ABSTRACT
Background
Named‐patient product sublingual immunotherapy (NPP‐SLIT) is widely used in France, yet real‐world evidence on patient‐perceived benefit remains limited.
Objective
To assess treatment expectations and patient‐perceived benefit over 12–15 months among recent NPP‐SLIT initiators using the Patient Benefit Index (PBI) and validated patient‐reported outcome measures (PROMs).
Methods
ERAPP is a prospective, multicenter, observational study in children and adults with IgE‐mediated respiratory allergy. Initiators (≤ 6 months on NPP‐SLIT at baseline) completed digital PROMs at baseline, Month 6, and Month 12–15. The primary endpoint was the proportion with PBI ≥ 1 at Months 12–15. Secondary endpoints were changes in PROMs; exploratory analyses examined higher PBI thresholds and item‐level fulfillment.
Results
Of 9439 enrolled, 4794 were initiators (950 children; 3844 adolescents/adults). At Month 12–15, PBI ≥ 1 was achieved by 83.8% of children and 84.0% of adolescents/adults. Symptom burden (T5SS) and rhinitis severity (ARIA) improved beyond published MIDs. Asthma control (ACT) improved, whereas changes in rhinitis control (ARCT, ≥ 12 years) and daytime sleepiness (ESS, adults) were below their respective MIDs. Treatment satisfaction (ESPIA‐Q11) increased, while adherence (GIRERD) decreased from baseline to follow‐up. Nearly half reached PBI ≥ 2 and about one‐fifth PBI ≥ 3. Item‐level analyses showed highest fulfillment for nasal obstruction relief, improved sleep, and overall symptom relief; fatigue, mood, and social aspects were less frequently fulfilled. Children generally reported slightly higher fulfillment than adolescents/adults.
Conclusion
NPP‐SLIT provides sustained, clinically meaningful benefit from the patient's perspective in both age groups. ERAPP supports the PBI as a complementary endpoint that links patient expectations to outcomes and informs patient‐centered allergy care.
Keywords: NPP, patient's benefit, PROMs, questionnaires, sublingual allergen immunotherapy
Evaluation en vie Réelle de l'Allergo‐Prescription en Pratique (ERAPP) is a large, prospective, real‐world cohort of children and adults initiating named‐patient product sublingual immunotherapy (NPP‐SLIT) in France. More than 80% of patients reported a clinically meaningful, expectation‐anchored benefit (Patient Benefit Index ≥ 1) at 12–15 months. The Patient Benefit Index complements conventional patient‐reported outcome measures by capturing what matters most to patients in routine allergy care. ACT, asthma control test; ARIA, allergic rhinitis and its impact on asthma; SLIT, sublingual immunotherapy; T5SS, total 5 symptom score.
Abbreviations
- ACT
Asthma Control Test
- AIT
Allergen Immunotherapy
- ARCT
Allergic Rhinitis Control Test
- ARIA
Allergic Rhinitis and its Impact on Asthma
- ERAPP
Real‐world study on patient‐perceived outcomes of Named‐Patient Products (originally: Étude sur le Ressenti des APSI Par le Patient)
- ESPIA
Satisfaction Scale for Patients Undergoing Allergen Immunotherapy (originally developed in Spanish and translated into French: Échelle de Satisfaction des Patients vis‐à‐vis de leur Immunothérapie Allergénique)
- ESS
Epworth Sleepiness Scale
- GIRERD
Adherence Questionnaire by Girerd
- HTA
Health Technology Assessment
- NPP‐SLIT
Pre‐packed liquid allergen extracts prepared for individual prescriptions
- PBI
Patient Benefit Index
- PBQ
Patient Benefit Questionnaire
- PNQ
Patient Need Questionnaire
- PROMs
Patient‐Reported Outcome Measures
- PROs
Patient‐Reported Outcomes
- RCTs
Randomized Clinical Trials
- SLIT
Sublingual Immunotherapy
- SNDS
Système National des Données de Santé (France)
- T5SS
Total 5 Symptom Score
1. Introduction
Allergic rhinitis and asthma are among the most prevalent chronic respiratory diseases, affecting patients of all ages and substantially impairing daily functioning. Allergen immunotherapy (AIT) is an etiological intervention for allergic rhinitis and asthma, aiming not only to relieve symptoms but also to modulate the immune response and alter disease progression [1, 2]. Among the available modalities, sublingual immunotherapy (SLIT) is widely prescribed in Europe due to its favorable safety profile and patient convenience. In France, a commonly used form of SLIT is delivered as a named‐patient product (NPP‐SLIT), a liquid formulation prescribed on an individual basis and prepared by authorized companies. In this context, named‐patient products (also referred to as allergen extracts prepared for an individual patient; Allergènes Préparés Spécialement pour un Individu, APSI) are prepared for an individual patient on prescription within a dedicated national framework.
While its clinical use is widespread, real‐world evidence on patient‐perceived effectiveness remains limited. Controlled trials and real‐life studies have demonstrated the clinical efficacy and safety of SLIT in children and adults [3, 4, 5], and their controlled settings and strict eligibility criteria may not fully reflect routine practice. In this context, patient‐reported outcome measures (PROMs) and instruments such as the Patient Benefit Index (PBI) provide a complementary, patient‐centered evaluation of treatment value.
Despite strong evidence for SLIT efficacy from randomized trials, current evaluation frameworks often rely on symptom scores or physician‐reported endpoints, which may not fully capture individual patient goals or perceptions. In real‐world settings, patients may prioritize aspects such as daily functioning, sleep quality, or ease of use over classical symptom‐based endpoints. Thus, there is a need for more comprehensive outcome measures that reflect real‐life impact and value.
The PBI is a validated tool that quantifies the extent to which patients perceive that their personal treatment goals have been achieved [6]. Unlike standard PROMs, the PBI links baseline expectations with reported benefit, offering a patient‐defined measure of therapeutic value. It has been successfully applied in allergy studies and complements conventional clinical endpoints by capturing what matters most to patients in previous observational research [7].
The ERAPP study (Évaluation en vie Réelle de l'Allergo‐Prescription en Pédiatrie et en Pratique.) was designed to assess real‐world patient benefit, disease control, sleep and daily functioning, treatment adherence, and NPP‐SLIT treatment satisfaction. Using a comprehensive set of validated PROMs, the ERAPP study followed individuals treated with NPP‐SLIT over a 12‐ to 15‐month period, in both pediatric and adult populations. The objective of the present analysis is to evaluate treatment expectations and patient‐perceived benefit of NPP‐SLIT over 12–15 months, with the aim to inform clinical practice, supporting individualized care, and providing evidence relevant to healthcare decision‐makers, especially in terms of treatment value in routine practice.
2. Methods
The design and rationale of the ERAPP study have been described previously [8]. ERAPP is a prospective, multicenter, observational cohort conducted in routine allergy practices across France. Eligible patients had a confirmed diagnosis of IgE‐mediated respiratory allergy (rhinitis, conjunctivitis, and/or asthma) and received a prescription for prepacked liquid NPP‐SLIT between September 2020 and February 2022. Prescriptions could include one or more allergen extracts, as part of routine clinical practice. The present analysis focused exclusively on initiators, defined as patients who had been on NPP‐SLIT for ≤ 6 months at baseline. Patients already treated for > 6 months (n = 4645) were excluded from this analysis.
Data were collected electronically via a secure digital platform at baseline (T0), Month 6 (T6), and Month 12–15 (T12–15). Participants (or caregivers, for children) completed a comprehensive set of validated PROMs, including
the Patient Needs Questionnaire (PNQ) and the Patient Benefit Questionnaire (PBQ), used to derive the PBI [6, 7], as per protocol, the PNQ was administered only to initiators, making PBI calculation applicable solely in this subgroup.
the Allergic Rhinitis and its Impact on Asthma (ARIA) score for rhinitis severity [9];
the Asthma Control Test (ACT) [10];
the Allergic Rhinitis Control Test (ARCT), a validated five‐item tool for patients aged ≥ 12 years [11]; the same version was used for adolescents and adults. A pediatric adaptation including three additional items, under development, was not analyzed in this study—Study ongoing (RCB # 2016‐A01504‐47, EC approval 10–04‐17);
the Total 5 Rhinitis Symptom Score (T5SS) [12];
the 11th question on quality of life of the Satisfaction with Allergen Immunotherapy (ESPIA) scale [13];
the Epworth Sleepiness Scale (ESS) [14];
and the GIRERD adherence questionnaire [15].
All questionnaires were completed independently online, under standardized conditions. To support the interpretation of PROM changes, literature‐based minimal important difference (MID) thresholds are summarized in Supplementary Table S1. These serve as interpretive references, not predefined analytical cutoffs.
The primary outcome was the proportion of patients achieving a PBI score ≥ 1 at 12–15 months, reflecting clinically meaningful benefit. Analyses included individuals having both 12 to 15 months PBQ and baseline PNQ available questionnaires. As PNQ was administered only to initiators, PBI was evaluable solely in this subgroup. Secondary outcomes included changes of PROM scores over time (ARIA, ACT, ARCT, T5SS, ESS, ESPIA‐Q11, and GIRERD).
Additional exploratory analyses were conducted to provide further descriptive insights. These included the following:
proportion of patients achieving a PBI score ≥ 1 at 6 months, reflecting clinically meaningful benefit.
higher thresholds of perceived benefit (PBI ≥ 2 and PBI ≥ 3) at 12–15 months.
item‐level analyses of PNQ/PBQ expectations at baseline and their fulfillment at 6 and 12–15 months.
and subgroup analyses of PBI ≥ 1 at 12–15 months according to demographic and clinical categories (sex, asthma comorbidity, baseline ARIA, T5SS, and ACT classes)
These exploratory analyses were based on complementary field analyses of the PNQ/PBQ data and were not prespecified in the SAP.
All analyses were descriptive. Categorical variables are presented as counts and percentages and continuous variables as means with standard deviations. Missing data were not imputed. PROM scores were summarized at each timepoint, with changes described in absolute terms. No formal hypothesis testing was prespecified.
3. Results
3.1. Study Population
A total of 9439 patients were included in the ERAPP study. Of these, 4794 were classified as NPP‐SLIT initiators (treatment duration ≤ 6 months at inclusion) and constituted the primary analysis population. Among them, 950 (19.8%) were children (< 12 years) and 3844 (80.2%) were adolescents or adults (≥ 12 years). The baseline demographic and clinical characteristics of NPP‐SLIT initiators, including age, sex, residence, smoking status, allergy history, comorbid asthma, indication for treatment, and attrition across time‐points, are summarized in Table 1. Prescribed allergen groups were predominantly house dust mite and grass/tree pollens; multiple allergens could be prescribed per patient (Table 1).
TABLE 1.
Characteristics of the study population (NPP‐SLIT initiators only) and attrition across time‐points, stratified by age group (< 12 vs. ≥ 12 years).
| Characteristics | Children < 12y (n = 950) | Adolescents/Adults ≥ 12y (n = 3844) |
|---|---|---|
| Female sex, n (%) | 325 (34.2) | 2327 (60.5) |
| Mean age, years (±SD) | 8.4 (1.9) | 34.2 (14.6) |
| Urban residence, n (%) | 473 (49.8) | 2412 (62.7) |
| Non‐smoker, n (%) | 935 (98.4) | 2956 (76.9) |
| History of allergy > 10y, n (%) | 8 (0.8) | 2134 (55.7) |
| Asthma as comorbidity, n (%) | 258 (27.2) | 756 (19.7) |
| AIT prescribed for asthma, n (%) | 464 (48.8) | 1332 (34.7) |
| Main indication: allergic rhinitis, n (%) | 786 (82.7) | 3469 (90.2) |
| Polysensitized, n (%) | 202 (21.3) | 1208 (31.4) |
| Prescribed allergen: house dust mite, n (%) | 583 (61.4) | 1369 (35.6) |
| Prescribed allergen: grass pollen, n (%) | 320 (33.7) | 1740 (45.3) |
| Prescribed allergen: tree pollen, n (%) | 196 (20.6) | 1426 (37.1) |
| Prescribed allergen: other(s), n (%) | 109 (11.5) | 850 (22.1) |
| Evaluable PNQ, n (%) | 933 (98.2) | 3783 (98.4) |
| Evaluable PBI at Month 6, n (%) | 532 (56.0) | 1942 (50.5) |
| Evaluable PBI at Month 12–15, n (%) | 439 (46.2) | 1371 (35.7) |
Abbreviations: PNQ: Patient Needs Questionnaire; PBQ: Patient Benefit Questionnaire; PBI: Patient Benefit Index. For each questionnaire (PNQ and PBQ), both the number of collected and evaluable responses are reported. Evaluable responses were defined as having no missing items or a maximum of 6 missing responses. Allergen categories are not mutually exclusive; multiple allergens could be prescribed per patient.
3.2. Primary Outcome—Patient‐Perceived Benefit
The primary outcome was the proportion of initiators achieving a clinically meaningful benefit, defined as a PBI ≥ 1 at Months 12–15. This threshold was reached by 83.8% (368/439) of children and 84.0% (1151/1371) of adolescents/adults (Figure 1). At Month 6, the corresponding proportions were 77.4% (412/532) and 78.8% (1531/1942), confirming a sustained and consistently high level of perceived benefit over time.
FIGURE 1.
Evolution of PBQ scores and patient‐perceived benefit (PBI) over time among NPP‐SLIT initiators (≤ 6 months at baseline) with evaluable PNQ/PBQ data, by age group. Bar charts present the mean symptom burden scores (PBQ; left side) and the proportion of patients achieving a clinically meaningful benefit (PBI ≥ 1; right side) at Month 6 and Month 12–15 among children (< 12 years) and adolescents/adults (≥ 12 years) initiating NPP‐SLIT. Analyses included only initiators (≤ 6 months at baseline) with evaluable PNQ/PBQ.
3.3. Secondary Outcomes—Symptom Trajectories and PROMs
Changes in PROMs are summarized in Table 2. PROMs improved from baseline to follow‐up, particularly for rhinitis severity and symptom burden. ARIA decreased from 2.5 ± 1.2 (n = 828 a) at baseline to 1.9 ± 1.3 (n = 343 a) at Months 12–15 in children and from 2.6 ± 1.1 (n = 3559 a) to 2.1 ± 1.3 (n = 1165 a) in adolescents/adults. T5SS decreased from 11.3 ± 3.8 (n = 827 a) to 8.1 ± 4.2 (n = 342 a) in children and from 12.7 ± 3.6 (n = 3546 a) to 9.2 ± 4.3 (n = 1161 a) in adolescents/adults. Among patients with asthma and evaluable ACT, the proportion with controlled asthma increased from 77.1% at baseline to 83.3% at Month 12–15 in children and from 60.7% to 70.9% in adolescents/adults. ARCT increased modestly from 18.3 ± 4.6 (n = 3561 a) to 20.3 ± 4.0 (n = 1167 a) (≥ 12 years), and ESS decreased from 8.5 ± 4.9 (n = 3160 c) to 7.4 ± 4.5 (n = 1180 c) (adults). Treatment satisfaction (ESPIA‐Q11 “often/always”) increased from 11.5% (n = 109 d) to 26.6% (n = 253 d) in children and from 10.2% (n = 393 d) to 19.5% (n = 750 d) in adolescents/adults, whereas adherence (GIRERD) declined over time (children: observant 34.8% at baseline vs. 11.2% at Month 12–15; adolescents/adults: 42.1% vs. 19.6%).
TABLE 2.
Summary of patient‐reported outcome measures (PROMs) and disease control in NPP‐SLIT initiators.
| PROM/Tool | Population | Baseline | Month 6 | Month 12–15 | Interpretation |
|---|---|---|---|---|---|
| ARIA (rhinitis severity, 0–4) | Children < 12y | 2.5 ± 1.2 (n = 828 a ) | 2.0 ± 1.3 (n = 431 a ) | 1.9 ± 1.3 (n = 343 a ) | Consistent reduction in symptom severity |
| Adolescents/Adults ≥ 12y | 2.6 ± 1.1 (n = 3559 a ) | 2.2 ± 1.3 (n = 1708 a ) | 2.1 ± 1.3 (n = 1165 a ) | ||
| ACT (categorical distribution of asthma control, % of patients b ) | Children < 12y | Controlled 77.1%; Partly controlled 18.8%; Uncontrolled 4.1% | Controlled 81.6%; Partly controlled 17.3%; Uncontrolled 1.2% | Controlled 83.3%; Partly controlled 13.7%; Uncontrolled 3.1% | Improved asthma control over time (higher proportion controlled) |
| Adolescents/Adults ≥ 12y | Controlled 60.7%; Partly controlled 26.5%; Uncontrolled 12.8% | Controlled 67.9%; Partly controlled 25.8%; Uncontrolled 6.3% | Controlled 70.9%; Partly controlled 22.4%; Uncontrolled 6.7% | ||
| ARCT (rhinitis control, 5–25) | Adolescents/Adults ≥ 12y | 18.3 ± 4.6 (n = 3561 a ) | 19.2 ± 4.1 (n = 1711 a ) | 20.3 ± 4.0 (n = 1167 a ) | Modest improvement below MID |
| T5SS (total rhinitis symptom score, 0–20) | Children < 12y | 11.3 ± 3.8 (n = 827 a ) | 8.3 ± 3.9 (n = 427 a ) | 8.1 ± 4.2 (n = 342 a ) | Reduction > MID of 2 points |
| Adults ≥ 12y | 12.7 ± 3.6 (n = 3546 a ) | 9.4 ± 4.2 (n = 1703 a ) | 9.2 ± 4.3 (n = 1161 a ) | ||
| ESS (Epworth Sleepiness Scale, 0–24) | Adults ≥ 18y | 8.5 ± 4.9 (n = 3160 c ) | 7.9 ± 4.7 (n = 1648 c ) | 7.4 ± 4.5 (n = 1180 c ) | Modest improvement below MID |
| ESPIA‐Q11 (quality of life impact, % “often/always”) | Children < 12y | 11.5% (n = 109 d ) | 26.7% (n = 254 d ) | 26.6% (n = 253 d ) | Increased satisfaction over time |
| Adolescents/Adults ≥ 12y | 10.2% (n = 393 d ) | 23.2% (n = 891 d ) | 19.5% (n = 750 d ) | Increased satisfaction over time | |
| GIRERD (adherence to NPP‐SLIT, % of patients e ) | Children < 12y | Observant 34.8%; Partially observant 57.6%; Non‐observant 7.7% | Observant 12.9%; Partially observant 67.5%; Non‐observant 19.5% | Observant 11.2%; Partially observant 65.1%; Non‐observant 23.7% | Decrease in adherence between baseline and both follow‐up visits |
| Adolescents/Adults ≥ 12y | Observant 42.1%; Partially observant 50.5%; Non‐observant 7.4% | Observant 18.6%; Partially observant 66.1%; Non‐observant 15.3% | Observant 19.6%; Partially observant 63.6%; Non‐observant 16.8% |
Note: Values are presented as mean ± SD unless otherwise specified. For ESPIA‐Q11 (treatment satisfaction, quality‐of‐life item) and GIRERD (adherence), data are expressed as proportions. MID: minimal, important difference. Evaluable: all responses to the items in the questionnaire (ARIA, T5SS, ARCT, ACT, GIRERD or ESS) are completed.
Number of patients with allergic rhinitis and the evaluable concerned questionnaire (ARIA, T5SS or ARCT) at the measure points: baseline or baseline and 6 months or baseline and 12–15 months.
% Among patients with asthma and the evaluable ACT questionnaire at the measure points: baseline or baseline and 6 months or baseline and 12–15 months.
Number of adults ≥ 18y with evaluable Epworth questionnaire at the measure points; baseline or baseline and 6 months or baseline and 12–15 months.
Number of patients with ESPIA questionnaire at the measure points; baseline or baseline and 6 months or baseline and 12–15 months.
% Among patients with evaluable GIRERD questionnaire at the measure points: baseline or baseline and 6 months or baseline and 12–15 months.
3.4. Exploratory Analysis
Further descriptive analyses explored stricter thresholds of perceived benefit, including higher PBI cutoffs and analyses in patients with complete follow‐up data (Table 3) and (Figure 2). At Months 12–15, PBI ≥ 2 was achieved by 46.5% (204/439) of children and 52.7% (722/1371) of adolescents/adults, while PBI ≥ 3 was reported by 14.8% (65/439) and 19.3% (264/1371), respectively. In the subset of initiators with complete data at baseline, Month 6, and Months 12–15, results were consistent, with PBI ≥ 2 achieved by 45.7% (177/387) of children and 48.7% (579/1190) of adolescents/adults, and PBI ≥ 3 by 13.4% (52/387) and 17.4% (207/1190) (Figure 2).
TABLE 3.
Proportion of NPP‐SLIT initiators achieving a clinically meaningful benefit (PBI ≥ 1) at Month 6 and Months 12–15, stratified by demographic and clinical subgroups (exploratory analyses).
| Subgroup | Children < 12y n/N, (%) | Adolescents/Adults ≥ 12y n/N, (%) | ||
|---|---|---|---|---|
| Month 6 | Month 12–15 | Month 6 | Month 12–15 | |
| Sex | ||||
| Male | 266/345 (77.1%) | 241/286 (84.3%) | 632/786 (80.4%) | 477/557 (85.6%) |
| Female | 146/186 (78.5%) | 127/152 (83.6%) | 899/1155 (77.8%) | 674/814 (82.8%) |
| Asthma/Rhinitis‐Conj. | ||||
| Asthma – Yes | 223/296 (75.3%) | 212/259 (81.9%) | 677/848 (79.8%) | 510/610 (83.6%) |
| Rhinitis/Conj. – Yes | 363/467 (77.7%) | 325/388 (83.8%) | 1446/1832 (78.9%) | 1090/1293 (84.3%) |
| ARIA at baseline | ||||
| ARIA = 0 | 4/10 (40.0%) | 9/14 (64.3%) | 21/29 (72.4%) | 18/21 (85.7%) |
| ARIA = 1 | 56/79 (70.9%) | 51/64 (79.7%) | 194/260 (74.6%) | 160/194 (82.5%) |
| ARIA = 2 | 136/180 (75.6%) | 177/146 (80.1%) | 453/588 (77.0%) | 365/437 (83.5%) |
| ARIA = 3 | 70/88 (79.5%) | 72/80 (90.0%) | 355/438 (81.1%) | 262/307 (85.3%) |
| ARIA = 4 | 92/107 (86.0%) | 72/82 (88.9%) | 417/512 (81.4%) | 279/332 (84.0%) |
| T5SS at baseline | ||||
| 0–7 | 53/78 (67.9%) | 61/69 (88.4%) | 122/162 (75.3%) | 100/125 (80.0%) |
| 8–11 | 97/129 (75.2%) | 96/115 (83.5%) | 266/355 (74.9%) | 196/254 (77.2%) |
| 11–13 | 78/93 (83.9%) | 63/72 (87.5%) | 284/354 (80.2%) | 215/249 (86.3%) |
| 13–20 | 96/116 (82.8%) | 73/91 (80.2%) | 586/726 (80.7%) | 439/508 (86.4%) |
| ARCT at baseline (≥ 12 y) | ||||
| Rhinitis uncontrolled | _ | _ | 808/1023 (79.0%) | 624/741 (84.2%) |
| Rhinitis controlled | _ | _ | 632/805 (78.5%) | 459/549 (83.6%) |
| ACT at baseline (asthma) | ||||
| Uncontrolled | 13/13 (100.0%) | 9/11 (81.8%) | 78/100 (78.0%) | 58/74 (78.4%) |
| Partly controlled | 45/62 (72.6%) | 41/50 (82.0%) | 163/208 (78.4%) | 132/158 (83.5%) |
| Controlled | 164/220 (74.5%) | 161/197 (81.7%) | 433/537 (80.6%) | 318/376 (84.6%) |
Note: Data are presented as n/N (%) among initiators (≤ 6 months of treatment at baseline) with at least two evaluable PNQ/PBQ questionnaires (baseline and one follow‐up). Subgroups include sex, asthma comorbidity, baseline rhinitis severity (ARIA), baseline symptom burden (T5SS), baseline asthma control (ACT), and rhinitis control (ARCT, ≥ 12 years only). These analyses were descriptive, based on complementary PNQ/PBQ analyses, and were not prespecified in the SAP. Percentages are calculated as n/N × 100 and rounded to one decimal place. PBI: Patient Benefit Index; PNQ: Patient Needs Questionnaire; PBQ: Patient Benefit Questionnaire; PROM: patient‐reported outcome measure.
FIGURE 2.
Proportion of NPP‐SLIT initiators reporting clinically meaningful and higher levels of patient‐perceived benefit (PBI) at Month 6 and Month 12–15. Panel A: Children (< 12 years). Panel B: Adolescents/adults (≥ 12 years). Bars show the percentage of initiators achieving PBI ≥ 1, PBI ≥ 2 or PBI ≥ 3 at Month 6 or at Month 12–15 by and age group. Results are displayed for two analysis populations: i) at Month 6, patients with at least two questionnaires available (baseline + Month 6); ii) at Month 12–15, patients with all three questionnaires available (baseline + Month 6 + Month 12–15).
Exploratory PNQ/PBQ item‐level analyses showed that the expectations most frequently reported at baseline were treatment easy to take, relief of all symptoms, trust in treatment, and nasal obstruction relief. At Month 12–15, fulfillment rates across the 25 PBQ items ranged from ~14% (e.g., improved mood, sexual life, or social aspects) to ~37% (relief of all symptoms in children and trust in treatment in adults). As the PBI is computed at the individual level as a weighted average across the items rated important at baseline, these cohort‐level item fulfillment proportions are not directly comparable with the overall PBI ≥ 1 proportion and primarily reflect heterogeneity in patients' needs and priorities. The highest fulfillment proportions were consistently observed for expectations that were also the most frequent at baseline, notably symptom relief, nasal obstruction, and sleep. Children generally reported slightly higher fulfillment rates across most domains compared with adolescents/adults (Figure 3). Subgroup analyses confirmed consistently high proportions of initiators achieving a clinically meaningful benefit (PBI ≥ 1) at Month 6 and Months 12–15 across all demographic and clinical categories. Rates were comparable across sex, asthma comorbidity, and baseline asthma control (ACT). At Month 6, the proportion of clinically meaningful benefit increased with baseline rhinitis severity (ARIA) and baseline symptom burden (T5SS) in both children and adolescents/adults. These trends remained at Months 12–15 for ARIA in children and for T5SS in adolescents/adults. Slightly higher proportions were reported in children compared with adolescents/adults.
FIGURE 3.
Fulfillment of all patients defined treatment benefits (PBQ items) at Month 6 and Month 12–15, by age group (initiators only). Panel A children < 12 years>. Panel B adolescents/adults ≥ 12 years. Bars show the proportion of patients who rated each expectation as “important” or “very important” at baseline (Patient Needs Questionnaire, PNQ) and subsequently reported fulfilment at follow‐up. Percentages are calculated with the PNQ item‐specific denominator. The x‐axis is truncated at 60% (no item exceeded this threshold) to enhance readability and allow clearer visual comparison across expectations. n (Children < 12y): Month 6 = 532; Month 12–15 = 439. N (Adolescents/Adults ≥ 12y): Month 6 = 1942; Month 12–15 = 1371.
4. Discussion
The ERAPP study demonstrates that patient‐perceived benefit, assessed by the PBI, was achieved by most NPP‐SLIT initiators at Months 12–15. Benefit rates remained high over time, particularly among children. This confirms the robustness of the primary finding and underlines the value of the PBI as an integrative, patient‐centered endpoint. By focusing on patients early in their SLIT course, ERAPP offers longitudinal insights into how benefit is experienced and evolves in routine practice.
A core strength of this study is the use of the PBI, which links treatment outcomes to individual expectations. Unlike conventional PROMs, the PBI captures the personal relevance and perceived value of therapy. In ERAPP, the proportion of patients reporting clinically meaningful benefit (PBI ≥ 1) remained consistently high across baseline severity levels. Item‐level analyses confirmed that the most frequently fulfilled expectations were related to nasal obstruction relief, improved sleep, and overall symptom control, particularly in children. Conversely, expectations related to fatigue, concentration, or emotional and social aspects were less frequently met, highlighting areas where complementary management strategies may be required.
PROM trajectories provided an additional perspective. Rhinitis severity (ARIA) and symptom burden (T5SS) improved over time and exceeded published MID thresholds, supporting clinically meaningful improvement. Asthma control (ACT) also improved (shift toward a higher proportion of controlled asthma among patients with evaluable ACT), whereas changes in rhinitis control (ARCT, available in patients ≥ 12 years) and daytime sleepiness (ESS, in adults) were more modest and remained below their respective MID thresholds. The partial divergence between symptom burden (T5SS) and control (ARCT) likely reflects differences in constructs and recall windows; together with robust PBI gains, this underscores the added value of the PBI as a complementary, expectation‐anchored endpoint.
These item‐level findings are in line with the PROM trajectories. The domains with the highest fulfillment (nasal obstruction relief, sleep, overall symptom relief) were consistent with PROMs showing the most pronounced or clinically meaningful changes, namely, ARIA and T5SS. Improvements in ACT and ESS were more modest and did not reach their established MIDs, although sleep‐related expectations remained among the most frequently fulfilled at the item level. Conversely, expectations related to fatigue, mood, or social functioning were less frequently fulfilled, which is expected since these dimensions are not directly targeted by AIT and are not fully captured by conventional PROMs. This coherence between PROMs and PBI strengthens the interpretability of our results and highlights how the PBI complements standard outcome measures by anchoring them to patient‐defined priorities.
Treatment satisfaction (ESPIA‐Q11) increased over time, whereas adherence (GIRERD) declined between baseline and follow‐up visits. This pattern is consistent with the well‐documented challenge of maintaining compliance in long‐term sublingual AIT [16, 17]. Although perceived benefit (PBI) remained high, one can hypothesize that sustained adherence might further amplify treatment effectiveness. Dialog between patients and physicians, regular re‐evaluation of treatment goals, and structured therapeutic education are therefore essential. In patients reporting limited benefit (e.g., low PBI), this re‐evaluation should explicitly consider whether AIT should be continued, adapted, or discontinued within a shared decision‐making process. Digital tools may also provide support: for instance, the French Drago mobile application has shown encouraging results in improving adherence and persistence in patients treated with HDM SLIT, particularly in children [18].
Exploratory analyses further illustrated the depth of benefit perceived by patients. Higher thresholds of benefit (PBI ≥ 2 and ≥ 3) confirmed that a substantial proportion of patients reported strong perceived improvements, with results consistent across patients with complete data at all timepoints. Subgroup analyses confirmed consistently high levels of benefit across sex, age group, asthma comorbidity, and baseline severity (ARIA, T5SS, and ACT). Slightly higher proportions were observed in children compared with adolescents/adults. As no formal statistical comparisons were performed, subgroup differences should be interpreted descriptively.
These findings are in line with those of prior real‐world studies in respiratory allergic diseases. In Germany, a large observational study of birch pollen SLIT including more than 1000 patients reported consistent improvements in PROMs and confirmed the relevance of assessing benefit from the patient's perspective [19]. In France, the BENEFICA study applied the PBI to evaluate the effect of antihistamines in allergic rhinitis and demonstrated that this tool was able to capture meaningful improvements in domains such as nasal obstruction, sleep, and daily functioning [7]. Together with ERAPP, these studies underscore the importance of systematically assessing patient benefit and expectations in routine allergy care. Moreover, as emphasized by Laferton et al. [20], addressing and reinforcing patients' treatment expectations is itself a determinant of therapeutic outcomes and long‐term engagement. They also echo recommendations from the French (SFA) and European (EAACI) allergy societies, which stress the need to elicit and strengthen expectations to optimize adherence and outcomes of allergen immunotherapy [19, 21]. The study has several strengths, including its very large and diverse real‐world population, the inclusion of both pediatric and adult patients, and the systematic use of validated PROMs combined with the PBI framework. Limitations include its observational design, the absence of a control group, and attrition at Months 12–15, which may introduce selection/attrition bias and overestimate benefit if more motivated or satisfied participants were more likely to remain in follow‐up. We also did not adjust for potential confounders such as seasonality (timing of follow‐up relative to pollen seasons), concomitant pharmacotherapy, disease duration, or regression to the mean; therefore, findings should be interpreted as descriptive real‐world trajectories rather than causal treatment effects. The exploratory nature of subgroups and PNQ/PBQ item‐level analyses also warrants cautious interpretation. In addition, adherence was measured with the GIRERD questionnaire, which provides a global assessment but does not capture daily fluctuations in treatment‐taking behavior.
Altogether, ERAPP highlights the relevance of the PBI as a sensitive and integrative outcome measure, capable of capturing both clinical improvement and fulfillment of individual treatment goals. While NPP‐SLIT provides robust, patient‐perceived benefits in both children and adults, optimizing long‐term adherence through education, shared decision‐making, and innovative tools such as Drago remains a key opportunity to maximize real‐world therapeutic impact.
5. Conclusion
In summary, the ERAPP study provides robust real‐world evidence supporting the multidimensional impact of NPP‐SLIT in patients with allergic rhinitis and/or asthma, including those with comorbid asthma. By combining subjective patient perspectives with objective disease‐control measures, ERAPP illustrates how modern AIT outcomes can, and should, be aligned with what matters most to patients. These findings reinforce the clinical relevance of the PBI as a complementary outcome alongside traditional endpoints, offering clinicians and healthcare systems a tool to personalize, monitor, and optimize AIT. As allergy care evolves toward precision and value‐based paradigms, PROMs and patient‐defined measures of success will become essential.
Author Contributions
Davide Caimmi and Pascal Demoly were responsible for the design and scientific coordination of the study. Abdelilah Abouelfath, Régis Lassalle, Séverine Lignot‐Maleyran, Emmanuelle Bignon, Laure Carcaillon‐Bentata, and Patrick Blin were responsible for the logistics and oversaw statistical methodology and data analysis. Evangéline Clark and Julien Cottet contributed to patient recruitment and data interpretation. All authors participated in the review of the manuscript, provided input on data interpretation, and approved the final version for submission. All authors had full access to the study data and are accountable for the integrity of the results.
Funding
This work was supported by Société Française d’Allergologie (SFA).
Conflicts of Interest
Davide Caimmi received personal fees for advisory or speaker roles from ALK, Astra Zeneca, Stallergenes Greer, GSK, and Sanofi. Pascal Demoly reports no direct financial interests; he has received institutional grants for teaching and research activities from ALK, AstraZeneca, GlaxoSmithKline, Menarini, Puressentiel, Stallergenes Greer, ThermoFisher Scientific, and Viatris. Evangéline Clark received personal fees for advisory or speaker roles from ALK, Stallergenes Greer, and Sanofi. Julien Cottet reported direct lecturing fees from Stallergenes Greer and ALK. The remaining authors declare no conflicts of interest related to the content of this article.
Supporting information
Table S1: Literature‐based MID thresholds used for interpretation of PROMs.
Acknowledgements
The ERAPP study was sponsored by the Société Française d’Allergologie (SFA). Logistics and statistical analyses were conducted by Bordeaux PharmacoEpi, Université de Bordeaux (INSERM CIC‐P 1401). Medical writing and editorial assistance for the current manuscript were provided by Catherine Bos (Pakamaya Medical Communications, Paris, France), in accordance with Good Publication Practice (GPP) guidelines. Open access publication funding provided by COUPERIN CY26.
Data Availability Statement
The data that support the findings of this study are available from the corresponding author upon reasonable request.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Table S1: Literature‐based MID thresholds used for interpretation of PROMs.
Data Availability Statement
The data that support the findings of this study are available from the corresponding author upon reasonable request.