The Phase 3 INVIGORATE Trial of Reproxalap in Patients with Seasonal Allergic Conjunctivitis

Starr CE, Nichols KK, Lang JR, Brady TC. Clin Ophthalmol. 2023 Dec 13;17:3867-3875. doi: 10.2147/OPTH.S441009.

Abstract

Purpose

There is an unmet need for new treatments for allergic conjunctivitis.

Objective

To assess the activity of reproxalap, a novel reactive aldehyde species modulator, in a real-world model of seasonal allergen exposure.

Methods

The INVIGORATE Trial, a prospective, quadruple-masked, vehicle-controlled, crossover, sequence-randomized Phase 3 trial, tested the efficacy of reproxalap in adults with a history of moderate to severe allergic conjunctivitis, ragweed pollen allergy, and allergen chamber-induced ocular itching and redness. Patients were randomly assigned (1:1) to receive 0.25% reproxalap ophthalmic solution or vehicle, followed by a 2-week washout period before crossing over to the other test article.

Regulation of Macrophage Polarization in Allergy by Noncoding RNAs

 

Ishibashi O, Muljo SA, Islam Z.  Noncoding RNA. 2023 Dec 11;9(6):75. doi: 10.3390/ncrna9060075. 

Abstract

Allergy is a type 2 immune reaction triggered by antigens known as allergens, including food and environmental substances such as peanuts, plant pollen, fungal spores, and the feces and debris of mites and insects. Macrophages are myeloid immune cells with phagocytic abilities that process exogenous and endogenous antigens. Upon activation, they can produce effector molecules such as cytokines as well as anti-inflammatory molecules.

Macrophage polarization

The dysregulation of macrophage function can lead to excessive type 1 inflammation as well as type 2 inflammation, which includes allergic reactions. Thus, it is important to better understand how macrophages are regulated in the pathogenesis of allergies. Emerging evidence highlights the role of noncoding RNAs (ncRNAs) in macrophage polarization, which in turn can modify the pathogenesis of various immune-mediated diseases, including allergies.

Circulating T follicular helper 2 cells, T follicular regulatory cells and regulatory B cells are effective biomarkers for predicting the response to house dust mite sublingual immunotherapy in patients with allergic respiratory diseases

Shigehara K, Kamekura R, Ikegami I et al. Front Immunol. 2023 Nov 24;14:1284205. doi: 10.3389/fimmu.2023.1284205. 

Abstract

The ratio of cTfh2/cTfr cells and the ratio of cTfh2/cBreg
cells at the start of HDM-SLIT showed significant odds
ratiosby two-way logistic analysis

The relationships between T follicular helper (Tfh) cells and antigen-specific immunoglobulins (sIgs) in patients with allergic respiratory diseases who are receiving antigen immunotherapy (AIT) have not been fully clarified. Therefore, we started to perform house dust mite sublingual immunotherapy (HDM-SLIT) for 20 patients with atopic asthma comorbid with allergic rhinitis (AA+AR) who were already receiving ordinary treatments including inhaled corticosteroid (ICS). We examined percentages of circulating T follicular helper (cTfh) and regulatory (cTfr) cells and percentages of circulating regulatory T (cTreg) and B (cBreg) cells by FACS and we examined levels of Der-p/f sIgs by ELISA. Based on the symptom score (asthma control questionnaire: ACQ) and medication score ((global initiative for asthma: GINA) treatment step score) in patients with AA, the patients were divided into responders and non-responders. The percentage of cTfh2 cells significantly decreased and the percentage of cTfh1 cells significantly increased within the first year.

How Does Mild Asthma Differ Phenotypically from Difficult-to-Treat Asthma?

Naftel J, Mistry H, Mitchell FA, Belson J, Kyyaly MA, Barber C, Haitchi HM, Dennison P, Djukanovic R, Seumois G, Vijayanand P, Arshad SH, Kurukulaaratchy RJ.  J Asthma Allergy. 2023;16:1333-1345

Background: Despite most of the asthma population having mild disease, the mild asthma phenotype is poorly understood. Here, we aim to address this gap in knowledge by extensively characterising the mild asthma phenotype and comparing this with difficult-to-treat asthma.

Methods: We assessed two real-world adult cohorts from the South of England using an identical methodology: the Wessex AsThma CoHort of difficult asthma (WATCH) (n=498) and a mild asthma cohort from the comparator arm of the Epigenetics Of Severe Asthma (EOSA) study (n=67). Data acquisition included detailed clinical, health and disease-related questionnaires, anthropometry, allergy and lung function testing, plus biological samples (blood and sputum) in a subset.

Lung function characteristics between the difficult
and mild asthma cohorts.

Results: Mild asthma is predominantly early-onset and is associated with type-2 (T2) inflammation (atopy, raised fractional exhaled nitric oxide (FeNO), blood/sputum eosinophilia) plus preserved lung function. A high prevalence of comorbidities and multimorbidity was observed in mild asthma, particularly depression (58.2%) and anxiety (56.7%). In comparison to difficult asthma, mild disease showed similar female predominance (> 60%), T2-high inflammation and atopy prevalence, but lower peripheral blood/airway neutrophil counts and preserved lung function.

Patient outcomes associated with subcutaneous C1INH prophylaxis for hereditary angioedema: a retrospective analysis

• Research
• Open access
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  Lumry, W., Craig, T., Anderson, J. et al. Allergy Asthma Clin Immunol 19, 105 (2023). https://doi.org/10.1186/s13223-023-00861-9

• details

Abstract

Background

Real-world data on subcutaneous C1INH (C1INH[SC]) usage and patient-level impacts on hereditary angioedema (HAE)-related outcomes and quality of life (QoL) are both lacking and challenging to generate using conventional study methodologies. Using a hybrid study design involving patient interviews supplemented by retrospective medical chart data review, we conducted a real-world assessment of the impact of C1INH(SC) prophylaxis on HAE attack patterns, QoL, and on-demand medication use.

Methods

The study was conducted at seven US sites and included 36 adults with HAE who had been treated with C1INH(SC) long-term prophylaxis following ≥ 12 months of on-demand management only. Patients underwent 30-min interviews, facilitated and analyzed by a trained qualitative research specialist.

Allergen immunotherapy for atopic dermatitis: Systematic review and meta-analysis of benefits and harms.

Yepes-Nuñez JJ, Guyatt GH, Gómez-Escobar LG et al.  J Allergy Clin Immunol. 2023 Jan;151(1):147-158. doi: 10.1016/j.jaci.2022.09.020. 

Background

Atopic dermatitis (AD, eczema) is driven by a combination of skin barrier defects, immune dysregulation, and extrinsic stimuli such as allergens, irritants, and microbes. The role of environmental allergens (aeroallergens) in triggering AD remains unclear.

Objective

We systematically synthesized evidence regarding the benefits and harms of allergen immunotherapy (AIT) for AD.

Methods

As part of the 2022 American Academy of Allergy, Asthma & Immunology/American College of Allergy, Asthma and Immunology Joint Task Force on Practice Parameters AD Guideline update, we searched the MEDLINE, EMBASE, CENTRAL, CINAHL, LILACS, Global Resource for Eczema Trials, and Web of Science databases from inception to December 2021 for randomized controlled trials comparing subcutaneous immunotherapy (SCIT), sublingual immunotherapy (SLIT), and/or no AIT (placebo or standard care) for guideline panel–defined patient-important outcomes: AD severity, itch, AD-related quality of life (QoL), flares, and adverse events. Raters independently screened, extracted data, and assessed risk of bias in duplicate. We synthesized intervention effects using frequentist and Bayesian random-effects models. The GRADE approach determined the quality of evidence.

Conception and pilot testing of a self-management health application for patients with pollen-related allergic rhinitis and allergic asthma-the APOLLO app.

Landesberger V, Grenzebach K, Schreiber F, Nowak D, Gröger M, Oppel E, Schaub B, French LE, Kutzora S, Quartucci C, Herr C, Heinze S. Sci Rep. 2023 Dec 7;13(1):21568. doi: 10.1038/s41598-023-48540-4. 

Abstract

It has been shown that pollen information services are an important self-management tool for patients with pollen-related allergic rhinitis (AR) and allergic asthma (AA). This study aimed to design an online application for patients with AR and AA, which supports patients to better manage their disease as well as to evaluate the app and present the first results of the pilot study. The pollen data were obtained from the electronic pollen information network of Bavaria, Germany. Participants were asked to fill in their allergy-related complaints in the app over a 60-day period. Subsequently, the app was evaluated. Indices and diagrams visualized the participants' individual complaints as well as the daily pollen concentration in the air. In order to motivate participants to complete the app on a daily basis, we used elements of gamification.

Sublingual immunotherapy adherence in patients with allergic rhinitis: Effects of an intervention based on the information-motivation-behavioral skills model

Wang Q, Zhu R, Cao Y, Ning Y, Feng Y, Feng Y, Han S. S. Heliyon. 2023 Nov 28;9(12):e22929. doi: 10.1016/j.heliyon.2023.e22929.

Abstract

Objective

This study aimed to confirm the efficacy of an intervention based on the information-motivation-behavior skills (IMB) model in improving the sublingual immunotherapy adherence score, medication beliefs score, self-efficacy score, and medication knowledge score of patients with allergic rhinitis.

Methods

A total of 120 patients with allergic rhinitis from an otorhinolaryngology clinic were divided into the control group (n = 60) and experimental group (n = 60); the study was conducted from August 2021 to March 2022. The control group received routine intervention, whereas the experimental group received intervention based on the IMB model.