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Omalizumab has demonstrated efficacy among patients with moderate to severe persistent allergic asthma, whose symptoms are inadequately controlled with other controller agents. This therapy is generally well tolerated, but there are some safety considerations, the most important of which is the rare, but potentially life-threatening, occurrence of omalizumab-associated anaphylaxis.

In Canada, data from the manufacturer of omalizumab indicate that the frequency of anaphylaxis attributed to Xolair in post-marketing use is approximately 0.2%. Other researchers, including the American Omalizumab Joint Task Force (OJTF), have suggested a lower overall frequency of 0.09%.

This paper provides a summary of the epidemiologic research carried out to date and presents a concise, practical set of recommendations for the prevention, monitoring and management of omalizumab-associated anaphylaxis. Prevention tips include advice on patient education measures, concomitant medications and optimal administration. For the first three injections, the recommendation is to monitor in clinic for two hours after the omalizumab injection; for subsequent injections, the monitoring period should be 30 minutes or an appropriate time agreed upon by the individual patient and healthcare professional.

In the event that a patient does experience omalizumab-associated anaphylaxis, the paper provides recommendations for handling the situation in-clinic and recommendations on how to counsel patients to recognize the potential signs and symptoms in the community and react appropriately.

Background

To evaluate the therapeutic efficacy of omalizumab and specific subcutaneous immunotherapy (SCIT) as a treatment modality in patients with more than one allergic-type condition.

Methods

In the first group (Group A), 2 males and 7 females with severe persistent asthma and a mean age of 34.2 years received omalizumab and SCIT. In the second group (Group B), 4 males and 2 females with severe persistent asthma and a mean age of 52.7 years received omalizumab only. In the third group (Group C), 1 male and 3 females with severe persistent asthma and a mean age of 28.8 years received omalizumab followed by SCIT. All patients were followed for 2 years and comparisons were made using pulmonary function tests and asthma control tests.

Results

The patients studied had severe persistent asthma for periods ranging from 2 to 10 years, and in addition had been diagnosed as allergic asthmatics for 5 to 40 years. The mean IgE levels were as follows: Group A: 553.9 IU/mL; Group B: 422.3 IU/Ml; and Group C: 383.5 IU/mL. In all 3 groups results in the asthma control test increased by 2.5 fold over the period of study.

Conclusions

After the addition of SCIT to omalizumab therapy at 48 week of our study, no change was detected in urticarial attack rates. In another 17 year old male patient with moderate allergic rhinoconjunctivitis, asthma and atopic dermatitis, omalizumab administration with SCIT at the same time, increased the severity of atopic dermatitis. We stopped the immunotherapy than the skin lesions lost.omalizumab therapy is continued.

Background

The worldwide prevalence of asthma is high and increasing. In India prevalence of asthma is variable from 4% to 20%. Despite ICS plus LABA therapy 72% of asthma patients were uncontrolled or not well controlled in INSPIRE study. Immunoglobulin-E plays a central role in inflammatory cascade. To study the efficacy of omalizumab in Indian patients with moderate to severe persistent asthma in terms of quality of life (QOL) improvement, reduction in severe exacerbation, ED visits and loss of working days.

Methods

52 patients aged from 12+ years to 86 years (23.3 % females, avg age: 33.6, avg S.IgE: 283) fulfilling omalizumab indication criteria were given 150 mg subcutaneously once in 2 or 4 weeks for 16 to 24 weeks during March 2007 till date. QOL assessment 52 weeks after treatment in terms of following parameters were studied: Asthma symptoms (Cough, wheezing, tightness in the chest) Night Symptoms (frequent awakening, sleep disturbances) Rescue medication use Loss of working days/school days Emergency visits.

Results

94% of patients were able to reduce or discontinue regular OCS use. 72% reduction in exacerbations, 76% reductions in emergency visits ICS/LABA dose was maintained/reduced in ∼ 93 % patients. –54% improvement in working/school days in the age group of 12 to 40 years. 60% improvement in uninterrupted sleep hours best improvement in QOL was observed in 12 to 40 years age group.

Conclusions

Omalizumab is well tolerated and effective as an add-on therapy in patients of moderate to severe persistent Asthma and offers a therapeutic and economic benefit to patient. Its potential as disease modifier and early intervention in treatment guidelines needs further studies.

Background

Current therapy for allergic bronchopulmonary aspergillosis (ABPA) uses oral corticosteroids, exposing patients to the adverse effects of these agents. There are reports of the steroid-sparing effect of anti-IgE therapy with omalizumab for ABPA in patients with cystic fibrosis (CF), but there is little information on its efficacy against ABPA in patients with bronchial asthma without CF.

Objective

To examine the effects of omalizumab, measured by asthma control, blood eosinophilia, total serum immunoglobulin E (IgE), oral corticosteroid requirements, and forced expiratory volume spirometry in patients with ABPA and bronchial asthma.

Methods

A retrospective review of charts from 2004–2006 of patients treated with omalizumab at an academic allergy and immunology practice in the Bronx, New York were examined for systemic steroid and rescue inhaler usage, serum immunoglobulin E levels, blood eosinophil counts, and asthma symptoms, as measured by the Asthma Control Test (ACT).

Results

A total of 21 charts were screened for the diagnosis of ABPA and bronchial asthma. Four patients with ABPA were identified; two of these patients were male. The median monthly systemic corticosteroid use at 6 months and 12 months decreased from baseline usage. Total serum IgE decreased in all patients at 12 months of therapy. Pre-bronchodilator forced expiratory vital capacity at one second (FEV1) was variable at 1 year of treatment. There was an improvement in Asthma Control Test (ACT) symptom scores for both daytime and nighttime symptoms.

Conclusions

Treatment with omalizumab creates a steroid-sparing effect, reduces systemic inflammatory markers, and results in improvement in ACT scores in patients with ABPA.

BACKGROUND:

A novel anti-immunoglobulin E (anti-IgE) therapy for asthma, omalizumab, has been approved for use in Canada.

OBJECTIVE:

To review the basic and clinical data for omalizumab, and to examine its possible role for asthma management in Canada.

METHODS:

A literature search from 1960 to 2006 was conducted in MEDLINE to identify studies of omalizumab. In addition, abstracts from recent respiratory and allergy scientific meetings were sought, and any unpublished data were requested from the manufacturer. A consensus panel of respiratory and allergy specialists reviewed and summarized the data, and derived a set of recommendations for omalizumab use.

RESULTS:

Omalizumab is a humanized monoclonal antibody designed to bind to the C epsilon 3 domain of the IgE molecule, forming soluble immune complexes that are cleared by the reticuloendothelial system. Subcutaneous injections, given at two- or fourweek intervals at the recommended dose, result in a rapid decrease in free circulating IgE levels. In two phase III clinical trials of 1405 adult and adolescent patients with moderate to severe asthma maintained on moderate doses of inhaled corticosteroids (ICS), omalizumab reduced exacerbation rates compared with placebo, and was associated with improved symptoms and a greater corticosteroid-sparing effect. In a trial of 419 patients with severe disease that was uncontrolled despite the use of high-dose ICS and concurrent long-acting beta2-agonists, severe exacerbations were 50% less frequent in omalizumab-treated patients than in control subjects. Retrospective analyses have identified the characteristics of patients most likely to respond to omalizumab treatment.

RECOMMENDATIONS:

Omalizumab may be considered as a potential adjunctive therapy in atopic patients with severe asthma uncontrolled by conventional therapy with optimal doses of ICS and appropriate adjunctive therapy (eg, long-acting beta2-agonists). Typically, patients are identified by the need for frequent short course or continuous oral corticosteroids. Therapy should be initiated only after review by a specialist to confirm the diagnosis and that conventional therapy is optimal.

Omalizumab, a humanized monoclonal antibody that binds circulating IgE antibody, is a treatment option for patients with moderate to severe allergic asthma whose asthma is poorly controlled with inhaled corticosteroids and inhaled long-acting β2 agonist bronchodilators. This review considers the mechanism of action, pharmacokinetics, efficacy, safety and place in management of omalizumab in asthma and focuses particularly on key articles published over the last three years. Omalizumab reduces IgE mediated airway inflammation and its effect on airway remodeling is under investigation. Recent long-term clinical trials confirm the benefits of omalizumab in reducing exacerbations and symptoms in adults and in children with moderate to severe allergic asthma. No clinical or immunological factor consistently predicts a good therapeutic response to omalizumab in allergic asthma. In responders, the duration of treatment is unclear. The main adverse effect of omalizumab is anaphylaxis, although this occurs infrequently. Preliminary data from a five-year safety study has raised concerns about increased cardiovascular events and a final report is awaited. Clinical trials are in progress to determine whether omalizumab has efficacy in the treatment of non-allergic asthma.

Background

Near-fatal asthma treated with Omalizumab. The near-fatal asthma is a severe form of asthma that threatens the life of patients and is associated with poorly controlled chronic asthma, accounting for limitations in the quality of life. Presents with ongoing chronic inflammation and irreversible changes in the airway. Treatment is difficult, however with the use of omalizumab can decrease the risk of mortality in these patients.

Objective

Evaluating clinical improvement, spirometric and income to the emergency hospitalization and intensive care unit, as well as near-fatal asthma episodes in patients with uncontrolled asthma in treatment with con Omalizumab.

Methods

We evaluated 4 patients with poorly controlled asthma and near-fatal episodes of asthma who were administered doses of omalizumab and IgE established according to weight, evaluating clinical, spirometric well as income to the emergency room and hospital intensive care unit.

Results

There was a significant clinical improvement in 4 patients after treatment with omalizumab with improved daytime symptoms by 75% and 68% nocturnal P ≤ 0.001, as well as 100% improvement in revenue and hospitalizations to floor, well as income to the ICU with P ≤ 0.001. No further episodes of near-fatal asthma. In addition to decreased use of systemic steroids 90% (P 0.003) and inhaled steroids 60% (P 0.005).

Conclusions

Omalizumab is a good treatment option in patients with poorly controlled asthma with near-fatal asthma episodes.

Background

Treating asthmatics with the humanized IgE-scavenging antibody, omalizumab (rhuMAb-E25, Xolair®), reduces airways inflammation and asthma symptoms. Previously, omalizumab was shown to cause a dramatic and reversible loss of cell surface high-affinity IgE receptors, Fc∊RI, from the peripheral blood basophils of asthmatics. The consequences of receptor loss for the Fc∊RI-mediated synthesis and release of cytokines implicated in allergic asthma have not been examined.

Methods

Fifteen asthmatic volunteers each received omalizumab for 12 weeks. Peripheral blood basophils were isolated before, during, 2 weeks after and 6 months after omalizumab. Basophils were assayed for the basal and anti-IgE-stimulated release of cytokines, chemokines and histamine. Pooled data were analyzed by repeated measures ANOVA and by paired t tests.

Results

Anti-IgE-stimulated human basophils synthesize and release Th2 cytokines (IL-4, IL-13) and chemokines (IL-8, RANTES). The anti-IgE-stimulated release of IL-4, IL-13 and IL-8 was reduced during omalizumab treatment and returned to pretreatment levels after omalizumab withdrawal. Omalizumab did not alter basophil histamine levels or basal and anti-IgE-stimulated histamine release.

Conclusions

Omalizumab may reduce asthma symptoms in part by suppressing the Fc∊RI-mediated production by basophils of Th2 cytokines and selected chemokines. Anti-IgE-stimulated basophil cytokine synthesis appears more sensitive than histamine release to the loss of Fc∊RI caused by omalizumab treatment.

Omalizumab is a recombinant humanized monoclonal antibody that blocks the high-affinity Fc receptor of IgE. Omalizumab has been approved for the treatment of moderate to severe asthma; however, there is currently more and more data showing promising results in the management also of chronic urticaria. We present a case series of 19 patients with chronic urticaria treated in a university department with omalizumab and give an overview of the existing literature comprising an additional 59 cases as well as a total of 139 patients enrolled in two randomized controlled trials comparing omalizumab with placebo. The collective evidence points to omalizumab as a safe and effective treatment option for patients with chronic urticaria who do not sufficiently respond to standard therapy as recommended by existing guidelines.

Background

Omalizumab (trade name Xolair) is approved by the US Food and Drug Administration for treatment of moderate-to-severe allergic asthma. Given the high acquisition cost of omalizumab, its role and cost-effectiveness in disease management require definition.

Objective

We sought to identify the clinical and economic circumstances under which omalizumab might or might not be a cost-effective option by using a mathematic model.

Methods

We merged published data on clinical and economic outcomes (including acute event incidence, frequency/severity of hospitalizations, and health-related quality of life) to project 10-year costs, quality-adjusted life years (QALYs), and cost-effectiveness of treatment with omalizumab in addition to inhaled corticosteroids. Sensitivity analyses were conducted by using input data ranges from a variety of sources (published clinical trials and observational databases).

Results

For patients with baseline acute event rates, omalizumab conferred an additional 1.7 quality-adjusted months at an incremental cost of $131,000 over a 10-year planning horizon, implying a cost-effectiveness ratio of $821,000 per QALY gained. For patients with 5 times the baseline acute event rate, the cost-effectiveness ratio was $491,000 per QALY gained. The projected cost-effectiveness ratio could fall within a range of other programs that are widely considered to be cost-effective if the cost of omalizumab decreases to less than $200.

Conclusion

Omalizumab is not cost-effective for most patients with severe asthma. The projected cost-effectiveness ratios could fall within a favorable range if the cost of omalizumab decreases significantly.

Clinical implications

Based on the high cost of omalizumab, it is especially important that clinicians explore alternative medications for asthma before initiating omalizumab.

Background

Eosinophil Associated Gastrointestinal Disorders (EGIDs) are commonly associated with atopy and are being recognized with increasing frequency. Current therapy for EGIDs is inadequate.

Objective

We sought to determine the efficacy of anti-IgE therapy in EGIDs and investigate the role of IgE in disease pathogenesis.

Methods

Nine subjects with EGIDs received omalizumab every 2 weeks for 16 weeks while other therapy was held constant. Blood absolute eosinophil counts, tissue eosinophil counts, symptom scores, and free IgE were serially measured. Allergen skin testing, and flow cytometry for basophil activation and FcεRI were determined at baseline and at week 16.

Results

Omalizumab was associated with a decrease in absolute eosinophil count at both the 16 week (34%, p=0.004) and combined weeks 12–16 (42%, p=0.012) time points. Tissue eosinophils decreased in the duodenum (59%) and gastric antrum (69%), but did not reach statistical significance (p=0.074 and 0.098, respectively). Esophageal eosinophil counts remained unchanged. Basophil and dendritic cell FcεRI expression, and free IgE were all significantly decreased (p<0.005). Omalizumab increased the concentration of allergen required to trigger half-maximal basophil activation by 170-fold. Allergen skin test wheal and erythema responses decreased by 78% and 82%, respectively. Symptom scores were decreased at both the midstudy (63%) and end of study (70%) time points (p<0.005 for both).

Conclusion

These results demonstrate that IgE-mediated processes contribute to the generation of eosinophilic inflammation in EGIDs, and suggest that anti-IgE therapy may be effective in these disorders.

Clinical implications

Anti-IgE may be a potential therapy for EGIDs.

Background

Keratoconjunctivitis is a severe form of ocular allergy, difficult to control and with poor prognosis. The purpose of this study was to verify the clinical efficacy of humanized monoclonal antibody omalizumab treatment in children with this condition.

Methods

Report of 2 cases of children with severe vernal keratoconjunctivitis poorly controlled by the conventional therapeutic scheme that were submitted to treatment with Omalizumab.

The disease was scored according to the severity by ophthalmologic evaluation (amount of viscous mucus, giant papillae >1 mm, aspect of cornea/keratitis) and graduation of allergic symptons (itching, tearing, photophobia), before and after the last subcutaneous administration of Omalizumab.

Evaluation by Parents/ guardians using the same score, regarding to itchy eyes, runny eyes and photophobia, after Omalizumab application, was also requested.

Results

Case 1: MPOS (7 years) with vernal keratoconjunctivitis and atopic dermatitis since childhood, both with progressive severity. Recalcitrant ocular itching and photophobia, in addition had other atopic conditions such as mild asthma, rhinitis and egg allergy. Total IgE = 1323 IU/mL. Ocular manifestations poorly controlled with topical use of antihistamines, cromolyn, tacrolimus and cyclosporine. The use of topical corticosteroids was frequent, but resulted in brief improvement.

Case 2: HCS (6 years) with vernal keratoconjunctivitis since 3 years age, and mild asthma and moderate persistent rhinitis. Continued use of topical tacrolimus 0.03% showed an initial improvement, but subsequent relapses resulted in frequent use of systemic prednisolone and eye drops antibiotics to control symptoms. Total IgE = 1530 IU/mL.

After the second Omalizumab application, good or excellent improvement in ocular symptoms of both children was observed by allergists and parents. Ophthalmologic evaluation showed moderate improvement in the amount of slime and little or no improvement in the structural changes of the eye (cornea and appearance of giant papillae).

Conclusions

There are few reports about the use of Omalizumab in allergic keratoconjunctivitis. Our work points to the need for further research in this area as the Anti-IgE may become a promising therapy for this difficult to control condition.

Background:

Peripheral nerve palsies of the upper extremities presenting at birth can be distressing for families and care providers. It is therefore important to be able to identify patients whose diagnosis is compatible with full recovery so that their families can be reassured.

Methods:

We conducted a retrospective review of all infants presenting with weakness of the upper extremity to our clinic between July 1995 and September 2009. We also conducted a review of the current literature.

Results:

During the study period, 953 infants presented to our clinic. Of these patients, 25 were identified as having isolated radial nerve palsy (i.e., a radial nerve palsy in isolation with good shoulder function and intact flexion of the elbow). Seventeen infants (68.0%) had a subcutaneous nodule representing fat necrosis in the inferior posterolateral portion of the affected arm. Full recovery occurred in all patients within a range of one week to six months, and 72.0% of the patients (18/25) had fully recovered by the time they were two months old.

Interpretation:

Although the outcome of obstetrical brachial plexus palsy is highly variable, isolated radial nerve palsy in the newborn carries a uniformly favourable prognosis.

Objective: Although the anterior approach is normally used for elective laparoscopic splenectomy (LS), the posterolateral approach may be superior. We have retrospectively compared the effectiveness and safety of these approaches in patients with non-severe splenomegaly scheduled for elective total LS.

Methods: Patients with surgical spleen disorders scheduled for elective LS between March 2005 and June 2011 underwent laparoscopic splenic mobilization via the posterolateral or anterior approach. Main outcome measures included operation time, intraoperative blood loss, frequency of postoperative pancreatic leakage, and length of hospital stay.

Results: During the study period, 203 patients underwent LS, 58 (28.6%) via the posterolateral and 145 (71.4%) via the anterior approach. Three patients (1.5%) required conversion to laparotomy due to extensive perisplenic adhesions. The posterolateral approach was associated with significantly shorter operation time (65.0 ± 12.3 min vs. 95.0 ± 21.3 min, P < 0.01), reduced intraoperative blood loss (200.0 ± 23.4 mL vs. 350.0 ± 45.2 mL, P < 0.01), and shorter hospital stay (5.0 ± 2.0 d vs. 9.0 ± 3.0 d, P < 0.01) than the anterior approach. The frequency of pancreatic leakage was slightly lower in patients undergoing LS via the posterolateral than the anterior approach (0.0% vs. 3.4%, P > 0.05)

Conclusions: The posterolateral approach is more effective and safer than the anterior approach in patients without severe splenomegaly (< 30 cm).

Case report of a complete arcuate foramen in a human atlas vertebra inhibiting the placement of lateral mass screw instrumentation at C1.

Our objective is to report the presentation of the case, the operative considerations, and the management for this anatomic variation.

The groove for the vertebral artery on the posterolateral surface of the atlas (C1) varies in size and depth from a slight impression to a clear sulcus. With anomalous ossification the sulcus can be bridged which results in a posterolateral tunnel within the posterior arch of the atlas. With increasing rates of screw fixation instrumentation that include the atlas, it is of paramount importance to know the location and course of the vertebral artery in relation to the planned route of instrumentation.

The patient underwent a posterolateral fusion from C1 to C4 using autogenous iliac crest bone graft. Internal fixation from C2 to C4 was obtained using lateral mass screw instrumentation. After the vertebral artery was identified passing through the posterior arch of C1, sublaminar wires were utilized for fixation from C1 to C2. The patient responded well to surgical intervention without complications.

Abnormal vertebral artery coursing through a posterolateral tunnel in the posterior arch of C1 has been described and its incidence has a range from 1.14% to 18%. When this variant is present, lateral mass screw fixation at C1 may be contraindicated. We recommend close scrutiny of preoperative radiographs to avoid the possibility of endangering the vertebral artery when this situation exists.

Background

Posterolateral rotatory instability of elbow is considered to be due to the disruption of the ulnar part of the lateral collateral ligament (LUCL). This instability pattern may also be induced by a fracture of components of the lateral column.

Results

We present the case of a 16-year-old boy who fell on his left outstretched arm as he attempted to jump over a tennis net. On initial physical examination, the elbow had instability found on varus stress and the radial head could be felt posteriorly. With attempted valgus and supination force combined with axial loading, the elbow gapped open and the patient had a sense of increased instability. X-rays showed a fracture of the lateral humeral epicondyle and posterolateral subluxation of the elbow. In the operating room, the patient was found to have reproducible posterolateral instability of the elbow. The lateral epicondyle was found to be fractured off the humerus with the LUCL still attached to the fragment. The elbow was reduced, and the injury was stabilized with small screws and suture anchors. At 6-month follow-up, the patient was pain-free, and physical examination revealed 170° of flexion, full extension, 90° of pronation, and 65° of supination. X-rays showed healing of the fracture with concentric reduction of the elbow joint.

Conclusion

In lateral epicondyle fractures, the affected elbow should be assessed for any signs of associated instability. If signs of clear instability are seen that would prohibit proper postinjury rehabilitation, then surgical reduction and fixation of the epicondyle with reinforcement of the LUCL is an effective method of treatment.

Objective

Anti IgE treatment with omalizumab is efficacious in the treatment of patients suffering from allergic asthma, improving asthma control and improving quality of life. Furthermore, this approach could be beneficial for patients with concomitant atopic dermatitis. We assessed quality of life and asthma control in atopic patients with allergic asthma and concomitant atopic dermatitis versus those with asthma and without atopic dermatitis treated with omalizumab.

Methods

A total of 22 patients with severe allergic asthma were treated with omalizumab for 12 months. 13 patients with allergic asthma without concomitant atopic dermatitis (IgE 212 ± 224 IU/ml) and 9 patients with concomitant allergic asthma and atopic dermatitis (IgE 3,528 ± 2,723 IU/ml) were included. Asthma-related quality of life (AQLQ), atopic dermatitis related quality of life (DLQI), and asthma-related treatment were compared between both groups at baseline and after initiating omalizumab treatment.

Results

DLQI was significantly in favor of omalizumab after 2 months in the atopic dermatitis/asthma group (P = 0.01); AQLQ was improved after 6 months in the asthma group (P = 0.01), while no change was seen in AQLQ in the atopic dermatitis/asthma group (P = 0.12). Omalizumab controlled oral corticosteroid use more effective (P < 0.01) in patients with asthma and atopic dermatitis (in 9/9 cases) compared to patients with asthma alone (9/13). Baseline IgE as well as other factors do not predict response to omalizumab.

Conclusions

Omalizumab is effective in improving atopic dermatitis-related quality of life scores and modulates oral corticosteroid use in patients with concomitant asthma and atopic dermatitis in a positive fashion.

Purpose

Chronic urticaria (CU) is a common and debilitating disease, and the need for effective treatment has increased. Omalizumab may be an alternative regimen in patients with CU who do not respond to conventional treatments. The aim of this study is to investigate the efficacy and to observe the clinical results of omlizumab in patients with refractory CU.

Methods

We conducted a retrospective analysis of 26 patients with refractory CU who were treated with omalizumab. Omalizumab was administered every 2 or 4 weeks, depending on body weight and the total serum IgE level, for 24 weeks.

Results

Fourteen patients (53.8%) achieved remission after the treatment; they had a significantly higher prevalence of personal (P=0.033) and family history of allergic diseases (P=0.002) than those who did not achieve remission. During omalizumab treatment, the urticaria activity score declined significantly (12.11±1.97 to 2.7±4.23; P=0.001) and the CU-quality of life score improved significantly (34.65±13.58 to 60.88±11.11; P=0.004). There were significant decreases in the use of systemic steroids (42.3%-11.5%; P=0.027) and immunomodulators (65.4%-19.2%; P=0.002). The dose of antihistamines required to control CU also decreased significantly (215.66±70.06 to 60.85±70.53 mg/week of loratadine equivalents; P<0.001). No serious adverse event was noted.

Conclusions

These findings suggest that omalizumab can be an effective and safe treatment in patients with refractory CU.

We report 2 patients with cold urticaria with different response to treatment with omalizumab (Xolair®). Cold contact urticaria (CCU) is a common subtype of physical urticaria. It is characterized by the development of wheal and/or angioedema within minutes after cold contact. Clinical manifestation of CCU can range from mild, localized whealing to life-threatening anaphylactic shock reactions. Omalizumab has been described to be useful in cases of chronic urticaria and may be an interesting option for treatment of CCU. We describe one patient with significant and long-lasting improvement of symptoms and one without any improvement after anti-immunoglobulin E therapy. In our case reports, we want to highlight that there is still a small group of patients without benefit from omalizumab treatment. It is necessary to identify this minor subgroup of patients where omalizumab does not represent an effective treatment possibility.

Background

There is evidence that humanized monoclonal antibody against IgE (Omalizumab) is effective in severe allergic asthma. In this study, we examined the effectiveness of omalizumab on asthma and nasal symptoms in Japanese patients with severe allergic asthma and rhinitis.

Methods

An open-label study that enrolled 7 patients with both severe allergic asthma and rhinitis who visited Allergy Center, Saitama Medical University was performed. All patients presented uncontrolled asthma despite medication including high-dose inhalational corticosteroids, long-acting beta2-agonist, leukotriene receptor antagonist, theophylline, and oral predonisolone. Omalizumab was added on their treatments and symptoms score using Asthma Contol Test (ACT), peak expiratory flow rate (PEFR), exhaled nitric oxide (eNO), sputum eosinophils and nasal symptoms were evaluated before and 12 to 16 weeks after omalizumab.

Results

Omalizumab significantly improved ACT scores especially dose of rescue use of short-acting beta2-agonist (P < 0.05) and PEFR (P < 0.05). Furthermore, omalizumab significantly decreased exhaled both eNO (P < 0.05) and the percentage of eosinophils in induced sputum. On the other hand, nasal symptoms were not change following induction of omalizumab.

Conclusions

Clinical effectiveness of omalizumab was confirmed in Japanese population of severe allergic asthma, but not rhinitis. The therapeutic potency of omalizumab on asthma likely involves anti-inflammatory properties such as decreasing eNO or airway eosinophilia.

Introduction:

Asthma is a chronic inflammatory airways disease associated with reversible airflow obstruction and bronchial hyperresponsiveness. Asthma is prevalent worldwide and results in significant morbidity, mortality, and healthcare costs, the majority of which arise from those with severe disease. Omalizumab is a monoclonal antibody to immunoglobulin E (IgE) that has been developed for the treatment of severe persistent allergic (IgE mediated) asthma.

Aims:

The aim of this review is to evaluate the available clinical evidence on omalizumab to determine the role it has to play in the treatment of persistent allergic asthma.

Evidence review:

There is clear evidence to show that omalizumab is effective in reducing the rate of asthma exacerbations, inhaled corticosteroid dose, and the need for rescue medication in patients with allergic asthma. Clinical data indicate beneficial effects on patient-reported symptoms and perceived quality of life, as well as a reduction in unscheduled healthcare visits. There is little evidence to suggest omalizumab may enhance lung function or reduce the requirement for oral corticosteroids. Omalizumab has a favorable safety profile, although anaphylaxis has occurred. A study in children showed similar results to those achieved in adults and adolescents, with fewer asthma exacerbations and school days missed. Omalizumab may be cost effective in patients when used as add-on therapy to inhaled corticosteroids and long-acting beta2 agonists (LABA).

Place in therapy:

Omalizumab is an effective add-on therapy to inhaled corticosteroids and LABAs in adults and adolescents with severe persistent allergic asthma. Currently there is insufficient evidence to support the use of omalizumab in children.

Chronic urticaria is a common skin disease. In about 45% of patients the cause is an autoantibody directed at the α-subunit of the high-affinity IgE receptor (chronic autoimmune urticaria; CAU). Omalizumab is a monoclonal anti-IgE antibody that has a proven role in the treatment of various allergic diseases. We gave omalizumab once every month for 16 weeks to three patients that were refractory to standard treatment, including high doses of antihistamines, leukotriene receptor antagonist, and corticosteroid. There was dramatic improvement in the primary efficacy variable—the change in mean urticaria activity score (UAS) from baseline (i.e., the average over the first 4-week period before omalizumab) to the final 4-week period of omalizumab treatment. There was improvement in the secondary efficacy variables, which included change from baseline in interference with sleep, interference with daily activities, daily diary record of urticaria signs and symptoms based on a scoring system, and rescue medication use. These improvements persisted for 12 weeks after discontinuation of the drug. Omalizumab may have a role in treating refractory cases of CAU.

Omalizumab is a humanized monoclonal anti-IgE antibody recently approved for the treatment of severe allergic asthma. This drug inhibits allergic responses by binding to serum IgE, thus preventing interaction with cellular IgE receptors. Omalizumab is also capable of downregulating the expression of high affinity IgE receptors on inflammatory cells, as well as the numbers of eosinophils in both blood and induced sputum. The clinical effects of omalizumab include improvements in respiratory symptoms and quality of life, paralleled by a reduction of asthma exacerbations, emergency room visits, and use of systemic corticosteroids and rescue bronchodilators. Omalizumab is relatively well-tolerated, and only rarely induces anaphylactic reactions. Therefore, this drug represents a valid option as add-on therapy for patients with severe persistent allergic asthma inadequately controlled by high doses of standard inhaled treatments.

The MRI findings in a case of decubital ischemic fasciitis located posterolateral to the right greater trochanter, in a 72-year-old woman, are presented. Decubital ischemic fasciitis is an uncommon entity encountered mostly in debilitated, elderly patients, in the deep subcutaneous tissue, at pressure points or bony prominences. It can simulate soft-tissue sarcomas. Recognition of this lesion radiologically is important to prevent unnecessary interventions.

Anti-IgE therapy was proposed to two teenagers with cystic fibrosis (CF) with allergic bronchopulmonary aspergillosis (ABPA) exacerbation, reluctant to a further course of oral steroids. Both patients experienced ABPA exacerbations within the past 3 years, requiring oral steroid bursts. Clinical, laboratory and radiographic features were consistent with ABPA exacerbations (representing at the time of evaluation the fourth and third episodes for patient 1 and 2, respectively). Total serum IgE was very high, >1000 kU/litre in both cases. Treatment consisting of subcutaneous injections of 375 mg anti-IgE (omalizumab) twice monthly was successful in rapidly improving respiratory symptoms and lung function. Based on clinical and functional improvement, interval between injections was progressively increased and treatment could be withdrawn after 11 injections, without recurrence at 20 weeks of follow-up after withdrawal.