2. Ann Allergy Asthma Immunol. January 2020;124(1):2-12
New Treatments for Chronic Urticaria
Pavel Kolkhir, PhD
Sabine Altrichter, MD
Melba Munoz, PhD
Tomasz Hawro, MD
Marcus Maurer, MD
3. New Treatments for Chronic Urticaria
Key Messages
• Omalizumab is currently the mainstay of treatment of antihistamine-resistant chronic spontaneous
urticaria.
• The use of omalizumab in chronic inducible urticaria, up-dosing in chronic spontaneous urticaria
and treatment of children younger than 12 years, currently off-label, are supported by evidence, and
further studies should be performed.
• Ligelizumab and UB-221 are novel anti-IgE monoclonal antibodies with a 40- to 50-fold and 8-fold
greater affinity to IgE, respectively, compared with omalizumab and are currently being studied in
clinical trials of chronic spontaneous urticaria.
• Other drugs for the treatment of CSU are promising, including interleukin (IL) 5–targeted
monoclonal antibodies (mAbs), a chemoattractant receptor–homologous molecule expressed on
TH2 cell antagonist, a mAb to Siglec-8, Bruton tyrosine kinase inhibitors, a spleen tyrosine kinase
inhibitor, and dupilumab, an anti–IL-4/13 mAb.
• New pathogenically important targets in chronic spontaneous urticaria include Mas-related G-
protein–coupled receptor X2; the histamine4 receptor; C5a and its receptor; inhibitory mast cell
receptors other than Siglec-8; IL-33, IL-25, and thymic stromal lymphopoietin, and stem cell factor.
Kolkhir P, et al. Ann Allergy Asthma Immunol. January 2020;124(1):2-12
4. Promising Drugs and Potential Targets in Chronic Urticaria
Kolkhir P, et al. Ann Allergy Asthma Immunol. January 2020;124(1):2-12
5. Anti-Inflammatory Reliever Therapy for Asthma
Brian Lipworth, MD
Rory Chan, MBChB
Chris RuiWen Kuo, MBChB
Ann Allergy Asthma Immunol. January 2020;124(1):13-15
6. Escalation and De-Escalation of Budesonide-Formoterol (BUD/FM)
Combination for the Treatment of Mild to Moderate Persistent Asthma
Lipworth B, et al. Ann Allergy Asthma Immunol. January 2020;124(1):13-15
7. New Treatments for Atopic Dermatitis
Targeting Beyond IL-4/IL-13 Cytokines
Ann Allergy Asthma Immunol. January 2020;124(1):28-35
Yael Renert-Yuval, MD
Emma Guttman-Yassky, MD, PhD
8. New Treatments for Atopic Dermatitis Targeting Beyond
IL-4/IL-13 Cytokines Key Messages
• Atopic dermatitis (AD) is a common and heterogeneous inflammatory skin disease, with various subtypes
differing by clinical, demographic, and molecular characteristics.
• Most patients can be managed by conventional interventions, but for those who require systemic
immunosuppressive therapies, safe and effective alternative treatment options are limited.
• Some of the emerging broad- and narrow-targeting agents have shown significant benefit in clinical trials
of patients with moderate-to-severe atopic dermatitis, paving the way for novel therapeutic paradigms.
• Beyond IL-4/IL-13 inhibitors, recent favorable outcomes were seen in clinical trials of JAK inhibitors
(baricitinib, upadacitinib, and abrocitinib), a dual JAK-SYK inhibitor (ASN002), a histamine H4R
antagonist (ZPL-3893787), antagonists of the TSLP-OX40L axis (GBR 830, etokinumab), an IL-22
inhibitor (fezakinumab), and an IL-17C antagonist (MOR106).
• These trials, with special attention to the variability among AD subpopulations, will also help to expand
the current knowledge on AD pathogenesis, and to dissect the contribution of different molecular factors,
to ultimately portray the full immunologic fingerprint of each AD subtype.
Renert-Yuval R, et al. Ann Allergy Asthma Immunol. January 2020;124(1):28-35
9. The Immune Dysregulations of AD, With
Corresponding Targeted Agents
Renert-Yuval R, et al. Ann Allergy Asthma Immunol. January 2020;124(1):28-35
10. Mechanism of Action of JAK and SYK Inhibitors
Renert-Yuval R, et al. Ann Allergy Asthma Immunol. January 2020;124(1):28-35
11. Ann Allergy Asthma Immunol. January 2020;124(1):36-43
Catherine Drislane, MB
Alan D. Irvine, MD, DSc
The Role of Filaggrin in Atopic Dermatitis and
Allergic Disease
12. The Role of Filaggrin in Atopic Dermatitis and Allergic
Disease Key Messages
• Filaggrin is both an important risk factor for atopic dermatitis (AD) and a disease modifier of
AD.
• AD patients carrying FLG loss-of-function mutations (AD FLG) have a distinct clinical and
microbiological phenotype.
• Th2 immune skewing causes down-regulation of filaggrin, so that filaggrin is down-regulated
in all AD patients, regardless of FLG mutation status.
• New sequencing technology allows us to process filaggrin mutations across all ethnic groups
and allows identification of previously underreported LoF variants.
• Filaggrin expression is affected by environmental influences such as climate, pollution, water
hardness, and the microbiome.
Drislane C, et al. Ann Allergy Asthma Immunol. January 2020;124(1):36-43
14. The Atopic Dermatitis Filaggrin Phenotype
Drislane C, et al. Ann Allergy Asthma Immunol. January 2020;124(1):36-43
15. Ann Allergy Asthma Immunol. January 2020;124(1):44-56
Ali Doroudchi, MD
Mohini Pathria, MD
Brian D. Modena, MD, MSc
Asthma Biologics: Comparing Trial Designs, Patient
Cohorts and Study Results
16. Asthma Biologics Key Messages
Doroudchi A, et al. Ann Allergy Asthma Immunol. January 2020;124(1):44-56
• Although 5 biologic therapies have Food and Drug Administration (FDA)-approved indications for difficult-to-control asthma, the clinical trials
that proved the efficacy and safety of these biologics were similar in their inclusion criteria, study protocols, and measured outcomes. Initial
trial results are now being reanalyzed and reinterpreted in subsets of patients with asthma that demonstrate enhanced responses. As a result,
keeping up with the growing body of literature surrounding asthma biologic therapy has become increasingly difficult. This review summarizes
and compares trial designs, patient cohorts, and study results of the major trials involving these therapies.
• Because of variations in inclusion criteria and natural variations in enrolled cohorts, the baseline clinical traits and severity of study
populations in asthma biologic trials have differed significantly. For example, baseline annualized exacerbation rates in the year before
enrollment and blood eosinophilia, which are both strong predictors of a biologic's success, differed strongly among populations.
• Early omalizumab efficacy trials did not stratify subjects by blood eosinophils or include patients taking long-acting beta agonists or oral
steroids but showed relative reductions in exacerbation rates comparable to those of the newer asthma biologics among less severe cohorts.
• If a care provider's aim is to reduce clinically significant exacerbations in a patient with peripheral blood eosinophilia, it is our opinion that
dupilumab, mepolizumab, and reslizumab have the strongest supporting data. Mepolizumab has also demonstrated an ability to reduce
emergency department visits and hospitalizations.
• If the goal is to improve lung function, dupilumab therapy has demonstrated the largest numeric improvements in prebronchodilator forced
expiratory volume in 1 second (FEV1) % predicted compared with placebo, with consistent results across all phase II and phase III trials,
including its steroid-sparing trial (QUEST LIBERTY VENTURE). Benralizumab also demonstrated improvements in lung function in 2 phase
III trials (SIROCCO, CALIMA) and its long-term safety trial (BORA).
• If the objective is to reduce daily oral steroids, benralizumab and dupilumab have the strongest supporting data, with
roughly 50% of subjects in both trials demonstrating an ability to stop steroids altogether. Of note, a strong difference
was seen across studies in the ability to reduce steroids among the placebo groups, which makes comparisons
between these 3 steroid-sparing trials challenging.
17. Mechanisms of FDA-Approved Asthma Biologics
Doroudchi A, et al. Ann Allergy Asthma Immunol. January 2020;124(1):44-56
18. Relationships of Common Asthma Phenotypes to Severity
and Eosinophilia
Doroudchi A, et al. Ann Allergy Asthma Immunol. January 2020;124(1):44-56
