Data from Lauren McCracken - Curated by EPG Health - Last updated 06 June 2018

Our understanding of AIT has been growing for over a century; beginning in 1911 when Leonard Noon discovered that vaccinating with a grass pollen extract was an effective means of suppressing immediate conjunctival sensitivity. By 1954 the first controlled clinical trial of AIT was being performed and fast forward to 2018 AIT is no longer just a theory but everyday practice in many allergic conditions such as allergic asthma, allergic rhinitis (AR) and food allergies (Durham et al., 2011). At this years European Academy of Allergy and Clinical Immunology (EAACI) Congress AIT was a hot topic with debates discussing its use in asthma, along with presentations on its use in food allergy and AR.

AIT in asthma – is it as clear as we think?

Stepping up to debate the pros and cons of AIT recommendations for allergic asthma was Professor Susanne Lau (Charité University Medicine Berlin) and Professor Guy Joos (University of Ghent). Before starting the debate, the chair, Dr Jasper Kappen (Sint Franciscus Gasthuis) identified that 74% of the audience agreed with the statement: ‘allergen-specific immunotherapy is recommended for asthma’. These debates at EAACI not only gave the opportunity to share evidence but also tested the speaker's persuasive skills – so were the audience swayed?

First up, on the pro side, Professor Susanne Lau argued that the latest GINA guidelines recommend AIT in patients with allergic asthma. Fighting her corner, she shared recent evidence in both children and adult patients where AIT had been successful in improving asthma symptoms. Firstly, children with AR and asthma were seen to have a reduction in asthma symptom scores after pre- and co-seasonal treatment with grass pollen tablets (Bufe et al., 2009). Improvements in medication use have also been demonstrated, with a 3-fold reduction in inhaled corticosteroid (ICS) use when combined with subcutaneous immunotherapy (SCIT) for mite allergy in comparison to ICS treatment alone (Zielen et al., 2010). The GAP trial is another example of asthma symptom improvement in grass pollen allergy treated with sublingual immunotherapy (SLIT) (Valovirta, 2018), as is the study conducted by Virchow et al., that saw a substantial reduction in exacerbation rates in adult patients with house dust mite allergic asthma treated with SLIT (Virchow et al., 2016). Finally, Professor Lau presented the efforts of a recent EAACI task force meta-analysis that found AIT more favourable than controls.

So, with the mounting evidence, how would Professor Guy Joos approach the argument against AIT use in asthma? Interestingly, Professor Joos took a different view to some of the same data Professor Lau had presented – starting with the GINA guidelines stating that the first step of treating patients with allergic asthma should be regular low dose ICS as this has been shown to be highly effective at reducing asthma symptoms, risk of asthma-related exacerbations, hospitalisations, and death. As a next step for patients with persistent symptoms, GINA recommends a step-up treatment combining ICS and long-acting beta2-antagonist (LABA). As a final step-up for the most severe patients, the use of biologics can be considered (GINA, 2018).

Moving on, Professor Joos, highlighted a paper which Professor Lau was an author on that concluded ‘AIT has the potential to achieve reductions in symptom and medication scores, but there is no clear or consistent evidence that measures of lung function can be improved’ (Asamoah et al., 2017). He continued with a meta-analysis review of SLIT studies in asthma that concluded there was a lack of data for important outcomes such as exacerbations and quality of life. Most of the studies included patients with intermittent or mild asthma meaning the safety of SLIT in patients with moderate or severe asthma is unknown, and further research is required (Normansell et al., 2015).

Finally, Professor Joos took us back to the Virchow et al., study, critiquing the methods and highlighting that the patients didn’t follow a typical treatment pathway that you would see in routine practice. In this study the ICS dose was reduced and LABA was not added as step-up treatment, furthering his argument that despite this being a good clinical model with potential it doesn’t translate into routine practice (Virchow et al., 2016).

Closing the pro and con session, after two compelling arguments backed by clinical data the audience voted again, seeing a slight shift in opinions but with the majority, 68%, still agreeing that AIT should be recommended for the treatment of asthma.

Food for thought

Food allergies have been described as ‘the second wave of the allergy epidemic’ with peanut and milk allergies being some of the most prevalent and severe. Dr Robert Wood (The Johns Hopkins Hospital, Baltimore) is known for his research in peanut allergy using Viaskin – a novel investigational immunotherapy consisting of once-daily applications of an allergen patch. The results have been successful in peanut allergy, leading him and his colleagues to explore the method for the treatment of cows’ milk protein allergy (CMPA), a very common and serious childhood condition.

Dr Wood presented the results of the MILES study, a phase I/II multicentre, double-blind, placebo-controlled clinical trial which aimed to find the optimal dose of Viaskin Milk and test the safety and efficacy of the treatment. Three doses and a placebo were randomly assigned to patients; interestingly, the optimal dose was discovered not to be the highest dose, but the middle dose of 300 μg. This dose showed a response rate of 49% and a significant treatment effect, allowing patients to consume up to 1000 mg of cows’ milk protein with no adverse reaction. It’s unclear why the highest dose had a lower response rate, something Dr Wood and his team were surprised by. Although all doses were considered well tolerated. The team plan to continue their research with the 300 μg dose.

The future of AIT – can we expect long-term benefits?

AIT has been demonstrated to have positive effects in reducing symptoms of both AR and allergic asthma – but the long-term benefits of these treatments are still unknown. Hoping to shed some light on the longer-term effects of AIT were Professor Stefan Zielen (Goethe University Frankfurt) and Professor Claus Bachert (University of Ghent).

The pair described the retrospective, comparative cohort analysis of a German longitudinal prescription database. The database followed patients with birch-pollen-induced allergic rhinitis and/or asthma over a 9-year period being treated with one of 6 AITs or non-AIT treatment as a control comparison. The investigators were able to follow the patients’ symptoms by the prescriptions they received – those patients without asthma were of particular interest, to see if they developed new asthma. It was discovered that AIT was associated with reduced progression of AR and asthma up to 6 years after stopping treatment (28.6% and 32% greater vs. non-AIT treated patients, respectively). In addition, decreased new use of asthma medication during treatment was also seen.

100+ years, have we waited long enough?

With all the exciting and promising data presented at this year’s EAACI Congress it seems we’ve come a long way in the last century of immunotherapy. It’s clear from the audience opinions that there is still a lot to learn and more convincing to be done, but do you think it’s ready for routine practice in your clinic?

References

Asamoah F, Kakourou A, Dhami S, Lau S, Agache I, Muraro A, et al. Allergen immunotherapy for allergic asthma: a systematic overview of systematic reviews. Clin Transl Allergy. 2017:7;25.

Bufe A, Eberle P, Franke-Beckmann E, Funck J, Kimmig M, Kilmek L, et al. Saftey and efficacy in children of an SQ-standardized grass allergen tablet for sublingual immunotherapy. J Allergy Clin Immunol. 2009:123;167–173.

Durham S, Nelson H. Allergen Immunotherapy: A Centenary Celebration. World Allergy Organ J. 2011:4;104–6.

Global Initiative for Asthma (GINA), 2018. Available from: http://ginasthma.org/2018-gina-report-global-strategy-for-asthma-management-and-prevention/ (accessed May 2018).

Normansell R, Kew KM, Bridgman AL. Sublingual immunotherapy for asthma. Cochrane Database Syst Rev. 2015:8;CD011293.

Valovirta E, Petersen T, Piotrowska T, Laursen M, Andersen J, Sørensen H, et al. Results from the 5-year SQ grass sublingual immunotherapy tablet asthma prevention (GAP) trial in children with grass pollen allergy. JACI. 2018:141;529–38.

Virchow JC, Backer V, Kuna P, Prieto L, Nolte H, Villesen HH, et al. Efficacy of a House Dust Mite Sublingual Allergen Immunotherapy Tablet in Adults With Allergic Asthma: A Randomized Clinical Trial. JAMA. 2016:315;1715–25.

Zielen S, Kardos P, Madonini E. Steroid-sparing effects with allergen-specific immunotherapy in children with asthma: a randomized controlled trial. J Allergy Clin Immunol. 2010:126;942–9.

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