The use of omalizumab has been evaluated in several allergic conditions, including allergic rhinitis, asthma, Churg-Strauss syndrome, atopic eczema, urticaria, angioedema, latex allergy, and concurrently with allergy immunotherapy to try to blunt reactions [1-10]. While approved by US Food and Drug Administration for asthma, the other indications need to be studied further. In this study, the omalizumab treatment efficacy was studied on severe persistent asthma patients with co-morbid allergic conditions.

The prevalence of respiratory symptoms, asthma, allergic rhinoconjunctivitis and respiratory function impairment among our Mediterranean region of Turkey; Antalya is considered to be higher than rest of the continent because of the climatic conditions [11]. So that omalizumab becomes more important to be used in stabilizing the clinical features of patients having more than one allergic condition.

Patients

Eleven patients were included in this follow-up study with severe persistent asthma whose mean age was 43 years and patient characteristics were given in Table 1. They were all treated with omalizumab, had allergic rhinoconjunctivitis and all had a family history of atopia. All of the patients were followed-up in the Immunology-Allergy Clinics of Antalya Training and Research Hospital. The clinical findings of nasal polyposis, anaphylaxis history, drug allergy, latex allergy, food allergy, autoimmune urticaria, angioedema and venom allergy was evaluated.

Table 1: Patient characteristics.

Study design

The patients’ written consent was obtained. All patients received omalizumab therapy for 24 months. Doses of omalizumab were administered every 2 weeks. Symptoms and severity of allergic reactions were recorded before and after being on omalizumab treatment. Assessments of clinical changes and adverse effects were made at every bimonthly patient visit. These assessments included vital signs, full physical examination, detailed possible allergy incidents, pulmonary function test and asthma control test (QualityMetric Inc.). Serum IgE levels, thyroid antibodies and eosinophil levels were evaluated in all patients.

Skin prick test (SPT)

SPTs were performed in all patients with standardized latex extract containing high ammonia natural rubber latex, with a battery of 35 common and 35 food allergens on the forearm. In additon, venom SPT was performed in 1 patient based on history. SPTs were performed by skilled nursing personnel. Positive tests were counted as wheals of 3 mm in diameter after 20 minutes. Tests were compared with positive histamine controls and negative saline controls. Commercial extracts used were manufactured by Alyostal ST-IR (Starallergenes S.A.- France). No intradermal testing was performed.

Autologous serum skin test

The test was performed by injecting 0.05 ml of the patient’s own serum intradermally into the left flexor forearm, 2 inches below the antecubital crease and a saline control into the right forearm. A reading of the wheal was taken after 30 minutes. A wheal and flare of more than 1.5 mm diameter than that of the control was considered positive.

In this clinical follow-up study, 11 patients were on omalizumab treatment and they were all clinically analyzed at our clinic. The patients had severe persistent asthma for periods ranging from 3 to 8 years. All patients maintained significant improvement by history as shown by a decrease in clinical symptoms and increase in asthma control test. The allergic symptoms were improved clinically and summarized in Table 2 and the changes in steroid usage were in table 3.

Table 2: Clinical follow-up criteria and changes with omalizumab.

Table 3: Steroid doses of the patients pre- and post-omalizumab.

The Asthma Control Test (ACT) and an Asthma Control Questionnaire were completed by all patients at three clinical visits at the beginning of the omalizumab treatment and 48 to 56 weeks apart. Pulmonary function was also measured. All of the patients had an ACT score of <20, indicating that asthma was not well controlled on previous treatment, before the omalizumab therapy. As shown in Figure 1, after the treatment period of 12 to 24 months of omalizumab, the ACT score increased up to 20-24 which was indicated as ’’well-controlled’’ asthma.

Figure 1: Asthma control test.

Omalizumab was developed for the treatment of severe allergic asthma. It blocks binding of free IgE on basophils and mast cells, thus inhibiting their activation by allergens. Omalizumab treatment significantly reduces the nasal and conjunctival symptom scores of all patients. This demonstrates the effectiveness of omalizumab and these findings agree with recently published data [12,13].

In this follow-up, omalizumab significantly improved asthma control and pulmonary function in patients with severe persistent asthma. Patients no 1, 2 and 4 did not show an increase of ACT up to 20. Although, they showed no asthma exacerbation after the treatment, there was a 2.5 fold increase in ACT scoring.

Seven of the patients’ had chronic urticaria, while 2 of them with chronic autoimmune urticaria. There is a significant improvement in urticaria attacks beginning from the 3^rd dose in all of these patients. However, the patients with autoimmune urticaria had been under treatment for longer period before the symptoms were decreased. Similar results were also reported in previous study about the omalizumab effectivity in the treatment of chronic autoimmune urticaria [9,14].

Patient no 5, 6 and 8 had a history of food allergy. While treating asthma patients with omalizumab, patients subjectively observed a reduction in their concomitant food allergy symptoms as previously reported [8,15].

There is a history of honey-sting allergy in patients no 4 and 9. The patient no 4 had previously reported honeybee induced anaphylaxis. Interestingly in this patient, while having the omalizumab treatment on the 12^th dose, she had 48 bee-stings and developed only a slight local reaction which resolved spontaneously. The results were in concordance with similar cases that were treated with omalizumab in the literature [16,17]. Allergen immunotherapy has been used in the management of allergic diseases for nearly 100 years [18]. It is the only specific treatment for hymenoptera venom anaphylaxis [19-21]. Various venom immunotherapy schedules have been designed to treat anaphylaxis [22-27]. Though the effect of venom immunotherapy is well documented, there is also an increased risk of side-effects that were in a large range from itchy eyes, sneezing to Jessner lymphocytic infiltrate and severe anaphylaxis in bee-venom-treated patients and in those with rapid dose increase [28-30]. This case suggests that omalizumab may be able to prevent severe anaphylaxis during immunotherapy.

Latex allergy is another important health problem since 1980s. Latex sensitivity was found as 18.1% in our previous study [31]. The patient no 6 had a history of latex allergy; the improvement in this allergy persists after the 5^th dose of omalizumab similar to previously reported in the literature [32].

The most recent studies on severe persistent allergic asthma and the effect of omalizumab treatment, provided novel perspectives on using serum soluble TNF-related apoptosis inducing ligand, nitric oxide, malondialdehyde, hydrogen peroxide and albumin levels, total antioxidant capacity and ceruloplasmin activity as an efficacy marker [33-36].

As a conclusion, our clinical follow-up of omalizumab treated patients with severe persistent asthma suggests that omalizumab is an effective therapy for asthma and as well as for several allergic conditions.

Clinical follow-up: Arzu Didem Yalcin analyzed the data; Atil Bisgin wrote the paper; Arzu Didem Yalcin and Atil Bisgin drafted the figures. All authors read and approved the final manuscript.