Treating the trigger: assessing the evidence for sublingual immunotherapy for asthma

1. What is sublingual immunotherapy and how might it help people with asthma?

For about half of the 300 million people worldwide with asthma, allergies may be an important trigger for their symptoms and asthma attacks. People can be allergic to many different things, but common triggers are house dust mite, pollen, and animals.

Allergies are harmful immune overreactions to substances that are normally considered safe. Immunotherapy is a way teaching the immune system to react more normally. This is done by giving repeated, increasing doses of what the person is allergic to, either as an injection (aka subcutaneous immunotherapy) or in liquid or tablet form under the tongue (aka sublingual immunotherapy or SLIT). Immunotherapy has been shown to help people with allergic rhinitis (for example, hay fever) and for people with severe reactions to wasp or bee stings, although to be effective treatment may need to continue for 3 to 5 years.

However, it’s not so clear if it works, or is safe, for people with asthma. There is a small but important risk that when you deliberately give a person something they are allergic to, they might have a very bad reaction. This could be particularly serious if the person has asthma, as it might lead to difficulties breathing, which could be life-threatening.

Despite these concerns, SLIT is particularly exciting for two reasons; firstly, it can be given without the use of needles, meaning it can be taken at home and is much more acceptable to children or adults who do not like injections; and secondly, it has the theoretical potential to be a ‘cure’ for the asthma trigger: that is, the benefits of the treatment may continue even after the treatment has been stopped.

2. Is SLIT available now for people with asthma?

Many countries produce evidence-based guidelines about treatments for asthma, and the most well-known international guideline comes from the Global Initiative for Asthma (GINA). This guideline does not recommend the routine use of SLIT for asthma. In fact, current opinion is that SLIT should not be used at all in people with more severe asthma or whose symptoms are not well controlled at the time it is given.  Although SLIT is sometimes given to people with well-controlled mild or moderate asthma, it is usually because they also have allergic rhinitis or a wasp or bee sting allergy and this is the main reason for the prescription, rather than their asthma.

3. What did we find in our review?

We found a lot of relevant trials – 52 studies on 5077 adults and children with asthma, most of whom were allergic to house dust mite or pollen. Typical courses of SLIT were a year, but some lasted 3 years – so quite a commitment for people embarking on this treatment!

The main problem we found was a mismatch in the information we were interested in, and what the studies reported. To make decisions about funding of treatments, healthcare systems need to know about costs associated with diseases – like hospital admissions and medications. Patients are also interested in these outcomes – along with quality of life and whether they can get on with their lives.

In our review, trials sometimes reported quality of life, but the scales used to measure this were different in the trials, so we couldn’t come up with a conclusion. Very few trials reported the number of asthma attacks people had. The bottom line is that from our review we cannot tell whether SLIT reduces asthma attacks or improves quality of life for people with asthma. Our findings suggest that it is unlikely to cause more serious side effects than standard treatments in people mild or moderate asthma.

4. Why can’t we be more confident in our findings?

When new treatments emerge for chronic diseases like asthma, it’s easy for researchers, doctors, and patients to get swept up in the hype. It is unfortunate and frustrating that it often takes a while to say with relative certainty whether something is helpful or, perhaps more importantly, harmful. The amount of time needed to test immunotherapy properly makes this particularly frustrating for those who might see a benefit.

Despite including more than 50 studies involving over 5000 people, the conclusions of our review are rather inconclusive!

Firstly, because SLIT is a new treatment and there are many different products available for testing. Work to assess each of the different products was carried out using different methods and measures, making it very difficult make an overall judgement.

Secondly, many of the tools used to measure whether the treatment works in the studies are not properly  ‘validated’, which means we cannot be sure they are properly measuring what they intend to measure. This can be misleading.

Finally, most of the people studied had mild or moderate asthma, which is not surprising given the current recommendation that SLIT should not be used in people with more severe asthma. This means we are not sure whether people with more severe asthma might actually benefit more, but we are also not sure if it would be safe to give SLIT to them.

Interestingly, there have been several other reviews of SLIT for people with asthma and these have included many of the same trials as in our review. The other reviews came out more positively than ours did because they used different outcomes. Cochrane is committed to using patient important outcomes rather than biological markers, so that we can provide evidence about what makes a difference in people’s lives and not just the results of blood tests. Some of the other reviews also chose to combine the different unvalidated measures (e.g. for asthma symptoms) used in the individual studies, but we chose not to do this.

5. How do we see future for SLIT and asthma research?

This is an exciting and important area of research as, unlike other treatments, SLIT has the theoretical potential to be a ‘cure’ for one of the major triggers of asthma: allergies. Sadly, however, there is not yet enough evidence to be sure about this and about whether it is safe.

Rebecca Normansell is Deputy Coordinating Editor, Cochrane Airways St George’s, University of London, London, UK

This article was first published on Cochrane. 

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