Proof-of-concept study of anti-Fel d 1 IgY antibodies in cat food using the MASK-air® app.

BACKGROUND: An innovation to better manage cat-allergic patients utilises anti-Fel d 1 IgY antibodies to neutralise Fel d 1 after its production by the cat. However, there is no published study showing its clinical efficacy in humans in a home setting. A longitudinal, open-label, proof-of-concept study was carried out to approach clinical efficacy of the cat food in cat-allergic patients. METHODS: After a baseline evaluation, the cats ate only the cat food for the following 4 months. Daily evaluation of efficacy was performed for 2 weeks at baseline and after 1, 2 and 3 months of intervention for periods of 2 weeks. The MASK-air app was used daily to assess symptoms, work productivity and medications. RESULTS: Of the 49 patients screened, 42 were followed up and 33 (78.5%) reported MASK-air data at all 3 evaluation periods. The primary end point (visual analogue scale [VAS] for global allergy symptoms) was significantly improved (p < 0.0001). All symptoms (VAS nose, eye, and asthma), VAS work and the combined symptom-medication score significantly improved after 1 month. The percentage of uncontrolled days (VAS>20/100) decreased from 64% at baseline to 35% at 1 month (p < 0.0001) and 14% at 3 months. A sensitivity analysis in patients with uncontrolled disease at baseline found similar results. DISCUSSION: A cat diet containing anti-Fel d 1 antibodies was able to (i) show decreased allergic symptoms and related outcomes, (ii) inform the design and feasibility of future studies with a control arm and (iii) estimate the sample size of the study. STUDY REGISTRATION NUMBER: clinicaltrials.gov: NCT05656482.

Asthma and rhinitis control in adolescents and young adults: A real-world MASK-air study.

BACKGROUND: In allergic rhinitis and asthma, adolescents and young adult patients are likely to differ from older patients. We compared adolescents, young adults and adults on symptoms, control levels, and medication adherence. METHODS: In a cross-sectional study (2015-2022), we assessed European users of the MASK-air mHealth app of three age groups: adolescents (13-18 years), young adults (18-26 years), and adults (>26 years). We compared them on their reported rhinitis and asthma symptoms, use and adherence to rhinitis and asthma treatment and app adherence. Allergy symptoms and control were assessed by means of visual analogue scales (VASs) on rhinitis or asthma, the combined symptom-medication score (CSMS), and the electronic daily control score for asthma (e-DASTHMA). We built multivariable regression models to compare symptoms or medication accounting for potential differences in demographic characteristics and baseline severity. RESULTS: We assessed 965 adolescent users (15,252 days), 4595 young adults (58,161 days), and 15,154 adult users (258,796 days). Users of all three age groups displayed similar app adherence. In multivariable models, age groups were not found to significantly differ in their adherence to rhinitis or asthma medication. These models also found that adolescents reported lower VAS on global allergy, ocular, and asthma symptoms (as well as lower CSMS) than young adults and adults. CONCLUSIONS: Adolescents reported a better rhinitis and asthma control than young adults and adults, even though similar medication adherence levels were observed across age groups. These results pave the way for future studies on understanding how adolescents control their allergic diseases.

Impairment of EQ-5D-5L Domains According to Allergic Rhinitis and Asthma Control: A MASK-air Real-World Study.

BACKGROUND: EQ-5D-5L (EuroQOL, 5 Domains, 5 Levels) is a widely used health-related quality-of-life instrument, comprising 5 domains. However, it is not known how each domain is impacted by rhinitis or asthma control. OBJECTIVE: To assess the association between rhinitis or asthma control and the different EQ-5D-5L domains using data from the MASK-air mHealth app. METHODS: In this cross-sectional study, we assessed data from all MASK-air users (2015-2021; 24 countries). For the levels of each EQ-5D-5L domain, we assessed rhinitis and asthma visual analog scales (VASs) and the combined symptom-medication score (CSMS). We built ordinal multivariable models assessing the adjusted association between VAS/CSMS values and the levels of each EQ-5D-5L domain. Finally, we compared EQ-5D-5L data from users with rhinitis and self-reported asthma with data from users with rhinitis alone. RESULTS: We assessed 5354 days from 3092 users. We observed an association between worse control of rhinitis or asthma (higher VASs and CSMS) and worse EQ-5D-5L levels. In multivariable models, all VASs and the CSMS were associated with higher levels of pain/discomfort and daily activities. For anxiety/depression, the association was mostly observed for rhinitis-related tools (VAS nose, VAS global, and CSMS), although the presence of self-reported asthma was also associated with worse anxiety/depression. Worse mobility ("walking around") was particularly associated with VAS asthma and with the presence of asthma. CONCLUSIONS: A worse rhinitis control and a worse asthma control are associated with higher EQ-5D-5L levels, particularly regarding pain/discomfort and activity impairment. Worse rhinitis control is associated with worse anxiety/depression, and poor asthma control with worse mobility.

Development and validation of an electronic daily control score for asthma (e-DASTHMA): a real-world direct patient data study.

BACKGROUND: Validated questionnaires are used to assess asthma control over the past 1-4 weeks from reporting. However, they do not adequately capture asthma control in patients with fluctuating symptoms. Using the Mobile Airways Sentinel Network for airway diseases (MASK-air) app, we developed and validated an electronic daily asthma control score (e-DASTHMA). METHODS: We used MASK-air data (freely available to users in 27 countries) to develop and assess different daily control scores for asthma. Data-driven control scores were developed based on asthma symptoms reported by a visual analogue scale (VAS) and self-reported asthma medication use. We included the daily monitoring data from all MASK-air users aged 16-90 years (or older than 13 years to 90 years in countries with a lower age of digital consent) who had used the app in at least 3 different calendar months and had reported at least 1 day of asthma medication use. For each score, we assessed construct validity, test-retest reliability, responsiveness, and accuracy. We used VASs on dyspnoea and work disturbance, EQ-5D-VAS, Control of Allergic Rhinitis and Asthma Test (CARAT), CARAT asthma, and Work Productivity and Activity Impairment: Allergy Specific (WPAI:AS) questionnaires as comparators. We performed an internal validation using MASK-air data from Jan 1 to Oct 12, 2022, and an external validation using a cohort of patients with physician-diagnosed asthma (the INSPIRERS cohort) who had had their diagnosis and control (Global Initiative for Asthma [GINA] classification) of asthma ascertained by a physician. FINDINGS: We studied 135 635 days of MASK-air data from 1662 users from May 21, 2015, to Dec 31, 2021. The scores were strongly correlated with VAS dyspnoea (Spearman correlation coefficient range 0·68-0·82) and moderately correlated with work comparators and quality-of-life-related comparators (for WPAI:AS work, we observed Spearman correlation coefficients of 0·59-0·68). They also displayed high test-retest reliability (intraclass correlation coefficients range 0·79-0·95) and moderate-to-high responsiveness (correlation coefficient range 0·69-0·79; effect size measures range 0·57-0·99 in the comparison with VAS dyspnoea). The best-performing score displayed a strong correlation with the effect of asthma on work and school activities in the INSPIRERS cohort (Spearman correlation coefficients 0·70; 95% CI 0·61-0·78) and good accuracy for the identification of patients with uncontrolled or partly controlled asthma according to GINA (area under the receiver operating curve 0·73; 95% CI 0·68-0·78). INTERPRETATION: e-DASTHMA is a good tool for the daily assessment of asthma control. This tool can be used as an endpoint in clinical trials as well as in clinical practice to assess fluctuations in asthma control and guide treatment optimisation. FUNDING: None.

Tocilizumab-treated convalescent COVID-19 patients retain the cross-neutralization potential against SARS-CoV-2 variants.

Although tocilizumab treatment in severe and critical coronavirus disease 2019 (COVID-19) patients has proven its efficacy at the clinical level, there is little evidence supporting the effect of short-term use of interleukin-6 receptor blocking therapy on the B cell sub-populations and the cross-neutralization of SARS-CoV-2 variants in convalescent COVID-19 patients. We performed immunological profiling of 69 tocilizumab-treated and non-treated convalescent COVID-19 patients in total. We observed that SARS-CoV-2-specific IgG1 titers depended on disease severity but not on tocilizumab treatment. The plasma of both treated and non-treated patients infected with the ancestral variant exhibit strong neutralizing activity against the ancestral virus and the Alpha, Beta, and Delta variants of SARS-CoV-2, whereas the Gamma and Omicron viruses were less sensitive to seroneutralization. Overall, we observed that, despite the clinical benefits of short-term tocilizumab therapy in modifying the cytokine storm associated with COVID-19 infections, there were no modifications in the robustness of B cell and IgG responses to Spike antigens.

Digitally-enabled, patient-centred care in rhinitis and asthma multimorbidity: The ARIA-MASK-air® approach.

MASK-air® , a validated mHealth app (Medical Device regulation Class IIa) has enabled large observational implementation studies in over 58,000 people with allergic rhinitis and/or asthma. It can help to address unmet patient needs in rhinitis and asthma care. MASK-air® is a Good Practice of DG Santé on digitally-enabled, patient-centred care. It is also a candidate Good Practice of OECD (Organisation for Economic Co-operation and Development). MASK-air® data has enabled novel phenotype discovery and characterisation, as well as novel insights into the management of allergic rhinitis. MASK-air® data show that most rhinitis patients (i) are not adherent and do not follow guidelines, (ii) use as-needed treatment, (iii) do not take medication when they are well, (iv) increase their treatment based on symptoms and (v) do not use the recommended treatment. The data also show that control (symptoms, work productivity, educational performance) is not always improved by medications. A combined symptom-medication score (ARIA-EAACI-CSMS) has been validated for clinical practice and trials. The implications of the novel MASK-air® results should lead to change management in rhinitis and asthma.

Cutoff Values of MASK-air Patient-Reported Outcome Measures.

BACKGROUND: In clinical and epidemiological studies, cutoffs of patient-reported outcome measures can be used to classify patients into groups of statistical and clinical relevance. However, visual analog scale (VAS) cutoffs in MASK-air have not been tested. OBJECTIVE: To calculate cutoffs for VAS global, nasal, ocular, and asthma symptoms. METHODS: In a cross-sectional study design of all MASK-air participants, we compared (1) approaches based on the percentiles (tertiles or quartiles) of VAS distributions and (2) data-driven approaches based on clusters of data from 2 comparators (VAS work and VAS sleep). We then performed sensitivity analyses for individual countries and for VAS levels corresponding to full allergy control. Finally, we tested the different approaches using MASK-air real-world cross-sectional and longitudinal data to assess the most relevant cutoffs. RESULTS: We assessed 395,223 days from 23,201 MASK-air users with self-reported allergic rhinitis. The percentile-oriented approach resulted in lower cutoff values than the data-driven approach. We obtained consistent results in the data-driven approach. Following the latter, the proposed cutoff differentiating "controlled" and "partly-controlled" patients was similar to the cutoff value that had been arbitrarily used (20/100). However, a lower cutoff was obtained to differentiate between "partly-controlled" and "uncontrolled" patients (35 vs the arbitrarily-used value of 50/100). CONCLUSIONS: Using a data-driven approach, we were able to define cutoff values for MASK-air VASs on allergy and asthma symptoms. This may allow for a better classification of patients with rhinitis and asthma according to different levels of control, supporting improved disease management.

The Allergic Rhinitis and Its Impact on Asthma (ARIA) Approach of Value-Added Medicines: As-Needed Treatment in Allergic Rhinitis.

Drug repurposing is a major field of value-added medicine. It involves investigating and evaluating existing drugs for new therapeutic purposes that address unmet healthcare needs. Several unmet needs in allergic rhinitis could be improved by drug repurposing. This could be game-changing for disease management. Current medications for allergic rhinitis are centered on continuous long-term treatment, and medication registration is based on randomized controlled trials carried out for a minimum of 14 days with adherence of 70% or greater. A new way of treating allergic rhinitis is to propose as-needed treatment depending on symptoms, rather than classical continuous treatment. This rostrum will discuss existing clinical trials on as-needed treatment for allergic rhinitis and real-world data obtained by the mobile health app MASK-air, which focuses on digitally-enabled, patient-centered care pathways.

Academic Productivity of Young People With Allergic Rhinitis: A MASK-air Study.

BACKGROUND: Several studies have suggested an impact of allergic rhinitis on academic productivity. However, large studies with real-world data (RWD) are not available. OBJECTIVE: To use RWD to assess the impact of allergic rhinitis on academic performance (measured through a visual analog scale [VAS] education and the Work Productivity and Activity Impairment Questionnaire plus Classroom Impairment Questions: Allergy Specific [WPAI+CIQ:AS] questionnaire), and to identify factors associated with the impact of allergic rhinitis on academic performance. METHODS: We assessed data from the MASK-air mHealth app of users aged 13 to 29 years with allergic rhinitis. We assessed the correlation between variables measuring the impact of allergies on academic performance (VAS education, WPAI+CIQ:AS impact of allergy symptoms on academic performance, and WPAI+CIQ:AS percentage of education hours lost due to allergies) and other variables. In addition, we identified factors associated with the impact of allergic symptoms on academic productivity through multivariable mixed models. RESULTS: A total of 13,454 days (from 1970 patients) were studied. VAS education was strongly correlated with the WPAI+CIQ:AS impact of allergy symptoms on academic productivity (Spearman correlation coefficient = 0.71 [95% confidence interval (CI) = 0.58; 0.80]), VAS global allergy symptoms (0.70 [95% CI = 0.68; 0.71]), and VAS nose (0.66 [95% CI = 0.65; 0.68]). In multivariable regression models, immunotherapy showed a strong negative association with VAS education (regression coefficient = -2.32 [95% CI = -4.04; -0.59]). Poor rhinitis control, measured by the combined symptom-medication score, was associated with worse VAS education (regression coefficient = 0.88 [95% CI = 0.88; 0.92]), higher impact on academic productivity (regression coefficient = 0.69 [95% CI = 0.49; 0.90]), and higher percentage of missed education hours due to allergy (regression coefficient = 0.44 [95% CI = 0.25; 0.63]). CONCLUSION: Allergy symptoms and worse rhinitis control are associated with worse academic productivity, whereas immunotherapy is associated with higher productivity.

Allergen immunotherapy in MASK-air users in real-life: Results of a Bayesian mixed-effects model.

BACKGROUND: Evidence regarding the effectiveness of allergen immunotherapy (AIT) on allergic rhinitis has been provided mostly by randomised controlled trials, with little data from real-life studies. OBJECTIVE: To compare the reported control of allergic rhinitis symptoms in three groups of users of the MASK-air® app: those receiving sublingual AIT (SLIT), those receiving subcutaneous AIT (SCIT), and those receiving no AIT. METHODS: We assessed the MASK-air® data of European users with self-reported grass pollen allergy, comparing the data reported by patients receiving SLIT, SCIT and no AIT. Outcome variables included the daily impact of allergy symptoms globally and on work (measured by visual analogue scales-VASs), and a combined symptom-medication score (CSMS). We applied Bayesian mixed-effects models, with clustering by patient, country and pollen season. RESULTS: We analysed a total of 42,756 days from 1,093 grass allergy patients, including 18,479 days of users under AIT. Compared to no AIT, SCIT was associated with similar VAS levels and CSMS. Compared to no AIT, SLIT-tablet was associated with lower values of VAS global allergy symptoms (average difference = 7.5 units out of 100; 95% credible interval [95%CrI] = -12.1;-2.8), lower VAS Work (average difference = 5.0; 95%CrI = -8.5;-1.5), and a lower CSMS (average difference = 3.7; 95%CrI = -9.3;2.2). When compared to SCIT, SLIT-tablet was associated with lower VAS global allergy symptoms (average difference = 10.2; 95%CrI = -17.2;-2.8), lower VAS Work (average difference = 7.8; 95%CrI = -15.1;0.2), and a lower CSMS (average difference = 9.3; 95%CrI = -18.5;0.2). CONCLUSION: In patients with grass pollen allergy, SLIT-tablet, when compared to no AIT and to SCIT, is associated with lower reported symptom severity. Future longitudinal studies following internationally-harmonised standards for performing and reporting real-world data in AIT are needed to better understand its 'real-world' effectiveness.

Behavioural patterns in allergic rhinitis medication in Europe: A study using MASK-air® real-world data.

BACKGROUND: Co-medication is common among patients with allergic rhinitis (AR), but its dimension and patterns are unknown. This is particularly relevant since AR is understood differently across European countries, as reflected by rhinitis-related search patterns in Google Trends. This study aims to assess AR co-medication and its regional patterns in Europe, using real-world data. METHODS: We analysed 2015-2020 MASK-air® European data. We compared days under no medication, monotherapy and co-medication using the visual analogue scale (VAS) levels for overall allergic symptoms ('VAS Global Symptoms') and impact of AR on work. We assessed the monthly use of different medication schemes, performing separate analyses by region (defined geographically or by Google Trends patterns). We estimated the average number of different drugs reported per patient within 1 year. RESULTS: We analysed 222,024 days (13,122 users), including 63,887 days (28.8%) under monotherapy and 38,315 (17.3%) under co-medication. The median 'VAS Global Symptoms' was 7 for no medication days, 14 for monotherapy and 21 for co-medication (p < .001). Medication use peaked during the spring, with similar patterns across different European regions (defined geographically or by Google Trends). Oral H1 -antihistamines were the most common medication in single and co-medication. Each patient reported using an annual average of 2.7 drugs, with 80% reporting two or more. CONCLUSIONS: Allergic rhinitis medication patterns are similar across European regions. One third of treatment days involved co-medication. These findings suggest that patients treat themselves according to their symptoms (irrespective of how they understand AR) and that co-medication use is driven by symptom severity.

Development and validation of combined symptom-medication scores for allergic rhinitis.

BACKGROUND: Validated combined symptom-medication scores (CSMSs) are needed to investigate the effects of allergic rhinitis treatments. This study aimed to use real-life data from the MASK-air® app to generate and validate hypothesis- and data-driven CSMSs. METHODS: We used MASK-air® data to assess the concurrent validity, test-retest reliability and responsiveness of one hypothesis-driven CSMS (modified CSMS: mCSMS), one mixed hypothesis- and data-driven score (mixed score), and several data-driven CSMSs. The latter were generated with MASK-air® data following cluster analysis and regression models or factor analysis. These CSMSs were compared with scales measuring (i) the impact of rhinitis on work productivity (visual analogue scale [VAS] of work of MASK-air® , and Work Productivity and Activity Impairment: Allergy Specific [WPAI-AS]), (ii) quality-of-life (EQ-5D VAS) and (iii) control of allergic diseases (Control of Allergic Rhinitis and Asthma Test [CARAT]). RESULTS: We assessed 317,176 days of MASK-air® use from 17,780 users aged 16-90 years, in 25 countries. The mCSMS and the factor analyses-based CSMSs displayed poorer validity and responsiveness compared to the remaining CSMSs. The latter displayed moderate-to-strong correlations with the tested comparators, high test-retest reliability and moderate-to-large responsiveness. Among data-driven CSMSs, a better performance was observed for cluster analyses-based CSMSs. High accuracy (capacity of discriminating different levels of rhinitis control) was observed for the latter (AUC-ROC = 0.904) and for the mixed CSMS (AUC-ROC = 0.820). CONCLUSION: The mixed CSMS and the cluster-based CSMSs presented medium-high validity, reliability and accuracy, rendering them as candidates for primary endpoints in future rhinitis trials.

Allergy Prevalence in France and Skin Impact - Epidemiological Survey of a Representative Sample of French Adults.

BACKGROUND: Increased allergy frequency may have a significant impact on the skin, one of the largest targeted organs for allergic and immunological responses. METHODS: An online survey of 2036 adults as a representative sample of the French general population was conducted to evaluate the prevalence of self-reported allergies, the populations who report allergies and the skin conditions related to allergies. RESULTS: In general, 20.2% of French adults (average age 45 ± 15.8 years) reported allergies. These allergies were respiratory allergies (55.3%), skin allergies (48.8%) and food allergies (27.9%), and 78.9% indicated that their reported allergies were diagnosed by a doctor. In addition, 53.2% of individuals reporting an allergy also indicated that they experienced associated skin reactions. In comparison to those who did not report an allergy, these individuals were 1.5 to 4 times more likely to have a skin disease and 3 times more likely to have sensitive skin or skin reactions when using skincare products. CONCLUSION: It is estimated that over 10 million French adults have allergies. These data will help increase awareness among the allergic population and healthcare professionals about the burden associated with allergies and the need for management to reduce their health impact.

Heterogeneity of the pharmacologic treatment of allergic rhinitis in Europe based on MIDAS and OTCims platforms.

BACKGROUND: The practice of allergology varies widely between countries, and the costs and sales for the treatment of rhinitis differ depending on practices and health systems. To understand these differences and their implications, the rhinitis market was studied in some of the EU countries. METHODS: We conducted a pharmaco-epidemiological database analysis to assess the medications that were being prescribed for allergic rhinitis in the years 2016, 2017 and 2018. We used the IQVIA platforms for prescribed medicines (MIDAS®- Meaningful Integration of Data, Analytics and Services) and for OTC medicines (OTC International Market Tracking-OTCims). We selected the five most important markets in the EU (France, Germany, Italy, Poland and Spain). RESULTS: Intranasal decongestants were excluded from the analyses because they are rarely prescribed for allergic rhinitis. For both Standard Units (SU) and costs, France is leading the other countries. In terms of SU, the four other countries are similar. For costs, Poland is lower than the three others. However, medication use differs largely. For 2018, in SU, intranasal corticosteroid is the first treatment in Poland (70.0%), France (51.3%), Spain (51.1%) and Germany (50.3%), whereas the Italian market is dominated by systemic antihistamines (41.4%) followed by intranasal corticosteroids (30.1%). Results of other years were similar. DISCUSSION: There are major differences between countries in terms of rhinoconjunctivitis medication usage.

ARIA digital anamorphosis: Digital transformation of health and care in airway diseases from research to practice.

Digital anamorphosis is used to define a distorted image of health and care that may be viewed correctly using digital tools and strategies. MASK digital anamorphosis represents the process used by MASK to develop the digital transformation of health and care in rhinitis. It strengthens the ARIA change management strategy in the prevention and management of airway disease. The MASK strategy is based on validated digital tools. Using the MASK digital tool and the CARAT online enhanced clinical framework, solutions for practical steps of digital enhancement of care are proposed.

Correlation between work impairment, scores of rhinitis severity and asthma using the MASK-air® App.

BACKGROUND: In allergic rhinitis, a relevant outcome providing information on the effectiveness of interventions is needed. In MASK-air (Mobile Airways Sentinel Network), a visual analogue scale (VAS) for work is used as a relevant outcome. This study aimed to assess the performance of the work VAS work by comparing VAS work with other VAS measurements and symptom-medication scores obtained concurrently. METHODS: All consecutive MASK-air users in 23 countries from 1 June 2016 to 31 October 2018 were included (14 189 users; 205 904 days). Geolocalized users self-assessed daily symptom control using the touchscreen functionality on their smart phone to click on VAS scores (ranging from 0 to 100) for overall symptoms (global), nose, eyes, asthma and work. Two symptom-medication scores were used: the modified EAACI CSMS score and the MASK control score for rhinitis. To assess data quality, the intra-individual response variability (IRV) index was calculated. RESULTS: A strong correlation was observed between VAS work and other VAS. The highest levels for correlation with VAS work and variance explained in VAS work were found with VAS global, followed by VAS nose, eye and asthma. In comparison with VAS global, the mCSMS and MASK control score showed a lower correlation with VAS work. Results are unlikely to be explained by a low quality of data arising from repeated VAS measures. CONCLUSIONS: VAS work correlates with other outcomes (VAS global, nose, eye and asthma) but less well with a symptom-medication score. VAS work should be considered as a potentially useful AR outcome in intervention studies.

Next-generation Allergic Rhinitis and Its Impact on Asthma (ARIA) guidelines for allergic rhinitis based on Grading of Recommendations Assessment, Development and Evaluation (GRADE) and real-world evidence

The selection of pharmacotherapy for patients with allergic rhinitis aims to control the disease and depends on many factors. Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines have considerably improved the treatment of allergic rhinitis. However, there is an increasing trend toward use of real-world evidence to inform clinical practice, especially because randomized controlled trials are often limited with regard to the applicability of results. The Contre les Maladies Chroniques pour un Vieillissement Actif (MACVIA) algorithm has proposed an allergic rhinitis treatment by a consensus group. This simple algorithm can be used to step up or step down allergic rhinitis treatment. Next-generation guidelines for the pharmacologic treatment of allergic rhinitis were developed by using existing GRADE-based guidelines for the disease, real-world evidence provided by mobile technology, and additive studies (allergen chamber studies) to refine the MACVIA algorithm.