We reviewed the evidence for the effect of omalizumab on people with asthma when compared with placebo. We focused on whether omalizumab is a beneficial but safe treatment for adults and children with asthma.
Asthma is a respiratory condition that affects millions of people worldwide. It is thought that allergy may be an important part of the disease for many people with asthma. Omalizumab is a drug that targets a protein, called IgE, and removes it from free circulation in the body. IgE is centrally involved in allergy. Omalizumab is an expensive drug that is usually given by injection under the skin every two to four weeks. It is licenced for use in asthma sufferers who are not being adequately treated with standard therapy and who require frequent courses or continuous use of oral steroid tablets. We looked for evidence on whether administration of omalizumab is better or worse than giving placebo.
Twenty-five studies, involving 6382 people, were included in this review. These studies lasted between eight and 60 weeks. All of the people included in the studies had asthma, of different severity. Both men and women were included, and some of the studies included children and young people.
All studies compared omalizumab versus placebo. In keeping with current medical practice, most studies (21 of 25) used omalizumab given by injection under the skin. Some of the older studies used omalizumab injected into a vein or given by inhalation. The evidence presented here is current to June 2013. Most of the studies were sponsored by the pharmaceutical industry.
We found that people receiving omalizumab were less likely to have a flare-up (‘exacerbation’) of their asthma. For example, on average, 26 of 100 people who were receiving placebo (over a 16 to 60-week period) had an exacerbation compared with an average of 16 of 100 people receiving omalizumab.
People receiving omalizumab were also more likely to be able to reduce the doses of inhaled steroids. For example, on average, 21 of 100 people with moderate or severe asthma who were receiving placebo were able to completely stop their inhaled steroids (over a 28 to 32-week period) compared with an average of 40 of 100 receiving omalizumab.
People receiving omalizumab also experienced improvement in their asthma symptoms and in their health-related quality of life.
People receiving omalizumab were no more or less likely to have unwanted side effects overall. However, people receiving omalizumab were more likely to have skin reactions at the site of the injection.
Perhaps unfortunately, many of the trials in this review included participants with moderate asthma, and this drug is not licenced for this group. More trials need to focus on whether this drug is effective in people with the most severe asthma; evidence for efficacy in this group is poor, in spite of current guidelines.
Quality of the evidence
The evidence presented in this review is generally of moderate quality. Most of the studies did not clearly explain how investigators decided which people would receive omalizumab and which would receive placebo, and this decision is an important part of well-conducted studies.
Omalizumab was effective in reducing asthma exacerbations and hospitalisations as an adjunctive therapy to inhaled steroids and during steroid tapering phases of clinical trials. Omalizumab was significantly more effective than placebo in increasing the numbers of participants who were able to reduce or withdraw their inhaled steroids. Omalizumab was generally well tolerated, although more injection site reactions were seen with omalizumab. Further assessment in paediatric populations is necessary, as is direct double-dummy comparison with ICS. Although subgroup analyses suggest that participants receiving prednisolone had better asthma control when they received omalizumab, it remains to be tested prospectively whether the addition of omalizumab has a prednisolone-sparing effect. It is also not clear whether there is a threshold level of baseline serum IgE for optimum efficacy of omalizumab. Given the high cost of the drug, identification of biomarkers predictive of response is of major importance for future research.
Asthma is a respiratory (airway) condition that affects an estimated 300 million people worldwide and is associated with significant morbidity and mortality. Omalizumab is a monoclonal antibody that binds and inhibits free serum immunoglobulin E (IgE). It is called an 'anti-IgE' drug. IgE is an immune mediator involved in clinical manifestations of asthma. A recent update of National Institute for Health and Care Excellence (NICE) guidance in 2013 recommends omalizumab for use as add-on therapy in adults and children over six years of age with inadequately controlled severe persistent allergic IgE-mediated asthma who require continuous or frequent treatment with oral corticosteroids.
To assess the effects of omalizumab versus placebo or conventional therapy for asthma in adults and children.
We searched the Cochrane Airways Group Specialised Register of trials for potentially relevant studies. The most recent search was performed in June 2013. We also checked the reference lists of included trials and searched online trial registries and drug company websites.
Randomised controlled trials examining anti-IgE administered in any manner for any duration. Trials with co-interventions were included, as long as they were the same in each arm.
Two review authors independently assessed study quality and extracted and entered data. Three modes of administration were identified from the published literature: inhaled, intravenous and subcutaneous injection. The main focus of the updated review is subcutaneous administration, as this route is currently used in clinical practice. Subgroup analysis was performed by asthma severity. Data were extracted from published and unpublished sources.
In all, 25 trials were included in the review, including 11 new studies since the last update, for a total of 19 that considered the efficacy of subcutaneous anti-IgE treatment as an adjunct to treatment with corticosteroids.
For participants with moderate or severe asthma who were receiving background inhaled corticosteroid steroid (ICS) therapy, a significant advantage favoured subcutaneous omalizumab with regard to experiencing an asthma exacerbation (odds ratio (OR) 0.55, 95% confidence interval (CI) 0.42 to 0.60; ten studies, 3261 participants). This represents an absolute reduction from 26% for participants suffering an exacerbation on placebo to 16% on omalizumab, over 16 to 60 weeks. A significant benefit was noted for subcutaneous omalizumab versus placebo with regard to reducing hospitalisations (OR 0.16, 95% CI 0.06 to 0.42; four studies, 1824 participants), representing an absolute reduction in risk from 3% with placebo to 0.5% with omalizumab over 28 to 60 weeks. No separate data on hospitalisations were available for the severe asthma subgroup, and all of these data were reported for participants with the diagnosis of moderate to severe asthma. Participants treated with subcutaneous omalizumab were also significantly more likely to be able to withdraw their ICS completely than those treated with placebo (OR 2.50, 95% CI 2.00 to 3.13), and a small but statistically significant reduction in daily inhaled steroid dose was reported for omalizumab-treated participants compared with those given placebo (weighted mean difference (WMD) -118 mcg beclomethasone dipropionate (BDP) equivalent per day, 95% CI -154 to -84). However, no significant difference between omalizumab and placebo treatment groups was seen in the number of participants who were able to withdraw from oral corticosteroid (OCS) therapy (OR 1.18, 95% CI 0.53 to 2.63).
Participants treated with subcutaneous omalizumab as an adjunct to treatment with corticosteroids required a small but significant reduction in rescue beta2-agonist medication compared with placebo (mean difference (MD) -0.39 puffs per day, 95% CI -0.55 to -0.24; nine studies, 3524 participants). This benefit was observed in both the moderate to severe (MD -0.58, 95% CI -0.84 to -0.31) and severe (MD -0.30, 95% CI -0.49 to -0.10) asthma subgroups on a background therapy of inhaled corticosteroids; however, no significant difference between subcutaneous omalizumab and placebo was noted for this outcome in participants with severe asthma who were receiving a background therapy of inhaled plus oral corticosteroids. Significantly fewer serious adverse events were reported in participants assigned to subcutaneous omalizumab than in those receiving placebo (OR 0.72, 95% CI 0.57 to 0.91; 15 studies, 5713 participants), but more injection site reactions were observed (from 5.6% with placebo to 9.1% with omalizumab).
To reflect current clinical practice, discussion of the results is limited to subcutaneous use, and trials involving intravenous and inhaled routes have been archived.