumab use during pregnancy

For many asthma medications, pregnancy safety data remains insufficient. The omalizumab pregnancy registry, EXPECT, evaluates maternal, pregnancy, and infant outcomes after exposure to omalizumab, including incidence of congenital anomalies. EXPECT is a prospective, observational study of pregnant women exposed to ≥1 dose of omalizumab within 8 weeks prior to conception or at any time during pregnancy. Primary outcome measures include rates of live births, elective terminations, stillbirths, and congenital anomalies. Data were collected at enrollment, each trimester, birth, and every 6 months up to 18 months post-delivery. As of November 2012, 188 of 191 pregnant women were exposed to omalizumab during their first trimester. Of 169 pregnancies with known outcomes (median exposure during pregnancy, 8.8 months), there were 156 live births of 160 infants (4 twin pairs), 1 fetal death/stillbirth, 11 spontaneous abortions, and 1 elective termination. Among 152 singleton infants, 22 (14.5%) were born prematurely. Of 147 singleton infants with weight data, 16 (10.9%) were small for gestational age. Among 125 singleton full-term infants, 4 (3.2%) had low birth weights. Overall, 20 infants had congenital anomalies confirmed, 7 (4.4%) of whom had 1 major defect. No pattern of anomalies was observed. To date, proportions of major congenital anomalies, prematurity, low birth weight, and small size for gestational age observed in the EXPECT registry are not inconsistent with findings from other studies in this asthma population. Recognizing the small sample size available, no apparent increased birth prevalence of major anomalies or patterns of major anomalies has been observed.

Commentary: Omalizumab for the treatment of chronic idiopathic or spontaneous urticaria.

Chronic urticaria affects approximately 0·1% of the population. The disease is not life threatening, but it is very disabling and has a significant effect on quality of life.1 Approximately 50% of patients are unresponsive to H1‐antihistamines,2 and commonly used second‐line agents such as ciclosporin or prednisolone have marked adverse effects. Thus there is a need for a safe and effective second‐line therapy. Omalizumab, a recombinant humanized monoclonal anti‐IgE antibody that is effective in asthma and has a very good safety record,3 appears to fulfil this need. The main drawback at present is its cost. In this multicentre, phase 3 study, Maurer et al.4 gave three different doses of omalizumab to 323 patients with chronic spontaneous urticaria (CSU) resistant to treatment with antihistamines. Short‐term use of omalizumab produced a significant reduction in urticaria scores, particularly at the highest dose of 300 mg monthly, with little in the way of adverse events.

Omalizumab in Asthma: An Update on Recent Developments

IgE is central to the pathophysiology of allergic asthma. Omalizumab, a humanized anti-IgE mAb, specifically binds free IgE and interrupts the allergic cascade by preventing binding of IgE with its high-affinity FcεRI receptors on mast cells, antigen-presenting cells, and other inflammatory cells. The clinical efficacy of omalizumab has been well documented in a number of clinical trials that involve adults, adolescents, and children with moderate-to-severe and severe allergic asthma. In these studies, omalizumab reduced exacerbations, asthma symptoms, inhaled corticosteroid and rescue medication use, and improved quality of life relative to placebo or best standard of care. Similar benefits have been reported in observational studies in "real-world" populations of patients. Results from recent pooled data from randomized clinical trials and from a large prospective cohort study provide reassurance about the long-term safety of omalizumab. Omalizumab dosing is individualized according to body weight and serum-IgE level, and recent adjustments to the dosing algorithm in Europe have enabled more patients to be eligible for treatment. Ongoing and future research is investigating the optimal duration of therapy, accurate predictors of response to treatment, and efficacy in nonatopic asthma as well as other IgE-mediated conditions.

Long-term efficacy of omalizumab in seven patients with treatment-resistant chronic spontaneous urticaria

BackgroundMonoclonal anti-IgE antibody omalizumab is a promising therapeutic option in patients with chronic urticaria (CU) resistant to non-sedating H1-antihistamines (nsAH). However, data about its long-term efficacy and safety are still scant. ObjectiveWe retrospectively analysed the clinical course of patients with severe recalcitrant CU that were treated in our department with omalizumab for a period greater than 24 months. Methods and patientsSeven patients (six females, median 43 years) treated for a median of 35 months have been evaluated. Before treatment, all suffered from persistent symptoms despite receiving high doses of nsAH [4×/day], leukotriene antagonists and prednisolone (10–30mg/day for a median duration of 48 months). Response to treatment was assessed using urticaria activity score (UAS) and a combined symptom/medication score. ResultsThere was a complete remission of disease in four patients after the first dose of omalizumab. Before the 5th administration, all patients had a UAS of 0. We found a significant improvement in UAS between pre-treatment and first dose (p=0.017) and a gradual decrease in the symptom/medication score over the course of the first five administrations. Tapering of prednisolone was possible in all patients. Administration intervals were gradually increased, although all experienced resurgence of symptoms in cycles greater than six weeks. There were no reported adverse reactions attributable to the drug. ConclusionOmalizumab was a safe and effective corticosteroid alternative for maintaining long-term remission of symptoms in these patients. Treatment intervals required individual patient-by-patient determination. The drug did not seem to alter the natural history of the disease.

Omalizumab in patients with allergic (IgE-mediated) asthma and IgE/bodyweight combinations above those in the initially approved dosing table

BackgroundWhen first approved in the European Union (EU), the omalizumab dosing table had upper bodyweight and IgE limits of 150 kg and 700 IU/mL, respectively. In this study, we assessed the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of omalizumab in patients with IgE/bodyweight combinations above those in the original dosing table. MethodsA multicentre, open-label, parallel-group study assessed the safety, PK and PD of omalizumab in 32 patients with mild-to-moderate allergic (IgE-mediated) asthma. Patients received two subcutaneous injections of omalizumab at one of three dosage levels (450, 525, or 600 mg), chosen according to baseline IgE (300–2000 IU/mL) and bodyweight (40–150 kg), with a 14-day interval between injections. ResultsOverall, 69 adverse events (AEs), none of them serious, were reported by 26 (81.3%) patients. Analysis of laboratory measurements, vital signs and ECG data revealed no adverse findings of clinical relevance. The PK profile was consistent with previous data for lower doses. Mean maximum decrease of free IgE from screening was ≥99% for all three doses, and mean free IgE concentrations remained <25 ng/mL for at least 2 weeks after the second dose. The reductions in free IgE were consistent with levels previously associated with clinical improvements. ConclusionsThe safety and PK/PD findings from this study are consistent with previous data, and supported the extension of the omalizumab dosing table to include those patients with higher IgE/bodyweight combinations.Clinical trial registry and registration number: clinicaltrials.gov (NCT00546143).

Evaluation of two commercial omalizumab/free IgE immunoassays: implications of use during therapy

Background:The anti-IgE monoclonal antibody, omalizumab, is approved in the US as add-on therapy for patients ≥12 years of age with moderate-to-severe persistent allergic asthma. Omalizumab is administered according to the US Food and Drug Administration approved dosing table included in the prescribing information. The dosing table was developed using Genentech’s free IgE assay and is designed to achieve free serum IgE levels of <50 ng/mL, known to be associated with clinical benefit. Lack of clinical benefit in a subset of patients on omalizumab has prompted demand for commercial free IgE assays to guide omalizumab dosing. To date, two commercial free IgE assays marketed by ViraCor-IBT (no longer offered) and BioTeZ have been available to physicians.Objective:This study compares the results generated from the two commercial free IgE assays with the free IgE levels generated by the Genentech assay.Methods:Two serum sample sets were prepared using 20 samples from patients with a wide range of IgE and omalizumab from an omalizumab clinical trial and 36 samples from omalizumab-naïve patients. Different amounts of omalizumab were added to the 36 omalizumab naïve samples based on measured total IgE levels to ensure that a good range of IgE and omalizumab was represented in the study samples. Samples were randomized for blinded analysis of free IgE levels using the Genentech, ViraCor-IBT and BioTeZ free serum IgE assays. Analysis of samples in the ViraCor-IBT assay were conducted by ViraCor-IBT and the analysis of samples using the Genentech and BioTeZ assay methods were conducted by a third party contract research organization.Results:The ViraCor-IBT and BioTeZ free IgE assays demonstrated significantly higher free IgE levels than the Genentech free IgE assay. Twenty-nine of 56 samples tested <50 ng/mL in the Genentech assay; of these, 12/29 (41%) and 20/29 (69%) tested >50 ng/mL in the BioTeZ and ViraCor-IBT assays, respectively. In the BioTeZ free IgE evaluations, 11/20 samples that were re-tested had inter-assay differences ranging from 40–190%.Conclusions:Free ligand (such as IgE) measurements are challenging and dependent on the method and reagents used. The Viracor-IBT and BioTeZ methods tend to over-estimate free serum IgE levels compared with the Genentech free IgE assay. Using these assays to monitor therapy and adjust omalizumab doses post treatment is considered off-label use and could lead to a potential risk for unnecessary treatment and/or risk to patient safety.

Improvements In Health-Related Quality Of Life From Asteria I & II: Phase III Studies To Evaluate The Efficacy and Safety Of Omalizumab In Patients With Chronic Idiopathic/Spontaneous Urticaria Who Remain Symptomatic Despite H1 Antihistamine Treatment

To describe changes in health-related quality of life (HRQOL) in patients with chronic idiopathic/spontaneous urticaria (CIU/CSU) using pooled data from the 12-week treatment periods of the ASTERIA I & II studies. Subjects (n=640) were randomized 1:1:1:1 and received placebo or omalizumab 75, 150 or 300 mg (PLB, OMA75, OMA150, OMA 300) at Baseline and Weeks 4 and 8. HRQOL was assessed by the Dermatology Life Quality Index (DLQI; overall score and subscales for symptoms and feelings, daily activities, leisure, work and school, personal relationships and treatment) at Baseline, Weeks 4 and 12. At Baseline, patients reported substantial HRQOL impairment. All treatment arms improved from Baseline to Week 12 in many of the DLQI domains; however, the largest improvements were seen in the omalizumab-treated patients (change from Baseline to Week 12 in overall DLQI, PLB -6.11, OMA75 -6.93, OMA150 -8.15, OMA300 -10.22). Compared to placebo, change from Baseline to Week 12 in overall DLQI was statistically significant for higher doses of omalizumab (OMA150, p=0.01 and OMA300 mg, p< 0.0001). Improvements in DLQI were observed after one administration of study drug, by the first post-Baseline assessment at Week 4, with additional improvement observed at Week 12. For all DLQI domains assessed, the greatest improvements were seen in patients treated with omalizumab 300 mg. In CIU/CSU patients who are symptomatic despite H1 antihistamine treatment, omalizumab was efficacious in improving a broad array of HRQOL domains, as measured by the DLQI instrument.

Omalizumab vs. placebo in the management of chronic idiopathic urticaria: a systematic review

Objectives To examine the evidence derived from randomized controlled clinical trials on the efficacy and safety of omalizumab compared to placebo in controlling symptoms of chronic idiopathic urticaria/chronic spontaneous urticaria (CIU/CSU).Data source The electronic databases PubMed, Medline, EMBASE, Biomed Central, The Cochrane Central Register of Controlled Trials (CENTRAL), Wiley, OVID, and HighwirePress were reviewed. The date limit was set to May 31th, but it was extended to September 30th of 2014 due to a new publication. No language restriction was used. The articles included were randomized trials controlled with placebo in individuals older than 12 years diagnosed with CIU/CSU refractory to conventional treatment, the intervention being, omalizumab at different doses, and the comparison, placebo. The primary outcome was symptom improvement according to the weekly score of urticaria severity (UAS7), the itch severity score (ISS), the weekly score of number of urticarial lesions, the dermatology life quality index, and the chronic urticaria quality of life questionnaire (CU-QoL). Databases were searched using the following Mesh or EMTREE key words including as intervention “omalizumab” or “humanized monoclonal antibody,” compared to placebo and the disease of interest “urticaria” or “angioedema”. The title, abstract and article were reviewed by two independent investigators, according to the selection criteria in each of the databases. An assessment of the quality of the articles was performed according to the bias tool from the studies of the Cochrane Collaboration. Information such as author data, date of study, number of participants, interventions, dose and frequency of administration, comparison, time of follow-up, measurements of weekly score of urticaria activity, pruritus severity score, weekly urticarial lesions, percentage of angioedema and post-treatment change were extracted. Frequency of adverse events and the ones suspected to be caused by the intervention drug were included.Results 770 records were identified in all databases described. 720 were eliminated for failing to meet the inclusion criteria in the first review or for duplicate records. 24 articles were reviewed by abstract, 18 additional articles were further removed, leaving 6 records for inclusion. An experimental study was excluded because it wasn’t randomized. Five studies were finally included, with 1117 patients, of these 831 received a dose of omalizumab of 75 mg (183 patients, 16.38%), 150 mg (163 patients, 14.59%), 300 mg (437 patients, 39.12%) or 600 mg (21 patients, 1.8%), as a single dose, or every 4 weeks until 24 weeks maximum. The average age was 42.07 years, predominantly female gender and white ethnicity. It was observed that the use of omalizumab 300 mg lowered the weekly scores of urticarial activity in 19.9 vs. 6.9 on placebo (p <0.01), 19 vs 8.5 and 20.7 vs 8.01 in three studies, the weekly ISS (−9.2 vs. - 3.5, p <0.001, −9.8 vs −5.1 p < 0.01, −8.6 vs −4.0 and −9.4 vs −3.63 p <0.001 in four studies), and the percentage of angioedema-free days (omalizumab 95.5% vs. placebo 89.2% p <0.001, and 91.95% vs. 88.1% p <0.001 in two of the studies respectively).Limitations The different doses used throughout the study, time of administration and follow-up periods ranged from single dose to monthly dose for 24 weeks. Therefore no meta-analysis of the review was conducted.Conclusions and implications of the main findings Despite the limitations, it is considered that omalizumab 300 mg is effective in treating chronic idiopathic urticaria refractory to H1 antihistamines. Further studies are required to determine the duration of effective treatment.Registration number of the systematic review CRD42014010029 (PROSPERO. International Prospective Register of Systematic Reviews).

Anti-IgE therapy and severe atopic dermatitis: A pediatric perspective

Anti-IgE therapy and severe atopic dermatitis: A pediatric perspective

Effectiveness of Omalizumab in Severe Allergic Asthma: A Retrospective UK Real-World Study

Objective. The aim of this study was to evaluate the “real world” effects of the monoclonal antibody omalizumab (OMB) when used to treat severe persistent allergic asthma in UK clinical practice. Methods. A 10-center retrospective observational study was carried out to compare oral corticosteroid (OCS) use and exacerbation frequency in 12 months pre- versus post-OMB initiation in 136 patients aged ≥12 years with severe persistent allergic asthma. All patients received ≥1 dose of OMB. Patients who had received OMB in a clinical trial were excluded. Data were obtained from hospital and if necessary general practitioners’ (GPs’) records on OCS use, lung function, hospital resource use, and routinely used quality of life (QoL) measures at baseline (pre-OMB), 16 weeks, and up to 12 months post-OMB initiation. Results. Mean total quantity of OCS prescribed per year decreased by 34% between the 12 months pre- and post-OMB initiation. During the 12 months post-OMB initiation, 87 patients (64%) stopped/reduced OCS use by 20% or more and 66 (49%) stopped OCS completely. Mean percent predicted forced expiratory volume in one second (FEV1) increased from 66.0% at baseline to 75.2% at week 16 of OMB therapy. The number of asthma exacerbations decreased by 53% during the 12 months post-initiation. Accident and emergency visits reduced by 70% and hospitalizations by 61% in the 12 months post-OMB initiation. Conclusion. This retrospective analysis showed a reduction in exacerbations and improved QoL as per previous studies with OMB. However, the total reduction in annual steroid burden and improved lung function in this severely ill group of patients taking regular or frequent OCS is greater than that seen in previous trials.

Population-Based Efficacy Modeling of Omalizumab in Patients with Severe Allergic Asthma Inadequately Controlled with Standard Therapy

Omalizumab, a recombinant humanized monoclonal antibody, is the first approved anti-immunoglobulin E (IgE) agent for the treatment of subjects with moderate to severe persistent allergic asthma that are inadequately controlled by the standard of care. The objective of this study was to quantitatively characterize relationships between serum free IgE and pulmonary function (as measured by forced expiratory volume in 1 s [FEV1]) as well as serum free IgE and airway inflammation (as measured by fractional exhaled nitric oxide [FeNO]) using population-based efficacy models. Data were collected from patients in the EXTRA trial who received omalizumab or placebo 150 to 375 mg subcutaneously every 2 or 4 weeks from week 0 to 48 with constant standard of care as background therapy. None of the covariates evaluated, including demographics, disease status, and baseline pharmacodynamic biomarkers, were significant in explaining the variability in the FEV1 or FeNO response to omalizumab. Results from the efficacy models further confirmed the current omalizumab dosing rationale based on the mean target free IgE level of 25 ng/ml and quantified the variability for the target. In addition, the resulting population models could be used to predict population FEV1 or FeNO response for omalizumab and/or other anti-IgE therapeutics for which PK-IgE models are constructed.

Role of Omalizumab in Rush Cow's Milk Desensitization in the Outpatients Office

Milk desensitization protocols are widely extended at inpatients Allergy clinics. The main objetive was to complete a cow′s milk (CM)desensitization rush protocol with the adyuvant use of omalizumab under outpatients setting. We present a 7 year-old girl with a confirmed diagnosis of severe persistent anaphylaxis to CM. No other atopic conditions were present. No controlled challenges were performed as minimal unwanted contacts with dairy products (even traces) were able to elicit immediate systemic symptoms. Diagnostic work-up showed a total IgE of 614 UI/L with specific IgE (kU/l) to casein: 20.0; alfa-lactoalbumin: 16.7 and beta-lactoglobulin: 18.4. A total cummulative dose of Omalizumab 600 mg (300 mg every two-weeks) was only administered four weeks prior to desensitization. Clinical follow-up was strictly observed during the whole protocol. On the first day, the proposed rush schedule included dosing up (every 30 minutes) with both diluted (1/10) and undiluted CM up to a maximal dose of 4 ml.This daily manteinance dose (4 ml) was also weekly –doubled to a maximal dose of 250 ml. in seven weeks. A final dose of 250 ml were reached in seven weeks. No adverse reactions were observed and no medication was needed either. No late-phase adverse events reactions were present. The inclusion of Omalizumab in the food desensitization protocols could play a role as a usefull adyuvant tool specially in those patients with a high sensitization who require to be managed in the outpatient office. Further studies are needed to evaluate the optimal duration of Omalizumab in long-term food desensitization