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Copyright of Zeitschrift für Rheumatologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective: To evaluate progression from nonradiographic (nr‐) to radiographic axial spondyloarthritis (r‐axSpA) over 5 years in patients with recently diagnosed (≤1 year) axSpA fulfilling the Assessment of SpondyloArthritis international Society (ASAS) classification criteria. Methods: A prospsective, observational study (Patients with Axial Spondyloarthritis: Multi‐Country Registry of Clinical Characteristics) was conducted in rheumatology practices in 29 countries. Baseline and follow‐up radiographs of sacroiliac joints were centrally evaluated by three readers according to the grading system of the modified New York criteria for patients initially classified as nr‐axSpA. Radiographic progression from nr‐axSpA to r‐axSpA was evaluated by Kaplan‐Meier analysis. Cox proportional regression analyses for progression from nr‐axSpA to r‐axSpA were also conducted. Results: Among 2,165 patients with axSpA, 1,612 (74%) were classified as having r‐axSpA (1,050 [65%]) or nr‐axSpA (562 [35%]) by central reading. Of 246 patients with nr‐axSpA (mean [SD] symptom duration: 4.4 [6.2] years) who had at least one follow‐up sacroiliac joint radiograph, progression from nr‐axSpA to r‐axSpA at any follow‐up visit was observed in 40 patients (16%) over 5 years. Mean time to radiographic progression was 2.4 years (ranging from 0.9 to 5.1 years). Progression to r‐axSpA was associated with male sex (hazard ratio [HR] 3.16 [95% CI 1.22–8.17]), fulfillment of the imaging arm of the ASAS classification criteria (HR 6.64 [1.37–32.25]), and good response to nonsteroidal anti‐inflammatory drugs (HR 4.66 [1.23–17.71]). Conclusion: 16% of patients with nr‐axSpA progressed to r‐axSpA within 5 years. Male sex, fulfillment of the imaging arm of the ASAS criteria, and good response to nonsteroidal anti‐inflammatory drugs were predictors of radiographic progression in patients with recently diagnosed axSpA. [ABSTRACT FROM AUTHOR]

Objectives To compare MRI and conventional radiography of SI joints for detection of structural lesions typical for axial spondyloarthritis (axSpA). Methods Adult patients from the Assessment of SpondyloArthritis international Society (ASAS) cohort with symptoms suggestive of axSpA and both SI joint MRI and radiographs available for central reading were included. Radiographs were evaluated by three readers according to the modified New York (mNY) criteria grading system. The presence of structural damage on radiographs was defined as fulfilment of the radiographic mNY criterion and, additionally, a lower threshold for sacroiliitis of at least grade 2 unilaterally. MRI scans were assessed for the presence of structural changes indicative of axSpA by seven readers. Diagnostic performance [sensitivity, specificity, positive and negative predictive values (PPV and NPV) and positive and negative likelihood ratios (LR+ and LR−)] of MRI and radiographs (vs rheumatologist's diagnosis of axSpA) were calculated. Results Overall, 183 patients were included and 135 (73.7%) were diagnosed with axSpA. Structural lesions indicative of axSpA on MRI had sensitivity 38.5%, specificity 91.7%, PPV 92.9%, NPV 34.6%, LR+ 4.62 and LR− 0.67. Sacroiliitis according to the mNY criteria had sensitivity 54.8%, specificity 70.8%, PPV 84.1%, NPV 35.8%, LR+ 1.88 and LR− 0.64. Radiographic sacroiliitis of at least grade 2 unilaterally had sensitivity 65.2%, specificity 50.0%, PPV 78.6%, NPV 33.8%, LR+ 1.30 and LR− 0.69. Conclusion Structural lesions of the SI joint detected by MRI demonstrated better diagnostic performance and better interreader reliability compared with conventional radiography. [ABSTRACT FROM AUTHOR]

Copyright of Zeitschrift für Rheumatologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objectives: To evaluate the efficacy and safety of upadacitinib, a Janus kinase inhibitor, in patients with active ankylosing spondylitis (AS) with an inadequate response (IR) to biological disease-modifying antirheumatic drugs (bDMARDs).Methods: Adults with active AS who met modified New York criteria and had an IR to one or two bDMARDs (tumour necrosis factor or interleukin-17 inhibitors) were randomised 1:1 to oral upadacitinib 15 mg once daily or placebo. The primary endpoint was Assessment of SpondyloArthritis international Society 40 (ASAS40) response at week 14. Sequentially tested secondary endpoints included Ankylosing Spondylitis Disease Activity score, Spondyloarthritis Research Consortium of Canada MRI spine inflammation score, total back pain, nocturnal back pain, Bath Ankylosing Spondylitis Functional Index, Bath Ankylosing Spondylitis Metrology Index and Maastricht Ankylosing Spondylitis Enthesitis Score. Results are reported from the 14-week double-blind treatment period.Results: A total of 420 patients with active AS were randomised (upadacitinib 15 mg, n=211; placebo, n=209). Significantly more patients achieved the primary endpoint of ASAS40 at week 14 with upadacitinib vs placebo (45% vs 18%; p<0.0001). Statistically significant improvements were observed with upadacitinib vs placebo for all multiplicity-controlled secondary endpoints (p<0.0001). Adverse events were reported for 41% of upadacitinib-treated and 37% of placebo-treated patients through week 14. No events of malignancy, major adverse cardiovascular events, venous thromboembolism or deaths were reported with upadacitinib.Conclusion: Upadacitinib 15 mg was significantly more effective than placebo over 14 weeks of treatment in bDMARD-IR patients with active AS. No new safety risks were identified with upadacitinib.Trial Registration Number: NCT04169373. [ABSTRACT FROM AUTHOR]

Objective: The objective of the current study was to analyse the association between treatment with tumour necrosis factor inhibitors (TNFi) and radiographic spinal progression in patients with axial spondyloarthritis (axSpA) from a long-term inception cohort.Methods: A total of 243 patients with axSpA from the German Spondyloarthritis Inception Cohort with at least two sets of spinal radiographs obtained at least 2 years apart during a 10-year follow-up were included. Spinal radiographs were evaluated by three trained and calibrated readers according to the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). The association between the current TNFi, previous TNFi and radiographic spinal progression defined as the absolute mSASSS change score over 2 years was analysed using longitudinal generalised estimating equations analysis.Results: TNFi treatment in the current 2-year interval was not associated with retardation of radiographic spinal progression (β=-0.02 (95% CI -0.37 to 0.34) and -0.17 (95% CI -0.54 to 0.20) for any and ≥12 months treatment duration, respectively, adjusted for sex, the Ankylosing Spondylitis Disease Activity Score, smoking, presence of definite radiographic sacroiliitis, mSASSS at baseline and non-steroidal anti-inflammatory drug intake). TNFi treatment in the previous 2-year interval, was, however, significantly associated with reduction of mSASSS progression, which was especially evident in patients who received TNFi in the previous and in the current intervals: β=-0.58 (95% CI -1.02 to -0.13), adjusted for the same variables.Conclusion: TNFi treatment was associated with a time-shifted effect on radiographic spinal progression in axSpA that became evident between years 2 and 4 after treatment initiation. [ABSTRACT FROM AUTHOR]

Objective: To investigate the longitudinal association between radiographic sacroiliitis progression and treatment with tumor necrosis factor inhibitors (TNFi) in patients with early axial spondyloarthritis (SpA) in a long‐term inception cohort. Methods: We included patients from the German Spondyloarthritis Inception Cohort who underwent radiographic assessment of the sacroiliac joints at baseline and at least once more during the 10‐year follow‐up. Two central readers scored the radiographs according to the modified New York criteria for ankylosing spondylitis. The sacroiliac sum score was calculated as a mean of the scores determined by both readers. TNFi use was assessed according to exposure in the current and/or previous 2‐year radiographic interval. The association between TNFi use and radiographic sacroiliitis progression was examined by longitudinal generalized estimating equation analysis with adjustment for potential confounders. Results: In this long‐term inception cohort, 10‐year follow‐up data on 737 radiographic intervals assessed in 301 patients with axial SpA (166 patients with nonradiographic axial SpA and 135 patients with radiographic axial SpA) were obtained. Having received ≥12 months of treatment with TNFi in the previous 2‐year radiographic interval was associated with a significant decrease in the sacroiliitis sum score (β = –0.09 [95% confidence interval (95% CI) –0.18, –0.003]; analyses adjusted for age, sex, symptom duration, HLA–B27 status, Bath Ankylosing Spondylitis Disease Activity Index score, C‐reactive protein, and nonsteroidal antiinflammatory drug intake). In contrast, among patients receiving TNFi in the current radiographic interval, there was no significant association with change in the sacroiliitis sum score (β = 0.05 [95% CI –0.05, 0.14]). This effect of having received ≥12 months of treatment with TNFi in the previous 2‐year radiographic interval was stronger in patients with nonradiographic axial SpA as compared to patients with radiographic axial SpA (β = –0.16 [95% CI –0.28, –0.03] versus β = –0.04 [95% CI –0.15, 0.07]). Conclusion: Treatment with TNFi was associated with the reduction in radiographic sacroiliitis progression in patients with axial SpA. This effect became evident between 2 and 4 years after treatment was initiated. [ABSTRACT FROM AUTHOR]

Objectives To compare demographic and clinical characteristics of patients with axial SpA (axSpA) across geographic regions. Methods Patients With Axial Spondyloarthritis: Multicountry Registry of Clinical Characteristics (PROOF) is an observational study that enrolled recently diagnosed (≤1 year) axSpA patients fulfilling the Assessment of SpondyloArthritis international Society classification criteria from rheumatology clinical practices in 29 countries across six geographic regions. Demographics and disease-related parameters were collected. Here we present baseline data for patients who were classified as radiographic axSpA (r-axSpA) or non-radiographic axSpA (nr-axSpA) confirmed by central reading. Results Of the 2170 patients enrolled, 1553 were classified based on central evaluation of sacroiliac radiographs [r-axSpA: 1023 (66%); nr-axSpA: 530 (34%)]. Patients with nr-axSpA had a significantly higher occurrence of enthesitis (40% vs 33%), psoriasis (10% vs 5%) and IBD (4% vs 2%) vs r-axSpA patients. Significant differences in axSpA characteristics were observed between geographic regions. The highest occurrence of peripheral arthritis (60%), enthesitis (52%) and dactylitis (12%) was in Latin America, and the lowest was in Canada (9%, 9% and 2%, respectively). The occurrence of uveitis and psoriasis was highest in Canada (18% and 14%, respectively) and lowest in China (6% and <1%, respectively). IBD was highest in Arabia (21%), and no cases were observed in China. In multivariable analysis adjusted for factors potentially affecting peripheral and extramusculoskeletal manifestations, geographic regions still exhibited significant differences in frequencies of uveitis (P  < 0.01), psoriasis (P  < 0.0001) and peripheral arthritis (P  < 0.0001). Conclusion The multinational PROOF study of axSpA patients showed significant regional differences in peripheral and extramusculoskeletal manifestations of SpA, which could be considered in management guidelines and clinical trials. [ABSTRACT FROM AUTHOR]

Objectives We report the open-label extension (OLE) of the GO-AHEAD study evaluating the long-term efficacy and safety of golimumab (GLM) in patients with non-radiographic axial spondyloarthritis (nr-axSpA). Methods Patients [both GLM- and placebo (PBO)-treated in the double-blind phase] received GLM 50 mg every 4 weeks during the OLE (36-week treatment; additional 8-week safety follow-up; GLM/GLM and PBO/GLM groups). All patients who entered and received ≥1 dose of study treatment in the OLE were included in the efficacy and safety analyses. The primary efficacy evaluations were the proportions of patients achieving 20% and 40% improvement in the ASAS criteria (ASAS20 and ASAS40, respectively). Responders' analyses were calculated using a non-responder imputation approach. Results Of 198 patients randomised, 189/198 (95.5%) entered the OLE; 174/198 patients (87.9%) completed all visits. Although the proportion of responders increased from week 16 to week 52 in the OLE in both GLM/GLM and PBO/GLM groups, the GLM/GLM group had a higher proportion of responders than the PBO/GLM group throughout the OLE from week 16 to week 52 (ASAS20: 71.1% to 83.9% vs 40.0% to 75.0%, respectively; ASAS40: 56.7% to 76.3% vs 23.0% to 59.4%, respectively; ASAS partial remission: 33.0% to 53.8% and 18.0% to 45.8%). In the OLE, the overall incidence of AEs was lower in the GLM/GLM vs PBO/GLM groups (41.9% and 54.2%). Conclusions Sustained improvement in clinical efficacy was observed at 52 weeks in patients with nr-axSpA following GLM treatment. GLM was well tolerated and provided substantial long-term benefits to patients with nr-axSpA. Trial registration NCT01453725; United States National Library of Medicine clinical trials database; www.clinicaltrials.gov. [ABSTRACT FROM AUTHOR]

Objective: To report the efficacy and safety of upadacitinib through 1 year in patients with ankylosing spondylitis (AS). Methods: In the SELECT‐AXIS 1 study, adults with active AS and an inadequate response to nonsteroidal antiinflammatory drugs were randomized to receive upadacitinib 15 mg once daily or placebo. At week 14, patients who had been randomized to receive placebo were switched to upadacitinib, and all patients continued in the open‐label extension and received upadacitinib up to week 104; interim data up to week 64 are reported herein. Results: Of 187 patients, 178 completed week 14 on study drug and entered the open‐label extension. Similar proportions of patients in either group (continuous upadacitinib or placebo‐to‐upadacitinib) achieved Assessment of SpondyloArthritis international Society 40% response (ASAS40) or Ankylosing Spondylitis Disease Activity Score (ASDAS) showing low disease activity at week 64: ≥70% of patients achieved these end points based on nonresponder imputation (NRI) and ≥81% based on as‐observed analyses. Furthermore, ≥34% (NRI) and ≥39% (as‐observed analysis) achieved ASDAS showing inactive disease or ASAS showing partial remission at week 64. Mean changes from baseline (week 0) to week 64 in pain, function, and inflammation showed consistent improvement or sustained maintenance through the study. Among 182 patients receiving upadacitinib (237.6 patient‐years), 618 adverse events (260.1 per 100 patient‐years) were reported. No serious infections, major adverse cardiovascular events, venous thromboembolic events, gastrointestinal perforation, or deaths were reported. Conclusion: Upadacitinib 15 mg once daily showed sustained and consistent efficacy over 1 year. Patients who switched from placebo to upadacitinib at week 14 showed similar efficacy versus those who received continuous upadacitinib. [ABSTRACT FROM AUTHOR]

Objective To evaluate the diagnostic value of SpA parameters and their combination for the diagnosis of axial SpA in patients with an a priori different probability of the diagnosis. Methods A total of 361 patients with chronic back pain and suspicion of axial SpA (181 referred by primary care physicians or orthopaedists, 180 recruited via an online screening tool) received a structured rheumatologic examination, which resulted into a diagnosis or exclusion of axial SpA. The prevalence of axial SpA indicating the pre-test probability was 40% in the physician-referred subgroup and 20% in the online screening subgroup. Sensitivities, specificities and likelihood ratios for SpA features were determined in both subgroups and the respective post-test probabilities of axial SpA were calculated. Results The relative diagnostic value of single SpA features varied substantially between the groups with different referral pathways. For instance, HLA-B27 positivity increased the probability of the presence of axial SpA by 35% to 55% in online-screened patients and by 22% to 62% in physician-referred patients. The absence of HLA-B27 resulted in a sharp decrease in the probability of the presence of axial SpA in physician-referred patients (from 40% to 6%). This decrease was less sharp in the online screening group (from 20% to 10%). These differences were especially relevant in patients with a small number (one to two) of positive SpA features. Conclusion The diagnostic value of SpA features varies in different patient populations, which should be considered in the diagnostic approach. [ABSTRACT FROM AUTHOR]

Objectives To determine quantitative SI joint MRI lesion cut-offs that optimally define a positive MRI for inflammatory and structural lesions typical of axial SpA (axSpA) and that predict clinical diagnosis. Methods The Assessment of SpondyloArthritis international Society (ASAS) MRI group assessed MRIs from the ASAS Classification Cohort in two reading exercises where (A) 169 cases and 7 central readers; (B) 107 cases and 8 central readers. We calculated sensitivity/specificity for the number of SI joint quadrants or slices with bone marrow oedema (BME), erosion, fat lesion, where a majority of central readers had high confidence there was a definite active or structural lesion. Cut-offs with ≥95% specificity were analysed for their predictive utility for follow-up rheumatologist diagnosis of axSpA by calculating positive/negative predictive values (PPVs/NPVs) and selecting cut-offs with PPV ≥ 95%. Results Active or structural lesions typical of axSpA on MRI had PPVs ≥ 95% for clinical diagnosis of axSpA. Cut-offs that best reflected a definite active lesion typical of axSpA were either ≥4 SI joint quadrants with BME at any location or at the same location in ≥3 consecutive slices. For definite structural lesion, the optimal cut-offs were any one of ≥3 SI joint quadrants with erosion or ≥5 with fat lesions, erosion at the same location for ≥2 consecutive slices, fat lesions at the same location for ≥3 consecutive slices, or presence of a deep (i.e. >1 cm depth) fat lesion. Conclusion We propose cut-offs for definite active and structural lesions typical of axSpA that have high PPVs for a long-term clinical diagnosis of axSpA for application in disease classification and clinical research. [ABSTRACT FROM AUTHOR]

Aims: Long-term data on TNFi treatment in patients with axSpA is scarce. The objective of this analysis was to assess long-term clinical efficacy of etanercept in early axSpA [including both non-radiographic and radiographic axSpA forms], who participated in the long-term (until year 10) extension of the ESTHER-trial. Methods: In the previously reported ESTHER-trial, patients with early active axSpA were randomized to treatment with etanercept (n = 40) or sulfasalazine (n = 36) during the first year. Patients in remission discontinued their therapy and were followed up until the end of year 2; in case of remission-loss, etanercept was (re)-introduced and continued until the end of year 10. If remission was not achieved at year 1, patients continued receiving (or were switched to) etanercept for up to 10 years. Results: A total of 19 patients (12 with r-axSpA and 7 with nr-axSpA at baseline) out of the initial 76 patients (= 25%) completed year 10 of the study. In the entire group, a sustained clinical response was seen over 10 years of follow up in the as-observed analysis. Completers were significantly more often male and showed lower values of patient and physician global assessments of disease activity, Ankylosing Spondylitis Disease Activity Score (ASDAS), and Ankylosing Spondylitis Quality of Life questionnaire (ASQoL) scores at baseline as compared with non-completers. When analyzing clinical data of the completers, mean Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Bath Ankylosing Spondylitis Functional Index (BASFI) values were constantly below 2 and mean ASDAS below 2.1 during follow up with no statistically significant differences between the r-axSpA and nr-axSpA subgroups. A total of 39 serious adverse events were documented over the 10 years, while six of them were seen as possibly associated with the etanercept treatment, which led in five patients to treatment discontinuation. Conclusion: A sustained clinical response was observed over the 10 years of the study with comparable response and drop-out rates between r-axSpA and nr-axSpA. Etanercept was well tolerated across the entire treatment period and showed a good safety profile with no new safety signals. [ABSTRACT FROM AUTHOR]

Objective The aim was to investigate the reliability and validity of radiographic sacroiliitis assessment in anteroposterior (AP) lumbar radiographs compared with conventional pelvic radiographs in patients with axial spondyloarthritis (axSpA). Methods Patients from the German Spondyloarthritis Inception Cohort were selected based on the availability of pelvic and AP lumbar radiographs with visible SI joints at baseline and year 2. Two readers scored the images independently in a random order according to the modified New York criteria. The sacroiliitis sum score was calculated as the mean of both readers. Patients were classified as radiographic (r-)axSpA if radiographic sacroiliitis of grade ≥2 bilaterally or grade ≥3 unilaterally was present in the opinion of both readers and as non-radiographic (nr-)axSpA otherwise. The reliability and validity of sacroiliitis assessment in AP lumbar radiographs was assessed using intraclass correlation coefficients (ICCs), absolute agreement and κ statistics. Results A total of 226 sets of radiographs were scored from 113 patients included in the study. The ICC for the sacroiliitis sum score was 0.91 at both baseline and year 2. A total of 62 (54.9%) and 55 (48.7%) patients were classified as r-axSpA at baseline and 65 (57.5%) and 60 (53.1%) patients at year 2 based on evaluation of pelvic and AP lumbar radiographs, respectively. The absolute agreement between the methods on the classification was 84.9 and 85.0% at baseline and year 2, respectively, with the κ of 0.70 at both time points. Conclusion Radiographic sacroiliitis can be assessed in AP lumbar radiographs with a similar reliability to conventional pelvic radiographs. [ABSTRACT FROM AUTHOR]

Aims: Long-term data on TNFi treatment in patients with axSpA is scarce. The objective of this analysis was to assess long-term clinical efficacy of etanercept in early axSpA [including both non-radiographic and radiographic axSpA forms], who participated in the long-term (until year 10) extension of the ESTHER-trial. Methods: In the previously reported ESTHER-trial, patients with early active axSpA were randomized to treatment with etanercept (n = 40) or sulfasalazine (n = 36) during the first year. Patients in remission discontinued their therapy and were followed up until the end of year 2; in case of remission-loss, etanercept was (re)-introduced and continued until the end of year 10. If remission was not achieved at year 1, patients continued receiving (or were switched to) etanercept for up to 10 years. Results: A total of 19 patients (12 with r-axSpA and 7 with nr-axSpA at baseline) out of the initial 76 patients (= 25%) completed year 10 of the study. In the entire group, a sustained clinical response was seen over 10 years of follow up in the as-observed analysis. Completers were significantly more often male and showed lower values of patient and physician global assessments of disease activity, Ankylosing Spondylitis Disease Activity Score (ASDAS), and Ankylosing Spondylitis Quality of Life questionnaire (ASQoL) scores at baseline as compared with non-completers. When analyzing clinical data of the completers, mean Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Bath Ankylosing Spondylitis Functional Index (BASFI) values were constantly below 2 and mean ASDAS below 2.1 during follow up with no statistically significant differences between the r-axSpA and nr-axSpA subgroups. A total of 39 serious adverse events were documented over the 10 years, while six of them were seen as possibly associated with the etanercept treatment, which led in five patients to treatment discontinuation. Conclusion: A sustained clinical response was observed over the 10 years of the study with comparable response and drop-out rates between r-axSpA and nr-axSpA. Etanercept was well tolerated across the entire treatment period and showed a good safety profile with no new safety signals. [ABSTRACT FROM AUTHOR]

Objectives Osteitis condensans ilii (OCI) has become an important differential diagnosis for axial spondyloarthritis (axSpA). The objective of this matched case–control study was to investigate demographic, clinical, laboratory and MRI characteristics of OCI as compared with axial spondyloarthritis (axSpA). Methods A total of 60 patients diagnosed with OCI were included in the final analysis. From 27 of these patients, MRIs of the sacroiliac joints were available. OCI patients were matched with a 1:1 ratio by back pain duration to patients with definite axSpA in order to compare clinical, laboratory and MRI characteristics. Results The OCI patients were nearly all females (96.7 vs 46.7%), had a significantly lower prevalence of inflammatory back pain (39.5 vs 88.9%), a significantly lower percentage of HLA-B27 positives (35.2 vs 80.0%) and a lower prevalence of the majority of other SpA features as compared with axSpA patients. Interestingly, there was no difference in the prevalence of osteitis in the sacroiliac joints (92.6 vs 85.2% in OCI and axSpA, respectively, P  = 0.44), but there was a difference in the prevalence of erosions (7.4 vs 66.7%, respectively, P  = 0.0001). In addition, in OCI nearly all lesions were localized in the anterior part of the sacroiliac joints while in axSpA lesions were localized predominantly in the middle part of the joint (for osteitis: 96 vs 4% in OCI and 28.6 vs 71.4% in axSpA; P  = 0.0002 for the inter-group difference). Conclusion Clinical and imaging features of OCI compared with axSpA are described that should help in differential diagnosis. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to investigate the association of extra-musculoskeletal manifestations (EMMs) with disease activity, functional status, and treatment patterns in a large population-based cohort of patients with axial spondyloarthritis (axSpA). Methods: A stratified random sample of patients with axSpA, drawn from health insurance data, received a survey on disease-related characteristics including history (ever presence) of the following EMMs: inflammatory bowel disease (IBD), psoriasis (PSO), and anterior uveitis (AU). Survey data were linked to health insurance data, gathering additional information on current occurrence (within one year) of EMMs and drug prescriptions. Separate multivariable linear regression models were calculated to determine the association of EMMs with disease activity (Bath Ankylosing Spondylitis Disease Activity Index), and functional status (Bath Ankylosing Spondylitis Functional Index) after adjustment for relevant parameters, including treatment. Results: A total of 1729 patients with axSpA were included in the analyses (response: 47%; mean age: 56 years; 46% female) of whom 6% (9%) had current (ever) IBD, 10% (15%) had current (ever) PSO, and 9% (27%) had current (ever) AU. Ever presence of IBD and history of PSO were significantly associated with higher level of disease activity. Ever presence of PSO was also associated with higher level of functional impairment, whereas current AU was significantly associated with lower disease activity. Patients with current IBD or PSO received more frequently biological and conventional synthetic disease-modifying anti-rheumatic drugs as well as systemic steroids. AU was associated with a higher use of conventional synthetic disease-modifying anti-rheumatic drugs only. Conclusion: Disease activity is higher in patients with axSpA with history of IBD or history of PSO. Functional impairment is also higher in patients with axSpA with history of PSO. The presence of different EMMs was associated with different treatment patterns in axSpA. [ABSTRACT FROM AUTHOR]

Objectives: The Assessment of SpondyloArthritis international Society (ASAS) MRI working group conducted a multireader exercise on MRI scans from the ASAS classification cohort to assess the spectrum and evolution of lesions in the sacroiliac joint and impact of discrepancies with local readers on numbers of patients classified as axial spondyloarthritis (axSpA).Methods: Seven readers assessed baseline scans from 278 cases and 8 readers assessed baseline and follow-up scans from 107 cases. Agreement for detection of MRI lesions between central and local readers was assessed descriptively and by the kappa statistic. We calculated the number of patients classified as axSpA by the ASAS criteria after replacing local detection of active lesions by central readers and replacing local reader radiographic sacroiliitis by central reader structural lesions on MRI.Results: Structural lesions, especially erosions, were as frequent as active lesions (≈40%), the majority of patients having both types of lesions. The ASAS definitions for active MRI lesion typical of axSpA and erosion were comparatively discriminatory between axSpA and non-axSpA. Local reader overcall for active MRI lesions was about 30% but this had a minor impact on the number of patients (6.4%) classified as axSpA. Substitution of radiography with MRI structural lesions also had little impact on classification status (1.4%).Conclusion: Despite substantial discrepancy between central and local readers in interpretation of both types of MRI lesion, this had a minor impact on the numbers of patients classified as axSpA supporting the robustness of the ASAS criteria for differences in assessment of imaging. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the efficacy and safety of ixekizumab for up to 52 weeks in two phase 3 studies of patients with active radiographic axial spondyloarthritis (r-axSpA) who were biological disease-modifying antirheumatic drug (bDMARD)-naive (COAST-V) or tumour necrosis factor inhibitor (TNFi)-experienced (COAST-W).Methods: Adults with active r-axSpA were randomised 1:1:1:1 (n=341) to 80 mg ixekizumab every 2 (IXE Q2W) or 4 weeks (IXE Q4W), placebo (PBO) or 40 mg adalimumab Q2W (ADA) in COAST-V and 1:1:1 (n=316) to IXE Q2W, IXE Q4W or PBO in COAST-W. At week 16, patients receiving ixekizumab continued their assigned treatment; patients receiving PBO or ADA were rerandomised 1:1 to IXE Q2W or IXE Q4W (PBO/IXE, ADA/IXE) through week 52.Results: In COAST-V, Assessment of SpondyloArthritis international Society 40 (ASAS40) responses rates (intent-to-treat population, non-responder imputation) at weeks 16 and 52 were 48% and 53% (IXE Q4W); 52% and 51% (IXE Q2W); 36% and 51% (ADA/IXE); 19% and 47% (PBO/IXE). Corresponding ASAS40 response rates in COAST-W were 25% and 34% (IXE Q4W); 31% and 31% (IXE Q2W); 14% and 39% (PBO/IXE). Both ixekizumab regimens sustained improvements in disease activity, physical function, objective markers of inflammation, QoL, health status and overall function up to 52 weeks. Safety through 52 weeks of ixekizumab was consistent with safety through 16 weeks.Conclusion: The significant efficacy demonstrated with ixekizumab at week 16 was sustained for up to 52 weeks in bDMARD-naive and TNFi-experienced patients. bDMARD-naive patients initially treated with ADA demonstrated further numerical improvements after switching to ixekizumab. Safety findings were consistent with the known safety profile of ixekizumab.Trial Registration Number: NCT02696785/NCT02696798. [ABSTRACT FROM AUTHOR]

Objectives: To detail the greatest areas of unmet scientific and clinical needs in rheumatology.Methods: The 21st annual international Advances in Targeted Therapies meeting brought together more than 100 leading basic scientists and clinical researchers in rheumatology, immunology, epidemiology, molecular biology and other specialties. During the meeting, breakout sessions were convened, consisting of 5 disease-specific groups with 20-30 experts assigned to each group based on expertise. Specific groups included: rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, systemic lupus erythematosus and other systemic autoimmune rheumatic diseases. In each group, experts were asked to identify unmet clinical and translational research needs in general and then to prioritise and detail the most important specific needs within each disease area.Results: Overarching themes across all disease states included the need to innovate clinical trial design with emphasis on studying patients with refractory disease, the development of trials that take into account disease endotypes and patients with overlapping inflammatory diseases, the need to better understand the prevalence and incidence of inflammatory diseases in developing regions of the world and ultimately to develop therapies that can cure inflammatory autoimmune diseases.Conclusions: Unmet needs for new therapies and trial designs, particularly for those with treatment refractory disease, remain a top priority in rheumatology. [ABSTRACT FROM AUTHOR]

The authors discuss their research on the radiographic sacroiliitis progression in patients with axial spondyloarthritis (axSpA) who were included in the Assessment of SpA International Society cohort. Topics mentioned include the use of the modified New York criteria in scoring the pelvic radiographs of patients, the procedure of calculating the sacroiliitis sum score, and the parameters associated with the radiographic axSpA classification including male sex and HLA-B27 positivity.

Objectives The objective of this study was to examine whether adding biomarkers to routine clinical parameters improves prediction of radiographic spinal progression in axial spondyloarthritis. Methods One hundred and seventeen patients with ankylosing spondylitis who completed the Effects of NSAIDs on RAdiographic Damage in Ankylosing Spondylitis (ENRADAS) trial were included. Radiographic spinal progression was defined as worsening of the modified Stoke Ankylosing Spondylitis Spine Score by ⩾2 points after 2 years. A clinical prediction model was constructed out of baseline syndesmophytes, elevated CRP, cigarette smoking and male sex. The following serum biomarkers were measured at baseline by ELISA: MMP3, VEGF, calprotectin, leptin, high molecular weight adiponectin, osteoprotegerin, sclerostin, N-terminal telopeptide, procollagen type II N-terminal propeptide and serum amyloid A. Results Repeated cross-validation analyses revealed one biomarker combination with potential added predictive value in addition to the clinical model: leptin + high molecular weight adiponectin + VEGF. This biomarker combination showed an area under the curve (AUC)Biomarkers = 0.731 (95% CI: 0.614, 0.848), which was numerically superior to the clinical model [AUCClinical = 0.665 (95% CI: 0.553, 0.776)]. A combination of clinical parameters + biomarkers showed an improved predictive value compared with the clinical model reflected by AUCClinical+Biomarkers = 0.768 (95% CI: 0.666, 0.871), though not statistically significant (P = 0.051). However, by considering the part of the receiver operating characteristic curve with a specificity ⩾75% resulting in partial AUC (pAUC), the improvement becomes significant (pAUCClinical+Biomarkers = 0.119; pAUCClinical = 0.053; P = 0.01). Conclusion Biomarkers show potential to improve the prediction of radiographic spinal progression in axial spondyloarthritis when used in addition to the clinical parameters, though the added value seems to be rather small. [ABSTRACT FROM AUTHOR]

Objectives The objective of this study was to assess the current diagnostic delay in axial SpA (axSpA) and to analyse factors associated with it. Methods A stratified sample of subjects with a diagnosis of axSpA (International Classification of Diseases, 10th Revision code M45) was drawn from health insurance data in Germany and was questioned on disease-related, lifestyle and socio-economic characteristics. The diagnostic delay was calculated as the time from back pain onset until a diagnosis of axSpA. A multivariable linear regression analysis was performed to explore factors associated with the diagnostic delay. Results Among 1677 patients with axSpA included in the analysis, the mean diagnostic delay was 5.7 years (median 2.3). Of those, 407 patients were diagnosed in 1996–2005 and 484 patients in 2006–2015. The mean diagnostic delay was not substantially different in both periods: 6.3 years (median 2.6) and 7.4 (2.7), respectively. Multivariable linear regression revealed that female sex [β = 1.85 (95% CI 1.06, 2.65)], negative HLA-B27 status [β = 3.61 (95% CI 2.07, 5.14)], presence of psoriasis [β = 1.40 (95% CI 0.08, 2.73)] and younger age at symptom onset [β = 1.91 (95% CI 1.53, 2.29)] were factors associated with a longer diagnostic delay. Conclusion The diagnostic delay in axSpA is still unacceptably long. Patients who are female, young at symptom onset, HLA-B27 negative or have psoriasis have a longer diagnostic delay. Specific referral strategies might be necessary in order to decrease the diagnostic delay in patients presenting with these characteristics. [ABSTRACT FROM AUTHOR]

Objectives A positive family history (PFH) of spondyloarthritis, in particular a PFH of AS or acute anterior uveitis, is associated with HLA-B27 carriership in chronic back pain patients. As it is unknown, the study aimed to investigate if a PFH contributes to diagnosing axial spondyloarthritis (axSpA) once HLA-B27 status is known. Methods In axSpA-suspected patients from the Assessment of SpondyloArthritis international Society (ASAS), DEvenir des Spondyloarthropathies Indifférenciéés Récentes (DESIR) and SPondyloArthritis Caught Early (SPACE) cohorts, logistic regression analyses were performed with HLA-B27 status and PFH according to the ASAS definition (ASAS-PFH) as determinants and clinical axSpA diagnosis as outcome at baseline. Analyses were repeated with a PFH of AS or acute anterior uveitis. Results In total, 1818 patients suspected of axSpA were analysed (ASAS n = 594, DESIR n = 647, and SPACE n = 577). In patients from the ASAS, DESIR and SPACE cohorts, respectively 23%, 39% and 38% had an ASAS-PFH, 52%, 58% and 43% were HLA-B27 positive, and 62%, 47% and 54% were diagnosed with axSpA. HLA-B27 was independently associated with an axSpA diagnosis in each cohort but an ASAS-PFH was not [ASAS cohort: HLA-B27 odds ratio (OR): 6.9 (95% CI: 4.7, 10.2), ASAS-PFH OR: 0.9 (95% CI: 0.6, 1.4); DESIR: HLA-B27 OR: 2.1 (95% CI: 1.5, 2.9), ASAS-PFH OR: 1.0 (95% CI 0.7, 1.3); SPACE: HLA-B27 OR: 10.4 (95% CI: 6.9, 15.7), ASAS-PFH OR: 1.0 (95% CI: 0.7, 1.5)]. Similar negative results were found for PFH of AS and acute anterior uveitis. Conclusion In three independent cohorts with different ethnical backgrounds, ASAS, DESIR and SPACE, a PFH was not associated independently of HLA-B27 with a diagnosis of axSpA. This indicates that in the vast majority of patients presenting with back pain, a PFH does not contribute to the likelihood of an axSpA diagnosis if HLA-B27 status is known. [ABSTRACT FROM AUTHOR]

To develop a comprehensive listing of the greatest unmet scientific and clinical needs in rheumatology. The 20th annual international Targeted Therapies meeting brought more than 100 leading basic scientists and clinical researchers in rheumatology, immunology, epidemiology, molecular biology and other specialties. During the meeting, breakout sessions were convened, consisting of five disease-specific groups with 20-30 experts assigned to each group based on expertise. Specific groups included rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, systemic lupus erythematosus, connective tissue diseases and a basic science immunology group spanning all of these clinical domains. In each group, experts were asked to consider recent accomplishments within their clinical domain in the last year and update the unmet needs in three categorical areas: basic/translational science, clinical science and therapeutic development, and clinical care. While progress was noted among some of previously identified needs, both new needs were identified and themes from prior meetings were re-iterated: the need for better understanding the heterogeneity within each disease, and for identifying preclinical states of disease allowing treatment and prevention of disease in those at risk, and the elusive ability to cure disease. Within the clinical care realm, improved comorbidity management and patient-centred care continue to be unmet needs, and the need for new and affordable therapeutics was highlighted. Unmet needs for new and accessible targeted therapies, disease prevention and ultimately cure remain a priority in rheumatology. [ABSTRACT FROM AUTHOR]

Objective: To evaluate radiographic progression in the sacroiliac (SI) joints and to identify its predictors during long‐term treatment (up to 6 years) with the tumor necrosis factor (TNF) inhibitor etanercept in patients with early axial spondyloarthritis (SpA). Methods: Patients with early axial SpA who were treated with etanercept for up to 6 years in the Etanercept versus Sulfasalazine in Early Axial Spondyloarthritis (ESTHER) trial were selected based on the availability of radiographs of the SI joints. Two readers who were blinded with regard to clinical data scored the radiographs according to the modified New York criteria (range 0–4 per SI joint). A sacroiliitis sum score (total range 0–8) was calculated as the mean of the scores of the 2 readers. Active and chronic inflammatory changes in the SI joints on magnetic resonance imaging (MRI) performed at baseline, year 2, and year 4 were assessed according to the Berlin MRI scoring system. Results: Of the 76 patients originally included in the study, 42 had radiographs of the SI joints available at baseline and at least 1 follow‐up time point (year 2, 4, or 6). The mean ± SD change in the sacroiliitis sum score was 0.13 ± 0.73, −0.27 ± 0.76, and −0.09 ± 0.68, in the time intervals baseline to year 2, year 2 to year 4, and year 4 to year 6, respectively. In the longitudinal mixed model analysis, elevated C‐reactive protein level (β = 0.58 [95% confidence interval 0.24, 0.91]) and MRI SI joint osteitis score (β = 0.06 [95% confidence interval 0.03, 0.10]) were independently associated with progression of the sacroiliitis sum score. Conclusion: Our findings indicate that long‐term anti‐TNF therapy decelerates the progression of structural damage in the SI joints. Elevated CRP level and presence of osteitis on MRI were independently associated with radiographic sacroiliitis progression. [ABSTRACT FROM AUTHOR]