Pain is the leading cause of disability worldwide, yet no harmonised self-reported reference framework exists to characterise how its burden is distributed across the lifespan and world regions. Here, we harmonised individual-level self-reported pain data from 6,075,021 participants across 894 population-based data sources in 118 countries to establish global reference trajectories of pain. We implemented these trajectories in an open-access benchmarking platform for positioning external datasets against global pain norms. Pain prevalence ranged from 2.5% for facial pain to 45.0% for back pain, was consistently higher in women across all eleven anatomical sites (risk ratio range 1.09 to 1.83), and increased most steeply before age 55 years. Contrary to existing estimates that generally project higher prevalence of pain conditions in higher Human Development Index (HDI) regions, we found that individuals in the lowest HDI countries experienced nearly twice the late-life prevalence of any bodily pain compared with those in the highest (risk difference 31.8 percentage points [95% CI 30.1–33.6]). Globally, 18.3% of pain burden across anatomical sites was attributable to three modifiable risk factors (smoking, obesity, and low income) but this varied from 12.6% in sub-Saharan Africa to 27.1% in eastern Europe, indicating that the drivers of pain in lower-HDI settings remain poorly characterised.

OBJECTIVES:Ultrasound (US) is a valuable tool to detect inflammation in peripheral psoriatic arthritis (pPsA). This multicentre study assessed the intra- and inter-reader reliability of US-detected elementary lesions in peripheral psoriatic arthritis (pPsA) and evaluated the impact of standardized training on reliability, as a first step to guide multicentre assessment in the APACHE cohort. METHODS:A cross-sectional study was conducted to analyse the reliability of pPsA US lesions, as a first step in an ongoing predictive cohort (APACHE, NCT03768271) study. Three web-based reliability exercises were carried out between 2020 and 2024. Inter-rater and intra-rater reliability were assessed using Light's kappa (κ). During the third reliability exercise, a reference atlas of elementary US lesions in dactylitis was developed. RESULTS:Experienced and trainee sonographers from 30 recruiting centres participated into the study. In step 1, intra-reader kappas were moderate-to-good for synovitis (0.50-0.80), tenosynovitis (0.51-0.63), enthesitis (0.62-0.73), and poor for dactylitis (0.31-0.47); inter-reader kappas were lower for synovitis (0.32-0.70), tenosynovitis (0.40-0.49), enthesitis (0.47-0.60) and dactylitis (0.13-0.24). In Step 2, reliability improved notably in expert and trainees except for dactylitis [intra-reader: synovitis (0.81-0.90), tenosynovitis (0.66-0.83), enthesitis (0.61-0.81), dactylitis (0.37-0.47); inter-reader: synovitis c(0.72-0.84), tenosynovitis (0.55-0.76), enthesitis (0.37-0.59), dactylitis (0.12-0.30)]. Step 3 achieved moderate-to-good reliability for dactylitis (intra 0.69-0.80, inter 0.46-0.68). An atlas was produced based on expert consensus and lesion identification rates among sonographers. CONCLUSION:Standardized training was associated with a marked improvement in intra- and inter-reader reliability for the assessment of elementary pPsA lesions. The consensus-based US atlas provides practical guidance for identifying challenging dactylitis-related lesions in clinical and research settings.

INTRODUCTION:The concept of difficult-to-treat (D2T)/difficult-to-manage (DTM) disease was first defined in rheumatoid arthritis (RA). Recent definitions for axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) combine non-response to treatment including targeted and biologic treatment, inflammatory disease activity, and patient symptoms. This concept could apply to other chronic inflammatory diseases such as psoriasis (PsO) and inflammatory bowel disease (IBD). A consensus definition of D2T IBD is available but is yet to be fully articulated in PsO. AREAS COVERED:This article aims to provide an expert overview of the shared elements and potential differences between the definitions and concepts of D2T/D2M in these diseases. EXPERT OPINION:D2T/D2M definitions should allow better evaluation of refractory diseases, accurate determination of disease severity, and effective treatment of the D2T areas or domains. Definitions should consider response to previous lines of treatment, control of inflammation, and global disease improvement, and consider the impact of D2T disease on patient status/quality of life. Proof-of-concept studies need to assess the current and future definitions of D2T/D2M populations in axSpA, PsA, PsO, and IBD, to accurately determine the prevalence of patients meeting each of those D2T criteria sets, and to identify risk factors, disease burden, and appropriate management strategies.

OBJECTIVE:This study aimed to investigate the relationship between spinal axial spondyloarthritis (axSpA)-related lesions and degenerative lesions (DLs) over 10 years (10Y). METHODS:Whole spine MRI and cervical/lumbar spine radiographs at baseline/5Y/10Y from patients with axSpA from the DESIR cohort were assessed for axSpA-related lesions and DLs by three independent readers, different teams for the two lesion types. We used multilevel (patient and vertebra, considering consensus across readers), standard and time-lagged autoregressive generalized estimating equation (GEE) models. The relationship between syndesmophytes and the subsequent development of osteophytes/syndesmophytes in adjacent vertebrae on radiographs was analysed using a time-lagged autoregressive GEE model, after excluding vertebrae with both lesions. All models were adjusted for age, sex, HLA-B27 status, BMI, smoking and job type, and bDMARDs during follow-up. RESULTS:Data from 326 patients (35 [S.D. = 9] years; 46% men) showed a significant association between axSpA-related lesions on MRI and the total number of DLs on MRI, though the effect sizes were small (β-coefficients: 0.07-0.17). On radiographs, paravertebral syndesmophytes were significantly associated with the total number of DLs (β-coefficient: 0.37; 95%CI: 0.26-0.48). However, these associations were not found in time-lagged autoregressive models. Syndesmophytes increased the risk of adjacent syndesmophyte [odds ratio (OR):6.92; 95%CI: 2.44-19.61], but not of osteophytes (OR: 1.05; 95%CI: 0.25-4.36). CONCLUSION:Although significant associations were found between axSpA-related lesions and DLs at the same time point, no temporal relationship was observed. On radiographs, syndesmophytes increased the risk of syndesmophytes at adjacent levels, but there was no association with osteophyte development. AxSpA-related lesions and DLs coexist, but progress independently of each other.

OBJECTIVE:To assess the association between duration of targeted therapy exposure and cancer risk in patients with spondyloarthritis (SpA), including those with psoriatic arthritis, axial SpA, and other subtypes. METHODS:This nationwide cohort study used the French health insurance database to identify adults with SpA initiating a targeted therapy (tumor necrosis factor inhibitors [TNFi], interleukin-17 inhibitors [IL-17i], IL-12/23i, IL-23i, JAK inhibitors [JAKi]) from January 2014 to September 2022. Patients with prior cancer, HIV infection, or organ transplantation were excluded. Follow-up began after a three-month delay and continued until December 2024. Exposure was assessed annually and classified as ≤6 or >6 months per year. Incident cancer was the primary outcome. Weighted Cox marginal structural models with inverse probability of treatment and censoring weights were used. A post hoc sensitivity analysis evaluated cumulative exposure trajectories over time. RESULTS:We included 56,591 patients (53.9% women; mean ± SD age 44 ± 13 years; median follow-up 5.0 years). During follow-up, 1,224 cancers occurred (1,029 solid, 116 hematological, 79 unclassified). Exposure >6 months versus ≤6 months was associated with a lower risk of overall cancer (weighted hazard ratio [wHR] 0.86, 95% confidence interval [CI] 0.75-0.99). In subgroup analyses, this association was observed for hematological malignancies (wHR 0.65, 95% CI 0.42-0.99) but not for solid cancers (wHR 0.92, 95% CI 0.79-1.07). Cumulative exposure history was not associated with cancer risk. CONCLUSION:In this nationwide study, prolonged exposure to targeted therapies was not associated with an increased cancer risk. Exposure >6 months per year was associated with a lower cancer risk, mainly for hematological malignancies, whereas cumulative exposure over multiple years was not associated with cancer risk.

Background Spinal degenerative lesions are prevalent on MRI scans and radiographs in the general population and axial spondyloarthritis (axSpA) cohorts. However, their interrelationships remain poorly understood. Purpose To investigate longitudinal relationships between spinal degenerative lesions in axSpA over 10 years. Materials and Methods This secondary analysis of a prospective cohort (Devenir des Spondylarthropathies Indifférenciées Récentes [DESIR]) included whole-spine MRI scans and cervical and lumbar radiographs from individuals with axSpA assessed for 10 MRI and six radiographic degenerative lesions by three readers at baseline, 5 years, and 10 years. Patients with two or more time points were included. Multilevel logistic regression analyses using a generalized estimating equations approach (logit link, binomial family) were developed to assess whether the presence of a lesion at one time point was associated with subsequent lesions at the same and adjacent vertebral units. Time-lagged and autoregressive models evaluated inter- and intralesion temporal relationships, accounting for within-patient, within-reader, and within-vertebral unit dependence, and were adjusted for age, sex, HLA-B27 status, body mass index, smoking, job type, and biologic agents during follow-up. Results Imaging was available for 329 patients (mean age, 35 years ± 9 [SD]; 175 women). At MRI, longitudinal associations were found between disk degeneration and subsequent herniation (odds ratio [OR], 3.97 [95% CI: 3.41, 4.62]; P < .001), high-intensity zone (OR, 1.77 [95% CI: 1.49, 2.11]; P < .001), and Modic type 1 lesions (OR, 4.53 [95% CI: 3.53, 5.80]; P < .001) within the same vertebral unit. Modic type 1 lesions were associated with subsequent Modic type 2 lesions within the same unit (OR, 49.36 [95% CI: 34.66, 70.28]; P < .001). Herniations persisted over time (OR, 184.00 [95% CI: 154.00, 221.00]; P < .001). On radiographs, disk height loss was associated with osteophyte formation (OR, 4.33 [95% CI: 3.63, 5.17]; P < .001). MRI lesions were associated with the appearance of corresponding degenerative lesions on subsequent radiographs at the same level (OR, 2.49 [95% CI: 2.18, 2.83]; P < .001). Conclusion Long-term imaging analyses in axial spondyloarthritis demonstrated temporal relationships between spinal degenerative lesions on MRI scans and radiographs, highlighting the progressive nature of spinal degeneration. © RSNA, 2026 Supplemental material is available for this article.

Objectives To investigate whether the initial location of inflammatory axial pain in axial spondyloarthritis (axSpA) is associated with the development of peripheral or extra-rheumatological manifestations over a 10-year period.Methods Data were drawn from the 10-year prospective DESIR (Devenir des Spondylarthropathies Indifférenciées Récentes; French Cohort of Undifferentiated Spondyloarthritis) cohort of axSpA at disease onset. Patients with available data on the initial location of inflammatory axial pain were included. The main outcomes were the occurrence of extra-axial manifestations (arthritis, dactylitis, enthesitis) and extra-rheumatological manifestations (psoriasis, uveitis, inflammatory bowel disease). Patients were categorised according to the initial location of inflammatory axial pain as cervicothoracic, lumbosacral or diffuse (involving both regions). Associations between inflammatory axial pain location and extra-axial or extra-rheumatological manifestations were assessed using multivariate Cox models, adjusted for age, sex, exposure to conventional synthetic and biological disease-modifying antirheumatic drugs (as time-dependent covariates) and the presence of these manifestations at baseline.French Cohort of Undifferentiated Spondyloarthritis cohort of axSpA at disease onset. Patients with available data on the initial location of inflammatory axial pain were included. The main outcomes were the occurrence of extra-axial manifestations (arthritis, dactylitis, enthesitis) and extra-rheumatological manifestations (psoriasis, uveitis, inflammatory bowel disease). Patients were categorised according to the initial location of inflammatory axial pain as cervicothoracic, lumbosacral or diffuse (involving both regions). Associations between inflammatory axial pain location and extra-axial or extra-rheumatological manifestations were assessed using multivariate Cox models, adjusted for age, sex, exposure to conventional synthetic and biological disease-modifying antirheumatic drugs (as time-dependent covariates) and the presence of these manifestations at baseline.Results Among 662 included patients, 94 (14.2%) had cervicothoracic, 466 (70.3%) had lumbosacral and 102 (15.5%) had diffuse involvement at baseline. Patients with diffuse involvement were older, had a lower education level, a lower prevalence of prior dactylitis and higher modified Stoke Ankylosing Spondylitis Spinal Score compared with other groups. Over 10 years, diffuse involvement was independently associated with an increased risk of developing arthritis (HR 1.61; 95% CI 1.15 to 2.25) compared with lumbosacral involvement. No other significant associations were observed.Conclusion Diffuse initial axial involvement identifies a subgroup of patients with axSpA at increased risk of developing peripheral arthritis. This finding has practical implications for clinicians in early risk stratification, patient counselling and interpretation of therapeutic trial outcomes.

Les progrès observés depuis 30 ans dans le domaine de la spondyloarthrite axiale (axSpA) n’ont pas permis de répondre à toutes les questions se posant actuellement dans cette pathologie. Ce manuscrit présente les conclusions de la réunion de la French spondyloArthitiS Task force (FAST) qui s’est tenue à Besançon les 28 et 29 septembre 2023. Un travail préalable en sous-groupe a eu pour objectif d’évaluer l’état actuel des connaissances et d’identifier les besoins non couverts dans différents domaines de la axSpA sélectionnés par le comité de pilotage. Ces différents éléments ont fait l’objet d’une discussion collégiale durant les deux jours de réunion en présentiel. Les différents points de discussion ont ainsi été individualisés en tant que besoins non satisfaits : des biomarqueurs pour le diagnostic précoce et l’activité de la maladie, un dossier électronique commun dédié à la SpA à l’échelle nationale, une meilleure compréhension de la dysbiose dans la maladie, une check-list pour l’adressage au rhumatologue, l’adaptation des seuils des autoquestionnaires au sexe féminin, la mise en place de programmes de dépistage des comorbidités, les nouveaux outils d’imagerie, les approches cellulaires et multi-omiques en recherche, le regroupement, au niveau national, de différentes cohortes et registres, les études de stratégies thérapeutiques, la définition consensuelle de la maladie difficile à traiter et de sa prise en charge, le stade préclinique de la maladie, la maîtrise de l’IA en tant qu’outil dans les différents aspects de la recherche. Ces éléments peuvent représenter un cadre pour l’agenda de la recherche sur l’axSpA pour les années à venir.

OBJECTIVES:The objectives of this study were to evaluate the effectiveness of short message service (SMS) and/or email reminders in improving influenza vaccination coverage rates among RA patients treated with anti-TNF therapies, and to identify factors associated with vaccination. METHODS:This study was a nested randomized controlled trial in the ART e-cohort, an ongoing French nationwide multicentre prospective cohort of RA patients treated with anti-TNF therapy. Patients were 1:1 randomized, with stratification on age. The intervention consisted of regular reminders via SMS and/or emails to get vaccinated against influenza during the vaccination campaign. At the end, all participants received a questionnaire. The primary outcome was influenza vaccination coverage. Secondary outcomes included the vaccination coverage before and after the COVID-19 pandemic, and factors associated with vaccination. RESULTS:Between October 2021 and April 2022, 446 participants were randomized (224 to the intervention group and 222 to the control group). Among them, 325 (73%) reported their vaccination status and 221 (68%) were vaccinated against influenza: 116/158 (73%) in the intervention group, vs 105/167 (63%) in the control group (relative risk 1.08; 95% CI 0.95-1.23). The vaccination coverage before and after the COVID-19 pandemic did not differ (72% vs 72%; 95% CI -8% to 8%). Age ≥65 years [odds ratio (OR) 6.25; 95% CI 2.88-13.60] and previous influenza vaccination in the years before inclusion (OR 7.81; 95% CI 4.36-14.02) were associated with higher rates of vaccination. CONCLUSION:SMS and/or e-mail reminders did not significantly improve influenza vaccination rates in our cohort. The COVID-19 pandemic did not substantially impact the influenza vaccination coverage. Our results might be counterbalanced by an already high vaccination coverage. TRIAL REGISTRATION:ClinicalTrials.gov, http://clinicaltrials.gov, NCT05220423, NCT03062865.

To investigate the occurrence of spinal degenerative lesions (DL)s in axial spondyloarthritis (axSpA) inception cohort in radiographs and MRI over 10 years (10Y), to assess their changes over time and factors associated with them. Whole spine MRI and cervical and lumbar spine radiographs at baseline/5Y/10Y of patients with axSpA from the DESIR cohort were assessed for DLs by three readers. For descriptive analyses, DLs were defined by agreement between ≥ 2/3 readers or using the average of their assessments, at the patient level (≥ 1 lesion/patient). To assess the progression of DLs over time, we used multilevel generalised estimating equation models considering individual reader data. Imaging was available for 330 patients (mean age 34 [9] years, 47

OBJECTIVES:To describe the design and methodology of APACHE, a cohort of patients with early peripheral psoriatic arthritis (pPsA), and to assess the main baseline clinical characteristics of the first included patients. METHODS:APACHE is an ongoing prospective multicentre national cohort (NCT03768271) with a planned follow-up of 10years. Included patients have recent-onset (<12months) peripheral arthritis, a personal and/or family history of psoriasis, pPsA diagnosed by a rheumatologist, and no history of targeted disease-modifying antirheumatic drug therapy. At inclusion, demographic data, disease activity, comorbidities, and imaging results (not reported here) are collected. A descriptive analysis of these data was performed. RESULTS:The first 186 study patients had a mean age of 44±11years and mean arthritis duration of 6±4months; 84 (45%) were women; 169 (91%) had a history of psoriasis (mean duration, 14years) and 71 (38%) were receiving methotrexate. Disease activity was moderate with a mean DAPSA score of 19±14 and mean swollen and tender joint counts of 2.1±3.2 and 6.0±8.0, respectively. The initially involved joints were mainly the hands (40%) and knees (28%). Entheseal pain (39%) was more prevalent than dactylitis (27%). Comorbidities were common, with obesity in 27% and at least one cardiovascular risk factor or disease in 49% of patients. CONCLUSION:Patients with early peripheral PsA had moderate disease activity, a predominant oligoarticular profile, and a high prevalence of entheseal pain.