Clinical and Translational Allergy最新文献

Background

A double-blind, randomized Phase 3 study (NCT04426890) confirmed that CT-P39 and European Union-approved reference omalizumab (ref-OMA) were comparable in terms of efficacy, quality of life (QoL), pharmacokinetics (PK), pharmacodynamics (PD), safety, and immunogenicity up to week 24. Here, we report results from the 16-week follow-up period.

Methods

The study included two 12-week treatment periods (TPs) and a 16-week off-treatment follow-up period. In TP1, 619 patients with chronic spontaneous urticaria (CSU) were randomized to CT-P39 300 mg, ref-OMA 300 mg, CT-P39 150 mg, or ref-OMA 150 mg. A total of 579 patients continued into TP2, in which patients treated with ref-OMA 300 mg were rerandomized to CT-P39 300 mg or to continue on ref-OMA 300 mg; patients initially randomized to CT-P39 300 mg continued this regimen; and patients initially randomized to CT-P39 or ref-OMA 150 mg increased their dose to 300 mg. Efficacy, PK, PD, QoL, safety, and immunogenicity were assessed during the follow-up period.

Results

Improvements in efficacy outcomes observed in the TPs gradually decreased during the follow-up period, but did not return to baseline values. Omalizumab serum concentrations that had increased during treatment subsequently decreased during the follow-up period. After completing treatment at week 24, total and free immunoglobulin E levels returned toward baseline levels. No clinically meaningful differences in QoL, safety, or immunogenicity outcomes were observed across the treatment groups.

Conclusion

Follow-up results support the biosimilarity of CT-P39 and ref-OMA in terms of efficacy, PK, PD, QoL, safety, and immunogenicity in patients with CSU.

Background

In current clinical practice, primary diffuse chronic rhinosinusitis with nasal polyps (CRSwNP) is classified into two endotypes: type 2 and non-type 2. Previous studies on sinonasal health-related quality of life (HRQoL) in CRS have primarily focused on differences between phenotypes. This study aimed to compare HRQoL between the two endotypes in patients with CRSwNP.

The type 2 endotype had a higher median nasal polyp score (NPS) than non-types (4 and 2, respectively), but this difference did not reach significance. Loss of smell was associated with NPS, and facial pain/pressure was inversely correlated with age. Age was significantly associated with loss of smell, but only in non-type 2 CRSwNP.

Methods

This was a prospective, monocentric study conducted between 2018 and 2023 on CRSwNP patients referred for surgery. Health-related quality of life was assessed using the German standardized SNOT-20 questionnaire. Type 2 was defined according to the updated EPOS/EUFOREA 2023 criteria.

Results

A total of 122 patients with CRSwNP were included, 113 (92.6%) of whom were classified as type 2. Type 2 was associated with a significantly worse SNOT-20 German Adapted Version score. Two of the four cardinal symptoms of CRS—loss of smell and rhinorrhea—were significantly more severe and prevalent in the type 2 endotype, with loss of smell being very specific. The most prevalent symptom in both endotypes was nasal obstruction, with no difference between both endotypes.

The type 2 endotype had a higher median nasal polyp score (NPS) than non-types (4 and 2, respectively), but this difference did not reach significance. Loss of smell was associated with NPS, and facial pain/pressure was inversely correlated with age. Age was significantly associated with loss of smell, but only in non-type 2 CRSwNP.

Conclusion

Type 2 CRSwNP has a more severe impact on HRQoL compared with non-type 2 CRSwNP. Hyposmia, rhinorrhea, and potentially NPS may offer endotypic and pathophysiological insights.

Introduction

There are limited data on the relationship between eosinophilic esophagitis (EoE) and asthma. We aimed to assess the risk of asthma in EoE patients compared with matched controls and siblings.

Methods

Through the ESPRESSO study, a Swedish nationwide population-based histopathology cohort, we identified EoE patients diagnosed between 1989 and 2017 (n = 1146) and up to 5 age- and sex-matched controls (n = 5022). Cox regression generated hazard ratios (HRs) for developing asthma. We compared EoE patients with sibling controls.

Results

The median age at EoE diagnosis was 42 years. During a median follow-up of 3.8 years, 140 EoE patients (28.1/1000 person-years) and 174 controls (7.2/1000 person-years) developed asthma (HR = 3.96; 95% confidence interval [CI] = 3.16–4.96, p < 0.001). An increased risk of asthma was seen in the first 10 years after EoE diagnosis but not thereafter. EoE patients diagnosed in childhood or young adulthood were at a particularly high risk of asthma (HR = 4.74; 95% CI = 2.93–7.67, p < 0.001 and HR = 5.84; 95% CI = 3.68–9.29, p < 0.001, respectively). Compared with their non-EoE siblings, EoE patients were at a 5-fold increased risk of asthma (HR = 4.97; 95% CI = 3.13–7.92, p < 0.001).

Conclusion

EoE patients are at an increased risk of asthma compared with the general population, which is unlikely to be entirely explained through unmeasured intrafamilial factors given that the positive association remained in sibling analyses. Physicians caring for EoE should have a high awareness of concomitant asthma.

Background

Atopic dermatitis is a common chronic skin disease in children. Whether telomere length is associated with atopic dermatitis remains unclear. This population-based case-control study aimed to investigate the association between telomere length and atopic dermatitis in school-age children.

Methods

In this cross-sectional analysis, we included 1084 singleton term-born children (608 males; mean age 6.4 years) from the Longitudinal Investigation of Global Health in Taiwanese Schoolchildren cohort. Telomere length was measured using quantitative real-time polymerase chain reaction, log-transformed and was analyzed in quartiles. The main outcome was atopic dermatitis defined as having physician-diagnosed atopic dermatitis and the presence of atopic dermatitis in the last 12 months. Regression analyses were used to assess the relationship between telomere length and atopic dermatitis.

Results

Telomere length was significantly inversely associated with childhood atopic dermatitis after adjusting for child's age, sex, overweight or obesity, birth season, childhood allergic diseases, environmental tobacco smoke, parental history of allergic diseases, parental educational level, and breastfeeding status (p__trend = 0.01). Specifically, when telomere length was classified into quartiles, children in the shortest (fourth) telomere length quartile had a 1.88-fold higher probability of atopic dermatitis compared to those in the longest (first) quartile (95% confidence interval: 1.13–3.14). Stratified analyses showed that the associations were stronger in males and non-breastfed children, with no significant associations observed in females or breastfed children.

Conclusion

This study provides new evidence suggesting an association between shorter telomere length and atopic dermatitis in school-age children.

Background

Sensitisation to Lipid Transfer Proteins (LTP), usually ascertained by undertaking a test to the peach LTP allergen Pru p 3, is common but does not always indicate LTP allergy. Improving the diagnostic process would ensure the correct diagnosis and management of this complex condition.

Objectives

To determine the diagnostic value of Pru p 3 and other LTP component allergens in UK adults.

Methods

A retrospective review was undertaken of adults referred to the Allergy Unit at the Royal Brompton & Harefield Hospitals (RBHT) London (UK), between 2012 and 2022 who were sensitised to Pru p 3. Those with a final diagnosis of LTP allergy were compared to those sensitized to Pru p 3 but not diagnosed with LTP allergy.

Results

Of 285 patients with a positive Pru p 3, 157 (55%) were diagnosed with LTP allergy. LTP allergic patients were more likely to have a higher level of Pru p 3, and a lower level of total IgE. The ratio of Pru p 3:total IgE was the most accurate diagnostic marker of LTP allergy, with a receiver operating characteristics AUC of 0.880. A diagnosis of LTP allergy was also significantly associated with sensitisation to the LTP in peanut (Ara h 9, p < 0.001), and hazelnut (Cor a 8, p < 0.001).

Conclusion

Sensitisation to Pru p 3 may not always indicate an LTP allergy. Our data suggests that the Pru p 3:total IgE ratio, and sensitisation to Ara h 9 and Cor a 8 can support the diagnosis of LTP allergy in individuals sensitised to Pru p 3.

Background

Patients with severe asthma experience decreased quality of life due to fixed airway obstruction, hospitalisations and potential fatalities. However, to date, the requalification of severe asthma patients eligible for biological therapy in daily clinical practice remains unstudied.

Objective

The aim of the study was to prepare a universal decision-making algorithm for requalifying patients for biological therapy based on available clinical data obtained from a leading reference centre in Poland.

Methods

All severe asthma patients treated with biologics since 2013 at the Internal Medicine, Asthma and Allergy Department (Medical University of Lodz, Poland), were analysed. The analysis included demographic (age, sex), pre-treatment (reported at qualification: oral glucocorticosteroids use, total IgE serum level, peripheral blood eosinophilia, co-morbidities: atopic dermatitis, chronic allergic rhinitis or sinusitis) and treatment-related data (treatment time, current treatment status, reason for early termination of therapy, year of discontinuation, rediagnostics, requalification).

Results

Rediagnostics were performed in only 4.76% of all requalifications. The following additional data were used to requalify patients: blood eosinophilia (n = 63; 100.00% of requalifications), atopic comorbidities (n = 30; 47.62%) and total IgE serum level (n = 8; 12.70%). Kaplan–Meier curve analysis of all source data revealed the longevity of maintenance as follows: the highest for mepolizumab, then omalizumab, benralizumab, dupilumab and tezepelumab (p = 0.016). Based on the results, requalification model ‘ReQuaBi’, was constructed.

Conclusion

The most important criteria for selecting a biological agent in requalification are peripheral blood eosinophilia, followed by comorbidities and IgE levels. In most cases, extensive additional re-diagnosis may not be necessary.

Background

Targeting the interleukin-4 receptor alpha (IL-4Rα) subunit has proven clinical efficacy in atopic dermatitis (AD).

Objective

This study assessed the peripheral phenotype and function of T-cells, but also levels of total and sIgE and its receptors in AD patients receiving dupilumab.

Methods

AD patients were clinically assessed (n = 75) and peripheral blood samples were taken (n = 25). Multiparametric flow cytometry was performed to characterize T-cell subsets (before treatment and 6 months later). Total and specific IgE were measured by ImmunoCap, soluble CD23 and FcεR1 in serum by ELISA, and eosinophils by differential blood analysis.

Results

SCORing Atopic Dermatitis scores and body surface area involvement decreased upon treatment after 6 months of treatment to 67% and 77% from baseline. At the T cell level, we observed a 0.55-fold reduction of Th2-cells and a mean 27% increase in regulatory T-cells from baseline, accompanied by shifts towards Th1 and Th17 phenotypes. Furthermore, circulating CD4⁺CXCR5⁺TFH17 and CD4⁺CXCR5⁺TFH17.1 positive cells (mean 40% and 42%) and T-cell-specific IL-2 (+0.96-fold) and IL-10 (+1.96-fold) secretion increased, whereas IL-4 (mean −55%) and IL-17A (mean −27%) were reduced. Eosinophil counts (mean −22%), total IgE (mean −47%) and House Dust Mite sIgE (mean −40%) decreased, whereas CD23 and FcεR1 remained unchanged.

Conclusions

The T-cell and cytokine profiles during anti-IL4-Ra treatment suggest that targeting this pathway promotes a systemic shift of the T-cell compartment by reducing the T helper type 2 and complementary IgE responses. The sustainability of these disease-modifying effects requires further investigation.

Background

Angioedema (AE) rarely occurs as a potentially life-threatening adverse drug reaction (ADR) to angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB). The aim of the present study was to investigate non-genetic association factors with ACEi-/ARB-induced angioedema in the European ADR database EudraVigilance and the database of the vARIANCE study.

Methods

The cohort of the vARIANCE study comprised 114 patients who suffered from ACEi- or ARB-induced angioedema. In addition, 171 angioedema reports and 4650 reports on other ADRs of ACEi/ARB were identified in the ADR database EudraVigilance with the latter serving as a reference group. Odds ratios were calculated and a logistic regression analysis was performed using angioedema versus reference reports.

Results

Increased age, smoking, allergies and a history of previous angioedema were identified as associated factors for ACEi-/ARB-induced angioedema. In most patients, the swelling affected the face, lips and tongue. In the vARIANCE study, about 70% of angioedema occurred after 1 year of treatment. For one in two patients in the vARIANCE study (84.2% with ACEi treatment) and one in three patients from the EudraVigilance reports (59.6% with ARB treatment), the angioedema resulted in hospitalization.

Conclusions

We found small to moderate associations with certain individual patient-related factors in this pharmaco-epidemiological study. As a future perspective, combining non-genetic association factors with corresponding genetic data might provide an option to compose stronger and individual risk scores.