NICE consults on treatment for asthma in children and adults
In draft guidance published today (9 November), NICE has not recommended omalizumab (Xolair, Novartis Pharmaceuticals UK) for treating severe, persistent allergic asthma in adults and children.
People currently taking omalizumab should be able to continue treatment until they and their clinician consider it appropriate to stop. For children and adolescents, this decision should be made jointly by the clinician, the child or adolescent and their parents or carers.
Omalizumab has a UK marketing authorisation as an add-on therapy to standard care to improve control of asthma in adults and adolescents (12 years and over) and children aged 6 to 11 years with severe persistent allergic asthma. It is currently only offered to those whose asthma remains poorly controlled. Standard therapies for asthma include high-dose inhaled corticosteroids (which NICE has recommended), long-acting beta-2 agonists and, where appropriate, oral corticosteroids.
This appraisal of omalizumab is a review of NICE technology appraisal guidance 133 (omalizumab for severe persistent allergic asthma in adults, 2007) and NICE technology appraisal guidance 201 (omalizumab for the treatment of severe persistent allergic asthma in children aged 6 to 11 years, 2011). TA 133 recommended omalizumab for adults, and TA 201 did not recommend it for use in children. After considering new evidence that has become available since the original guidance was published - particularly new mortality data - the NICE draft guidance does not recommend omalizumab for either adults or children. In addition, the Committee took into account changes to the dosing schedule for omalizumab and the effect this has had on the cost effectiveness of the treatment. This, combined with uncertainties in the evidence and analysis presented, did not support a positive recommendation for omalizumab.
Omalizumab works by blocking immunoglobulin E (IgE) antibodies from attaching to allergens. When IgE attaches to an allergen, it sets off a process that eventually leads to the symptoms of an allergic reaction.
The Committee recognised that omalizumab was an effective therapy for children, adolescents and adults with severe persistent allergic asthma, but the clinical trials submitted as evidence included people whose asthma was less severe than those currently being treated with omalizumab in the UK. Therefore, the Committee concluded that the analyses presented may not have been applicable to the population of people with very severe asthma for whom omalizumab is used in clinical practice. The Committee requested more information from clinicians, the manufacturer and the independent Assessment Group to see whether it was possible to describe the clinical characteristics of the population more clearly to try to identify a group of people with very severe asthma for whom omalizumab may potentially be cost effective.
The updated cost effectiveness analysis still included a number of uncertainties related to the mortality risk among the subgroups of people with very severe, persistent asthma, to whom omalizumab is offered in clinical practice. However, even when assuming higher mortality rates to reflect people with very severe asthma, omalizumab could not be considered a cost-effective use of NHS resources. The Committee was aware of health-related quality of life benefits that were not included in the economic modelling but considered that these benefits are currently not quantifiable, and was not persuaded that the inclusion of these additional benefits would be sufficient to make omalizumab good value for money.
Sir Andrew Dillon, Chief Executive of NICE said: "The Committee is aware that severe, persistent allergic asthma can have a detrimental effect on a person's life and that omalizumab is an effective therapy for children, adolescents and adults with severe persistent allergic asthma. But new evidence that has become available since our original appraisal of omalizumab in 2007 indicates that it is not as clinically or cost-effective as was first thought. The Committee explored ways to identify a subgroup of people for whom omalizumab might provide a cost effective treatment, including using favourable assumptions in the modelling. In addition, the Committee recognised that there could be additional health-related benefits for patients and carers as a result of using omalizumab. However, there was no quantifiable data relating to these benefits. Unfortunately, the Committee was unable to continue to recommend omalizumab for use in the NHS. The next step is for the manufacturer and other consultees to respond to the Committee's concerns."
The draft guidance (appraisal consultation document / ACD) can be found from Friday 9 November on the NICE website at: http://guidance.nice.org.uk/TA/WaveR/110
NICE has not yet issued final guidance to the NHS; these decisions may change after consultation.
Until NICE issues final guidance, NHS bodies should make decisions locally on the funding of specific treatments. Once NICE issues its guidance on a technology it replaces local recommendations across the country.
Final guidance is expected to be published in April 2013.
Notes to editors
About the guidance
1. The draft guidance (appraisal consultation document / ACD) can be found from 00:01hrs on Friday 9 November on the NICE website at: http://guidance.nice.org.uk/TA/WaveR/110
2. Closing date for comments is Friday 30 November 2012. The second appraisal committee meeting is Tuesday 22 January 2013.
3. Final guidance is expected to be published in April 2013.
4. This appraisal on omalizumab for treating severe, persistent allergic asthma in adults and children over 6 is a review of NICE technology appraisal guidance 133 (omalizumab for severe persistent allergic asthma in adults, 2007, available at: www.nice.org.uk/guidance/TA133) and NICE technology appraisal guidance 201 (omalizumab for the treatment of severe persistent allergic asthma in children aged 6 to 11 years, 2011, available at: www.nice.org.uk/guidance/TA201).
5. Following publication of TA 201, NICE recognised that it would be preferable to have a single piece of guidance covering recommendations for omalizumab for all age groups.
6. Omalizumab (Xolair, Novartis) is a monoclonal (derived from a single cell) antibody that binds to IgE. It has a UK marketing authorisation as add-on therapy to improve control of asthma in adults and adolescents (12 years and over) and children aged 6 to 11 years with severe persistent allergic asthma who have:
- a positive skin test or in vitro reactivity to a perennial aeroallergen
- reduced lung function (forced expiratory volume at 1 second [FEV1] less than 80% (in adults and adolescents aged 12 years and over)
- frequent daytime symptoms or night-time awakenings
- multiple documented severe exacerbations despite daily high-dose inhaled corticosteroids plus a long-acting inhaled beta2 agonist.
7. The marketing authorisation states that omalizumab treatment “should only be considered for patients with convincing IgE (immunoglobulin E) mediated asthma”. It also specifies that, 16 weeks after the start of omalizumab, physicians should assess how effective the treatment is, and should continue omalizumab only in patients whose asthma has markedly improved.
8. Omalizumab is given by injection every 2 or 4 weeks. The dose is determined by a person's body weight and IgE level.
9. The summary of product characteristics lists injection site pain, swelling, erythema and pruritus, and headaches as the most commonly reported adverse reactions for omalizumab treatment in people aged 12 years and over. The most commonly reported adverse reactions for omalizumab treatment in children under 12 years are headaches, pyrexia and upper abdominal pain. For full details of adverse reactions and contraindications, see the summary of product characteristics.
10. The price of omalizumab is £256.15 for a 150-mg vial and £128.07 for a 75-mg vial (excluding VAT; 'British national formulary' [BNF] edition 63). The dosage administered is 75-600 mg every 2 or 4 weeks, up to a maximum dosage of 600 mg every 2 weeks. The cost of omalizumab ranges from approximately £1665 per patient per year (excluding VAT) for a 75 mg dose administered every 4 weeks to approximately £26,640 per patient per year (excluding VAT) for a 600 mg dose (the maximum recommended dose in the summary of product characteristics) administered every 2 weeks. Costs may vary in different settings because of negotiated procurement discounts.
11. The Committee concluded that using the most optimistic assumptions in the subgroup of people with the most severe asthma, the most plausible ICERs were between £31,000 and £42,000 per QALY gained and could not therefore, be considered an acceptable use of NHS resources.
12. The Committee noted that the probabilistic base-case ICERs presented by the manufacturer for omalizumab, as an add-on treatment to standard care compared with standard care alone, using the Watson et al. mortality rates, were £33,300 per QALY gained for adults and adolescents and over £89,000 per QALY gained for children. By contrast, the Committee noted that the Assessment Group's base-case ICERs, using the De Vries et al. mortality rates were £83,800 per QALY gained for adults and adolescents and £78,000 per QALY gained for children, and using the Watson et al. mortality data the ICERs were £46,000 per QALY gained for adults and adolescents and £98,700 per QALY gained for children. The Committee acknowledged that using the mapped utility values, as done in the manufacturer's model, would reduce the ICERs from £83,800 to £52,200 per QALY gained. The Committee concluded that the ICERs for omalizumab for the whole population were higher than what can be considered a cost-effective use of NHS resources.
13. A patient access scheme has not been submitted by the manufacturer.
14. Omalizumab is accepted for restricted use within NHS Scotland.
15. Asthma is a long-term, inflammatory disorder affecting the airways. It is characterised by symptoms including breathlessness, wheezing and coughing, particularly at night. Allergic asthma is the most common type of asthma and is triggered by immunoglobulin E (IgE) antibodies produced in response to environmental allergens such as pollen, dust mites, or moulds.
16. There are currently more than 5.2 million people in the UK being treated for asthma; about 1.1 million of these are children. In its development of the appraisal, the Committee heard from clinical specialists and patient experts that, in current UK clinical practice, the population for which omalizumab would be considered was smaller than that covered by the marketing authorisation. One clinical specialist noted that the number of people currently being offered omalizumab in his practice accounts for approximately 1 in 200 people. The Committee concluded that only people with the most severe persistent allergic asthma despite optimised treatment would currently be offered omalizumab.
17. Until final guidance is published, the current guidance on omalizumab, TA133 and TA 201, is applicable.
Related NICE guidance
1. Omalizumab for the treatment of severe persistent allergic asthma in children aged 6 to 11 years. NICE technology appraisal guidance 201 (2011). Available from www.nice.org.uk/guidance/TA201
2. Omalizumab for severe persistent allergic asthma. NICE technology appraisal guidance 133 (2007). Available from www.nice.org.uk/guidance/TA133
3. Corticosteroids for the treatment of chronic asthma in adults and children aged 12 years and over. NICE technology appraisal guidance 138 (2008). Available from www.nice.org.uk/guidance/TA138
4. Corticosteroids for the treatment of chronic asthma in children under the age of 12 years. NICE technology appraisal guidance 131 (2007). Available from www.nice.org.uk/guidance/TA131
5. Bronchial thermoplasty for severe asthma. NICE interventional procedure guidance 419 (2012). Available from www.nice.org.uk/guidance/IPG419
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This page was last updated: 08 November 2012