1. Recent Developments in Allergy Diagnosis and Treatment
Miman MC, MD, Professor.

2. Disclosure
Speaker has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the speak.

3. Introduction Allergic diseases
most prevalent, major socio-economic burden.
Up to 25% of the population in industrialized countries and their incidence is continuously rising, particularly in children and young adults.

5. Recent Advances Diagnosis Pharmacological treatment Immunotherapy
Future???

6. Advances in Diagnosis
Molecular allergy diagnosis -> more accurate diagnosis -> accurate prescription of therapeutic intervention.
in vitro allergy diagnosis -> discriminate between sensitization and true allergy.
Recombinant technology ->
tremendous advances in allergen characterization
vaccine development
the knowledge of immune mechanisms involved in allergic diseases.

8. Standardized allergen
Classic allergen extracts’ problem:
standardization difficulties
Due to their biologic nature, extracts represent a heterogeneous mixture of proteins, glycoprotein, and polysaccharides from a given allergenic source
the allergen content of extracts varies between different manufacturers as well as between batches.

9. Standardized allergen
To use of purified recombinant allergens
To develop and validate methods for the quantification of allergen content of extracts
limitations of allergens extracts
molecular allergy diagnosis as an alternative
to investigate specific IgE binding to purified molecules (natural as well as recombinant).
advantages of molecular allergy diagnosis over extract-based methods
the ability to distinguish between genuine sensitization versus cross-reactivity

11. Advances in Pharmacological Treatment
For years, the mainstay of treatment, recommended first line by all AR treatment guidelines
Intranasal steroids and antihistamines

12. Promising recent advances
MP-AzeFlu  (a novel intranasal formulation of azelastine hydrochloride and fluticasone propionate in a single spray),
histamine H3 and H4 receptor antagonists
toll-like receptor (TLR) targeted treatment.
recently discovered compounds (e.g. ciclesonide and phosphodiesterase-4 inhibitors)
immunological therapies like omalizumab
new biomolecular preparations, cellulose powders and microemulsions are under investigation.

13. MP-AzeFlu consists of two drugs from two different medication classes
with complementary effects,
benefiting from antihistamine, mast cell stabilizing, antileukotriene, anti-inflammatory properties
targeting both the early- and late-phase allergic responses
the volume per spray is greater than that of marketed INS sprays.
MP-AzeFlu has surpassed the efficacy of INS for the first time for the treatment of AR
the most promising new treatment option.

16. New antihistamines An H3 receptor antagonist (PF-03654746)
targeting multiple histamine receptors (GSK , GSK and WO )
tested in combination with oral H1 antihistamine (fexofenadine)
showed reduction in nasal symptoms of patients suffering from out-of-season AR.

17. TLR (Toll-Like Receptor) agonists
TLRs are the first line of defense against invading aeroallergens.
TLR agonists show strong immunogenicity and can enhance the efficacy of immunotherapy
when used as adjuvants for allergy vaccines.
Specific immunomodulation via co-administration of the allergen and TLR2/6 agonist, BPPcysMPEG, reduced allergic airway inflammation from sub-sequent allergen contact in mice.
Intranasal administration of AZD8848 (a TLR7 agonist) and VTX-1463 (a TLR8 agonist) as stand-alone therapeutics improved nasal and ocular symptoms in AR, revealing their potential in treatment of AR.

18. Cellulose powder and microemulsions
Barrier protection measures by application of
topical nasal cellulose powders or microemulsion
to avoid contact with allergens.
good promise for the treatment of PAR where aeroallergens are hard to avoid.

19. Novel Biologicals Biologicals are therapeutic agents with
large molecular weights
synthesized by living organisms
targeting a specific determinant, e.g., monoclonal antibodies (mAbs)
that bind to cytokines or receptors involved in the inflammatory pathways.

22. Novel Biologicals Omalizumab
an IgE inhibiting recombinant humanized monoclonal antibody
used to treat patients sensitive to perennial aeroallergens who have not responded to more traditional treatment strategies.
rapidly reduces free serum IgE levels by over 95%
the reduction of receptor density on the mast cells or basophils

23. bispecific antibodies targeting more than one cell or receptor is an innovative approach for the future

24. Advances in Immunotherapy
Immunotherapies delivered in novel biomolecular preparations
reduced allergenicity while maintaining immunogenicity
to enable safe and slow release of lower doses
over a short period of time.
wider applicability of IT
Current advances and research focus on
novel routes of administration,
modification of allergens
utilization of new adjuvants
adjunct therapies

27. Advances in Immunotherapy
Focusing aspects:
The identification of the most important disease- relevant components to diminish the number of allergens necessary for effective therapy
The modification of these components to reduce IgE binding and consequently the possibility of side effects
Optimization of the formulation and route of application of the allergens in order to maximize therapeutic efficacy
The improving immunogenicity led to investigation of T-cell epitope-based peptides and recombinant allergen derivatives.

28. T-cell epitope peptides
the use of sets of short allergen-derived peptides
carefully selected and designed to comprise the dominant T-cell-reactive sites of the major allergen sequences
but lacking IgE binding and inflammatory cell- activating potential

30. Recombinant allergens
an alternative approach
to generate hypoallergenic molecules
with retained or potentially enhanced immunomodulatory activity

31. Sublingual immunotherapy for mites
oro-dispersable sublingual tablets
its stability on room temperature is higher compared to liquid formulations.
The efficacy in patients with allergic rhinitis and asthma.

32. Adjuvants to immunotherapy
different adjuvants
increasing the duration of antigen presentation
direct effects on the immune response cascade
TLR engagement on APC plays an important role in regulating adaptive immunity
TLR ligands can be selected to promote Treg responses and immune deviation from Th2 to Th1 profile.

33. Future
biologics that cover a broader spectrum of cytokines involved in the immune response
Recombinant HDM allergen tablets are expected to strengthen the efficacy and immunogenity, and reduce allergenity and duration of treatment of allergen vaccines

34. Thanks for your interest.
References
Klimek L, Mullol J, Hellings P, et al. Recent pharmacological developments in the treatment of perennial and persistent allergic rhinitis, Exp Op Pharm, (2016) 17:5,
Tan HTT, Sugita K, Akdis CA. Novel Biologicals for the Treatment of Allergic Diseases and Asthma. Curr Allergy Asthma Rep (2016) 16:70,
Sandrini A, Rolland JM, O’Hehir RE. Current developments for improving efficacy of allergy vaccines. Exp Rev Vac, (2015) 14:8,
Bahceciler NN, Hocaoglu AB, Galip N. A milestone in house dust-mite- allergen immunotherapy: the new sublingual tablet S (actair), Expert Review of Vaccines, (2014) 13:12,
Thanks for your interest.