Maximal Exercise Tolerance, Objective Trunk Strength, and Mobility Measurements in Axial Spondyloarthritis.

OBJECTIVE: Although exercise therapy is safe, effective, and recommended as a nonpharmacological treatment for axial spondyloarthritis (axSpA), there is a lack of guidelines regarding type and dosage. Insufficient knowledge about physical and physiological variables makes designing effective exercise programs challenging. Therefore, the goal of this study was to simultaneously assess trunk strength, spinal mobility, and the cardiorespiratory fitness of patients with axSpA. METHODS: In a cross-sectional study, 58 patients with axSpA (mean age 40.8 yrs, 50% male, mean symptom duration 10.3 yrs) performed maximal cervical and trunk mobility and isometric strength tests in all planes (using David Back Concept devices) and a maximal cardiopulmonary bicycle exercise test (n = 25). Mobility and strength data were compared to healthy reference data. Cut-off values for clinical cardiopulmonary exercise testing interpretation were used to judge normality. Patients were compared based on radiographic involvement and symptom duration. RESULTS: Both strength (P ≤ 0.02) and mobility (P ≤ 0.001) were significantly lower for the patients with axSpA compared to the reference. Strength deficits were comparable between the radiographic and nonradiographic groups (P > 0.05, except trunk extension [P = 0.03]), whereas mobility showed higher deficits in the radiographic group (cervical extension [P = 0.02] and rotation [P = 0.01], and trunk extension [P = 0.03] and rotation [P = 0.03]), regardless of symptom duration. Similarly, symptom duration positively affected oxygen pulse (P = 0.03), relative anaerobic threshold (P = 0.02), and aerobic capacity (P = 0.02). CONCLUSION: In patients with axSpA, strength is more affected than mobility when compared to healthy controls. Likewise, mainly the metabolic component of aerobic capacity is impaired, affecting cardiopulmonary fitness. These findings indicate that future personalized exercise programs in patients with axSpA should incorporate exercises for cardiopulmonary fitness next to strength and mobility training.

The OMERACT whole-body MRI scoring system for inflammation in peripheral joints and entheses (WIPE) in spondyloarthritis - reference image atlas for the knee region.

OBJECTIVE: To develop a reference image atlas for the Outcome Measures in Rheumatology whole-body MRI scoring system for inflammation in peripheral joints and entheses (OMERACT MRI-WIPE) of the knee region. METHODS: Image examples of each pathology, location and grade, were collected and discussed at web-based, interactive meetings within the OMERACT MRI in Arthritis Working Group. Subsequently, reference images were selected by consensus. RESULTS: Reference images for each grade, pathology and location are depicted, along with definitions, reader rules and recommended MRI-sequences. CONCLUSION: The atlas guides scoring whole-body MRIs for inflammation in joints and entheses of the knee region according to MRI-WIPE methodology in clinical trials and cohorts.

Hip and pelvis region MRI reference image atlas for scoring inflammation in peripheral joints and entheses according to the OMERACT-MRI WIPE scoring system in patients with spondyloarthritis.

OBJECTIVE: To develop a reference image atlas for scoring the hip/pelvis region according to the OMERACT whole-body MRI scoring system for inflammation in peripheral joints and entheses (MRI-WIPE). METHODS: We collected image examples of each pathology, location and grade, discussed them at web-based, interactive meetings and, finally, selected reference images by consensus. RESULTS: Reference images for each grade and location of osteitis, synovitis and soft tissue inflammation are provided, as are definitions, reader rules and recommended MRI-sequences. CONCLUSION: A reference image atlas was created to guide scoring whole-body MRIs for arthritis and enthesitis in the hip/pelvis region in spondyloarthritis/psoriatic arthritis clinical trials and cohorts.

Association of anatomical variants of the sacroiliac joint with bone marrow edema in patients with axial spondyloarthritis.

OBJECTIVE: To determine the prevalence of sacroiliac joint variants in patients with axial spondyloarthritis (axSpA) using MRI-based synthetic CT images and to evaluate their relationships with the presence of bone marrow edema, as this may potentially complicate diagnosing active sacroiliitis on MRI in patients with suspected axSpA. METHODS: 172 patients were retrospectively included. All patients underwent MRI because of clinical suspicion of sacroiliitis. The diagnosis of axSpA was made by a tertiary hospital rheumatologist. Two readers independently determined the presence of bone marrow edema and the presence of one or more of the nine known sacroiliac joint (SIJ) variants. RESULTS: SIJ variants were common in axSpA patients (82.9%) and the non-SpA group (85.4%); there were no significant differences in prevalence. Bone marrow edema was frequently found in axSpA (86.8%) and non-SpA patients (34%). AxSpA patients with SIJ variants (except for accessory joint) demonstrated 4 to 10 times higher odds for bone marrow edema, however not statistically significant. The more variants were present in this group, the higher the chance of bone marrow edema. However, some multicollinearity cannot be excluded, since bone marrow edema is very frequent in the axSpA group by definition. CONCLUSION: SIJ variants are common in axSpA and non-SpA patients. SIJ variants were associated with higher prevalence of bone marrow edema in axSpA patients, potentially due to altered biomechanics, except for accessory joint which may act as a stabilizer.

Effects of secukinumab on synovitis and enthesitis in patients with psoriatic arthritis: 52-week clinical and ultrasound results from the randomised, double-blind ULTIMATE trial with open label extension.

OBJECTIVES: In the ULTIMATE study with an open label extension, we assessed the long-term effect of secukinumab at tissue level on synovitis and enthesitis, and across all psoriatic arthritis (PsA) manifestations, using both clinical evaluations and power Doppler ultrasonography (PDUS). METHODS: This randomised, placebo-controlled, Phase 3 study (ULTIMATE) included biologic-naïve patients with PsA with active PDUS synovitis and clinical enthesitis, and inadequate response to conventional synthetic disease-modifying antirheumatic drugs. The study consisted of 3 treatment periods; in the first period (baseline to week 12) patients were randomised to receive subcutaneous secukinumab (150 mg or 300 mg according to severity of skin psoriasis) or placebo every week until week 4 and once every 4 weeks up to week 12. In the second period (weeks 12-24) all patients received open-label secukinumab with placebo patients switching to secukinumab (150 mg or 300 mg). The third period (weeks 24-52) was an extended open-label treatment period. The long-term responsiveness of the Global EULAR-OMERACT Synovitis Score (GLOESS), clinical enthesitis and global PDUS-detected enthesitis score (using two candidate definitions of activity) at patient level, together with clinical efficacy across key manifestations of PsA and safety were assessed. RESULTS: Of the 166 patients enrolled, 144 completed week 52. A significant reduction in GLOESS was demonstrated in the secukinumab group vs placebo at week 12, followed by a stable reduction of synovitis until week 52 in the secukinumab group while placebo switchers from week 12 reached a similar level of reduction at week 24 with stability thereafter. Likewise, a significant reduction in the Spondyloarthritis Research Consortium of Canada (SPARCC) enthesitis index was shown in the secukinumab group vs placebo at week 12 with sustained improvement to week 52. Global OMERACT PDUS enthesitis scores were numerically lower in secukinumab vs placebo switchers in the first two treatment periods, with some stability in the third period in both groups. Improvements in clinical responses were also observed across all key domains of PsA up to week 52 in both treatment groups with no new or unexpected safety signals. CONCLUSIONS: ULTIMATE showed consistent improvements in clinically and ultrasound-assessed synovitis and enthesitis and sustained clinical efficacy through week 52 in patients with PsA treated with secukinumab and placebo switched to secukinumab.

To taper or not to taper biological disease-modifying antirheumatic drugs in axial spondyloarthritis anno 2023: That is the question.

The 2022 ASAS-EULAR recommendations for the management of axial spondyloarthritis (axSpA) propose to consider dose reduction of biological disease-modifying antirheumatic drugs (bDMARDs) for patients in sustained remission. However, this recommendation does not offer clear guidance for daily clinical practice. In this review, we analyze randomized clinical trials and real-world data on tapering and discontinuation of bDMARDs in patients with axSpA. We discuss the scientific rationale and benefits of tapering, identify advice to apply tapering in current practice, and delineate aspects to be investigated in future research.

The PROPER Study: A 48-Week, Pan-European, Real-World Study of Biosimilar SB5 Following Transition from Reference Adalimumab in Patients with Immune-Mediated Inflammatory Disease.

BACKGROUND: The non-interventional PROPER study generated real-world evidence on clinical outcomes following transition in routine practice from reference adalimumab to the EMA-approved SB5 biosimilar adalimumab in patients with immune-mediated inflammatory disease. METHODS: Adults with rheumatoid arthritis (RA), axial spondyloarthritis (axSpA), psoriatic arthritis (PsA), Crohn's disease (CD), or ulcerative colitis (UC) were enrolled at 63 sites across Europe. Eligible patients received ≥ 16 weeks of routine treatment with reference adalimumab before transitioning to SB5, and were followed for 48 weeks post-transition. The primary objective was to evaluate candidate predictors (clinically relevant baseline variables with incidence ≥ 15% by indication cohort) associated with persistence on SB5 at 48 weeks post-initiation. Key primary outcome measures were persistence on SB5 (estimated by Kaplan-Meier methodology) and clinical characteristics and disease activity scores at the time of transition to SB5 treatment (baseline). RESULTS: A total of 955 eligible patients were enrolled (RA, n = 207; axSpA, n = 127; PsA, n = 162; CD, n = 447; UC, n = 12), of whom 932 (97.6%) completed follow-up and 722 (75.6%) were still receiving SB5 at week 48. Kaplan-Meier estimates (95% confidence interval, CI) of persistence on SB5 at week 48 for RA, axSpA, PsA, and CD were 0.86 (0.80-0.90), 0.80 (0.71-0.86), 0.81 (0.74-0.86), and 0.72 (0.67-0.76), respectively. The single candidate predictor associated with probability of SB5 discontinuation before week 48 was female sex [RA, axSpA, and CD cohorts; HR (95% CI): 3.53 (1.07-11.67), 2.38 (1.11-5.14), and 2.21 (1.54-3.18), respectively]. Disease activity scores remained largely unchanged throughout the study, with proportions by cohort in remission at baseline versus week 48 being 59.2% versus 57.2%, 81.0% versus 78.0%, 94.7% versus 93.7%, and 84.0% versus 85.1% for patients with RA, axSpA, PsA, and CD, respectively. Similarly, the SB5 dosing regimen remained unchanged for the majority of patients from baseline to week 48, the most common regimen being 40 mg every 2 weeks. In total, 232 patients (24.3%) reported at least one adverse drug reaction, and most events were mild; eight patients (3.9%) in the RA cohort experienced nine serious adverse events (SAEs; two possibly related to SB5); eight patients (4.9%) in the PsA cohort experienced nine SAEs (one possibly related to SB5); 22 patients (4.9%) in the CD cohort experienced 27 SAEs (four possibly related to SB5); and no SAEs were observed in the UC cohort. CONCLUSIONS: With the exception of female sex in RA, axSpA, and CD, none of the candidate predictors were associated with SB5 discontinuation. Persistence on SB5 was high, treatment effectiveness was maintained, and no safety signals were detected. TRIAL REGISTRATION: This trial is registered with ClinicalTrials.gov: NCT04089514.

Machine Learning Pipeline for Predicting Bone Marrow Edema Along the Sacroiliac Joints on Magnetic Resonance Imaging.

OBJECTIVE: We aimed to develop and validate a fully automated machine learning (ML) algorithm that predicts bone marrow edema (BME) on a quadrant level in sacroiliac (SI) joint magnetic resonance imaging (MRI). METHODS: A computer vision workflow automatically locates the SI joints, segments regions of interest (ilium and sacrum), performs objective quadrant extraction, and predicts presence of BME, suggestive of inflammatory lesions, on a quadrant level in semicoronal slices of T1/T2-weighted MRI scans. Ground truth was determined by consensus among human readers. The inflammation classifier was trained using a ResNet18 backbone and five-fold cross-validated on scans of patients with spondyloarthritis (SpA) (n = 279), postpartum individuals (n = 71), and healthy subjects (n = 114). Independent SpA patient MRI scans (n = 243) served as test data set. Patient-level predictions were derived from aggregating quadrant-level predictions, ie, at least one positive quadrant. RESULTS: The algorithm automatically detects the SI joints with a precision of 98.4% and segments ilium/sacrum with an intersection over union of 85.6% and 67.9%, respectively. The inflammation classifier performed well in cross-validation: area under the curve (AUC) 94.5%, balanced accuracy (B-ACC) 80.5%, and F1 score 64.1%. In the test data set, AUC was 88.2%, B-ACC 72.1%, and F1 score 50.8%. On a patient level, the model achieved a B-ACC of 81.6% and 81.4% in the cross-validation and test data set, respectively. CONCLUSION: We propose a fully automated ML pipeline that enables objective and standardized evaluation of BME along the SI joints on MRI. This method has the potential to screen large numbers of patients with (suspected) SpA and is a step closer towards artificial intelligence-assisted diagnosis and follow-up.

Neural network algorithm for detection of erosions and ankylosis on CT of the sacroiliac joints: multicentre development and validation of diagnostic accuracy.

OBJECTIVES: To evaluate the feasibility and diagnostic accuracy of a deep learning network for detection of structural lesions of sacroiliitis on multicentre pelvic CT scans. METHODS: Pelvic CT scans of 145 patients (81 female, 121 Ghent University/24 Alberta University, 18-87 years old, mean 40 ± 13 years, 2005-2021) with a clinical suspicion of sacroiliitis were retrospectively included. After manual sacroiliac joint (SIJ) segmentation and structural lesion annotation, a U-Net for SIJ segmentation and two separate convolutional neural networks (CNN) for erosion and ankylosis detection were trained. In-training validation and tenfold validation testing (U-Net-n = 10 × 58; CNN-n = 10 × 29) on a test dataset were performed to assess performance on a slice-by-slice and patient level (dice coefficient/accuracy/sensitivity/specificity/positive and negative predictive value/ROC AUC). Patient-level optimisation was applied to increase the performance regarding predefined statistical metrics. Gradient-weighted class activation mapping (Grad-CAM++) heatmap explainability analysis highlighted image parts with statistically important regions for algorithmic decisions. RESULTS: Regarding SIJ segmentation, a dice coefficient of 0.75 was obtained in the test dataset. For slice-by-slice structural lesion detection, a sensitivity/specificity/ROC AUC of 95%/89%/0.92 and 93%/91%/0.91 were obtained in the test dataset for erosion and ankylosis detection, respectively. For patient-level lesion detection after pipeline optimisation for predefined statistical metrics, a sensitivity/specificity of 95%/85% and 82%/97% were obtained for erosion and ankylosis detection, respectively. Grad-CAM++ explainability analysis highlighted cortical edges as focus for pipeline decisions. CONCLUSIONS: An optimised deep learning pipeline, including an explainability analysis, detects structural lesions of sacroiliitis on pelvic CT scans with excellent statistical performance on a slice-by-slice and patient level. CLINICAL RELEVANCE STATEMENT: An optimised deep learning pipeline, including a robust explainability analysis, detects structural lesions of sacroiliitis on pelvic CT scans with excellent statistical metrics on a slice-by-slice and patient level. KEY POINTS: • Structural lesions of sacroiliitis can be detected automatically in pelvic CT scans. • Both automatic segmentation and disease detection yield excellent statistical outcome metrics. • The algorithm takes decisions based on cortical edges, rendering an explainable solution.

Does Adjunction of Autologous Osteoblastic Cells Improve the Results of Core Decompression in Early-stage Femoral Head Osteonecrosis? A Double-blind, Randomized Trial.

BACKGROUND: Osteonecrosis of the femoral head (ONFH) is a disabling disease that can ultimately progress to collapse of the femoral head, often resulting in THA. Core decompression of the femoral head combined with cell therapies have shown beneficial effects in previous clinical studies in patients with early-stage (Association Research Circulation Osseous [ARCO] Stage I and II) ONFH. However, high-quality evidence confirming the efficacy of this treatment modality is still lacking. QUESTIONS/PURPOSES: (1) Is core decompression combined with autologous osteoblastic cell transplantation superior to core decompression with placebo implantation in relieving disease-associated pain and preventing radiologic ONFH progression in patients with nontraumatic early-stage ONFH? (2) What adverse events occurred in the treatment and control groups? METHODS: This study was a Phase III, multicenter, randomized, double-blind, controlled study conducted from 2011 to 2019 (ClinicalTrails.gov registry number: NCT01529008). Adult patients with ARCO Stage I and II ONFH were randomized (1:1) to receive either core decompression with osteoblastic cell transplantation (5 mL with 20 x 10 6 cells/mL in the study group) or core decompression with placebo (5 mL of solution without cells in the control group) implantation. Thirty percent (68 of 230) of the screened patients were eligible for inclusion in the study; of these, 94% (64 of 68) underwent a bone marrow harvest or sham procedure (extended safety set) and 79% (54 of 68) were treated (study group: 25 patients; control group: 29). Forty-nine patients were included in the efficacy analyses. Similar proportions of patients in each group completed the study at 24 months of follow-up (study group: 44% [11 of 25]; control: 41% [12 of 29]). The study and control groups were comparable in important ways; for example, in the study and control groups, most patients were men (79% [27 of 34] and 87% [26 of 30], respectively) and had ARCO Stage II ONFH (76% [19 of 25] and 83% [24 of 29], respectively); the mean age was 46 and 45 years in the study and control groups, respectively. The follow-up period was 24 months post-treatment. The primary efficacy endpoint was the composite treatment response at 24 months, comprising the clinical response (clinically important improvement in pain from baseline using the WOMAC VA3.1 pain subscale, defined as 10 mm on a 100-mm scale) and radiologic response (the absence of progression to fracture stage [≥ ARCO Stage III], as assessed by conventional radiography and MRI of the hips). Secondary efficacy endpoints included the percentages of patients achieving a composite treatment response, clinical response, and radiologic response at 12 months, and the percentage of patients undergoing THA at 24 months. We maintained a continuous reporting system for adverse events and serious adverse events related to the study treatment, bone marrow aspiration and sham procedure, or other study procedures throughout the study. A planned, unblinded interim analysis of efficacy and adverse events was completed at 12 months. The study was discontinued because our data safety monitoring board recommended terminating the study for futility based on preselected futility stopping rules: conditional power below 0.20 and p = 0.01 to detect an effect size of 10 mm on the 100-mm WOMAC VA3.1 pain subscale (improvement in pain) and the absence of progression to fracture (≥ ARCO Stage III) observed on radiologic assessment, reflecting the unlikelihood that statistically beneficial results would be reached at 24 months after the treatment. RESULTS: There was no difference between the study and control groups in the proportion of patients who achieved a composite treatment response at 24 months (61% [14 of 23] versus 69% [18 of 26]; p = 0.54). There was no difference in the proportion of patients with a treatment response at 12 months between the study and control groups (14 of 21 versus 15 of 23; p = 0.92), clinical response (17 of 21 versus 16 of 23; p = 0.38), and radiologic response (16 of 21 versus 18 of 23; p = 0.87). With the numbers available, at 24 months, there was no difference in the proportion of patients who underwent THA between the study and control groups (24% [six of 25] versus 14% [four of 29]). There were no serious adverse events related to the study treatment, and only one serious adverse event (procedural pain in the study group) was related to bone marrow aspiration. Nonserious adverse events related to the treatment were rare in the study and control groups (4% [one of 25] versus 14% [four of 29]). Nonserious adverse events related to bone marrow or sham aspiration were reported by 15% (five of 34) of patients in the study group and 7% (two of 30) of patients in the control group. CONCLUSION: Our study did not show any advantage of autologous osteoblastic cells to improve the results of core decompression in early-stage (precollapse) ONFH. Adverse events related to treatment were rare and generally mild in both groups, although there might have been a potential risk associated with cell expansion. Based on our findings, we do not recommend the combination of osteoblastic cells and core decompression in patients with early-stage ONFH. Further, well-designed studies should be conducted to explore whether other treatment modalities involving a biological approach could improve the overall results of core decompression. LEVEL OF EVIDENCE: Level II, therapeutic study.

ASAS-EULAR recommendations for the management of axial spondyloarthritis: 2022 update

To update the Assessment of SpondyloArthritis international Society (ASAS)-EULAR recommendations for the management of axial spondyloarthritis (axSpA). Following the EULAR Standardised Operating Procedures, two systematic literature reviews were conducted on non-pharmacological and pharmacological treatment of axSpA. In a task force meeting, the evidence was presented, discussed, and overarching principles and recommendations were updated, followed by voting. Five overarching principles and 15 recommendations with a focus on personalised medicine were agreed: eight remained unchanged from the previous recommendations; three with minor edits on nomenclature; two with relevant updates (#9, 12); two newly formulated (#10, 11). The first five recommendations focus on treatment target and monitoring, non-pharmacological management and non-steroidal anti-inflammatory drugs (NSAIDs) as firstchoice pharmacological treatment. Recommendations 6­8 deal with analgesics and discourage long-term glucocorticoids and conventional synthetic diseasemodifying antirheumatic drugs (DMARDs) for pure axial involvement. Recommendation 9 describes the indication of biological DMARDs (bDMARDs, that is, tumour necrosis factor inhibitors (TNFi), interleukin-17 inhibitors (IL-17i)) and targeted synthetic DMARDs (tsDMARDs, ie, Janus kinase inhibitors) for patients who have Ankylosing Spondylitis Disease Activity Score ≥2.1 and failed ≥2 NSAIDs and also have either elevated C reactive protein, MRI inflammation of sacroiliac joints or radiographic sacroiliitis. Current practice is to start a TNFi or IL-17i. Recommendation 10 addresses extramusculoskeletal manifestations with TNF monoclonal antibodies preferred for recurrent uveitis or inflammatory bowel disease, and IL-17i for significant psoriasis. Treatment failure should prompt re-evaluation of the diagnosis and consideration of the presence of comorbidities (#11). If active axSpA is confirmed, switching to another b/ tsDMARD is recommended (#12). Tapering, rather than immediate discontinuation of a bDMARD, can be considered in patients in sustained remission (#13). The last recommendations (#14, 15) deal with surgery and spinal fractures. The 2022 ASAS-EULAR recommendations provide up-to-date guidance on the management of patients with axSpA.

ASAS-EULAR recommendations for the management of axial spondyloarthritis: 2022 update.

OBJECTIVES: To update the Assessment of SpondyloArthritis international Society (ASAS)-EULAR recommendations for the management of axial spondyloarthritis (axSpA). METHODS: Following the EULAR Standardised Operating Procedures, two systematic literature reviews were conducted on non-pharmacological and pharmacological treatment of axSpA. In a task force meeting, the evidence was presented, discussed, and overarching principles and recommendations were updated, followed by voting. RESULTS: Five overarching principles and 15 recommendations with a focus on personalised medicine were agreed: eight remained unchanged from the previous recommendations; three with minor edits on nomenclature; two with relevant updates (#9, 12); two newly formulated (#10, 11). The first five recommendations focus on treatment target and monitoring, non-pharmacological management and non-steroidal anti-inflammatory drugs (NSAIDs) as first-choice pharmacological treatment. Recommendations 6-8 deal with analgesics and discourage long-term glucocorticoids and conventional synthetic disease-modifying antirheumatic drugs (DMARDs) for pure axial involvement. Recommendation 9 describes the indication of biological DMARDs (bDMARDs, that is, tumour necrosis factor inhibitors (TNFi), interleukin-17 inhibitors (IL-17i)) and targeted synthetic DMARDs (tsDMARDs, ie, Janus kinase inhibitors) for patients who have Ankylosing Spondylitis Disease Activity Score ≥2.1 and failed ≥2 NSAIDs and also have either elevated C reactive protein, MRI inflammation of sacroiliac joints or radiographic sacroiliitis. Current practice is to start a TNFi or IL-17i. Recommendation 10 addresses extramusculoskeletal manifestations with TNF monoclonal antibodies preferred for recurrent uveitis or inflammatory bowel disease, and IL-17i for significant psoriasis. Treatment failure should prompt re-evaluation of the diagnosis and consideration of the presence of comorbidities (#11). If active axSpA is confirmed, switching to another b/tsDMARD is recommended (#12). Tapering, rather than immediate discontinuation of a bDMARD, can be considered in patients in sustained remission (#13). The last recommendations (#14, 15) deal with surgery and spinal fractures. CONCLUSIONS: The 2022 ASAS-EULAR recommendations provide up-to-date guidance on the management of patients with axSpA.

Work participation is unaffected in Belgian spondyloarthritis patients: data from the BelGian Inflammatory Arthritis and SpoNdylitis cohorT.

OBJECTIVES: This study aimed to (i) investigate actual work participation in Belgian spondyloarthritis (SpA) patients compared with the general population, and (ii) identify determinants of work-related outcomes. MATERIAL AND METHODS: Adult SpA patients from the Ghent University Hospital based Be-GIANT cohort (fulfilling ASAS classification criteria) were cross-sectionally questioned on their socio-economic status and completed a Work Productivity and Activity Impairment questionnaire (May 2018 to May 2019). Results were compared with national and regional data on the general population using indirect standardization. Associations between clinical and job characteristics and work-related outcomes were analysed with logistic regression (having a paid job) and negative binomial hurdle models (sick leave and presenteeism, i.e. restrictions while at work). RESULTS: A total of 215/262 (82%) patients of working age (<65 y/o) had a paid job, corresponding to an age- and sex-adjusted employment ratio of 1.00 (95% CI 0.88, 1.14). Patients worked 39.6h (10.5h)/week, and 49% (95% CI 42, 56%) reported sick leave in the previous year, similar to the general population (39.7h/week, 42%). In total, 56% reported presenteeism of median (IQR) 10% (0-20%). In multivariate analysis, functional impairment (BASFI) and health-related quality of life (HRQoL, EuroQoL-VAS) were associated with each work-related outcome, while contextual factors (education, physically demanding job) were positively associated with, respectively, having a paid job and presenteeism. Clinical characteristics showed no independent association with any of these outcomes. CONCLUSIONS: Evidence from this academic cohort study does not support a work participation gap between SpA patients and the general population, but confirms the role of physical function, overall HRQoL, and education or job type as risk factors for adverse work outcomes.

Management of Enthesitis in Patients With Psoriatic Arthritis: An Updated Literature Review Informing the 2021 GRAPPA Treatment Recommendations.

OBJECTIVE: Enthesitis is a key pathological and clinical feature of psoriatic arthritis (PsA) in children and adults. Enthesitis is typically assessed clinically using several validated enthesitis scoring systems that have been used in clinical trials. Enthesitis treatment response has been reported as change in the total enthesitis score or the proportion of patients who achieved complete resolution. The majority of trials in PsA did not require patients to have enthesitis at study entry since enthesitis was evaluated only as a secondary outcome. Despite the inherent limitations of the clinical assessment of enthesitis, imaging of the entheses using ultrasound or magnetic resonance imaging has rarely been used in clinical trials to assess response to treatment of enthesitis. This systematic review summarizes existing evidence regarding pharmaceutical and nonpharmaceutical interventions for enthesitis in patients with PsA to facilitate an evidence-based update of the Group for Research and Assessment in Psoriasis and Psoriatic Arthritis (GRAPPA) treatment recommendations for PsA. METHODS: We performed a systematic literature review to identify 41 randomized clinical trials that reported enthesitis treatment response in patients with PsA. For each intervention, the response effect size was summarized and the quality of evidence was graded. Recommendations were then formulated for the various pharmacological and nonpharmacological therapies. RESULTS: We included 41 randomized clinical trials in our review and graded each intervention. CONCLUSION: Several classes of systemic conventional and advanced therapies and local measures were recommended for active enthesitis in patients with PsA.

Performance of an MRI scoring system for inflammation of joints and entheses in peripheral SpA: post-hoc analysis of the CRESPA trial.

OBJECTIVES: The aim of this study was to investigate the reliability, validity, and sensitivity to change of a novel MRI scoring system in early peripheral SpA (pSpA). METHODS: MRI of the pelvis and lower extremities was performed before initiation of the TNF inhibitor golimumab in 56 patients and repeated in 46 patients who achieved sustained clinical remission after 24, 36 or 48 weeks. Three readers applied a semi-quantitative MRI scoring system for lower-extremity joint and entheseal inflammation. Four lesion types were assessed: entheseal osteitis, entheseal soft-tissue inflammation, joint osteitis, and joint synovitis/effusion. MRI response was defined as a decrease in MRI lower-extremity inflammation index (sum of scores from 75 sites, each scored 0-3) above the smallest detectable change (SDC). RESULTS: At follow-up, the MRI index decreased in 34 of 46 patients (74%), and 15 (33%) patients achieved MRI response, i.e. a decrease above SDC of 2.8. When restricting the analysis to patients with clinical involvement of lower-extremity sites that were assessed by MRI, 13 of 28 (46%) achieved MRI response. Interreader reliability was very good, with an average-measure intraclass correlation coefficient of 0.92 (95% CI: 0.85-0.95) for status scores and 0.89 (0.80-0.94) for change in scores. The MRI index correlated with other measures of disease activity, including CRP [Spearman's rho 0.41 (0.23-0.56)], swollen joint count of 6 joints [0.47 (0.27-0.63)], tender enthesis count of 14 entheses [0.32 (0.12-0.50)] and pain score [0.28 (0.08-0.46)], all P < 0.05. CONCLUSION: The proposed MRI lower-extremity inflammation index demonstrated reliability, validity, and sensitivity to change in patients with early pSpA. TRIAL REGISTRATION: Clinicaltrials.gov, http://clinicaltrials.gov, NCT01426815.

Use of Imaging in Axial Spondyloarthritis for Diagnosis and Assessment of Disease Remission in the Year 2022.

Medical imaging remains the cornerstone of diagnostics and follow-up of axial spondyloarthritis (axSpA) patients. With the lack of specific biomarkers allowing monitoring of disease activity and progression, clinicians refer to imaging modalities for accurate evaluation of the axSpA burden. Technological advances and increasing availability of modern imaging techniques such as MRI have enabled faster diagnosis of the disease, hence dramatically changed the diagnostic delay and improved the prognosis and functional outcomes for axSpA patients.Active sacroiliitis as visualized by MRI has been widely accepted as a diagnostic tool, and definitions of inflammatory and structural lesions within the axial skeleton have been developed. Recently, it has been acknowledged that bone marrow edema, suggestive of sacroiliitis, is a common finding among non-SpA patients, and could be attributed to mechanical loading or accumulate with age in healthy individuals. Therefore, it is crucial to distinguish between true pathological and concealing imaging findings, not only for diagnostic but also for disease remission purposes. New imaging modalities, aimed for in vivo visualization of specific molecular processes, could be employed to cross-validate findings from techniques used in daily clinical practice. This review critically evaluates the use of different imaging modalities for diagnosis and assessment of disease remission in axSpA in the year 2022.

Progressive Increase in Sacroiliac Joint and Spinal Lesions Detected on Magnetic Resonance Imaging in Healthy Individuals in Relation to Age.

OBJECTIVE: Magnetic resonance imaging (MRI) plays a pivotal role in spondyloarthritis (SpA) diagnosis. However, a detailed description of MRI findings of the sacroiliac (SI) joints and spine in healthy individuals is currently lacking. This study was undertaken to evaluate the occurrence of MRI-detected SI joint and spinal lesions in healthy individuals in relation to age. METHODS: Ninety-five healthy subjects (ages 20-49 years) underwent MRI of the SI joints and spine. Bone marrow edema (BME) and structural lesions of the SI joints were scored using the Spondyloarthritis Research Consortium of Canada (SPARCC) method. Spinal inflammatory and structural lesions were evaluated using the SPARCC MRI spine inflammation index and the Canada-Denmark MRI scoring system, respectively. Fulfillment of the Assessment of SpondyloArthritis international Society definition of a positive MRI for sacroiliitis/spondylitis was reviewed. Findings were compared to MRIs of axial SpA patients from the Belgian Inflammatory Arthritis and Spondylitis cohort. RESULTS: Of the subjects ≥30 years old, 17.2% fulfilled the definition of a positive MRI for sacroiliitis, but this occurred rarely in younger subjects. SI joint erosions (20.0%) and fat metaplasia (13.7%) were detected across all age groups. Erosions were more frequently visualized in subjects ages ≥40 years (39.3%). Spinal BME (35.7%) and fat metaplasia (28.6%) were common in subjects older than 40 years. Nonetheless, only 1 subject had ≥3 corner inflammatory lesions. SI joint and spinal SPARCC scores and total structural lesions scores increased progressively with age. CONCLUSION: Contrary to what is commonly believed, structural MRI-detected SI joint lesions are frequently seen in healthy individuals. Especially in older subjects, the high occurrence of inflammatory and structural MRI-detected lesions impacts their specificity for SpA, which has important implications for the interpretation of MRIs in patients with a clinical suspicion of SpA.

Response to secukinumab on synovitis using Power Doppler ultrasound in psoriatic arthritis: 12-week results from a phase III study, ULTIMATE.

OBJECTIVES: To investigate the dynamics of response of synovitis to IL-17A inhibition with secukinumab in patients with active PsA using Power Doppler ultrasound. METHODS: The randomized, placebo-controlled, Phase III ULTIMATE study enrolled PsA patients with active ultrasound synovitis and clinical synovitis and enthesitis having an inadequate response to conventional DMARDs and naïve to biologic DMARDs. Patients were randomly assigned to receive either weekly subcutaneous secukinumab (300 or 150 mg according to the severity of psoriasis) or placebo followed by 4-weekly dosing thereafter. The primary outcome was the mean change in the ultrasound Global EULAR and OMERACT Synovitis Score (GLOESS) from baseline to week 12. Key secondary endpoints included ACR 20 and 50 responses. RESULTS: Of the 166 patients enrolled, 97% completed 12 weeks of treatment (secukinumab, 99%; placebo, 95%). The primary end point was met, and the adjusted mean change in GLOESS was higher with secukinumab than placebo [-9 (0.9) vs -6 (0.9), difference (95% CI): -3 (-6, -1); one-sided P=0.004] at week 12. The difference in GLOESS between secukinumab and placebo was significant as early as one week after initiation of treatment. All key secondary endpoints were met. No new or unexpected safety findings were reported. CONCLUSION: This unique ultrasound study shows that apart from improving the signs and symptoms of PsA, IL-17A inhibition with secukinumab leads to a rapid and significant reduction of synovitis in PsA patients. TRIAL REGISTRATION: ClinicalTrials.gov; NCT02662985.

Peripheral manifestations are major determinants of disease phenotype and outcome in new onset spondyloarthritis.

OBJECTIVES: To delineate the impact of peripheral musculoskeletal manifestations on stratification of disease phenotype and outcome in new-onset spondyloarthritis (SpA), using a prospective observational nationwide inception cohort, the BelGian Inflammatory Arthritis and spoNdylitis cohorT (Be-Giant). METHODS: Newly diagnosed adult SpA patients, fulfilling the Assessment of SpondyloArthritis International Society (ASAS) criteria for axial or peripheral SpA, were included in Be-Giant and prospectively followed every six months. Peripheral involvement (defined as arthritis, enthesitis and/or dactylitis) was determined in relation to clinically similar patient subsets at baseline and disease activity patterns during two-year follow-up, identified through K-means cluster analysis and latent class growth analysis. RESULTS: From November 2010 to March 2020, 367 patients were enrolled in Be-Giant, of whom 162 (44%) had peripheral manifestations. Two patient clusters [A, axial predominant (n = 248) and B, peripheral predominant (n = 119)] were identified at diagnosis. Longitudinal analysis (n = 115) revealed two trajectories of disease activity in each cluster: one with persistently high disease activity over time ('High'), the other rapidly evolving to low disease activity ('Low'). In cluster A patients, peripheral manifestations predisposed to the 'High' trajectory [odds ratio (OR) = 2.0, 95% CI: 1.3, 3.1, P = 0.001], despite more rapid initiation of biologics compared with patients without peripheral manifestations (hazard ratio (HR) = 2.1, 95% CI: 1.0, 4.4, P = 0.04 - Cox proportional-hazards model). CONCLUSION: Peripheral musculoskeletal manifestations are major determinants of phenotypical diversity in new-onset SpA. Intriguingly, stratification of axial SpA according to concomitant peripheral involvement identified an endotype with an unfavorable outcome despite more prompt therapeutic intensification with biologics. These observations justify an endotype-tailored approach beyond current ASAS/EULAR management recommendations.

Very low prevalence of ultrasound-detected tenosynovial abnormalities in healthy subjects throughout the age range: OMERACT ultrasound minimal disease study.

OBJECTIVES: This study aimed to determine the prevalence of ultrasound-detected tendon abnormalities in healthy subjects (HS) across the age range. METHODS: Adult HS (age 18-80 years) were recruited in 23 international Outcome Measures in Rheumatology ultrasound centres and were clinically assessed to exclude inflammatory diseases or overt osteoarthritis before undergoing a bilateral ultrasound examination of digit flexors (DFs) 1-5 and extensor carpi ulnaris (ECU) tendons to detect the presence of tenosynovial hypertrophy (TSH), tenosynovial power Doppler (TPD) and tenosynovial effusion (TEF), usually considered ultrasound signs of inflammatory diseases. A comparison cohort of patients with rheumatoid arthritis (RA) was taken from the Birmingham Early Arthritis early arthritis inception cohort. RESULTS: 939 HS and 144 patients with RA were included. The majority of HS (85%) had grade 0 for TSH, TPD and TEF in all DF and ECU tendons examined. There was a statistically significant difference in the proportion of TSH and TPD involvement between HS and subjects with RA (HS vs RA p<0.001). In HS, there was no difference in the presence of ultrasound abnormalities between age groups. CONCLUSIONS: Ultrasound-detected TSH and TPD abnormalities are rare in HS and can be regarded as markers of active inflammatory disease, especially in newly presenting RA.