Lily Watson
email: lilywatson@tiscali.co.uk

Conor Coyle

Caroline Whately-Smith

Melanie Brooke

Uta Kiltz

Ennio Lubrano

Rubén Queiro

David Trigos

Jan Brandt-Juergens

Ernest Choy

Salvatore D'angelo

Andrea Delle Sedie

Emmanuelle Dernis

Sandrine Guis

Philip Helliwell

Pauline Ho

Axel J Hueber

Beatriz Joven

Michaela Koehm

Carlos Montilla

Jon Packham

José Antonio Pinto Tasende

Felipe Julio Ramirez

Adeline Ruyssen-Witrand

Rossana Scrivo

Sarah Twigg

Martin Welcker

Martin Soubrier

Théo Wirth

Laure Gossec

Laura C Coates

An international multi-centre analysis of current prescribing practices and shared decision-making in Psoriatic Arthritis

Keywords: Psoriatic arthritis, prescribing practices, shared decision-making, collaboration

Background: Psoriatic arthritis (PsA) is a multi-system disease with a range of treatment options. Shared decision-making (SDM) is advocated to improve patient outcomes. We aimed to analyse current prescribing practices and the extent of SDM in PsA consultations across Europe.

Methods:

The ASSIST study was a cross-sectional observational study of PsA patients aged 18 years and older, attending a face-to-face appointment between July 2021 and March 2022. Patient demographics, current treatment and treatment decisions were recorded. The extent of SDM was measured by the clinician's effort to collaborate (CollaboRATE questionnaire) and patient's communication confidence (Perceived Efficacy in Patient-Physician Interactions tool, PEPPI-5).

Results: 503 patients were included from 24 centres across 5 countries (UK, France, Germany, Italy and Spain). Physician-and patient-reported measures of disease activity were highest in the UK, where median patient age was lowest. Conventional synthetic (cs) DMARDS constituted a higher percentage of current PsA treatment in UK than continental Europe (66.4% vs 44.9%), whereas biologic use was more frequent in Europe than the UK (68.1% vs 36.4%). Implementing a treatment change was most common in the UK, predominantly being a treatment increase. CollaboRATE and PEPPI-5 scores were high throughout, indicating high levels of clinician collaborative effort and patient communication confidence. Mean CollaboRATE and PEPPI scores in those with and without treatment escalation were similar. Of 16 patients with low CollaboRATE scores (<5), no patients with low PsAID-12 scores (<5) had treatment escalation. However, of 226 patients with high CollaboRATE scores, 59 patients with low PsAID-12 scores received treatment escalation.

Conclusions: Disease characteristics and treatment strategies varied by country. Higher rates of treatment escalation seen in the UK may be explained by higher disease activity and a younger cohort. High levels of patient-reported collaboration in face-to-face PsA consultations reflects effective implementation of the SDM approach in this field. Our data that, in patients with mild disease activity, only those with higher perceived collaboration underwent treatment escalation may reflect the role of SDM in eliciting otherwise undetected symptoms/concerns that influence treatment decisions.

Background

Psoriatic arthritis (PsA) is a chronic inflammatory arthropathy, affecting 20-30% of patients with psoriasis [START_REF] Scotti | Prevalence and incidence of psoriatic arthritis: A systematic review and meta-analysis[END_REF][START_REF] Villani | Prevalence of undiagnosed psoriatic arthritis among psoriasis patients: Systematic review and metaanalysis[END_REF]. The condition has a heterogeneous phenotype, with inflammation affecting the joints, tendons, soft tissue, skin, nails and spine to differing extents between patients. PsA is associated with a reduced life expectancy and significant impact on quality of life through musculoskeletal symptoms and associated co-morbidities [START_REF] Gladman | Mortality studies in psoriatic arthritis: Results from a single outpatient center. II. prognostic indicators for death[END_REF][START_REF] Haroon | High prevalence of metabolic syndrome and of insulin resistance in psoriatic arthritis is associated with the severity of underlying disease[END_REF]. Multiple pharmacological treatment options exist, with significant developments in the field of disease-modifying antirheumatic drugs (DMARDs) in recent years [START_REF] Noviani | Choosing the right treatment for patients with psoriatic arthritis[END_REF]. There has been an expansion of treatment options beyond traditional conventional synthetic DMARDS (csDMARDS), such as methotrexate, sulfasalazine and leflunomide, to targeted therapies including i) biological agents (bDMARDS) that target underlying pathogenic molecules, such as tumour necrosis factor (TNF), interleukin (IL)-12/23, IL-23 and IL-17A/F, and ii) targeted synthetic DMARDs such as Janus kinases (JAKs) and phosphodiesterase-4 (PDE4). National and international guidelines have been developed to inform treatment decisions in PsA [START_REF] Gossec | Eular recommendations for the management of psoriatic arthritis with pharmacological therapies: 2019 update[END_REF][START_REF] Coates | Group for research and assessment of psoriasis and psoriatic arthritis (GRAPPA): Updated treatment recommendations for psoriatic arthritis 2021[END_REF]. However, treatment decisions must be tailored to the individual, given the heterogeneity in clinical phenotype and the varying efficacy of each treatment on different disease domains. Treatment approaches are likely to vary by geographical location, driven by differences in healthcare services and reimbursement, but an observational analysis of current prescribing practices in PsA has not been undertaken. Shared decision-making (SDM) is an important component of personalised healthcare, where treatment selection is guided by collaboration between the clinician and the patient to ensure the incorporation of patient priorities and values. SDM has been shown to improve outcomes and increase treatment compliance across multiple clinical groups [START_REF] Shay | Where is the evidence? A systematic review of shared decision making and patient outcomes[END_REF][START_REF] Deniz | The mediating role of Shared Decision-making in the effect of the patient-physician relationship on compliance with treatment[END_REF][START_REF] Lofland | Shared decision-making for biologic treatment of autoimmune disease: Influence on adherence, persistence, satisfaction, and health care costs[END_REF][START_REF] Raghunath | Qualitative assessment of medication adherence in patients with rheumatic diseases on biologic therapy[END_REF]. It relies on both the clinician's effort to incorporate patient priorities and the patient's confidence in voicing their values. The CollaboRATE questionnaire and Perceived Efficacy in Patient-Physician Interactions (PEPPI-5) tool are patient-reported measures of the clinician's collaborative effort and patient communication confidence, respectively [START_REF] Barr | The psychometric properties of collaborate: A fast and frugal patient-reported measure of the shared decisionmaking process[END_REF][START_REF] Maly | Perceived efficacy in patientphysician interactions (PEPPI): Validation of an instrument in older persons[END_REF][START_REF] Ten Klooster | Further validation of the 5-item perceived efficacy in patient-physician interactions (peppi-5) scale in patients with osteoarthritis[END_REF][START_REF] Gossec | An e-health interactive self-assessment website (Sanoia®) in rheumatoid arthritis. A 12-month randomized controlled trial in 320 patients[END_REF]. Despite SDM being a top international priority, there are no studies examining the degree of SDM in PsA consultations to date [START_REF] Smolen | Eular recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update[END_REF].

We undertook an international observational analysis to examine and compare current prescribing practices and SDM in PsA consultations across Europe.

Methods:

Study population and design

A subanalysis was undertaken using data from the international, cross-sectional study (ASSIST) to explore treatment decisions and SDM in adult PsA consultations across Europe. Patients aged 18 years and older attending a face-to-face rheumatology appointment at a specialist rheumatology centre between July 2021 and March 2022 were eligible for inclusion (NCT05171270). All patients had to have previously received a diagnosis of PsA by a rheumatologist according to the ClASsification of Psoriatic Arthritis criteria [START_REF] Taylor | Classification criteria for psoriatic arthritis: Development of new criteria from a large international study[END_REF]. Patients were selected by systematic sampling, with a different random starting patient "number" per centre, from 24 centres across the UK, France, Germany, Italy, and Spain. The target was 100 patients per country and at least 15 per centre. Patients were not eligible for the study if they had a new diagnosis of PsA at the current clinic visit, were not comfortable completing an app-based questionnaire or paper case-report form, or were unable to speak/read the local language.

Data

The following patient and disease characteristics were recorded: patient demographics, PsA duration, current treatment, number of comorbidities (according to the functional comorbidity index [START_REF] Groll | The development of a comorbidity index with physical function as the outcome[END_REF]) and disease activity. Disease components were measured by: i)

A clinical assessment of tender and swollen joint count, dactylitis count, body surface area of psoriasis and physician numerical rating score (NRS) of overall disease activity.

ii) Leeds Enthesitis Index (LEI) [START_REF] Healy | Measuring clinical enthesitis in psoriatic arthritis: Assessment of existing measures and development of an instrument specific to psoriatic arthritis[END_REF] iii) PsAID-12 questionnaire via the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) app on a tablet (scored from 0-10, with 10 reflecting worst possible health) [START_REF] Walsh | Impact of key manifestations of psoriatic arthritis on patient quality of life, functional status, and work productivity: Findings from a real-world study in the United States and Europe[END_REF]. The PsAID-12 score is a weighted sum of the scores for the 12 questions divided by 20.

iv)

Patient numerical rating scale (NRS) for global disease activity (psoriasis and arthritis) and pain (scored from 0-10, with 10 reflecting highest disease activity) [START_REF] Jensen | The measurement of clinical pain intensity: A comparison of six methods[END_REF] v)

The health assessment questionnaire (HAQ, scored 0-3 with 3 being worst health) [START_REF] Højgaard | A systematic review of measurement properties of patient reported outcome measures in psoriatic arthritis: A grappa-OMERACT initiative[END_REF] vi)

The EQ-5D VAS for current health (scored 0-100, with 100 being best possible health) [START_REF] Rabin | EQ-SD: A measure of health status from the EUROQOL Group[END_REF].

Treatment decisions were documented as no change in treatment, treatment escalation or treatment reduction. Treatment escalation included dose increase, frequency increase, altered route of administration, medication addition or medication switch.

Results:

Demographic and clinical characteristics

Five hundred and three patients were recruited from 24 centres across the UK, Spain, France, Italy and Germany. Patient demographics varied by country (Table 1). Overall, 247 (49.1%) patients were female and mean patient age was 53 years (range 18-83). The UK had the lowest mean patient age, whilst Italy and France had a notably higher proportion of males. In all countries, the most common PsA subtype was peripheral arthritis (83.7% of all patients) and the number of co-morbidities was low. Patient-and physician-markers of disease activity reflected mild disease across all countries (Table 1, Figure 1a-c), although median scores for tender joint counts, patient-reported and physician-reported disease activity, PsAID-12, EQ-VAS and HAQ were highest in the UK.

Prescribing practices

Current prescribing practices varied by country (Table 2). The use of glucocorticoids was uncommon across countries. CsDMARDs formed the predominant treatment in the UK (66.4% of UK patients) but were less frequently used in continental Europe (32.1-48.6% of patients per country). Conversely, bDMARDs) were the most frequently used medication in all countries other than the UK. Among csDMARDS, the most commonly used medication in all countries was methotrexate (38.6% of all patients). The preference for bDMARD varied: adalimumab was the most used bDMARD in the UK and Spain; adalimumab and secukinumab were equally used in Germany; and ixekizumab and adalimumab were joint-first in Italy.

A decision to alter the current treatment regime occurred in 36.2% (182 patients) of the cohort, with treatment escalation being the predominant change (160 patients) (Table 3). Only 22 patients (4.4%) had their treatment decreased after their consultation. Notably, the frequency of treatment escalation was highest in the UK, occurring in nearly half of all UK consultations (51 patients, 47.7%), and lower in continental Europe (ranging from 23.8% to 31.5% per country). The predominant method to achieve treatment escalation was medication addition in all countries except Italy, where medication switch was most common.

Shared decision-making

CollaboRATE (n=498) and PEPPI-5 scores (n=494) were positively-skewed to the upper limit (Figure 2a-b, Table 3). 52.9% of all patients gave the highest possible CollaboRATE score. The mean PEPPI-5 score in male and female patients were similar (21.4 in both), as were the mean CollaboRATE scores (8.0 in both). When comparing patients with the lowest 5% of PEPPI-5 scores to the remaining cohort, the mean age (53.4 vs 54.0 years), percentage of female patients (58.3% vs 48.4%) and mean disease duration (11.2 vs 10.8 years) were similar.

Discussion

The PsA cohort is highly heterogeneous in clinical phenotype and treatment responsiveness, making treatment decisions complex and multi-factorial [START_REF] Noviani | Choosing the right treatment for patients with psoriatic arthritis[END_REF]. Current prescribing practices are likely to vary by geographical location but this has not been well described. In this multi-centre international analysis of routine clinical practice, we found significant variation in prescribing practices by country. Notably, the frequency of bDMARD use in continental Europe was significantly higher than the UK, where csDMARD use predominated. National Institute for Health and Care Excellence (NICE) guidelines advise the use of at least 2 csDMARDs prior to starting biologic use in the UK and requires patients to have at least 3 tender and swollen joints, explaining the predominance of csDMARDs in the UK cohort [START_REF]Guidance | Etanercept, infliximab and adalimumab for the treatment of psoriatic arthritis | Guidance | NICE[END_REF]. In Europe, guidelines vary by country but the use of biologics is not generally restricted to a number of affected joints/enthesitis or a pre-requisite for failing 2 DMARDs [START_REF] Alonso | Recommendations of the Spanish Society of Rheumatology on treatment and use of systemic biological and non-biological therapies in psoriatic arthritis[END_REF][START_REF] Coates | The updated grappa and EULAR recommendations for the management of psoriatic arthritis: Similarities and differences[END_REF][START_REF] Marchesoni | Recommendations for the use of biologics and other novel drugs in the treatment of psoriatic arthritis: 2017 update from the Italian Society of Rheumatology[END_REF].

The level of disease activity across multiple patient-and physician-reported outcome measures was highest in the UK, potentially reflecting current prescribing differences or a selection bias. The UK has 25% fewer physicians per 1000 people than mainland Europe [28]. Post-Covid clinical pressures in the UK during ASSIST recruitment meant that those attending a face-to-face consultation were those with active disease flares. A higher capacity to review stable/non-flaring patients in Europe may explain some of the geographical differences in disease severity and treatment choices between UK and mainland Europe. Treatment escalation was more common in the UK (47.7% of patients) than Europe (23.8-31.5% of patients per country), in keeping with the higher level of physician-and patient-reported disease activity, the predominance of csDMARD use and the younger patient demographic in the UK, with treatment escalation being more likely earlier in the disease course.

SDM is crucial in PsA, given the variation of clinical phenotypes and treatment efficacies in different disease domains. SDM can also help overcome the discordance in assessment of disease activity by the patient and the clinician, which is particularly noted in mild disease [START_REF] Desthieux | Determinants of Patient-Physician Discordance in Global Assessment in Psoriatic Arthritis: A Multicenter European Study[END_REF]. Despite its importance, the extent of SDM in PsA has not been examined as of yet. We measured clinician collaborative effort and patient communication confidence with CollaboRATE and PEPPI-5 questionnaires [START_REF] Barr | The psychometric properties of collaborate: A fast and frugal patient-reported measure of the shared decisionmaking process[END_REF][START_REF] Maly | Perceived efficacy in patientphysician interactions (PEPPI): Validation of an instrument in older persons[END_REF]. Reassuringly, we found high CollaboRATE and PEPPI-5 scores across centres, irrespective of treatment decision. Patients were recruited by systematic sampling to minimise selection bias and questionnaires were completed independent from clinicians. These results differ from previous analyses of SDM which reported lower rates of SDM in other inflammatory arthropathies. A selfreported analysis of SDM amongst rheumatologists treating rheumatoid arthritis in Japan found only 27% practiced SDM and an independent observational analysis of recorded rheumatoid arthritis consultations in the Netherlands found a mean score of 28/100 on the observer patient involvement scale, an alternative measure of SDM [START_REF] Mathijssen | Shared decision making in routine clinical care of patients with rheumatoid arthritis: An assessment of audio-recorded consultations[END_REF][START_REF] Aoki | Preferences of Japanese rheumatoid arthritis patients in treatment decision-making[END_REF]. The contrast with our findings may reflect an increased awareness of-and/or training in-SDM over recent years.

In consultations with lower levels of reported collaboration, treatment escalation was only seen in patients with higher disease impact (PsAID-12 score >5). However, in consultations with high levels of clinician effort to collaborate, treatment escalation occurred in patients with mild or active disease (low or high PsAID-12 scores). This may reflect improved identification of symptoms/concerns in more collaborative consultations that subsequently justify treatment escalation, underlining the importance of SDM. However, the data could be explained by retrospective bias, where patients who receive treatment escalation are more likely to report their consultation as collaborative than those that don't.

Data generalisability was enhanced by undertaking an international analysis of over 500 participants, including multiple centres per country. However, all patients were recruited from specialist PsA clinics and disease activity was generally low, which may differ from other rheumatology clinics.

Limitations of our study also include clinician awareness of SDM assessment, the ineligibility of patients who were unable to speak/read the local language and inclusion only of face-to-face consultations. With an increasing frequency of virtual consultations, it is important to assess whether high levels of SDM are maintained on online platforms. Future qualitative work to identify factors associated with more collaborative consultations may guide improvements in clinical practice.

Conclusion

This study delineates current PsA prescribing practices, disease characteristics and shared decisionmaking across multiple centres in the UK, France, Germany, Italy and Spain. Disease characteristics and treatment strategies varied between countries, but particularly between UK and mainland Europe. In keeping with a greater restriction on bDMARD use, csDMARDs predominated in the UK. Patients reported high levels of SDM in face-to-face PsA consultations, unrelated to treatment escalation. In patients with low PsAID-12 scores, those with higher perceived collaboration were more likely to have treatment escalation than those without, which may reflect the identification of otherwise undetected symptoms/concerns.

Supplementary material

Tables Table 1. Patient demographics and disease characteristics by country France (

Figure 1 .

 1 Figure 1. Box plots of disease activity, physical function and medication class by country (a) Physician NRS of overall global assessment (scored 0-10, with 10 as worst disease), (b) PsAID-12 score (scored 0-10, with 10 as worst disease) (c) Health Assessment Questionnaire (HAQ, scored 0-3 with 3 as worst health) and (d) medication class by country.

Figure 2

 2 Figure 2 Box plots by country of (a) mean CollaboRATE score and (b) PEPPI-5 score.There was no clear association between treatment escalation and CollaboRATE or PEPPI-5 scores: the mean CollaboRATE and PEPPI-5 scores were similar in those with and without treatment escalation (mean CollaboRATE 8.12 vs 7.88, mean PEPPI-5 21.3 vs 21.5) and the percentage of patients providing a maximum CollaboRATE score was similar irrespective of treatment escalation or not (51.9% vs 53.4%). The relationship between CollaboRATE, PsAID-12 and treatment escalation was examined (Figure3). Of 16 patients with a low CollaboRATE score (CollaboRATE<4.5), treatment escalation only occurred in patients with a PsAID-12 >5 and not in any patients with PsAID-12 <5. In contrast, of 226 patients with CollaboRATE scores >4.5, treatment escalation occurred in patients with high and low PsAID-12 scores, including 59 patients with PsAID-12 <5.

Figure 3 .

 3 Figure 3. Treatment escalation (red) vs no escalation (blue), according to mean CollaboRATE and PsAID-12 scores per patient.

Figure 9A :

 9A Figure 9A: Relationship between mean Collaborate score and PsAID Points represent whether escalation occurred or not

France

  score, median (IQR) 3.7 (1.8-5.5) 2.0 (0.9-4.0) 2.5 (0.8-5.0) 3.1 (1.5-5.0) 5.1 (2.4-6.7) 3.3 (1.3-5.4) .0-80.0) 70.0 (42.5-85.0) 70.0 (50.0-80.0) 70.0 (55.0-80.0) 60.0 (40.0-75.0) 65.0 (50.0-80.0)

France

Table 2 .

 2 Current prescribing practices and treatment decisions by country Note that patients could have had more than one reason for increase/decrease so percentages may not sum to 100

		France	Germany	Italy	Spain	UK	All
		(n=100)	(n=101)	(n=84)	(n=111)	(n=107)	(n=503)
	Any csDMARDs,	52 (52.0)	45 (44.6)	27 (32.1)	54 (48.6)	71 (66.4)	249 (49.5)
	n (%)
	Methotrexate	43 (43.0)	38 (37.6)	23 (27.4)	40(36.0)	50 (46.7)	194 (38.6)
	Leflunomide	3 (3.0)	3 (3.0)	1 (1.2)	6 (5.4)	4 (3.7)	17 (3.4)
	Sulfasalazine	0 (0.0)	0 (0.0)	4 (4.8)	6 (5.4)	19 (17.8)	29 (5.8)
	Other	4 (4.0)	3 (3.0)	2 (2.4)	2 (1.8)	5 (4.7)	16 (3.2)
	Any bDMARDs,	63 (63.0)	69 (68.3)	62 (73.8)	69 (62.2)	39 (36.4)	302 (60.0)
	n (%)
	Anti-TNF	37 (37.0)	32 (31.7)	33 (39.2)	37 (33.3)	26 (24.3)	165 (32.8)
	Anti-IL17A	9 (9.0)	23 (22.8)	23 (27.4)	20 (18.0)	7 (6.5)	82 (16.3)
	Anti-IL12/23	10 (10.0)	5 (5.0)	4 (4.8)	7 (6.3)	2 (1.9)	28 (5.6)
	Other	5 (5.0)	8 (7.9)	1 (1.2)	5 (4.5)	3 (2.8)	22 (4.4)
	Oral	2 (2.0)	10 (9.9)	9 (10.7)	10 (9.0)	6 (5.6)	37 (7.4)
	glucocorticoids,
	n (%)
	Treatment
	decisions, n (%)
	No change in	70 (70.0)	67 (66.3)	60 (71.4)	72 (64.9)	52 (48.6)	321 (63.8)
	treatment
	Treatment	28 (28.0)	26 (25.7)	20 (23.8)	35 (31.5)	51 (47.7)	160 (31.8)
	Increase

*

Table 3 .

 3 CollaboRATE and PEPPI-5 scores by country

Acknowledgements

BJI has received speaker's honoraria from Lilly, Abbvie and Janssen; consultancy fees from Amgen, UCB and Janssen; support for attending congress from Novartis, Pfizer, UCB. Beatriz Joven has participated in clinical trials and/or research projects sponsored by Janssen, Lilly, Bristol Myers Squibb, Abbvie.

JAPT has received speaker's honoraria from Janssen, Novartis, Pfizer, AbbVie, Biogen, Lilly, Novartis, Sandoz, UCB; LCC has received grants/research support from AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Novartis, Pfizer and UCB; worked as a paid consultant for AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, GSK, Janssen, Medac, Novartis, Pfizer and UCB. LC is funded by a National Institute for Health Research Clinician Scientist award. The research was supported by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC), ADS. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health.

We acknowledge the support of the National Institute for Health Research Clinical Research Network (NIHR CRN) in the UK.

Funding

Amgen Grant number: AP-NI-PSA-PI-13894 Sponsor: University of Oxford Role of funding body in project: The study received financial support from Amgen through an unrestricted research grant.

Availability of data and materials

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Ethics approval and consent to participate

Ethics reference: 20/PR/0587 IRAS ID: 287039

Consent for publication

Not applicable .

Competing interests

CC, LW, CWS, MB, DT, ADS, TW, PH, PH, AH, MK, CMM, JP, MS, PS, and MW have nothing to declare.

UK has received grant and research support and consultancy fees from AbbVie, Amgen, Biocad, Biogen, Chugai, Eli Lilly, Fresenius, Gilead, Grünenthal, GSK, Hexal, Janssen, MSD, Novartis, onkowoessen.de, Pfizer, Roche, UCB and Viatris.

Authors contributions

LW and CC wrote the initial draft of the manuscript.

CW-S co-designed the statistical analysis and contributed to the methods and results of the manuscript.

LC was chief investigator.

The steering committee (LG, UK, EL, RQ) participated in designing the study, translated the documents, obtained the national ethical approvals and were national principal investigators.

All other co-authors aided in data collection at individual centres.

All authors read, contributed to and approved the final manuscript before submission.


Objectives : This study aimed to evaluate the 10-year clinical outcome of patients with recentonset axial spondyloarthritis (axSpA).

Methods : Study design : The DESIR cohort is an inception cohort of axSpA patients. Diagnosis and Management: The diagnosis and management of patients were based on the decision of the treating rheumatologist. Statistical Analysis: Both complete cases and imputed data analyses were conducted.

Results : Of the 708 enrolled patients, 45 were excluded due to a change in the baseline diagnosis, 3 patients died, and 300 were lost to follow-up over the 10y. In the completer population, one patient required bilateral total hip replacement, and 56 patients received a pension due to invalidity. The prevalence of main extra-musculoskeletal features increased from baseline to year 10: psoriasis from 18% to 30%, acute anterior uveitis from 10% to 18%, and inflammatory bowel disease from 5% to 10%. Page 3 of 20 Journal Pre-proof 3 The most frequent comorbidity was hypertension, with an increase from 5% to 15% from baseline to year 10. In the imputed data analysis the estimated proportions of patients with an acceptable status at year 10 were 70% [95% CI: 63; 77] for acceptable PASS, 43% [95% CI: 37; 49] for BASDAI < 3, and 48% [95% CI: 41; 56] for ASDAS < 2.1.

Conclusion: These findings suggest that despite a quite favorable 10-year outcome exists for severe outcomes, a large proportion of patients present with an important disease burden reflected by patient-reported outcomes. This information can be valuable for providing patients with information at the time of diagnosis.

Contributorship :

MD proposed the idea of this research project . Both MD,CS ,SA,TL and AM were in charge of the statistical analysis plan. CS and SA were in charge of the statistical analysis. All the co-authors have reviewed the manuscript and in particular the interpretation of the results.

Introduction

Historically, in the field of axial spondyloarthritis (axSpA) previous studies [START_REF] Kiltz | Spondylarthropathies: pathogenesis and clinical features[END_REF][START_REF] Van Der Horst-Bruinsma | Spondyloarthritis: treatment[END_REF][START_REF] Sieper | Clinical features of ankylosing spondylitis[END_REF] have portrayed a rather severe and poor long-term prognosis, not only in terms of disease severity (e.g., approximately 15% estimated coxitis prevalence in Western European countries [START_REF] Hajjaj-Hassouni | Comparison of patients evaluated for spondylarthropathy in France and Morocco[END_REF] and 50% in North Africa [START_REF] Hajjaj-Hassouni | Comparison of patients evaluated for spondylarthropathy in France and Morocco[END_REF][START_REF] Claudepierre | Predictive factors of severity of spondyloarthropathy in North Africa[END_REF], or the 5-10% requirement for total hip replacement within 10 years of disease onset) [START_REF] Sweeney | Total hip arthroplasty in ankylosing spondylitis: outcome in 340 patients[END_REF], but also in terms of comorbidities such as cardiovascular morbidity and reduced life expectancy [START_REF] Moltó | Prevalence of comorbidities and of their screening in spondyloarthritis: results of the international cross-sectional ASAS-COMOSPA study[END_REF][START_REF] Fakih | World mortality of ankylosing spondylitis, psoriatic arthritis and inflammatory bowel disease in 2015 and its evolution from 2001 to 2015[END_REF][START_REF] Bodur | Cardiovascular comorbidities in spondyloarthritis[END_REF].This description can be distressing for patients who have recently received a diagnosis and are concerned about their long-term prognosis. . Nevertheless, there have been in the past decades recent major therapeutical advances in the field [START_REF] Baraliakos | Treatment overview of axial spondyloarthritis in 2023[END_REF], and a growing emphasis on early diagnosis [START_REF] Van Der | ASAS consensus definition of early axial spondyloarthritis[END_REF][START_REF] Van Der Heijde | Justification for including MRI as a tool in the diagnosis of axial SpA[END_REF][START_REF] Rudwaleit | Referral strategies for early diagnosis of axial spondyloarthritis[END_REF] and proactive disease management [START_REF] Smolen | Treating axial spondyloarthritis and peripheral spondyloarthritis, especially psoriatic arthritis, to target: 2017 update of recommendations by an international task force[END_REF][START_REF] Molto | Efficacy of a tight-control and treat-to-target strategy in axial spondyloarthritis: results of the open-label, pragmatic, cluster-randomised TICOSPA trial[END_REF]. Consequently, this shift has raised important questions about whether the long-term prognosis for individuals with this condition has indeed improved compared to historical cohorts in particular for patients with a recent diagnosis.

Given these preliminary considerations, we seized the opportunity provided by the DESIR cohort, which followed patients with recent-onset (symptom duration of less than 3 years) axSpA for 10 years, and the baseline factors associated with a low-disease activity status after 10 years.

Patients -Methods

 Patients

The DESIR cohort (NCT01648907) has been previously described [START_REF] Dougados | Clinical presentation of patients suffering from recent onset chronic inflammatory back pain suggestive of spondyloarthritis: The DESIR cohort[END_REF]. Briefly, consecutive patients aged 18-50 with inflammatory back pain [START_REF] Calin | Clinical history as a screening test for ankylosing spondylitis[END_REF][START_REF] Rudwaleit | Inflammatory back pain in ankylosing spondylitis: a reassessment of the clinical history for application as classification and diagnostic criteria[END_REF] and a duration of ≥3 months and <3 years were included in 25 centers in France if the treating rheumatologist considered the symptoms suggestive of axSpA (a score ≥5 on a scale from 0 to 10, where 0 indicated "not suggestive" and 10 indicated "very suggestive"). Between December 2007 and April 2010, 708 patients were included. A detailed description of the study protocol is available on the DESIR website (http:/www.lacohortedesir.fr).

The research proposal for this analysis was approved in January 2022 by the scientific committee of the DESIR cohort.

The study was conducted according to good clinical practice guidelines and was approved by the local ethical committee (EUDRACT#2007-A00608-45, Ethical committee file#2457, dated September 17th, 2007). All enrolled patients provided written informed consent to participate.

• Data Collected

At baseline, the following variables were collected: demographics (age, gender), socioprofessional status, HLA B27 antigen, and symptom duration.

During all visits (semi-annually during the first 2 years and annually thereafter), the following variables were collected:

-Items to check if the patients fulfilled the ax-SpA criteria (Amor [START_REF] Amor | Criteria of the classification of spondylarthropathies[END_REF] and ASAS [START_REF] Rudwaleit | The development of Assessment of SpondyloArthritis international Society classification criteria for axial spondyloarthritis (part II): validation and final selection[END_REF] ).

-Disease activity and severity parameters, including BASDAI [START_REF] Garrett | A new approach to defining disease status in ankylosing spondylitis: the Bath Ankylosing Spondylitis Disease Activity Index[END_REF], ASDAS [START_REF] Lukas | Development of an ASASendorsed disease activity score (ASDAS) in patients with ankylosing spondylitis[END_REF], CRP, and BASFI [START_REF] Calin | A new approach to defining functional ability in ankylosing spondylitis: the development of the Bath Ankylosing Spondylitis Functional Index[END_REF].

-Impact of the disease on the daily life of the patients, including ASAS HI [START_REF] Kiltz | The ASAS Health Index (ASAS HI) -a new tool to assess the health status of patients with spondyloarthritis[END_REF] and SF-36 [START_REF] Ware | SF-36 Health Survey Manuel and Interpretation Guide[END_REF].

-Extra-spinal manifestations of the disease, including synovitis, dactylitis, and enthesitis.

-Extra-musculoskeletal manifestations of the disease, including psoriasis, uveitis, and inflammatory bowel disease (IBD).

-Main comorbidities, including severe gastrointestinal events, hypertension, major atherosclerotic cardiovascular events (MACE), diabetes, cancer, and infection (tuberculosis and other severe infections).

-Pharmacological treatment modalities, including NSAID intake according to the ASAS-NSAID scoring system [START_REF] Dougados | ASAS recommendations for collecting, analysing and reporting NSAID intake in clinical trials/epidemiological studies in axial spondyloarthritis[END_REF], conventional synthetic and targeted DMARDs (cs/tsDMARDs).

-Requirement for surgical treatment modalities, including total hip replacement due to coxitis and spinal vertebrotomy -Socio-professional status, including the number of days of sick leave and pension of invalidity, according to the procedures of the French health care system (category I: the patient can continue to work part-time, and the financial compensation is equal to 30% of the income of the previous 10 best years; category II: the patient is unable to work, and the financial compensation is equal to 50% of the income of the previous 10 best years; category III: same as category II, plus the necessity to get help from another person in daily life, and the financial compensation is the same as category II but increased by 40%).

 Statistical analysis

Studied populations :

This study includes two populations: "completers," referring to patients who had a full 10-year follow-up and "intention-to-follow" patients, including all patients that were originally included in the DESIR cohort (i.e. "completers" and patients who were lost-to-follow-up). For patients who were lost to follow-up,10-year outcomes were imputed by multiple imputation based on all the information available from the "completers" population and the patients who were excluded from the study for another diagnosis during follow-up (i.e., after year 2, as per protocol) [START_REF] Ramiro | ASAS-EULAR recommendations for the management of axial spondyloarthritis: 2022 update[END_REF].

Characteristics of the patients at year 10 are described. Quantitative variables are presented with their mean and standard deviation or median with interquartile range, and qualitative variables with their frequency and associated proportions.

Ten-year outcomes

Ten-year outcomes are presented in the two populations:

 Completers: all 10-year outcomes are described using the mean and standard deviation for quantitative variables, and frequency with proportions for qualitative variables.

 Intention-to-follow: to explore potential selection bias, a sensitivity analysis was conducted, including all patients thanks to previously imputed outcomes. In this analysis, patients with a documented change in the baseline diagnosis of AxSpA were excluded, as well as patients who died during the 10-year follow-up period. Estimations with their 95% confidence intervals are presented. This approach was not possible when there was too much missing data or too few events in completers for qualitative variables.

Baseline factors associated with long-term (10-year) low disease activity status

Finally, we evaluated the association between baseline potential predictive factors and low disease activity at year 10, defined as an ASDAS-CRP <2.1 [START_REF] Machado | Assessment of SpondyloArthritis international Society (ASAS). Ankylosing Spondylitis Disease Activity Score (ASDAS): 2018 update of the nomenclature for disease activity states[END_REF] using a multivariate logistic regression analysis. Patients with a documented change in the baseline diagnosis were excluded and the same variable selection principles were used than in the previous analyses. Odds-ratio with their 95% confidence interval are presented.

All statistical analyses were performed using SAS enterprise guide 7.1 software.

Results :

1

. Patients and study course

The flowchart of the patients is summarized in Figure 1.

Of the 708 enrolled patients, 45 were excluded from the cohort due to a change in the baseline diagnosis by their treating rheumatologist. These 45 patients represented 6.4% of the entire cohort and 12.4% of the completers. The diagnoses justifying the exclusion of the patients from the cohort were as follows: mechanical back pain (n = 30), fibromyalgia (n = 13), a non-axial spondyloarthritis (axSpA) undifferentiated inflammatory rheumatic disease (n = 1), and no information (n = 1). During the 10-year follow-up period, 3 patients died due to the following: suicide (n = 1), colorectal cancer (n = 1), sudden death (n = 1).

Of the remaining 660 patients, 300 were lost to follow-up during the 10-year period with the following estimations: 6%, 13%, 18%, 22%, 25%, 32%, 35%, 37%, 41%, 46% from the first to the tenth-year visits, respectively.

The baseline characteristics of the patients regarding these different populations are summarized in Table I. We also evaluated the fulfillment of axSpA classification criteria (e.g., AMOR and ASAS criteria) regarding the patients' status during the 10-year follow-up period.

It should be noted that 21 (49%) and 16 (36%) out of the 45 patients with a documented change in diagnosis fulfilled the baseline Amor and ASAS criteria, respectively. The proportion of patients fulfilling these criteria in the completer population went from 85% to 100% for the Amor criteria and from 68% to 83% for the ASAS criteria from baseline to year 10, respectively.

Ten-year outcomes

-Disease management during the 10 year follow-up period:

o Treatments: In the completers population, the percentage of patients with at least one session of supervised physiotherapy during the 6-month period preceding the visit was 42% and 39% at baseline and after 10 years of follow-up, respectively. Regarding pharmacological treatment, in the completer population the percentage of patients with NSAID intake (ASAS NSAID score >0) during the week preceding the visit was 72% and 42% at baseline and after 10 years of follow-up, respectively. The percentage of patients with at least one intake of conventional synthetic disease-modifying antirheumatic drugs during the 10-year follow-up period was 18%/17% and 55% for sulfasalazine/methotrexate and bDMARDs (mainly TNF inhibitors), respectively.

o Work impact: during the 10-year follow-up period, 273 (75.8%) patients required at least one day of sick leave due to the disease, and the average number of days on sick leave was 193 ± 296. Additionally, 56 patients received a pension for invalidity due to the disease (19, 22, 3, and 13 patients received this pension in category I, II, III, and unknown category, respectively). Finally, among patients with a professional activity, 65 had to change their job due to the disease.

-

Extra-musculoskeletal manifestations and comorbidities

The occurrence of the main extra-musculoskeletal manifestations and comorbidities in the completers is summarized in Figure 2. It is noteworthy that extra-musculoskeletal manifestations were frequent not only at baseline but also during the follow-up period.

Hypertension was the most frequent incident comorbidity over time.

-Disease activity/severity and its impact on the daily life of the patients Table II summarizes the observed (i.e. completers population) and imputed (i.e. in the intention-to-follow population) results in these different domains. These data suggest a favorable 10-year disease outcomes, particularly when looking at markers of severity, such as the requirement for total hip replacement (only 1 patient) or spinal vertebrotomy (not a single patient).

Moreover, the results in the completer population and in the intention-to-follow population are quite similar. This overall favorable outcome is also suggested by the high percentage (around 77%) of patients considering their status as acceptable at year 10. However, when considering either the quality of life and/or the impact of the disease on the daily life of the patients, as evaluated by the ASAS Health Index instrument, it seems that the percentage of patients in an acceptable condition was only around 40% to 50%. The same conclusion can be drawn regarding the percentage of patients in an acceptable condition when considering the composite indices evaluating axSpA disease activity (for example, around 48% to 55% of the patients with an ASDAS < 2.1).

Predisposing factors of a low disease activity status at year 10

The results of both the uni-and multivariate analyses are summarized in Table III. A few parameters have been identified in the multivariate analysis. However, for these parameters, the odds ratio could be considered relatively low (always below 2). The three parameters retained in the multivariate analysis reflect: 1) the management process of the patients (quick referral to a specialized center), 2) the patients' situation (better job situation), and 3) disease activity at baseline.

Discussion :

This study evaluates the 10-year outcome of patients enrolled in an inception cohort of recent-onset axSpA, allowing for a better understanding of the long-term prognosis of these patients.

Our results from this inception cohort in terms of long-term outcomes are quite reassuring, as a favorable outcome was observed in stringent parameters such as the need for surgery (only one patient requiring total hip replacement in our cohort, compared to 5 to 10% in conventional retrospective cohorts [START_REF] Sweeney | Total hip arthroplasty in ankylosing spondylitis: outcome in 340 patients[END_REF]).

The interpretation of the results in terms of Patient-Reported Outcomes is more debatable.

The data appear favorable when considering the overall evaluation by the patients, as around 77% of them rated their condition as acceptable at year 10. However, when examining other parameters, such as those evaluating disease activity levels (e.g., BASDAI, ASDAS) and/or the impact of the disease on daily life (e.g., ASAS-HI, SF 36), data suggest that a significant percentage of patients (around 50%) do not meet the recommended criteria to be considered as having an acceptable condition (e.g., ASDAS <2.1, for example [START_REF] Ramiro | ASAS-EULAR recommendations for the management of axial spondyloarthritis: 2022 update[END_REF]).

Furthermore, the analysis evaluating the baseline predisposing factors of an acceptable disease activity status (defined here as an ASDAS value <2.1 [START_REF] Machado | Assessment of SpondyloArthritis international Society (ASAS). Ankylosing Spondylitis Disease Activity Score (ASDAS): 2018 update of the nomenclature for disease activity states[END_REF]) identified different parameters: a) a baseline BASDAI <40/100; however, this parameter may be considered irrelevant due to circular reasoning, as some items of the ASDAS composite index are included in the BASDAI; b) the short delay from the onset of symptoms is more challenging to interpret but potentially supports early referral to a specialist [START_REF] Rudwaleit | Referral strategies for early diagnosis of axial spondyloarthritis[END_REF]; c) Anterior chest-wall pain is considered as "axial enthesitis," frequently associated with a polyenthesitis condition [START_REF] Wendling | Anterior chest wall pain in recent inflammatory back pain suggestive of spondyloarthritis. data from the DESIR cohort[END_REF], which contributes to a disabling disease [START_REF] Nadon | Clinical peripheral enthesitis in the DESIR prospective longitudinal axial spondyloarthritis cohort[END_REF]. Therefore, it is not surprising that the absence of these parameters at baseline is associated with an acceptable condition at year 10; d) socio-professional parameters (e.g., job, situation, and education level) highlight the issue of inequity observed in axSpA [START_REF] Nikiphorou | Inequity in biological DMARD prescription for spondyloarthritis across the globe: results from the ASAS-COMOSPA study[END_REF][START_REF] Capelusnik | Individual-level and country-level socio-economic factors and health outcomes in spondyloarthritis: analysis of the ASAS-perSpA study[END_REF] In summary, these data suggest a favorable 10-year outcome in terms of stringent measures, such as the need for surgery, much different from historic reports. Nevertheless, these contrast with a less favorable outcome in terms of disease activity parameters, with identified predictive factors. These data should improve and facilitate the information provided to patients at the time of diagnosis. Further studies are required to evaluate this long-term outcome in different countries, different healthcare systems, and potentially over longer durations. ° Data provided are the observed median, along with the minimal and maximal percentage values from the imputed datasets

FIGURES:

-

  University of Paris-Cité, Department of Rheumatology, Hôpital Cochin. Assistance Publique -Hôpitaux de Paris -INSERM (U1153): Clinical epidemiology and biostatistics (CRESS) -e-mail : maxime.dougados@aphp.fr -ORCID# : 000-0003-3009-6229 Chris SERRAND : -Title : MD -Affiliation : Department of biostatistics, epidemiology, public health and methodological innovation, Nîmes University Hospital, Nîmes, France. -E-mail : chris.serrand@chu-nimes.fr -ORCID # : 0000-0002-6074-8577 Sandrine ALONSO : -Title : MSc -Affiliation : Department of Biostatistics, Clinical Epidemiology, Public Health and Innovation in Methodology (BESPIM), CHU Nîmes, Univ Montpellier, Nîmes, France -E-mail : sandrine.alonso@chu-nimes.fr -ORCID # : 0000-0001-9838-0272 Francis BERENBAUM : -Title : MD, PhD -Affiliation : Sorbonne University, INSERM, AP-HP Saint-Antoine hospital, Paris, France -E-mail : francis.berenbaum@aphp.fr -ORCID # : 0000-0001-8252-7815 Pascal CLAUDEPIERRE : -Title : MD -Affiliation Aphp-Service de Rhumatologie, Hôpital Henri Mondor , AND Université Paris Est Créteil, EA 7379 -EpiDermE -E-mail : pascal.claudepierre@aphp.fr -ORCID # : 0000-0003-1911-0544 Bernard COMBE : -Title : MD,PhD -Affiliation : Montpellier University France -E-mail : bernard.combe@umontpellier.fr -ORCID # : 0000-0003-4002-1861 Laure GOSSEC : -Title : MD PhD -Affiliation : Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique, AP-HP, Pitié-Salpêtrière hospital, Rheumatology department, Paris, France. -E-mail : laure.gossec@aphp.fr -ORCID # : 0000-0002-4528-310X Adeline RUYSSEN-WITRAND : -Title : MD,PhD -Affiliation : Department of Rheumatology, Toulouse University Hospital, Centre d'Investigation Clinique de Toulouse CIC1436, Inserm, Paul Sabatier University Toulouse III, Toulouse, France -E-mail : adruyssen@hotmail.com -ORCID # : 0000-0002-9815-2138 Alain SARAUX -Title : MD, PhD -Affiliation : Department of Rheumatology, CHU Brest, université de Bretagne occidentale (UBO), Inserm, UMR1227, LabEx IGO, Brest, France -E-mail : alain.saraux@chu-brest.fr -ORCID # : 0000-0002-8454-7067 Daniel WENDLING : -Title : MD, PhD -Affiliation : Department of Rheumatology, CHU (university Hospital) Besançon; EA4266 EPILAB, Université de Franche-Comté, Besançon, France -E-mail : dwendling@chu-besancon.fr -ORCID # : 0000-0002-4687-5780 Thierry LE QUERRE : -Title : MD, PhD -Affiliation : Department of Rheumatology, Rouen University, INSERM (U1234), Institute de Recherche et d'Innovations Biomedicales, CIC/CRB 1404. -E-mail : thierry.lequerre@chu-rouen.fr -ORCID # : 0000-0001-8126 -6596 Anna MOLTO : -Title : MD PhD -Affiliation : Rheumatology Department, Cochin Hospital, AP-HP, Paris, France -E-mail : anna.molto@aphp.fr -ORCID # 0000-0003-2246-1986 Competing interests : See the COI filled by all the authors.

Figure 1 :Figure 2 :

 12 Figure 1: Flow-chart of the axSpA patients during their 10-year follow-up

II: Disease activity, severity and disease impact on the daily life of the patients after a 10

 10

Table I : Baseline characteristics of the patients with regard to their status during the 10 year follow-up period

 I

	Baseline characteristics	Baseline population	Completers a	Lost of follow-up
		n = 708	n = 360	n = 300
	Age (years) †	34 ±9	34 ± 9	32± 8
	Female	381 (54%)	192 (53%)	163 (54%)
	Ethnicity : white caucasien	641 (91%)	328 (91%)	266 (89%)
	Educational level : university	418 (59%)	231 (64%)	159 (54%)
	Time from first symptoms to baseline (years)	1.5 ± 0.9	1.5 ± 0.9	1.6 ± 0.9
	HLA B27 : positive	410 (58%)	231 (64%)	160 (54%)
	Extraspinal manifestations
	(past or present)
	-Enthesitis	348 (49%)	177 (49%)	147 (49%)
	-Synovitis	151 (21%)	85 (24%)	62 (21%)
	-Dactylitis	92 (13%)	50 (14 %)	39 (13%)
	Extra-musculoskeletal manifestations
	(past or present)
	-Psoriasis	119 (17%)	67 (19%)	48 (16%)
	-Uveitis	60 (8%)	35 (10%)	23 (8%)
	-IBD*	28 (4%)	17 (5 %)	11 (4%)

Table

Table II : Baseline predisposing factors of a low disease activity status (ASDAS <2.1) at year 10

 II

	Baseline characteristics	Low disease activity status at year 10 Yes No		Statistical analysis Univariate Multivariate
		48.1 [42.9 -51.7] 51.9 [48.3 -57.1]	(Odds ratio [95% CI]	(Odds ratio [95% CI]
	Male (%)	48.7 [47.6 -51.3] 58.8 [56.1 -60.2]	1.45 [0.99 ; 2.11]	-
	Delay from first syptoms to baseline < 1.5	57 [53.6 -58.6]	48 [45.9 -50.9]	1.39 [0.91 ; 2.13]	1.46 [0.93 ; 2.29]
	years (%)
	Job situation (white collar) (%)	56.7 [54.8 -61.1]	38.6 [36.6 -41]	2.11 [1.39 ; 3.21]	1.87 [1.20 ; 2.90]
	Education level (≥university) (%)	65.4 [64.8 -71.7]	53.3 [49.9 -54]	1.79 [1.11 ; 2.90]	-
	Absence of anterior chest wall pain (%)	57.5 [55.5 -58.7] 50.5 [49.1 -52.6]	1] 1.31 [0.91 ; 1.90]	-
			43 [37 ; 49]%
	BASDAI score < 40 (%)	70 [63 ; 77]% 49.8 [47.1 -53.7] 31.7 [30.2 -33.7]	2.13 [1.4 ; 3.23]	1.91 [1.23 ; 2.94]
			2.39 [1.80 ; 2.98]
			48 [41 ; 56]%
			25 [19 ; 32]%
			77 [NA]%
			34 [30 ; 39]%
			NA*
			41 [35 ; 47]%
			6.7 [5.8 ; 7.6]
			27.4 [22.9 ; 31.9]
			41.5 [39.5 ; 43.6]
			43.1 [40.3 ; 45.8]
	*NA= Not Available

Acknowledgements :

The DESIR cohort is conducted with Assistance Publique-Hopitaux de Paris (AP-HP, Paris France) as the sponsor and under the umbrella of the French Society of Rheumatology.

The DESIR cohort is run with the support of unrestricted grants from (in order of decreasing support) Pfizer France, Biogen, AbbVie, UCB, Lilly, Galapagos, Novartis, MSD, Fresenius and Celltrion HealthCare. We thank the Clinical Research Unit Paris Centre (AP-HP, Paris France), and the Institut national de la sante et de la recherche medicale (Inserm). We also thank the investigators: Pr Maxime Dougados, Pr André Kahan, Dr Julien Wipff and Dr Anna Molto (Paris-Cochin), Pr Olivier Meyer, Pr Philippe Dieudé (Paris-Bichat), Pr Pierre Bourgeois, Pr Laure Gossec (Paris-La Pitie-Salpétriere), Pr Francis Berenbaum (Paris-Saint-Antoine), Pr Pascal Claudepierre (Creteil), Pr Maxime Breban, Pr Maria-Antonietta D'Agostino, Pr Félicie Costantino (Boulogne-Billancourt), Pr Michel De Bandt, Dr Bernadette Saint-Marcoux (Aulnay-sous-Bois), Pr Philippe Goupille (Tours), Pr Jean-Françis Maillefert (Dijon), Pr Xavier Puechal, Dr Emmanuelle Dernis (Le Mans), Pr Daniel Wendling, Pr Clément Prati (Besançon), Pr Bernard Combe, Pr Cédric Lukas (Montpellier), Pr Liana Euller-Ziegler, Pr Véronique Breuil (Nice), Pr Pascal Richette (Paris Lariboisière), Pr Pierre Lafforgue, Pr Thao Pham (Marseille), Pr Patrice Fardellone, Dr Patrick Boumier, Dr Pauline Lasselin (Amiens), Pr Jean-Michel Ristori, Pr Martin Soubrier, Pr Anne Tournadre (Clermont-Ferrand), Dr Nadia Mehsen (Bordeaux), Pr Damien Loeuille (Nancy), Pr Rene-Marc Flipo (Lille), Pr Alain Saraux (Brest), Pr Corinne Miceli, Dr Stephan Pavy (Le Kremlin-Bicêtre), Pr Alain Cantagrel, Pr Adeline Ruyssen-Witrand (Toulouse), Pr Olivier Vittecoq, Pr Thierry Lequerre (Rouen).

Funding :

The DESIR cohort is run with the support of unrestricted grants from (in order of decreasing support) Pfizer France, Biogen, AbbVie, UCB, Lilly, Galapagos, Novartis, MSD, Fresenius