Omalizumab for urticaria

Introduction

Omalizumab is a humanized monoclonal antibody which joins the circulation immunoglobulin E (IgE) and reduces the release of inflammatory mediators mast cells and basophils.

In New Zealand, it is currently (as of 2018) licensed as complementary therapy for patients with severe and persistent allergic asthma and for patients 12 years of age or older with severe chronic spontaneous urticaria who remain symptomatic despite H₁- antihistamine treatment. It is funded in New Zealand by PHARMAC under the Special Authority under certain circumstances.

It is given by subcutaneous injection once every 4 weeks.

The brand name for omalizumab is Xolair ™.

What is spontaneous chronic urticaria?

Spontaneous chronic urticaria (also called chronic idiopathic urticaria) is defined as urticaria or cure lasting at least 6 weeks, with or without angioedema. Hives are often extremely itchy, interfering with sleep, daily activities, social interactions, school, and work life.

Symptoms can resolve after a few months; however, in approximately 50% of cases symptoms persist for 3-5 years, and in 20% of cases symptoms may persist for more than 10 years.

Urticaria is the most frequent result of the effect of histamine in H₁-receptors located in the endothelial cell lining blood vessels. The histamine causes the cells to separate, so the tissue fluid leaks out, forming a bump. Histamine also affects the senses. nerves, resulting in a neurogenic erythematous flare and pruritus.

Chronic urticaria can be refractory to antihistamines and be associated with a pronounced cellular infiltrate.

What is the role of omalizumab in the treatment of urticaria?

Omalizumab is intended to be used as second-line therapy for the treatment of chronic spontaneous urticaria that is refractory to oral antihistamines. Many patients also do not respond to a variety of others systemic therapies including systemic steroids and immunomodulatory drugs.

Omalizumab is currently in phase III clinical trials in chronic spontaneous urticaria.

How does omalizumab work in urticaria?

Immunoglobulin "E" (IgE) triggers a allergic reaction (eg, asthma) in response to a allergen (for example, cat dander). Although spontaneous chronic urticaria is not due to allergy, occurs through a similar route.

Omalizumab has been designed to recognize and bind to a specific structure in circulating human IgE. This prevents IgE from binding to high affinity receptors (FcεRI) on the surface of mast cells and basophils, thereby reducing receiver expression and release of inflammatory mediators.

What is the clinical evidence available for the effect of omalizumab?

The results of at least 2 published randomized controlled trials support the effectiveness of omalizumab in chronic spontaneous urticaria.

ASTERIA II

• This global, multicenter, randomized, double-blind, placebocontrolled study was funded by Genentech and Novartis Pharma; ClinicalTrials.gov number, NCT01292473. Omalizumab has been shown to reduce symptoms in chronic urticaria.
• The trial included 323 patients with a history of at least 6 months of chronic idiopathic urticaria resistant to antihistamines.
• Participants were randomly assigned to receive 3 subcutaneous injections at 4-week intervals of omalizumab: 75 mg, 150 mg, 300 mg, or placebo (a dummy treatment). This was followed by a 16 week observation period.
• the primary the end point was changed from base through week 12 on the weekly itch severity score; secondary endpoints including security, edema, wealth and quality of life.
• Throughout the treatment and follow-up period, patients were allowed to stay on antihistamines, and were also allowed to take rescue antihistamines.

• At the end of treatment, the 53% of the patients receiving the high dose were completely free of urticaria compared to 23% in the 150 mg group, 18% in the low dose group and 10% in the placebo group.
• The mean change from baseline in the weekly rescue dose of diphenhydramine was a decrease of 4.1 tablets in the 300 mg group (P = 0.01), a decrease of 3.7 tablets in the 150 mg group (P = 0.07), a decrease of 2.3 tablets in the 75 mg group (P = 0.91), and a decrease of 2.2 tablets in the placebo group.
• During the 16-week follow-up period after stopping treatment, patients were allowed to continue antihistamines; however, symptoms slowly returned for most patients.

ClinicalTrials.gov number NCT01264939

• In this phase III study, 332 patients aged 12 to 75 with spontaneous chronic hives resistant to antihistamines were randomized to receive 6 subcutaneous injections at 4-week intervals of 300 mg of omalizumab or placebo, followed by an observation period 16 weeks.
• The main objective was to evaluate the safety of omalizumab compared to placebo. Efficacy was assessed at weeks 12 and 24 and included the severity of itching, bump, and urticaria activity scores.
• The general incidence and the severity of adverse events and serious adverse events were similar between omalizumab and placebo recipients.
• At week 12, the mean change from baseline in the weekly itch severity score was −8.6 (95% CI, −9.3 to −7.8) in the omalizumab group compared to −4.0 (95% CI, - 5.3 to −2.7) in the placebo group ( P <0,001). Estos beneficios se mantuvieron hasta la semana 24.

Omalizumab in chronic urticaria with IgE against thyroperoxidase

• In a subgroup of patients with chronic spontaneous urticaria, IgE antibodies are directed against autoantigens, such as thyroperoxidase (TPO).
• A multicentre, randomized, double-blind, placebo-controlled study included patients aged 18 to 70 years with chronic urticaria with IgE. autoantibodies against TPO who had persistent symptoms (scarring and itching) despite standard antihistamine therapy. They were randomized to receive omalizumab (75-375 mg, dose determined using the approved asthma dosage table) or placebo subcutaneously once every 2 to 4 weeks for 24 weeks.
• 42 of the 49 randomized patients completed the study (omalizumab, n = 27; placebo, n = 22).
• The mean weekly urticaria activity score was calculated after 24 weeks of treatment, using the patients' diaries. Omalizumab patients had a mean reduction of 17.8 and placebo patients had a reduction of 7.9 (P = 0.0089).
• Omalizumab has been shown to be effective for patients with chronic urticaria who are refractory to conventional treatment and have IgE autoantibodies against TPO.

Disadvantages of omalizumab

So far, there is no evidence that omalizumab is modifying the disease. When patients discontinued the study drug, their symptoms reappeared. At the end of the 16 weeks without treatment, the symptoms of urticaria were similar to those of the placebo-treated patients. When omalizumab was restarted in previously responding patients, omalizumab was effective again.

What is the risk associated with the use of omalizumab?

• A headache and injection site reactions (swelling, redness, pain, and itching) affect approximately 10% in patients treated with omalizumab.
• Omalizumab should not be used in people who may be hypersensitive (allergic) to the medicine or to any ingredient in the injection vial.

Omalizumab in inducible-urticaria

Inducible chronic urticaria, like solar urticaria or cold urticaria, does not always respond well to antihistamines. To date, no randomized placebo-controlled trial of omalizumab has been conducted in inducible hives, but it has been reported to be effective in case reports.

Future directions

IgE autoantibodies are also detected in a large number of patients with atopic dermatitis and bullous Pemphigoid In individual case reports, omalizumab treatment has been reported to be effective in some patients with these conditions. Also reported to be effective in chronic cases recurrent angioedema A randomized trial of omalizumab in children with severe atopic eczema, 'ADAPT', he found useful for many children.