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.

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.

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.

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.

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.

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.

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.

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.

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.

MRI-based Synthetic CT in the Detection of Structural Lesions in Patients with Suspected Sacroiliitis: Comparison with MRI.

Background Evaluation of structural lesions in the sacroiliac (SI) joints can improve the accuracy for diagnosis of spondyloarthritis. However, structural lesions, such as erosions, are difficult to assess on routine T1-weighted MRI scans. Purpose To determine the diagnostic performance of MRI-based synthetic CT (sCT) in the depiction of erosions, sclerosis, and ankylosis of the SI joints compared with T1-weighted MRI, with CT as the reference standard. Materials and Methods A prospective study (clinical trial registration no. B670201837885) was performed from February 2019 to November 2019. Adults were referred from a tertiary hospital rheumatology outpatient clinic with clinical suspicion of inflammatory sacroiliitis. MRI and CT of the SI joints were performed on the same day. SCT images were generated from MRI scans using a commercially available deep learning-based image synthesis method. Two readers independently recorded if structural lesions (erosions, sclerosis, and ankylosis) were present on T1-weighted MRI, sCT, and CT scans in different reading sessions, with readers blinded to clinical information and other images. Diagnostic performance of sCT and T1-weighted MRI scans were analyzed using generalized estimating equation models, with consensus results of CT as the reference standard. Results Thirty participants were included (16 men, 14 women; mean age, 40 years ± 10 [standard deviation]). Diagnostic accuracy of sCT was higher than that of T1-weighted MRI for erosion (94% vs 86%, P = .003), sclerosis (97% vs 81%, P < .001), and ankylosis (92% vs 84%, P = .04). With sCT, specificity for erosion detection (96% [95% CI: 90, 98] vs 89% [95% CI: 81, 94], P = .01] and sensitivity for detection of sclerosis [94% [95% CI: 87, 97] vs 20% [95% CI: 10, 35], P < .001] and ankylosis (93% [95% CI: 78, 98] vs 70% [95% CI: 47, 87], P = .001) were improved. Conclusion With CT as the reference standard, synthetic CT of the sacroiliac joints has better diagnostic performance in the detection of structural lesions in individuals suspected of having sacroiliitis compared with routine T1-weighted MRI. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Fritz in this issue.

Axial involvement in patients with early peripheral spondyloarthritis: a prospective MRI study of sacroiliac joints and spine.

OBJECTIVES: To assess axial involvement on MRI in early peripheral spondyloarthritis (pSpA) and to evaluate whether axial inflammation predicts relapse on treatment withdrawal. METHODS: Fifty-six patients with early, active, newly diagnosed pSpA underwent MRI of the sacroiliac joints (SIJs) and spine prior to golimumab initiation. At sustained clinical remission of pSpA, treatment was withdrawn and a second MRI was performed. Bone marrow oedema (BME) was scored by three readers according to the Spondyloarthritis Research Consortium of Canada (SPARCC) method. Scores were compared with an axial spondyloarthritis cohort (Belgian Arthritis and Spondylitis cohort). Structural lesions were assessed using a similar method. Furthermore, fulfilment of the Assessment of Spondyloarthritis International Society (ASAS) definition of a positive MRI for sacroiliitis was assessed. Spinal images were evaluated for BME and structural lesions using the Canada-Denmark MRI spine scoring system by two readers. RESULTS: Thirty-six per cent showed SIJ BME at baseline, all fulfilling the ASAS definition of sacroiliitis. No association with back pain was found. Twenty-one per cent displayed SIJ structural lesions. Spinal BME was limited: the median inflammation scores were low and no patients had ≥5 inflammatory corner lesions. On clinical remission, a significant decrease in SIJ SPARCC scores was detected. On clinical remission, no significant differences in SIJ SPARCC scores were noted between patients relapsing and those maintaining remission after treatment discontinuation. CONCLUSION: In patients with early pSpA, a surprisingly high prevalence of sacroiliitis on MRI was observed; SPARCC scores decreased significantly on tumour necrosis factor inhibition. Residual inflammation on MRI was not predictive of relapse of peripheral manifestations. No relevant inflammatory spinal involvement was detected. Collectively, our findings suggest a higher inflammatory burden in patients with early pSpA than anticipated.

Efficacy of a tight-control and treat-to-target strategy in axial spondyloarthritis: results of the open-label, pragmatic, cluster-randomised TICOSPA trial.

OBJECTIVES: To compare the benefits of a tight-control/treat-to-target strategy (TC/T2T) in axial spondyloarthritis (axSpA) with those of usual care (UC). METHODS: Pragmatic, prospective, cluster-randomised, controlled, open, 1-year trial (NCT03043846). 18 centres were randomised (1:1). Patients met Axial Spondylo Arthritis International Society (ASAS) criteria for axSpA, had an Ankylosing Spondylitis Disease Activity Score (ASDAS) ≥2.1, received non-optimal treatment by non-steroidal anti-inflammatory drugs and were biologic-naive. INTERVENTIONS: (1) TC/T2T: visits every 4 weeks and prespecified strategy based on treatment intensification until achieving target (ie, ASDAS <2.1); (2) UC: visits every 12 weeks and treatment at the rheumatologist's discretion. MAIN OUTCOME: Percentage of patients with a ≥30% improvement on the ASAS-Health Index (ASAS-HI). Other efficacy outcomes and adverse events were recorded. A health economic evaluation was performed. STATISTICAL ANALYSIS: Two-level mixed models were used to estimate efficacy outcomes. Cost-effectiveness was assessed by the incremental cost per quality-adjusted life-year (QALY) gained for TC/T2T versus UC. RESULTS: 160 patients were included (80/group). Mean (SD) age was 37.9 (11.0) years and disease duration was 3.7 (6.2) years; 51.2% were men. ASDAS at inclusion was 3.0 (0.7), and ASAS-HI was 8.6 (3.7). ASAS-HI improved by ≥30% in 47.3% of the TC/T2T arm and in 36.1% of those receiving UC (non-significant). All secondary efficacy outcomes were more frequent in the TC/T2T arm, although not all statistically significant. Safety was similar in both arms. From a societal perspective, TC/T2T resulted in an additional 0.04 QALY, and saved €472 compared with UC. CONCLUSION: TC/T2T was not significantly superior to UC for the primary outcome, while many secondary efficacy outcomes favoured it, had a similar safety profile and was favourable from a societal health economic perspective. TRIAL REGISTRATION NUMBER: NCT03043846.

TNFi-induced sustained clinical remission in peripheral spondyloarthritis patients cannot be maintained with a step-down strategy based on methotrexate.

OBJECTIVES: Treatment with golimumab monotherapy in early peripheral SpA (pSpA) results in higher rates of clinical remission compared with treatment in more longstanding disease. When reaching remission, treat-to-target recommendations suggest tapering of treatment. We therefore explored whether addition of MTX would permit discontinuation of golimumab in patients with pSpA in sustained clinical remission. METHODS: After a 2-year extension phase with golimumab treatment, patients with pSpA reaching clinical remission in the CRESPA trial were offered a tapering strategy leading to discontinuation of golimumab and replacement by MTX monotherapy. Patients were prospectively followed to assess the rate of sustained biologic-free clinical remission. In case of relapse of arthritis, enthesitis or dactylitis under MTX monotherapy, golimumab was restarted. RESULTS: Of the original 60 pSpA patients, 25 entered the step-down strategy. Currently, only 4 patients (16%) are still in sustained remission under MTX monotherapy. In 21 patients (84%), golimumab was reinstalled because of relapse of disease activity (n = 19) or development of adverse events related to MTX (n = 2). Restarting golimumab treatment promptly restored clinical remission in all patients within 12 weeks. CONCLUSION: In patients with early pSpA achieving clinical remission after 2 years of golimumab treatment, step-down therapy to monotherapy with MTX led to high rates of clinical relapse. This underscores the overall weak efficacy of MTX in maintaining clinical remission in pSpA. TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT01426815.

High prevalence of spondyloarthritis-like MRI lesions in postpartum women: a prospective analysis in relation to maternal, child and birth characteristics.

OBJECTIVES: Bone marrow oedema (BMO) on MRI of sacroiliac joints (SIJs) represents a hallmark of axial spondyloarthritis (SpA), yet such lesions may also occur under augmented mechanical stress in healthy subjects. We therefore sought to delineate the relationship between pregnancy/delivery and pelvic stress through a prospective study with repeated MRI. Results were matched with maternal, child and birth characteristics. METHODS: Thirty-five women underwent a baseline MRI-SIJ within the first 10 days after giving birth. MRI was repeated after 6 months and, if positive for sacroiliitis according to the Assessment of SpondyloArthritis International Society (ASAS) definition, after 12 months. BMO and structural lesions were scored by three trained readers using the Spondyloarthritis Research Consortium of Canada (SPARCC) method. RESULTS: Seventy-seven per cent of the subjects (27/35) displayed sacroiliac BMO immediately postpartum, 60% fulfilled the ASAS definition of a positive MRI. After 6 months, 46% of the subjects (15/33) still showed BMO, representing 15% (5/33) with a positive MRI. After 12 months, MRI was still positive in 12% of the subjects (4/33). Few structural lesions were detected. Intriguingly, in this study, the presence of BMO was related to a shorter duration of labour and lack of epidural anaesthesia. CONCLUSION: A surprisingly high prevalence of sacroiliac BMO occurs in women immediately postpartum. Our data reveal a need for a waiting period of at least 6 months to perform an MRI-SIJ in postpartum women with back pain. This study also underscores the importance of interpreting MRI-SIJ findings in the appropriate clinical context.

Development of ASAS quality standards to improve the quality of health and care services for patients with axial spondyloarthritis.

OBJECTIVES: The Assessment of SpondyloArthritis International Society (ASAS) aimed to develop a set of quality standards (QS) to help improve the quality of healthcare provided to adult patients affected by axial spondyloarthritis (axSpA) worldwide. METHODS: An ASAS task force developed a set of QS using a stepwise approach. First, key areas for quality improvement were identified, discussed, rated and agreed on. Thereafter, areas were prioritised and statements for the most important key areas were phrased on consensus. Appropriate quality measures were defined to allow quantification of the QS at the community level. RESULTS: The ASAS task force, consisting of 20 rheumatologists, two physiotherapists and two patients, selected and proposed 34 potential key areas for quality improvement which were then commented by 140 ASAS members and patients. Within that process three new key areas came up, which led to a re-evaluation of all 37 key areas by 120 ASAS members and patients. Five key areas were identified as most important to determine quality of care: referral including rapid access, rheumatology assessment, treatment, education/self-management and comorbidities. Finally, nine QS were agreed on and endorsed by the whole ASAS membership. CONCLUSIONS: ASAS successfully developed the first set of QS to help improving healthcare for adult patients with axSpA. Even though it may currently not be realistic to achieve the QS in all healthcare systems, they provide high-quality of care framework for patients with axSpA that should be aimed for.

Bone marrow edema in sacroiliitis: detection with dual-energy CT.

OBJECTIVES: To evaluate the feasibility and diagnostic accuracy of dual-energy computed tomography (DECT) for the detection of bone marrow edema (BME) in patients suspected for sacroiliitis. METHODS: Patients aged 18-55 years with clinical suspicion for sacroiliitis were enrolled. All patients underwent DECT and 3.0 T MRI of the sacroiliac joints on the same day. Virtual non-calcium (VNCa) images were calculated from DECT images for demonstration of BME. VNCa images were scored by two readers independently using a binary system (0 = normal bone marrow, 1 = BME). Diagnostic performance was assessed with fluid-sensitive MRI as the reference standard. ROIs were placed on VNCa images, and CT numbers were displayed. Cutoff values for BME detection were determined based on ROC curves. RESULTS: Forty patients (16 men, 24 women, mean age 37.1 years ± 9.6 years) were included. Overall inter-reader agreement for visual image reading of BME on VNCa images was good (κ = 0.70). The sensitivity and specificity of BME detection by DECT were 65.4% and 94.2% on the quadrant level and 81.3% and 91.7% on the patient level. ROC analyses revealed AUCs of 0.90 and 0.87 for CT numbers in the ilium and sacrum, respectively. Cutoff values of - 44.4 HU (for iliac quadrants) and - 40.8 HU (for sacral quadrants) yielded sensitivities of 76.9% and 76.7% and specificities of 91.5% and 87.5%, respectively. CONCLUSIONS: Inflammatory sacroiliac BME can be detected by VNCa images calculated from DECT, with a good interobserver agreement, moderate sensitivity, and high specificity. KEY POINTS: • Virtual non-calcium images calculated from dual-energy CT can detect sacroiliac bone marrow edema in patients suspected for sacroiliitis. • Dual-energy CT has a high specificity in bone marrow edema detection. • Virtual non-calcium images for bone marrow edema in patients with a large amount of red bone marrow or obvious sclerosis near the articular surface should be interpreted with caution.

Effect of mechanical stress on magnetic resonance imaging of the sacroiliac joints: assessment of military recruits by magnetic resonance imaging study.

Objective: To assess the baseline condition of the SI joints (SIJs) in healthy individuals without symptoms of back pain and to study the effect of mechanical stress caused by intense physical training on MRI of the SIJs. Methods: Twenty-two military recruits underwent an MRI of the SIJs before and after 6 weeks of intense standardized physical training. Bone marrow oedema and structural lesions were scored based on the Spondyloarthritis Research Consortium of Canada (SPARCC) method, by three trained readers blinded for time sequence and clinical findings. Additionally, fulfilment of the Assessment of SpondyloArthritis international Society (ASAS) definition of a positive MRI was evaluated. Results: At baseline, 9/22 recruits (40.9%) already presented a SPARCC score ⩾1; this number increased to 11/22 (50.0%) at week 6 (P = 0.625). In these patients, the mean (SD) SPARCC score was 2.4 (0.4) at baseline, compared to 3.7 (1.3) at week 6. Overall, the mean (SD) change in SPARCC score over time in all 22 patients was 0.9 (0.6) (P = 0.109). A positive MRI according to the ASAS definition was present in 5/22 recruits (22.7%) at baseline, which increased to 8/22 (36.4%) at follow-up (P = 0.375). Structural lesions were present in 6/22 subjects (27.3%), both at baseline and after 6 weeks of training. Conclusion: A substantial proportion of healthy active individuals without any symptoms of back pain displayed bone marrow oedema lesions on MRI at baseline. However, MRI lesions did not increase significantly after 6 weeks of intensive physical training. Our study underscores the necessity to interpret MRI findings of the SIJs in the appropriate clinical context, even in a young active population.

Anti-TNF-induced remission in very early peripheral spondyloarthritis: the CRESPA study.

OBJECTIVE: To evaluate the efficacy and safety of golimumab to induce clinical remission in patients with very early, active peripheral spondyloarthritis (pSpA). METHODS: Clinical REmission in peripheral SPondyloArthritis is a monocentric study of golimumab treatment in patients with pSpA. All patients fulfilled the Assessment of SpondyloArthritis international Society classification criteria for pSpA, with a symptom duration ≤12 weeks. Patients were randomised 2:1 to receive golimumab 50 mg every 4 weeks or matching placebo for 24 weeks. The primary end point was the percentage of patients achieving clinical remission at week 24, defined as absence of arthritis, enthesitis and dactylitis. Secondary end points included joint and enthesis counts, patient-reported outcomes, erythrocyte sedimentation rate and C reactive protein. From week 12, non-responders were allowed to receive rescue medication with golimumab. Adverse events were recorded. RESULTS: 60 patients were randomised with similar baseline characteristics. At week 24, a significantly higher percentage of patients receiving golimumab achieved clinical remission compared with placebo (75% (30/40) vs 20% (4/20); p<0.001). At week 12, similar results were observed (70% (28/40) vs 15% (3/20); p<0.001). All secondary end points were met at week 24. Rescue medication was necessary in 50% in the placebo group opposed to only 10% in the golimumab arm. Rates of adverse events were low and similar in both groups. CONCLUSIONS: Markedly high remission induction rates were noted with golimumab in very early pSpA. Of interest, in placebo-treated patients, very low spontaneous remission rates were observed. TRIAL REGISTRATION NUMBER: NCT01426815; Results.