Stylianos Georgiadis

Objective: Identifying patient characteristics that predict treatment response in psoriatic arthritis (PsA) may help optimize treat-to-target strategies. We aimed to explore overall and sex-specific predictors of secukinumab (SEC) effectiveness in European patients with PsA treated in routine care. Methods: We analyzed data from 14 registries in the European Spondyloarthritis (EuroSpA) Research Collaboration. Patients aged ≥ 18 years at diagnosis, initiating SEC treatment from January 2015 to January 2021, were included. Multiple imputation was used for missing covariates at treatment start (baseline) and Disease Activity Index for Psoriatic Arthritis based on 28 joints (DAPSA28) at 6 months. Overall and sex-stratified analyses were performed by logistic and Cox regressions to identify baseline predictors of the following treatment outcomes: (1) DAPSA28 low disease activity (LDA; DAPSA28 ≤ 14) at 6 months, (2) DAPSA28 moderate response at 6 months, and (3) SEC discontinuation within 12 months. Results: In total, 2790 patients (43% male) were included. Median age was 43 years (IQR 34-52), and SEC was the first-line biologic/targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD) in 665 patients (24%). Positive predictors for both DAPSA28 LDA and DAPSA28 moderate response were male sex, fewer previous b/tsDMARDs, C-reactive protein (CRP) > 10 mg/L, and lower Health Assessment Questionnaire (HAQ) score. Absence of psoriasis, higher patient fatigue, and tender joint counts predicted SEC discontinuation within 12 months. For some outcomes, sex-specific predictors were fewer previous b/tsDMARDs and CRP > 10 mg/L among male patients and lower patient fatigue score among female patients. Conclusion: We identified overall and sex-specific predictors of SEC effectiveness in European patients with PsA. Our findings may support personalized treatment decisions.

Evidence on treat-to-target strategies in axial spondyloarthritis (axSpA) remains limited. We evaluated 1-year clinical and MRI outcomes of a secukinumab-b

Introduction: Evidence of treat-to-target strategies including secukinumab dose escalation in patients with axial spondyloarthritis (axSpA) remains limited. We investigated the effect of a treat-to-target approach aiming for Axial Spondyloarthritis Disease Activity Score (ASDAS) remission, assessed by clinical and MRI outcomes over 24 weeks. Methods: TRACE was a multicentre study including biologic-naïve patients with active axSpA. Sixteen weeks after secukinumab 150 mg initiation, patients in ASDAS remission (<1.3)(week 16 remitters) continued the same dose, while non-remitters (week 16 non-remitters) escalated to 300 mg/month. Sacroiliac joint (SIJ) and spine MRIs were performed at baseline, weeks 4, 16 and 24, and centrally scored using Spondyloarthritis Research Consortium of Canada (SPARCC) and Canada-Denmark scores for inflammation and structural lesions. The primary end point was total MRI-inflammation improvement ≥2 (weeks 16–24) comparing week 16 remitters and week 16 non-remitters. Results: Of 90 patients, 68% were male, mean age was 35.4 years. At week 16, 30 (35%) patients achieved ASDAS remission. At week 24, 36 (49%) patients were in ASDAS remission, including 10 (22%) week 16 non-remitters, who responded after dose escalation (dose-escalation responders). Already at week 4, marked reductions in total MRI inflammation (SPARCC spine+SIJ) (–14.7), and structural lesion remodelling (reduced SIJ erosion; increased SIJ fat and backfill), were observed. These changes continued through week 16, with only minor improvements thereafter. The primary end point occurred in 14 (52%) of week 16 remitters versus 19 (41%) of week 16 non-remitters (p=0.53). Dose-escalation responders had a numerically larger mean total MRI inflammation reduction (–6.1) than dose-escalation non-responders (–2.2). Conclusion: No statistically significant effect of secukinumab dose escalation on reducing MRI-detected inflammation was observed, except in a selected subgroup of patients. However, 22% achieved ASDAS remission after dose escalation. Notably, substantial MRI-detected inflammation reduction and structural remodelling occurred within the first 4 weeks. Trial registration number: NCT03639740 .

Le présent travail porte sur l’estimation d’un système en temps discret dont l’évolution est décrite par une chaîne semi-markovienne (CSM) d’espace d’état fini. Nous présentons le principe d’invariance sous forme multidimensionnelle pour le noyau semi-markovien (NSM), ainsi que diverses mesures du processus. Ensuite, nous étudions l’estimation non-paramétrique de la loi stationnaire de la CSM, en considérant deux estimateurs différents, et nous montrons qu’ils ont le même comportement asymptotique. La probabilité de la première entrée est également introduite. Nous proposons un estimateur et nous étudions ses propriétés asymptotiques : la convergence forte et la normalité asymptotique.D’autre part, nous nous concentrons sur l’étude de la fiabilité des systèmes semi-markoviens. Nous définissons la fiabilité sur intervalle d’un système dont la fiabilité et la disponibilité sont des cas particuliers et nous étudions les propriétés asymptotiques d’un estimateur proposé. De plus, nous présentons une comparaison de l’estimation des différentes mesures de fiabilité fondées sur deux estimateurs du NSM, en réalisant une trajectoire unique et des observations multiples indépendantes. Ce travail fournit aussi des résultats dans le cas semi-markovien à temps discret avec espace d’état général. Nous évaluons l’approximation de moyenne et de diffusion des chaînes de renouvellement markovien. Enfin, nous nous sommes aussi intéressés à une autre classe des processus pour laquelle nous obtenons des résultats dans le cadre des files d’attente. Nous étudions l’approximation de moyenne pour le modèle d’Engset en temps continu et nous appliquons ce résultat aux files d’attente avec ré-essais.

Objective: This study (the SpACT study) aimed to investigate the frequency and localisations of different types of spinal new bone formation (NBF) in patients with axial spondyloarthritis (axSpA), psoriatic arthritis (PsA), rheumatoid arthritis (RA) and healthy controls (HCs) using low-dose CT (ldCT). Methods: Patients with axSpA, PsA or RA, and HC without a history of chronic back pain were included and underwent ldCT of the entire spine. Three readers blinded to all clinical information, including diagnosis, assessed sagittal and coronal images for NBF: (1) marginal syndesmophytes, (2) non-marginal syndesmophytes and (3) osteophytes. Results: 69 participants (33 females, mean age 51.4 years) were included: AxSpA: 30; PsA: 19; RA: 10; HC: 10. Across all groups, the thoracic spine consistently showed the highest number of NBFs, especially for marginal syndesmophytes and osteophytes. Furthermore, on sagittal images, NBF, regardless of type, occurred predominantly at the anterior vertebral corners. Coronal images showed right-sided dominance of NBFs, particularly osteophytes and non-marginal syndesmophytes, whereas marginal syndesmophytes had an almost equal overall distribution. Both sagittal and coronal reconstructions demonstrated high inter-reader reliability (intraclass correlation coefficient >0.9) for almost all groups for detecting any type of NBF. Conclusion: AxSpA exhibited a distinct NBF pattern characterised by frequent marginal syndesmophytes, particularly in the thoracic spine. In contrast, the most prevalent findings in the other groups were osteophytes, and no consistent NBF pattern was observed to distinguish the groups from each other. Further studies, especially longitudinal assessments using ldCT or equally bone-sensitive imaging methods, are needed to further increase our understanding of NBF patterns.

Objective: The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) is widely used for assessing disease activity in patients with axial spondyloarthritis (axSpA), particularly in settings where markers of inflammation are unavailable. As no consensus on BASDAI cut‐off values exists for disease activity states in axSpA, we aimed to develop and validate such cut‐offs against external criteria. Methods: Routine care patients with axSpA initiating a biologic disease‐modifying antirheumatic drug in eight European registries were included. Receiver operating characteristic analyses against external criteria were performed to determine optimal BASDAI values for separating remission, low disease activity (LDA), high disease activity (HDA), and very high disease activity (VHDA). Follow‐up data at 6 months were used to select BASDAI cut‐off values between remission and LDA and between LDA and HDA, whereas baseline data were used to select the cut‐off for VHDA. The level of agreement between disease activity states based on BASDAI and Axial Spondyloarthritis Disease Activity Score (ASDAS) cut‐off values was assessed using the proportion of discordance and weighted kappa. Results: In this cohort of 4,633 patients, the optimal BASDAI cut‐off values between remission, LDA, HDA and VHDA were estimated to be 4,600 patients. These cut‐off values can be used for assessing disease activity and monitoring patients with axSpA, particularly when laboratory markers are unavailable.

To investigate a patient-level single imputation approach for patient reported outcomes (PROs) that express similar contents or associated PROs, where a PRO whose value is missing at a particular timepoint is substituted by another PRO whose value is available at the same timepoint. We performed a simulation study on registry-based spondyloarthritis data to explore the potential interchangeability between the patient pain (PPA) and fatigue (PFA) assessment scores and relevant Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) individual questions, and between PPA, PFA and patient global assessment (PGA). Performance was assessed per imputation method in terms of relative bias and coverage. Sample size, level of missingness and missing data pattern were included as parameters in the simulations. All applied scenarios to interchange PPA with BASDAI question 2 (axial pain), BASDAI question 3 (peripheral joint pain/swelling) or their average failed. Interchangeability between PFA and BASDAI question 1 (fatigue/tiredness) was acceptable for partially (up to 50%) missing data. When interchanging patient assessment scores (PPA, PFA and PGA), we observed inconsistent results in terms of performance. The performance of the applied methods depended on the sample size and the level of missingness, but not heavily on the underlying missing data pattern. Interchanging PFA and the BASDAI fatigue question was justified for partially missing data, while interchangeability between PPA, PFA and PGA, and between PPA and the BASDAI pain questions was not advised. Our findings suggest that registering patient assessment scores and BASDAI questions is recommended.

Objective: Salivary gland ultrasound (SGUS) is a non-invasive tool for the evaluation of parenchymal changes related to primary Sjögrens disease (pSjD) with the potential to reduce the need for minor salivary gland biopsies when diagnosing patients with pSjD. The aim was to assess the agreement between SGUS findings and minor salivary gland biopsy results in patients suspected of pSjD. Methods: All patients referred with a suspicion of pSjD and scheduled for a diagnostic minor salivary gland biopsy were included in the period 2017–2021. All underwent SGUS of the parotid and submandibular glands bilaterally, Schirmer’s test, unstimulated salivary flow, and blood samples including autoantibody analysis. Changes in the four glands were scored 0–3 using a previously developed ultrasound atlas based on the OMERACT SGUS scoring system for pSjD. All biopsies were scored at the same pathology department and a focus score > 1 was indicative of pSjD. Results: Of 103 patients included, 43 (42%) were diagnosed with pSjD and 40 (39%) fulfilled the 2016 ACR/EULAR classification criteria. Thirty-two (31%) had a positive minor salivary gland biopsy. The sensitivity of SGUS score ≥ 2 in at least 1 gland was 0.59 and the specificity 0.75. The positive predictive and negative predictive values were 0.51 and 0.80, respectively. The agreement slightly improved when combined with an abnormal salivary flow rate or abnormal Schirmer’s test. Conclusion: In patients with suspected pSjD, we found good agreement between the OMERACT SGUS scoring system and minor salivary gland biopsy; however, SGUS cannot yet fully replace biopsy in the diagnostic setup of SjD.