Development and validation of a relapsing polychondritis disease-specific quality of life instrument (ERN ReCONNET RP-QoL)

Abstract

Objectives

Relapsing polychondritis (RP) is a rare, multisystem inflammatory disease characterized by heterogeneous clinical manifestations and a substantial impact on patients’ daily functioning and well-being. Health-related quality of life (HR-QoL) in RP remains insufficiently characterized, and no disease-specific measurement tool is available so far. This study aimed to develop and validate the RP-QoL, a multilingual, patient-reported outcome instrument specifically designed to assess HR-QoL in individuals with RP.

Methods

The RP-QoL was developed within the European Reference Network ReCONNET using a structured four-step approach: (1) identification of relevant HR-QoL domains through systematic literature review, an international patient survey and expert consensus; (2) item generation; (3) pilot testing including cognitive debriefing; and (4) comprehensive psychometric validation. Validation analyses included assessment of internal consistency, structural validity, construct validity, convergent validity with the SF-36, and criterion-related validity.

Results

Domain identification incorporated input from 274 patients across 22 countries, leading to a 31-item pilot questionnaire with a 28-day recall period and 5-point response scale. Cognitive debriefing confirmed clarity, relevance, and feasibility. Validation in 239 patients from 19 countries (median age 55 years; 80% female) demonstrated excellent internal consistency (Cronbach’s α = 0.96). Exploratory factor analysis supported near-unidimensionality, with the first factor explaining 46.6% of variance. RP-QoL scores correlated strongly with disease impact (p = −0.62, P < 0.0001) and SF-36 physical (p = 0.65) and mental (p = 0.55, P < 0.0001) components (both P < 0.0001, P < 0.0001). Discriminative ability was high (AUC = 0.87).

Conclusion

The RP-QoL is the first validated, disease-specific HR-QoL instrument for RP, with robust psychometric performance and applicability in both clinical practice and research.

Rheumatology key messages.

• RP-QoL is the first validated, disease-specific instrument assessing quality of life in relapsing polychondritis.

• Developed internationally with patient input, RP-QoL shows excellent reliability, validity and cross-cultural applicability.

• RP-QoL enables standardized evaluation of disease impact, supporting clinical care and research outcomes.

Introduction

Relapsing polychondritis (RP) is a rare inflammatory disorder [1] characterized by recurrent inflammation of cartilaginous structures, primarily affecting the ears, nose and respiratory tract [2], and various systemic features [2, 3]. Typically, RP manifests as a chronic condition marked by fluctuating flares of varying frequency and severity, interspersed with periods of remission. Monitoring patients with RP poses significant challenges [4] due to the disease’s heterogeneity, intermittent symptoms and rarity [3]. These factors contribute to the wide variability in clinical management and hinder the development of standardized approaches and clinical trials [5].

Our research group has previously developed disease-specific instruments for evaluating disease activity and damage: the RP Disease Activity Index (RPDAI [6]) and the RP Damage Index (RPDAM [7]). Additionally, assessing health-related quality of life (HR-QoL) has become an essential component of chronic disease management, relevant for clinical practice, interventional trials and outcome monitoring [8]. However, data on HR-QoL in RP remain scarce. Generic HR-QoL instruments, such as the Short-Form 36 (SF-36), allow comparisons across diseases but may include items that are not relevant to RP or simply fail to capture disease-specific aspects, potentially limiting their sensitivity compared with a disease-specific HR-QoL tool. In this context, we report the multilingual development and validation of the RP-QoL, a self-reported, disease-specific instrument designed to assess HR-QoL in patients with relapsing polychondritis. This work was conducted within the framework of the European Reference Network (ERN) for rare connective tissue and musculoskeletal diseases (ReCONNET).

Methods

The study comprised four key steps (Fig. 1):

Figure 1.

Main key steps of the RP-QoL study. RP: relapsing polychondritis; QoL: Quality of Life; RPQoL-Eng: English version of the RP-QoL instrument; RPQoL-EU: other European languages and other languages version of the RP-QoL

• Step 1, identification of relevant domains for inclusion in the RP-QoL. This step was performed through a multilingual international qualitative survey and has recently been published [9].

• Step 2, derivation of items (i.e. self-assessable questions for patients) for each domain identified during step 1.

• Step 3, preliminary pilot testing of the draft RP-QoL questionnaire, to assess feasibility and content validity, as well as cross-cultural adaptation.

• Step 4, comprehensive validation of the RP-QoL, examining construct validity, internal reliability and concurrent validity.

Steering committee and participants

The steering committee comprised 12 active members from the ReCONNET RP disease group, including two patient representatives, one fellow, one clinical psychologist and one methodologist specialized in HR-QoL. The language committee, responsible for the cross-cultural adaptation of the RP-QoL, comprised five senior authors from the steering committee, as well as 10 additional members from France, Germany, Portugal, Romania and Italy. The RP-QoL was also translated into Catalan, Hindi and Japanese. The expert panel included five internationally recognized experts in RP (JCP, AM, MF, JS, AS). Patients with a self-reported, medically confirmed diagnosis of RP were involved in every stage of the study. The study was approved by the Ethics Committee of Strasbourg Academic Hospitals (#CE-2024–15).

Step 1: identification of RP-QoL domains

In the initial phase of the RP-QoL development process, the steering committee aimed to identify the main HR-QoL domains affecting patients with RP. This was achieved by integrating information from three sources: a systematic literature review, findings from a qualitative international patient survey [9] and input from a panel of RP experts.

A systematic literature review was performed in PubMed and Web of Science (full databases, search date: 1 March 2024) using the keywords: polychondritis and quality of life (and their synonyms, including Mesh terms). The authors were also aware of a previous study evaluating HR-QoL in RP using the generic short form-36 (SF-36) instrument, published as abstract only [10].

An online, structured qualitative survey with open-ended questions was conducted [9] to explore the impact of RP and of its treatments in patients living with RP. The survey script was developed by the steering committee with input from the clinical psychologist and two patient representatives and was translated and culturally adapted from English into French, Italian, Romanian, German and Portuguese, using the ERN ReCONNET CROSS-ADAPT methodology for cross-cultural adaptation of connective tissue disease documents in European languages [11].

The survey was disseminated via social media platforms (Twitter/X, Facebook) and direct contact with RP patient associations. Briefly, survey responses were analysed with thematic analysis: transcripts were systematically reviewed to identify aspects related to the impact of RP on patients’ daily lives, and these aspects were grouped into categories from which meaningful themes emerged. The themes were continuously verified against the original data and across language groups until the core HR-QoL domains associated with RP were identified.

Expert panel feedback was incorporated, by asking five international RP expert specialists (JCP, AM, MF, JS, AS) to describe the impact of the disease and of its treatments upon the lives of RP patients, based on their extensive experience.

The steering and expert committees carefully reviewed all HR-QoL domains identified across the three sources, with those generated from patients’ feedback as the primary source. An online meeting with RP patients and patient associations was organized within the framework of the ERN ReCONNET to ensure that identified HR-QoL domains were relevant and acceptable to patients.

Step 2: RP-QoL item generation

Based on the identified domains, a draft (pilot) version of the RP-QoL instrument was developed. Each domain was converted into one or multiple items, designed for patient self-assessment. Whenever possible, wording used by patients into the qualitative survey was retained, particularly when providing specific examples or meaningful elements of context.

The steering committee evaluated each potential item according to the established questionnaire development principles, ensuring that the items were clearly attributable to RP or its treatments, applied to the majority of patients and conveyed a single concept [12]. Discussions were held until agreement was reached for every item and for the overall pilot RP-QoL questionnaire. All steering committee members participated equally in these discussions and in the decision-making process. Discussions were continued until full consensus was achieved, with all members approving the final wording and inclusion of each item.

Step 3: Pilot testing and cognitive debriefing

Pilot testing was conducted with 16 patients with RP, who provided completion time and provide detailed feedback on the pilot RP-QoL questionnaire, including the clarity of instructions, wording of questions, response scale, cultural relevance, ease of completion and overall length. The expert panel also provided similar feedback on the draft instrument. All the feedback was reviewed and used to refine the questionnaire. Modifications were implemented to improve clarity, comprehensibility and acceptability. The final RP-QoL instrument was reviewed and approved by the steering committee, including the two patient representatives before being adapted into additional languages.

Step 4: Preliminary validation of the RP-QoL

Preliminary validation of the RP-QoL was performed through a concurrent evaluation of the RP-QoL scores and clinical variables hypothesized to demonstrate convergent or divergent associations with HR-QoL. These variables included disease duration, ongoing treatments, organ involvement, overall RP impact measured on a 0–10 Visual Analogue Scale (VAS), recent unplanned emergency consultations or hospitalizations attributable to RP, and the Short-Form 36 v1 questionnaire.

Statistical analysis

Continuous variables are reported as median with interquartile range (IQR: 25th–75th percentile), and categorical variables as counts and percentages.

Group comparisons used the χ² test for categorical variables and the Mann–Whitney U test for continuous variables.

Internal consistency reliability of the RP-QoL was assessed using Cronbach’s alpha and standardized Cronbach’s alpha. Structural validity (dimensionality) was evaluated by exploratory factor analysis of all items using maximum likelihood extraction. The number of factors was determined based on eigenvalues >1, scree-plot inspection and interpretability of factor loadings. Factor loadings ≥0.4 were considered acceptable, and the proportion of total variance explained by the factor(s) was reported. Construct validity was assessed by examining correlations (Spearman’s ρ) between RP-QoL scores and self-reported impact of RP on daily life. Convergent validity was evaluated via correlation with the SF36 v1.0 (SF36 USA norms were used for all participants, see Supplementary Table S1), and criterion-related validity was examined using receiver operating characteristic (ROC) curves, using the area under the curve (AUC) to quantify discriminative performance for identifying participants with impairment in QoL (VAS >3/10). Feasibility and acceptability were assessed based on patient-reported clarity, cultural relevance, ease of completion, instrument length and completion time. A two-sided P-value <0.05 was considered statistically significant. All statistical analyses were performed using JMP v13.0 (SAS Institute, Cary, NC, USA).

Results

Step 1: Identification of HR-QoL domains

Literature review

In addition to a previously available abstract [10] the systematic literature review (see Supplementary Data S1 for PRISMA reporting diagram) identified only one relevant publication [13]. This study highlighted several disease characteristics potentially impairing HR-QoL in patients with RP, including ear and/or nose cartilage pain, shortness of breath, eye inflammation, voice changes, hearing loss, dizziness, costochondritis, joint pain and fatigue. Impact on daily life included limitations in physical activity; impaired relationships, lack of sleep and the burden of pharmacological and non-pharmacological treatments.

Expert panel input

The expert panel identified several HR-QoL domains potentially affected by RP, including activities of daily living, personal relationships, pain and discomfort, mobility, energy and fatigue, sleep and rest, sensory functions, bodily image and appearance, self-esteem, negative feelings (including anxiety), communication capacity, work capacity and need for social support.

Qualitative patient survey

Detailed patient perspectives were obtained through an international qualitative survey, which included 274 participants with RP (median age: 54 years [IQR: 45–61], 86% female), from 22 countries. The largest groups of participants were from the United States (29.9%), France (17.9%) and the United Kingdom (14.6%). The study results have been previously published [9].

Briefly, the most impacted HR-QoL domains reported by patients were: ‘personal relationships’ (58.8%), ‘work capacity’ (51.8%) and ‘daily activities’ (47.8%). Additional concerns frequently reported included fatigue, pain, cognition, mental health and social life. A total of 67 patients (24.5%) identified 20 specific issues that were not adequately captured by generic QoL instruments, including difficulties with planning, verbal communication and vision impairment. To confirm and externally validate these findings, a publicly open ERN ReCONNET webinar was held in October 2024. The main survey results were presented and discussed, and participants, including RP patients and patient organizations were invited to comment on the relevance of the identified domains. Based on these tree sources, a final list of HR-QoL domains relevant to RP (Table 1) was assembled and unanimously approved by the steering committee.

Table 1.

Final list of HR-QoL domains potentially impaired in RP, as identified through the literature review, expert feedback and the qualitative survey of RP patients.

Main health-related quality of life domains impacted in RP	Literature review	Expert feedback	Patient qualitative survey
Personal relationships: family members	✓	✓	✓
Personal relationships: couple life			✓
Personal relationships: friends			✓
Work/studying capacity	NR	✓	✓
Activities of daily living	NR	✓	✓
Leisure activities	NR	NR	✓
Limitation in physical activities	✓	✓	✓
Sleep and rest	✓	✓	✓
Energy and fatigue	NR	✓	✓
Mobility	NR	✓	✓
Pain & discomfort	✓	✓	✓
Impact of chondritis (pain & deformities)	✓	✓	✓
Thinking, learning, memory and concentration (e.g. brainfog)	NR	NR	✓
Negative feelings: anxiety, depression, stress	NR	✓	✓
Negative feelings: Worry about health (unpredictability)	NR	NR	✓
Negative feelings: Worry about health because of the ‘low level of knowledge of physicians’	NR	NR	✓
Negative feelings: Self-esteem	NR	✓	✓
Negative feelings: Being a burden to others	NR	NR	✓
Need for (and impact) of medical care (visits, blood tests)	NR	NR	✓
Impact (adverse events) of medications/treatments	✓	NR	✓
Body image and appearance: gaining weight (e.g. GC-related)	✓	✓	✓
Body image and appearance: deformities	✓	✓	✓
Sexual activity/intimacy	NR	NR	✓
Impairment of sensory organs: for hearing	✓	✓	✓
Impairment of sensory organs: for vision	✓		✓
Impairment of voice (communication issues)	✓	✓	✓
Difficulties breathing	✓		✓
Financial resources	NR	NR	✓
Need for social support	NR	✓	✓
Difficulty planning (because of unpredictability of flares)	NR	NR	✓

NR: not reported; GC: glucocorticoids; RP: relapsing polychondritis.

Step 2: item generation

The domains identified during Step 1 were converted into questionnaire items using a standardized structure as follows (‘how much does RP impact …’ followed by the relevant domain) Whenever possible, wording and examples derived from patient narratives in the qualitative survey were incorporated to ensure relevance and clarity [9].

The steering committee agreed on a 28-day recall period, consistent with previously developed RP instruments (RPDAI [6] and RPDAM [7]) and a five-point response scale (‘not at all’, ‘a little’, ‘moderately’, ‘a lot’, ‘extremely’) to capture both the frequency and intensity of HR-QoL alterations experienced by RP patients. Following these discussions, a 31-item pilot version of the RP-QoL was finalized.

Step 3: Pilot testing and cognitive debriefing

The pilot RP-QoL was disseminated to 16 participants living with RP, who were asked to complete the instrument and provide detailed feedback for cognitive debriefing (see Supplementary Table S1). Briefly, all participants reported that the pilot RP-QoL was adequate regarding the clarity of the instructions, questions and the rating scale, as well as its cultural relevance, ease of completion and overall length. However, the cognitive debriefing also highlighted minor pagination and wording issues (cf. Supplementary Tables S2 and S3), including the need to display the recall period more prominently, to repeat the rating scale on each page, to group similar items together, and to phrase certain items using ‘how much’ instead of ‘how’.

Following this feedback, the final RP-QoL instrument was prepared and unanimously agreed upon by the steering committee members. For each question, the response anchors ranged from ‘not at all’ to ‘extremely’, reflecting the perceived impact of RP on the respective domain. The final RPQoL score is calculated by summing the item scores, each ranging from 0 to 4, in accordance with the final version of the instrument (Fig. 2). Finally, the revised version of the pilot was cross-culturally adapted into multiple European languages (French, German, Spanish, Catalan, Portuguese, Romanian, Italian) using the ERN ReCONNET CROSSADAPT methodology [11], and also translated into Japanese and Hindi.

Figure 2.

The ERN ReCONNET RP-QoL instrument

Step 4: Preliminary validation

The RP-QoL was evaluated in 248 patients with self-reported RP whose diagnosis had been confirmed by a medical doctor. Of these participants, 239 participants completed the study with fewer than three RP-QoL items marked as ‘I prefer not to answer’ or ‘not appropriate’ and were therefore included in the subsequent analyses. The 239 included participants (191 women, 46 men, two non-binary) had a median age of 55 years (IQR: 43–63) and originated from 19 countries (Supplementary Table S4), mostly the USA, UK, France, Germany and Australia. Their reported organ involvements and treatments are summarized in Table 2.

Table 2.

Main reported clinical manifestations and treatments of the 239 patients with RP, during the validation phase of the RP-QoL.

Main reported clinical manifestations	N (%)
Ear chondritis	208 (87.0)
Nose chondritis	141 (59.0)
Respiratory chondritis (larynx, tracheal, bronchial)	113 (47.3)
Costochondritis	133 (55.6)
Ear deformities	67 (28.0)
Nose deformities	33 (13.8)
Costochondral deformities	14 (5.9)
Laryngo-tracheobronchial stenosis/malacia	40 (16.7)
Arthralgia/Arthritis	147 (61.5)
Inflammatory eye involvement (episcleritis, scleritis, retinal vasculitis, etc.)	117 (49.0)
Cochlear involvement	74 (31.0)
Vestibular involvement	77 (32.2)
Pericarditis	10 (4.2)
Myocarditis	5 (2.1)
Vasculitis (excluding the aorta)	40 (16.7)
Aortitis	8 (3.3)
Valvular involvement	4 (1.7)
CNS involvement	18 (7.5)
PNS involvement	43 (18.0)
None of these manifestations	4 (1.7)
Reported treatment (use during the previous 28 days)
NSAIDs	83 (34.7)
Oral glucocorticoids	121 (50.6)
Intravenous glucocorticoids	7 (2.9)
Hydroxychloroquine	28 (11.7)
Colchicine	41 (17.2)
Immunosuppressive agents (methotrexate, azathioprine, mycophenolate mofetil)	148 (61.9)
Intravenous cyclophosphamide	2 (0.8)
Any biologics and/or targeted therapies	89 (37.6)
TNF inhibitors	52 (21.8)
Tocilizumab	26 (10.9)
Abatacept	2 (0.8)
Rituximab (in the last 12 months)	12 (5.0)
JAK inhibitors	11 (4.6)
Analgesics
Paracetamol/acetaminophen	72 (30.1)
Codeine/tramadol	41 (17.2)
Morphine or derivatives	26 (10.9)
No current treatment for RP	13 (5.4)

CNS: central nervous system; JAK: Janus kinase; NSAID: non-steroidal anti-inflammatory drug; PNS: peripheral nervous system; TNF: tumour necrosis factor.

Psychometric properties of the RP-QoL

The RP-QoL demonstrated excellent internal consistency, with both Cronbach’s alpha and standardized alpha equal to 0.96. Item-level response distributions across the five scale modalities for each of the 31 RP-QoL items during the validation phase supported appropriate use of the full-scale range (Supplementary Table S5).

Exploratory factor analysis revealed a dominant first factor (eigenvalue = 14.43), accounting for 46.6% of the total variance. The scree plot (Supplementary Fig. S1 and Supplementary Table S6) demonstrated a clear elbow after the first factor, with a substantial drop between the first and second eigenvalues (14.43 vs 1.81; ratio ≈ 8:1). Although several subsequent eigenvalues were >1, their magnitudes were small and the curve flattened markedly after the first component, supporting essential unidimensionality of the scale. All items loaded (≥0.40) on the first factor.

The distribution of RP-QoL scores showed no evident floor or ceiling effects (Fig. 3). The median score was 55 (IQR: 40–77) and the mean (±SD) was 59 (±27), spanning nearly the entire theoretical RP-QoL range from 0 (worst HR-QoL) to 120, out of a theoretical maximum of 124 (best HR-QoL).

Figure 3.

Distribution of RP-QoL scores of the 239 participants, during the validation phase

The median RP-QoL score was 53 (IQR: 38–71) in women vs 77 (IQR: 50–94) in men (P = 0.0008). While formal disease activity (RPDAI) and damage (RPDAM) indices were not collected in this validation cohort, we explored indirect indicators of disease burden, such as recent unplanned care and glucocorticoid use. The median RP-QoL score was 50 (IQR: 31–69) among participants who reported unplanned care—reflecting the burden of potential RP activity or complications—vs 61 (IQR: 46–82) among those without unplanned care (P = 0.0004). Similarly, the median RP-QoL score was 52 (IQR: 32–69) among participants using glucocorticoids (GC), possibly reflecting higher disease activity, compared with 63 (IQR: 46–87) among those not receiving GCs (P = 0.0004).

Construct validity was further supported by a strong inverse correlation (Supplementary Fig. S2) between RP-QoL scores and self-reported impact of RP on daily life (Spearman’s ρ = −0.62, P < 0.0001).

Convergent validity was demonstrated by strong correlations between RP-QoL scores and the Physical Component Summary Scores (ρ = 0.65, P < 0.0001) and Mental Component Summary Scores (ρ = 0.55, P < 0.0001) of the SF-36, a widely validated generic HR-QoL measure. Correlations between the RP-QoL and the subscales of the SF-36 are shown in Table 3.

Table 3.

Correlation between the RP-QoL and the subscales of the SF-36.

Domain & subdomains scores	Spearman’s	P-value
Physical component summary	0.65	<0.0001
Mental component summary	0.55	<0.0001
Physical functioning	0.62	<0.0001
Role physical	0.59	<0.0001
Body pain	0.72	<0.0001
General health	0.59	<0.0001
Vitality	0.57	<0.0001
Social functioning	0.71	<0.0001
Role emotional	0.40	<0.0001
Mental health	0.55	<0.0001

Criterion-related validity was further supported by the comparable discriminative performance of the RP-QoL and the SF36 in identifying participants with important RP burden (defined as a burden score ≥4 on the 0–10 scale) over the previous 28 days. The areas under the ROC curve were similar for the RP-QoL (AUC = 0.87) and the SF-36 Physical Component Summary (PCS) (AUC = 0.86) and outperforming the SF-36 Mental Component Summary (MCS) (AUC = 0.72).

Discussion

This study describes the development and validation of the RP-QoL, the first disease-specific patient-reported outcome instrument designed to assess HR-QoL in individuals living with RP. The instrument was developed within the framework of the ERN ReCONNET using a patient-centred and internationally collaborative approach.

Assessing outcomes in RP presents several challenges. The disease is rare, clinically heterogeneous and characterized by a wide spectrum of manifestations that may involve multiple organs, including the ears, nose, airway, eyes, joints and cardiovascular system. The severity and combination of manifestations vary greatly between individuals and may fluctuate over time [14, 15]. In addition, standardized definitions for several forms of organ involvement remain limited, and objective confirmation of certain manifestations, particularly airway disease, is not always feasible in routine practice. As a result, clinicians frequently rely on patient-reported symptoms and clinical judgment when evaluating disease burden. In this context, incorporating the patient perspective through a validated HR-QoL instrument represents an important complement to traditional clinical assessments.

The development of the RP-QoL was therefore grounded in the lived experiences of patients. The identification of relevant HR-QoL domains relied primarily on qualitative data from an international survey involving 274 individuals with RP, complemented by expert inputs and a literature review [9]. This approach ensured that the RP-QoL reflects the aspects of daily life most affected by the disease, including specific domains or items that are insufficiently captured by generic HR-QoL tools such as the SF-36. In particular, patients highlighted issues such as the unpredictability of disease flares, communication difficulties related to voice involvement, concerns related to physical appearance and the psychological impact of living with a rare condition that remains poorly recognized by many healthcare providers. Incorporating these perspectives was essential to ensure that the instrument captures the true burden of the disease as experienced by patients.

The psychometric evaluation of the RP-QoL supports its robustness as a measurement tool. The instrument demonstrated excellent internal consistency and a clear factor structure consistent with essential unidimensionality. This finding suggests that the different aspects of life affected by RP, including fatigue, pain, sleep disturbance, emotional well-being and social functioning are likely to deteriorate together when the disease imposes a greater burden. Rather than reflecting a single symptom or organ manifestation, the dominant factor likely represents a broader construct corresponding to the overall impact of RP on patients’ daily lives. The results suggest that diverse manifestations ultimately converge into a shared perception of reduced quality of life, and such a structure is consistent with the objective of a global HR-QoL instrument and supports the use of a single summary score to capture overall disease burden from the patient perspective.

Another important strength of the RP-QoL lies in its international and cross-cultural development and validation. Research on rare diseases often require multinational collaboration to achieve meaningful sample sizes. By making sure from the beginning of its development that linguistic and conceptual equivalence was maintained across several languages, the RP-QoL can be more readily applicable in international clinical studies and patient registries. This global applicability is particularly important for RP, given the rarity of the disease and the need to foster collaborative networks to advance research and improve patient care.

The study also has several limitations that should be acknowledged. Recruitment was largely conducted through online platforms and patient associations, which may have increased the participation of individuals who are particularly engaged with their disease or who experience a higher disease burden [9]. However, the cohort included participants from numerous countries and represents one of the largest international datasets of RP patients assembled for a patient-reported outcome study. While formal disease activity (RPDAI) and damage (RPDAM) indices were not collected in this validation cohort, we explored indirect indicators of disease burden, such as recent unplanned care and glucocorticoid use. Our analyses revealed that higher RP-QoL scores, reflecting worse quality of life, were significantly associated with these clinical proxies, suggesting a potential relationship between disease activity and QoL. Future studies incorporating validated disease activity and damage measures are warranted to further establish the construct validity of the RP-QoL instrument. In addition, the cross-sectional design does not allow assessment of test–retest reliability or responsiveness to clinical change so far. These aspects will need to be addressed in future studies. Longitudinal studies are needed to evaluate the stability of the instrument over time and its responsiveness to changes in disease activity or treatment. Such work will also help determine the minimal clinically important difference, which is necessary to interpret meaningful changes in scores. Finally, race and ethnicity data were not collected in this study in the context of differing national regulatory frameworks. The primary objective at this stage was to establish the overall validity and feasibility of the instrument in a broad international RP population. Nevertheless, we fully acknowledge the importance of evaluating potential cultural, linguistic and regional influences on QoL assessment in RP. In this regard, careful comparative analyses across existing cohorts from different countries and language groups are currently being planned. In parallel, future analyses could explore more broadly how RP-QoL scores relate to specific disease manifestations and patterns of organ involvement, including the relationship with disease activity (RPDAI) and damage (RPDAM). Understanding how different clinical phenotypes influence patient-reported quality of life may provide valuable insights into the mechanisms through which the disease affects everyday activities.

Beyond validation, the RP-QoL has potential applications in a variety of research contexts. The instrument could serve as an important outcome measure in interventional trials, where capturing the patient perspective is increasingly recognized as essential for evaluating therapeutic benefit. Similarly, incorporating the RP-QoL into international registries and observational cohorts could provide new opportunities to study the long-term impact of RP and its treatments on patients’ lives. Combining patient-reported outcomes with detailed clinical phenotyping may also help identify patient subgroups with particularly high HR-QoL burden and guide more individualized management strategies.

Ultimately, the RP-QoL should be viewed as part of a broader framework for outcome assessment in relapsing polychondritis. Together with the previously developed RP Disease Activity Index (RPDAI [6]) and RP Damage Index (RPDAM [7]), the RP-QoL provides a complementary patient-centred perspective that captures the everyday impact of the disease.

Conclusion

The RP-QoL is the first validated, disease-specific, self-report instrument designed to assess health-related quality of life in patients with relapsing polychondritis. Built upon a patient-centred, and internationally collaborative methodology within the ERN ReCONNET framework, it demonstrated excellent psychometric properties and meaningful discriminative ability across clinically relevant patient subgroups. Together with the previously validated RPDAI and RPDAM, the RP-QoL completes a comprehensive, disease-specific outcome measurement framework for RP. Now available in multiple languages, it is ready for deployment in clinical practice as well as in interventional and observational research, with the potential to meaningfully enrich the holistic assessment and management of patients living with this rare and challenging disease.

Supplementary material

Supplementary material is available at Rheumatology online.

Data availability

All data of this study are available within the paper.

Contribution statement

All authors participated in the design of the study. All authors contributed to the data collection. Laurent Arnaud and Philippe Mertz performed the statistical analysis. Laurent Arnaud, Philippe Mertz and Oliver Sander prepared the draft. All authors revised the draft manuscript for significant intellectual content and approved the final version.

Funding

The ERNs are funded by the European Union. This publication was supported by the ERN ReCONNET Grant Agreement 101157143.

Disclosure statement: The authors report no disclosure related to this manuscript.

Disclaimer

The content of this publication represents the views of the authors only and it is their sole responsibility; it cannot be considered to reflect the views of the European Commission and/or the Health and Digital Executive Agency (HaDEA) or any other body of the European Union. The European Commission and the Agency do not accept any responsibility for use that may be made of the information it contains.