Med motto “Pathways from precision medicine to personalized health care in allergy and asthma”, ønsket European Academy of Allergy and Clinical Immunology (EAACI) alle deltakerne velkommen til den årlige kongressen som ble avholdt i Hamburg, Tyskland. Denne kongressen er møtepunkt for forskere, helsepersonell og andre interessenter fra hele verden som er involverte i allergi og klinisk immunologi. Teet Pullerits ved Sahlgrenska Sykehus i Gøteborg, Sverige, har på vegne av ALK laget en kort oppsummering av noen få høydepunkter fra kongressen:
Three intensive EAACI congress days in sunny Hamburg proved that any concerns regarding the necessity of scientific meetings in physical form in the post-Covid era are unfounded. With more than 7400 engaged participants, the EAACI 2023 hybrid congress can be considered a success both scientifically and socially.
Mast cell under attack
Congress highlighted the exciting times in the field of mast cell-driven diseases. Although identified as primary effector cells in allergic diseases already a long time ago, mast cells themselves have enjoyed a relatively bullet-proof position regarding the possibility of specifically blocking their detrimental effect in allergy. But not anymore!
Currently available mast-cell associated targets are the blocking of mast cell mediators as with antihistamines or the inhibition of mast cell activation as with anti-IgE. In the latter group, oral small molecules which inhibit Bruton tyrosine kinase (Btk), are under development. Btk acts downstream of the IgE receptor FcƐRI in mast cells and thus inhibiting it can work independently whether mast cell is activated via IgE-mediated ”auto allergic” or via IgG-mediated ”autoimmune” mechanisms.
Professor Martin Metz presented data from a phase 2 study with Btk inhibitor remibrutinib in chronic spontaneous urticaria (CSU), leading to a clearly significant reduction with a score of -20 on weekly urticaria activity score (UAS7) already at week 2 and lasting over a whole treatment period of 12 weeks. This effect was present in both omalizumab-naïve and omalizumab-experienced patients. Phase 3 study with this oral treatment option is ongoing.1
Ways to improve AIT effectiveness and safety
In a plenary symposium on ”Novel developments in AIT”, professor Stephen Durham from London shared updates on the usage of AIT in combination with biologicals. The enhanced safety and added efficacy of AIT if combined with omalizumab has been previously demonstrated. Based on the mechanism of action of newer biologicals, the studies combining AIT with dupilumab or anti-TSLP tezepelumab are evolving. The rationale behind using dupilumab with AIT is that anti-IL4Ra blockade is likely to inhibit Th2 and Th17 cell activation , induce Tregs, block IgE synthesis, and inhibit mast cells, basophils as well as mucus production.
In a published study by Corren et al2 patients with allergic rhinitis received a short-term 12 week treatment of either SCIT, dupilumab, combination of both or placebo. The primary outcome of this study was negative, eg combination of SCIT+dupilumab did not have better effect on TNSS (total nasal symptom score) in nasal allergen challenge compared to SCIT alone. However, in objective measurements, peak nasal inspiratory flow (PNIF) was numerically most improved in the SCIT+dupilumab combination group, which was the only treatment arm showing significant improvement compared to placebo.
Even more interestingly, skin prick test wheal diameter in the SCIT+dupilumab group was significantly lower compared to all other treatment arms. This was also reflected in the antibody production switch from IgE to IgG4. From the clinical perspective, combination treatment resulted in reduction of SCIT side effects and marked reduction in withdrawal rates.
SCIT has also been evaluated in combination with anti-TSLP drug tezepelumab in a Catnip study3. In this study the treatment with either SCIT, tezepelumab, combination of SCIT+tezepelumab or placebo lasted for 1 year with a follow-up period of another year after treatment discontinuation, aiming to look at the tolerance induction. Combination treatment in the Catnip study was significantly better compared to either SCIT or tezepelumab alone in reducing the TNSS score during 1 hour following nasal cat allergen challenge after 1 year treatment, but not at the end of the follow-up period. Interestingly, however, looking at the very peak of the TNSS response after cat allergen chellenge, which can be considered the marker of mast cell activation, the significantly better protecting effect of combination therapy was maintained even at 1 year after treatment discontinuation. This significant protection was also associated with a reduced mast cell mRNA activation signature. Furthermore, tezepelumab treatment, either alone or in combination, demonstrated significant and lasting effect on cat-specific IgE production, but had no effect on specific IgG4 levels. Taken together, the combination of allergen immunotherapy with biologics targeting Th2 pathways was suggested to have potential to enhance short term efficacy while improving safety.
Environment, climate and venom allergy
EAACI is firmly devoted to keep a critical eye on climate change and it’s impact on the allergy development. The changes in the Hymenoptera distribution worldwide were discussed as a typical feature of that with examples of paper wasps (Polistes), which in Europe is a more typical Mediterranean vespid, having now been spotted in England and in Scandinavia. Professor Peter Korosec from Golnik, Slovenia addressed genetic risk factors which are important in hypersensitivity reactions to venom. Patients with hereditary alpha-tryptasemia (HAT) do not have increased senitization rate to venom but may experience more severe reactions upon sting. This is explained that the genetically different tryptase in HAT patients induces endothelial vascular leak. However, whether patients with HAT need life-long VIT is still a matter of discussion4. During the congress, the next year’s congress site was announced. EAACI 2024 congress will take place in Valencia, Spain.
- Marcus Maurer et al: Remibrutinib, a novel BTK inhibitor, demonstrates promising efficacy and safety in chronic spontaneous urticaria. https://pubmed.ncbi.nlm.nih.gov/36096203/
- Corren et al: Short-Term Subcutaneous Allergy Immunotherapy and Dupilumab are Well Tolerated in Allergic Rhinitis: A Randomized Trial, J Asthma Allergy, 2021 Aug 16;14:1045-1063.
- Corren et al: https://www.jacionline.org/article/S0091-6749(22)01333-1/pdf
- Lyons et al: Heritable risk for severe anaphylaxis associated with increased α-tryptase-encoding germline copy number at TPSAB1. J Allergy Clin Immunol. 2021 Feb;147(2):622-632