MD Juliette M S Drouet
email: juliettemsdrouet@gmail.com

MD, PhD Laure Gossec
email: laure.gossec@aphp.fr

Tel=+33626980553

Laure Pr

Gossec

Work-related issues and a high burden of disease are frequent in axial spondyloarthritis. What should we be doing better

Keywords: Axial Spondyloarthritis, Disease Activity, Quality of Life, Patient Reported Outcome, Work Related Issues

Axial Spondyloarthritis (axSpA) is a chronic progressive inflammatory disease leading to functional limitations, affecting physical and mental health [START_REF] Puyraimond-Zemmour | Similar alteration for mental and physical aspects in health-related quality of life over 5 to 8 years in 1347 patients with early arthritis and early inflammatory back pain[END_REF]. The impact of axSpA on work productivity is a matter of great concern to society, since this disease starts early in life, and the subsequent loss of productivity contributes to the important socioeconomic burden of axSpA. Furthermore, for patients themselves, work is a key aspect of impact. In a survey, the most important elements linked to quality of life were financial losses, work capacity, memory / concentration and activities of daily living [START_REF] Kwan | A systematic review of quality-of-life domains and items relevant to patients with spondyloarthritis[END_REF].

In this issue of the Journal of Rheumatology, R. Inman and colleagues have assessed factors associated with work-related issues in Canadian patients with axSpA [START_REF] Inman | Work-related Issues, Physical and Psychological Burden in Canadian Axial Spondyloarthritis Patients. Results From the International Map of Axial Spondyloarthritis[END_REF]. In all, 542

Canadian patients who participated in an international survey, the International Map of Axial Spondyloarthritis (IMAS) online survey, were analysed. A first important finding is that, although the mean age was 44 years, only 52.6% were employed. This number could be compared to the mean employment rate in Canada, which in 2021 was 61% [4]. In the IMAS survey, employment status was associated with lower disease activity and a more favorable overall health status. A second finding is related to difficulties when working. The authors found that 90% of patients who were either employed, unemployed, or on short-term disability (n=339) reported a work-related issue in the previous year, with the most frequent being absenteeism (49%) including missing work for healthcare provider visits, as well as difficulty fulfilling working hours (31%) [START_REF] Inman | Work-related Issues, Physical and Psychological Burden in Canadian Axial Spondyloarthritis Patients. Results From the International Map of Axial Spondyloarthritis[END_REF]. Work-related issues were associated with worse patient-reported outcomes (PROs), in particular higher functional limitations and psychological distress [START_REF] Inman | Work-related Issues, Physical and Psychological Burden in Canadian Axial Spondyloarthritis Patients. Results From the International Map of Axial Spondyloarthritis[END_REF]. The number of work-related issues was also associated with higher disease activity (mean BASDAI 6.1 vs. 4.0; p<0.001). Interestingly, the association between disease activity and work-related issues disappeared, when factoring in disability benefits.

These results indicate that even today in a country with wide access to targeted drugs (Canada), only half the patients who responded to a survey were working and 90% of those working suffered from consequences of their axSpA on their work. Of note, Inman's study only reflects the status of the survey respondents, since this was a survey based on voluntary participation. Furthermore, there was no confirmation of diagnosis by a healthcare provider, and no confirmation of work status. However, we advocate these results indicate that rheumatologists should take an interest in the work status of their patients.

The article by Inman et al confirms that axSpA is associated with substantial consequences on the ability to work, as has been shown in other countries [START_REF] Carvalho | Determinants of health-related quality of life in spondyloarthritis and rheumatoid arthritis -data from the COMOSPA and COMORA studies[END_REF]. For example, in Italy, the employment rate of axSpA patients was 53% (compared to 58% in the general population) [START_REF] Ramonda | Patient-reported impact of spondyloarthritis on work disability and working life: the ATLANTIS survey[END_REF]. It is probable that axSpA leads to lower employment rates through non-access to a working status for patients with an early disease onset, and through loss of work for patients starting their disease later in life. The adverse work consequences of axSpA include absenteeism as shown in the IMAS survey [START_REF] Inman | Work-related Issues, Physical and Psychological Burden in Canadian Axial Spondyloarthritis Patients. Results From the International Map of Axial Spondyloarthritis[END_REF] but also loss of productivity and less access to positions with responsibilities [START_REF] Hollick | Outcomes and treatment responses, including work productivity, among people with axial spondyloarthritis living in urban and rural areas: a mixed-methods study within a national register[END_REF]. This may be because axSpA often impact patients in the third decade of life, a crucial period in active life [START_REF] Nikiphorou | Association of Comorbidities in Spondyloarthritis With Poor Function, Work Disability, and Quality of Life: Results From the Assessment of SpondyloArthritis International Society Comorbidities in Spondyloarthritis Study[END_REF].

Since ability to work is an important outcome, what can rheumatologists and healthcare providers do to improve the status of their patients? To answer this, we need to look at the elements associated to adverse work outcomes. In the IMAS survey, Inman et al showed an association between diagnostic delay and work-related issues (mean diagnostic delay, 10.2 vs. 3.8 years; p<0.001). Other studies have reported a worsened health-related quality of life (HRQoL) in people experiencing longer delays before diagnosis [START_REF] Marzo-Ortega | The impact of gender and sex on diagnosis, treatment outcomes and health-related quality of life in patients with axial spondyloarthritis[END_REF]. These results may be an argument to consider closely the window of opportunity principle in axSpA [START_REF] Benavent | How is early spondyloarthritis defined in the literature? Results from a systematic review[END_REF].

A second element that healthcare providers should address is physical function and mobility [START_REF] Kiltz | Effects of patient and disease characteristics on global functioning in patients with axial spondyloarthritis in routine care[END_REF]. Unsurprisingly, adverse work outcomes in axSpA have been associated to labourintensive jobs, poor physical function, structural damage and impaired spinal mobility [START_REF] Nikiphorou | Association of Comorbidities in Spondyloarthritis With Poor Function, Work Disability, and Quality of Life: Results From the Assessment of SpondyloArthritis International Society Comorbidities in Spondyloarthritis Study[END_REF][START_REF] Dean | Five Potentially Modifiable Factors Predict Poor Quality of Life in Ankylosing Spondylitis: Results from the Scotland Registry for Ankylosing Spondylitis[END_REF].

Here, adapted and progressive physiotherapy may be key [START_REF] Ramiro | ASAS-EULAR recommendations for the management of axial spondyloarthritis: 2022 update[END_REF][START_REF] Elolemy | Health-Related Quality of Life in Patients with Ankylosing Spondylitis: Relationship with Disease-Related Variables[END_REF].

Importantly, disease activity plays a role in adverse work outcomes in axSpAas shown by several studies including Inman's article [START_REF] Inman | Work-related Issues, Physical and Psychological Burden in Canadian Axial Spondyloarthritis Patients. Results From the International Map of Axial Spondyloarthritis[END_REF][START_REF] Nikiphorou | Association of Comorbidities in Spondyloarthritis With Poor Function, Work Disability, and Quality of Life: Results From the Assessment of SpondyloArthritis International Society Comorbidities in Spondyloarthritis Study[END_REF]. In fact, disease activity indices have been shown to be associated to the impact of axSpA on work but also on other aspects of life, including pain, worse physical function but also depression, anxiety, fatigue, and sleep alterations [START_REF] Navarro-Compán | Axial spondyloarthritis[END_REF].

We previously explored the variance of HRQoL (SF-36) explained by the disease activity score, ASDAS-CRP, in the French inception cohort, Devenir des Spondylarthropathies Indifférenciées Récentes (DESIR), and found ASDAS explained 27.4% of altered physical composite scores, and 14.6% of mental composite scores [START_REF] Puyraimond-Zemmour | Similar alteration for mental and physical aspects in health-related quality of life over 5 to 8 years in 1347 patients with early arthritis and early inflammatory back pain[END_REF]. Many other studies and a recent systematic literature review have confirmed a link between disease activity and HRQoL [START_REF] Carvalho | Determinants of health-related quality of life in spondyloarthritis and rheumatoid arthritis -data from the COMOSPA and COMORA studies[END_REF][START_REF] Carvalho | Long-Term Association Between Disease Activity and Disability in Early Axial Spondyloarthritis: Results From a Prospective Observational Study of Inflammatory Back Pain[END_REF][START_REF] Hernandez Alava | Measuring quality of life of patients with axial spondyloarthritis for economic evaluation[END_REF]. The magnitude of this link varies according to the statistical methods used and the population analysed. One important point to consider when discussing the link between PROs and disease activity is that in axSpA, disease activity scores are deeply influenced by the patient's assessment of his/her symptoms. This is the case in the patientreported score BASDAI, but also (to a less extent) in the ASDAS [START_REF] Aouad | Defining and managing flares in axial spondyloarthritis[END_REF][START_REF] Costantino | Correspondence between patientreported flare and disease activity score variation in axial spondyloarthritis: A 12-months web-based study[END_REF]. This may lead to circularity.

Factors other than disease activity which contribute to HRQoL which healthcare professionals need to consider, include extra-musculoskeletal manifestations (uveitis, inflammatory bowel disease, psoriasis), widespread pain, and other comorbidities including anxiety and depression [START_REF] Puyraimond-Zemmour | Similar alteration for mental and physical aspects in health-related quality of life over 5 to 8 years in 1347 patients with early arthritis and early inflammatory back pain[END_REF][START_REF] Nikiphorou | Association of Comorbidities in Spondyloarthritis With Poor Function, Work Disability, and Quality of Life: Results From the Assessment of SpondyloArthritis International Society Comorbidities in Spondyloarthritis Study[END_REF]. In particular, fibromyalgia is frequent in axSpA and there is a strong link between fibromyalgia and worsened HRoL, fatigue and adverse work outcomes [START_REF] Macfarlane | Co-Occurrence and Characteristics of Patients With Axial Spondyloarthritis Who Meet Criteria for Fibromyalgia: Results From a UK National Register[END_REF].

In conclusion, axSpA is associated to frequent alterations in ability to work and productivity at work, including in the recent survey in Canada [START_REF] Inman | Work-related Issues, Physical and Psychological Burden in Canadian Axial Spondyloarthritis Patients. Results From the International Map of Axial Spondyloarthritis[END_REF]. Because of the link between disease activity and adverse work outcomes as well as worsened HRQoL overall, it is important to aim for a tight disease control in axSpA. Furthermore, because adverse work outcomes and HRQoL are multi-factorial, a holistic approach is warranted.

has received a Master's bursary from the Societe Française de Rhumatologie (n°4281)