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To analyse the prevalence of spondyloarthritis (SpA) in patients with acute anterior uveitis (AAU), to identify parameters associated with SpA presence, and to evaluate referral algorithms.Prospectively recruited consecutive patients with non-infectious AAU underwent structured rheumatologic assessment including magnetic resonance imaging of sacroiliac joints allowing a definitive diagnosis/exclusion of concomitant SpA. Fisher's exact test and Mann-Whitney U test were used to compare AAU patients with and without SpA. Furthermore, logistic regression analyses were performed. Sensitivity, specificity, positive predictive value, positive and negative likelihood ratios were analysed for referral strategies.Out of 189 AAU patients, 106 (56%) were diagnosed with SpA. The majority (93%) had predominantly axial SpA, 7 patients peripheral SpA. In 74 patients (70%), the SpA diagnosis was established for the first time. In multivariable logistic regression analysis, psoriasis (OR 12.5 [95%CI 1.3-120.2]), HLA-B27 positivity (OR 6.3 [95%CI 2.4-16.4]), elevated CRP (OR 4.8 [95%CI 1.9-12.4]) and male sex (OR 2.1 [95%CI 1.1-4.2]) were associated with SpA presence. None of the ophthalmologic parameters were predictive for SpA. The Dublin Uveitis Evaluation Tool showed higher specificity for SpA recognition than the ASAS referral tool (42% vs. 28%), which had a slightly higher sensitivity (78% vs. 80%). However, both referral strategies would have missed more than 20% of SpA patients.We revealed a high prevalence of both, overall and previously undiagnosed, SpA in AAU patients. Therefore, we propose rheumatologic evaluation for all AAU patients with musculoskeletal symptoms.

Background MRI is frequently used for early diagnosis of axial spondyloarthritis (axSpA). However, evaluation is time-consuming and requires profound expertise because noninflammatory degenerative changes can mimic axSpA, and early signs may therefore be missed. Deep neural networks could function as assistance for axSpA detection. Purpose To create a deep neural network to detect MRI changes in sacroiliac joints indicative of axSpA. Materials and Methods This retrospective multicenter study included MRI examinations of five cohorts of patients with clinical suspicion of axSpA collected at university and community hospitals between January 2006 and September 2020. Data from four cohorts were used as the training set, and data from one cohort as the external test set. Each MRI examination in the training and test sets was scored by six and seven raters, respectively, for inflammatory changes (bone marrow edema, enthesitis) and structural changes (erosions, sclerosis). A deep learning tool to detect changes indicative of axSpA was developed. First, a neural network to homogenize the images, then a classification network were trained. Performance was evaluated with use of area under the receiver operating characteristic curve (AUC), sensitivity, and specificity.

ObjectivesTo evaluate a dermatologist-centred screening tool followed by a structured rheumatological examination including MRI of sacroiliac joints and spine for the recognition of psoriatic arthritis with axial involvement (axPsA).MethodsThis was a prospective multicentre study. Adult patients with a confirmed diagnosis of psoriasis who had chronic back pain (≥3 months), onset ResultsRheumatologists examined 100 patients of those who qualified for referral. 14 patients (including 3 with both axial and peripheral involvement) were diagnosed with axPsA and 5 were diagnosed with peripheral PsA solely. All patients diagnosed with axPsA had active inflammatory and/or structural (post)inflammatory changes in the sacroiliac joints and/or spine on imaging. In five patients, MRI changes indicative of axial involvement were found only in the spine. All but one patient with PsA (13/14 with axPsA and 5/5 with pPsA) fulfilled the Classification Criteria for Psoriatic Arthritis criteria for PsA. The Assessment of SpondyloArthritis International Society criteria for axSpA were fulfilled in 9 (64.3%) patients diagnosed with axPsA.ConclusionsApplying a dermatologist-centred screening tool may be useful for the early detection of axPsA in at-risk patients with psoriasis .

ObjectivesTo define the instruments for the Assessment of SpondyloArthritis international Society–Outcomes Measures in Rheumatology (ASAS-OMERACT) core domain set for axial spondyloarthritis (axSpA).MethodsAn international working group representing key stakeholders selected the core outcome instruments following a predefined process: (1) identifying candidate instruments using a systematic literature review; (2) reducing the list of candidate instruments by the working group, (3) assessing the instruments’ psychometric properties following OMERACT filter 2.2, (4) selection of the core instruments by the working group and (5) voting and endorsement by ASAS.ResultsThe updated core set for axSpA includes seven instruments for the domains that are mandatory for all trials: Ankylosing Spondylitis Disease Activity Score and Numerical Rate Scale (NRS) patient global assessment of disease activity, NRS total back pain, average NRS of duration and severity of morning stiffness, NRS fatigue, Bath Ankylosing Spondylitis Function Index and ASAS Health Index. There are 9 additional instruments considered mandatory for disease-modifying antirheumatic drugs (DMARDs) trials: MRI activity Spondyloarthritis Research Consortium of Canada (SPARCC) sacroiliac joints and SPARCC spine, uveitis, inflammatory bowel disease and psoriasis assessed as recommended by ASAS, 44 swollen joint count, Maastricht Ankylosing Spondylitis Enthesitis Score, dactylitis count and modified Stoke Ankylosing Spondylitis Spinal Score. The imaging outcomes are considered mandatory to be included in at least one trial for a drug tested for properties of DMARD. Furthermore, 11 additional instruments were also endorsed by ASAS, which can be used in axSpA trials on top of the core instruments.ConclusionsThe selection of the instruments for the ASAS-OMERACT core domain set completes the update of the core outcome set for axSpA, which should be used in all trials.

BACKGROUND: The current core outcome set for ankylosing spondylitis (AS) has had only minor adaptations since its development 20 years ago. Considering the significant advances in this field during the preceding decades, an update of this core set is necessary.OBJECTIVE: To update the ASAS-OMERACT core outcome set for AS into the ASAS-OMERACT core outcome set for axial spondyloarthritis (axSpA).METHODS: Following OMERACT and COMET guidelines, an international working group representing key stakeholders (patients, rheumatologists, health professionals, pharmaceutical industry and drug regulatory agency representatives) defined the core domain set for axSpA. The development process consisted of: i) Identifying candidate domains using a systematic literature review and qualitative studies; ii) Selection of the most relevant domains for different stakeholders through a 3-round Delphi survey involving axSpA patients and axSpA experts; iii) Consensus and voting by ASAS; iv) Endorsement by OMERACT. Two scenarios are considered based on the type of therapy investigated in the trial: symptom modifying therapies and disease modifying therapies.RESULTS: The updated core outcome set for axSpA includes 7 mandatory domains for all trials (disease activity, pain, morning stiffness, fatigue, physical function, overall functioning and health, and adverse events including death). There are 3 additional domains (extra-musculoskeletal manifestations, peripheral manifestations and structural damage) that are mandatory for disease modifying therapies and important but optional for symptom modifying therapies. Finally, 3 other domains (spinal mobility, sleep, and work and employment) are defined as important but optional domains for all trials.CONCLUSION: The ASAS-OMERACT core domain set for AS has been updated into the ASAS-OMERACT core domain set for axSpA. The next step is the selection of instruments for each domain.

ObjectivesThis study aimed to evaluate the Disease Activity index for PSoriatic Arthritis (DAPSA) based on a quick quantitative C reactive protein (qCRP) assay (Q-DAPSA) in a multicentre, prospective, cross-sectional study in patients with psoriatic arthritis (PsA).MethodsThe assessment of prospectively recruited study patients included joint examination and patient reported outcome (PRO) measures (patient global assessment, patient pain assessment). Following, the DAPSA based on a routine laboratory CRP measurement, Q-DAPSA and clinical DAPSA (cDAPSA) were calculated. Cross-tabulations and weighted Cohen’s kappa were performed to analyse the agreement of disease activity categories. Bland-Altman plots and intraclass correlation coefficients were used to determine the agreement of numerical values regarding CRP and qCRP as well as different disease activity scores.ResultsAltogether, 104 patients with PsA could be included in the statistical analysis. With Q-DAPSA, 102 of 104 (98.1%) patients achieved identical disease activity categories in comparison to DAPSA with a weighted Cohen’s kappa of 0.980 (95% CI: 0.952 to 1.000). The agreement between DAPSA and cDAPSA was slightly lower with identical disease activity categories seen in 97 of 104 (93.3%) of patients and with a weighted Cohen’s kappa of 0.932 (95% CI 0.885 to 0.980).ConclusionsThe Q-DAPSA showed an almost perfect agreement with the conventional DAPSA regarding identical disease activity categories. Thus, the Q-DAPSA can be used as a timely available disease activity score in patients with PsA with the additional benefit of CRP involvement. Consequently, the Q-DAPSA could facilitate the implementation of the treat-to-target concept in clinical routine and clinical trials.

Spondyloarthritis (SpA) is a chronic inflammatory disease that is tightly linked to HLA-B*27 but the pathophysiological basis of this link is still unknown. It is discussed whether either the instability of HLA-B*27 molecules triggers predominantly innate immune reactions or yet unknown antigenic peptides presented by HLA-B*27 induce adaptive autoimmune reactions by CD8

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.

Objectives The diagnostic delay in axial spondyloarthritis (axial SpA) remains unacceptably high, with one of the reasons being a late referral. Structured physician-based referral programs are able to improve early diagnosis, but lack of implementation is still an issue. The objective of this study was to evaluate an online self-referral (OSR) tool for patients with back pain and to compare it to an established physician-based referral tool. Methods Patients with back pain were included if they either fulfilled the requirements of the OSR tool or were referred by a physician using the Berlin referral tool. Rheumatologists in the specialized center performed a structured assessment in all patients that resulted in the final diagnosis of axial SpA / no axial SpA. Furthermore, we attempted to optimize the OSR tool in terms of maximizing the specificity constrained by a sensitivity of at least 90% of the original strategy. Results 361 consecutive patients (180 via the OSR and 181 via the Berlin referral tool) were included in the study. A total of 35 patients (19.4%) in the self-referral group and 71 patients (39.2%) in the physician-referral group were finally diagnosed with axial SpA. Axial SpA patients from the OSR group were more often HLA-B27 negative, females, and were more frequently at a non-radiographic stage as compared to axial SpA patients who came via the physician-based tool. Both groups had, however, a similar disease burden. According to the pre-defined selection criterion we identified an optimized combination of ≥2 IBP parameters and ≥1 other SpA parameters (in addition to both stem parameters). Conclusions Despite the better performance of the physician-based referral strategy, the proportion of axial SpA among self-referred patients (19.4%) was clearly higher than the assumed 5% prevalence of axial SpA in patients with chronic back pain. Based on our data driven approach the performance of the OSR strategy could be further improved if at least two IBP parameters plus one additional SpA parameter had to be present in addition to the stem parameters. The OSR tool can be used in specialized centers in addition to a physician-based referral strategy to improve early diagnosis and to increase awareness of axial SpA.

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.

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.

To evaluate the performance of the Ankylosing Spondylitis Disease Activity Score based on a validated quick quantitative C-reactive protein assay (ASDAS-qCRP) as compared to ASDAS based on a routine lab CRP assay (ASDAS-CRP) and ASDAS based on erythrocyte sedimentation rate (ASDAS-ESR).Disease activity assessment was performed in 50 patients with axial spondyloarthritis (axSpA). Routine lab CRP was measured in the central lab while the quantitative quick-CRP assay and ESR measurements were performed locally. ASDAS-CRP, ASDAS-qCRP and ASDAS-ESR were subsequently calculated.The mean (±SD) serum level of the routine lab CRP (6.2±8.3mg/l) was lower than of the quick-CRP (7.4±8.4mg/l) (P0.05). Whereat, there was no significant difference in the mean values of ASDAS-CRP and ASDAS-qCRP in axSpA patients (2.70±0.94 and 2.74±0.96, respectively, P=0.069), while the ASDAS-ESR (2.85±1.0) was significantly higher than ASDAS-CRP (P=0.036) and numerically higher than ASDAS-qCRP (P=0.125). In 47 of the 50 cases of axSpA (94%), patients were assigned to the same disease activity category according to ASDAS-CRP and ASDAS-qCRP.ASDAS-qCRP performed similarly well compared to ASDAS-CRP with the absolute agreement on the disease activity category according to the ASDAS of 94%. ASDAS-qCRP is, therefore, feasible for an immediate decision-making in clinical practice and trials aimed at treating to target.

ObjectiveThe 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.MethodsA 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.ResultsTNFi 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.ConclusionTNFi 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.

Objectives: The objective of the study was to validate the Ankylosing Spondylitis Disease Activity Score (ASDAS) based on a quick quantitative C-reactive protein (qCRP) assay (ASDAS-Q) in a multicentre, prospective, cross-sectional study in patients with axial spondyloarthritis (axial SpA). Methods: Disease activity assessment was performed in prospectively recruited patients with axial SpA. Routine laboratory CRP was determined in the central laboratory of each study centre, while quick qCRP and erythrocyte sedimentation rate (ESR) were measured locally. Consequently, ASDAS-CRP, ASDAS-Q using the qCRP and ASDAS-ESR were calculated. The absolute agreement on the disease activity category ascertainment was analysed with cross-tabulations and weighted Cohen’s kappa. Bland–Altman plots and intraclass correlation coefficients (ICCs) were used to analyse the criterion validity. Results: Overall, 251 axial SpA patients were included in the analysis. The mean qCRP value (6.34 ± 11.13 mg/l) was higher than that of routine laboratory CRP (5.26 ± 9.35 mg/l). The ICC for routine laboratory CRP versus qCRP was 0.985 [95% confidence interval (CI): 0.972–0.991]. Comparing ASDAS-Q with ASDAS-CRP, 242 of 251 (96.4%) patients were assigned to the same disease activity categories with a weighted Cohen’s kappa of 0.966 (95% CI: 0.943–0.988) and ICC of 0.997 (95% CI: 0.994–0.999). Conclusions: ASDAS-Q showed an almost perfect agreement with ASDAS-CRP in the assignment to specific disease activity categories. Consequently, ASDAS-Q using the qCRP value can be applied as an accurate and quickly available alternative to ASDAS-CRP, thus facilitating the implementation of the treat-to-target concept in clinical trials and clinical routine.

To determine the SpA prevalence and identify its associated factors in Crohn's disease (CD) patients receiving a systematically rheumatological and imaging assessment, including magnetic resonance imaging (MRI) of the sacroiliac joints and spine.CD patients either naive to biologics or without them for three months prior enrollment were recruited in a subgroup of the German Spondyloarthritis Inception Cohort (GESPIC-Crohn). A structured assessment of SpA manifestations was performed by a rheumatologist, including MRI of sacroiliac joints and spine. Demographic and clinical parameters including disease activity in CD (Harvey Bradshaw Index-HBI) and SpA (C-reactive protein - CRP, Bath Ankylosing Spondylitis Disease Activity Index, and Ankylosing Spondylitis Disease Activity Score) were collected. Univariable and multivariable logistic regression analyses were performed to identify factors associated with the presence of SpA.A total of 103 patients with CD were included in the cohort. The mean CD disease duration was 1.3±2.4years and 95.1% were naïve to biologics. The most frequent musculoskeletal manifestation was back pain (65.0%), followed by chronic back pain (50.5%), and arthralgia (43.7%). Prevalence of SpA was 19.4% with slightly higher proportion of axial SpA than peripheral SpA, and higher proportion of radiographic axial SpA (7.4%) than non-radiographic axial SpA (2.8%). Changes in MRI compatible with axial SpA were found in 15 (14.7%) patients, of which 9 (81.1%) patients had the clinical diagnosis of axial SpA. HLA-B27 positivity (OR 9.02, CI 95% 2.29-35.55) and higher disease activity of CD as reflected by the HBI (OR 1.14, 95%CI 1.01-1.30) were significant and independently associated with the presence of SpA.SpA was present in nearly one out of five patients with CD and it was associated with the expression of HLA-B27 and a higher clinical activity of CD. Our findings raise awareness to rheumatologists and gastroenterologists on the high concomitance between both diseases and may help to reduce the delay in SpA diagnosis.

ObjectiveGenetic determinants of fibrin clot formation and fibrinolysis have an impact on local and systemic inflammatory response. The aim of the present study was to assess whether coagulation-related genotypes affect the predictive value of C-reactive protein (CRP) in regards of radiographic spinal progression in axial spondyloarthritis (axSpA).MethodsTwo hundred and eight patients with axSpA from the German Spondyloarthritis Inception Cohort were characterised for genotypes of α-fibrinogen, β-fibrinogen (FGB) and γ-fibrinogen, factor XIII A-subunit (F13A) and α2-antiplasmin (A2AP). The relation between CRP levels and radiographic spinal progression defined as worsening of the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) by ≥2 points over 2 years was assessed in dependence on the respective genetic background in logistic regression analyses.ResultsOverall, CRP was associated with mSASSS progression ≥2 points: time-averaged CRP ≥10 mg/L, OR: 3.32, 95% CI 1.35 to 8.13. After stratification for coagulation-related genotypes, CRP was strongly associated with mSASSS progression in individuals predisposed to form loose, fibrinolysis-susceptible fibrin clots (FGB rs1800790GG, OR: 6.86, 95% CI 2.08 to 22.6; A2AP 6Trp, OR: 5.86, 95% CI 1.63 to 21.0; F13A 34Leu, OR: 8.72, 95% CI 1.69 to 45.1), while in genotypes predisposing to stable fibrin clots, the association was absent or weak (FGB rs1800790A, OR: 0.83, 95% CI 0.14 to 4.84; A2AP 6Arg/Arg, OR: 1.47, 95% CI 0.35 to 6.19; F13A 34Val/Val, OR: 1.72, 95% CI 0.52 to 5.71).ConclusionsElevated CRP levels seem to be clearly associated with radiographic spinal progression only if patients are predisposed for loose fibrin clots with high susceptibility to fibrinolysis.

BackgroundTo analyse the added value of susceptibility-weighted imaging (SWI) compared with standard T1-weighted (T1) MRI for detecting structural lesions of the sacroiliac joint (SIJ) in patients with axial spondyloarthritis (axSpA) using CT as reference standard.Material and methodsSixty-eight patients with suspected or proven axSpA underwent both MRI and CT of the SIJ on the same day. Two readers separately scored CT, T1 and SWI for the presence of erosions, sclerosis and joint space changes using an established 24-region SIJ model. Disagreement was resolved by a third reader. Diagnostic accuracy (McNemar test), Cohen’s kappa (k), sensitivity (SE) and specificity were calculated on the joint level using CT as reference.ResultsIn CT, 38 joints showed erosions, 67 sclerosis and 37 joint space changes. Agreement with CT for erosions was 92.6% (k=0.811 (0.7–0.92)) in SWI and 87.5% (k=0.682 (0.54–0.82)) in T1 (p=0.143) and agreement for sclerosis 84.6% (k=0.69 (0.57–0.81)) and 62.5% (k=0.241 (0.13–0.35)) (pConclusionIn patients with axSpA, SWI depicts erosions and sclerosis more accurately than T1 spin echo MRI at 1.5 T.

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.

Objective: Coagulation and fibrinolysis are interrelated with the expression of vascular endothelial growth factor (VEGF), which frequently is increased in axial spondyloarthritis (axSpA). We tested whether (i) α2-antiplasmin (A2AP) Arg6Trp, (ii) fibrinogen, factor XIII A-subunit or B-subunit genotypes are associated with VEGF levels and assessed whether the known association between elevated VEGF and radiographic spinal progression in axSpA depends on genetic background. Methods: One hundred and eighty-six axSpA patients from the German Spondyloarthritis Inception Cohort were genotyped, characterized for VEGF levels, and statistically analyzed. The association between VEGF and radiographic spinal progression was assessed in dependence on genetic background in stratified analyses. Results: A2AP 6Trp carriage was associated with VEGF elevation (OR: 2.37, 95% CI: 1.06–5.29) and VEGF levels (6Trp, 455 ± 334 pg/mL; 6Arg/Arg, 373 ± 293 pg/mL; p < 0.008). Association between elevated VEGF and radiographic spinal progression in axSpA (OR: 3.11, 95% CI: 1.02–8.82) depended remarkably on the fibrinogen (FGA) genotype. When considering axSpA patients with elevated VEGF, in FGA rs6050A>G wild types, 42.1% of patients (8 of 19) progressed, while in G-allele carriers, no radiographic progression happened (0 of 13) (p < 0.04). Conclusions: The A2AP Arg6Trp genotype seems to influence VEGF levels in axSpA. The predictive value of VEGF elevations in respect of radiographic spinal progression in axSpA depends on FGA genotypes.

Objectives To develop and validate an artificial neural network for the detection of definite radiographic sacroiliitis as a manifestation of axial spondyloarthritis. Methods Conventional radiographs of sacroiliac joints from two independent cohorts of patients with axial spondyloarthritis (axSpA) were used. The first cohort consisted of 1669 radiographs and was used for training and validation of a neural network. The second cohort consisted of 525 radiographs, of which 100 radiographs were randomly selected for the test dataset. In both cohorts all radiographs underwent central reading; the final decision on the presence or absence of definite radiographic sacroiliitis was used as a reference. For performance evaluation of the neural network, areas under the receiver operating characteristic curves (AUROC) were calculated. Sensitivity and specificity for the prediction cut-offs were calculated. Cohen’s Kappa and the absolute agreement were used to assess the agreement between the neural network and the human readers. Results The neural network achieved an excellent performance in recognition of definite radiographic sacroiliitis with AUROC of 0.97 and 0.96 for the validation and test datasets, respectively. Sensitivity and specificity for the cut-off weighting both measurements equally were 0.90 and 0.93 for the validation and 0.87 and 0.97 for the test set. The Cohen’s kappa between the neural network and the reference judgements were 0.80 for both validation and test sets, and the absolute agreement on the classification yielded 91% and 90%, respectively. Conclusions Artificial neural networks enable the accurate detection of definite radiographic sacroiliitis relevant for the diagnosis and classification of axSpA.

We read with great interest the case report by Kuwabara et al .1 With this comment, we want to share the case of a 38-year-old male patient with a long history of radiographic axial spondyloarthritis (r-axSpA)—with HLA-B27 positivity, peripheral joint involvement and skin psoriasis—complicated by Takayasu arteritis (TAK), showing a favourable response to a combination therapy of Tofacitinib (TOF) and methotrexate (MTX) with the readers of the ‘Annals of the Rheumatic Diseases’ . The r-axSpA was well-controlled under tumour necrosis factor alpha inhibiton with infliximab and MTX between 2013 and 2017 (figure 1). At the beginning of 2017, he presented a worsening of his disease with peripheral arthritis/enthesitis in addition to fatigue and myalgia of the neck and shoulder region. Therefore, in 2017/2018, the treatment was changed to golimumab, and then—due to persistent symptoms—to etanercept, secukinumab and certolizumab pegol and additionally MTX was switched to sulfasalazine (SSZ). All treatment courses failed to achieve an adequate disease control (figure 1). Additionally, the patient self-administered oral prednisolone (PSL) (between 50 and 15 mg daily) during that period. Figure 1 Treatment and CRP courses overview of the different treatment strategies and the CRP course over time. bDMARDs, biological disease modifying antirheumatic …

INTRODUCTION Non-radiographic axial spondyloarthritis (nr-axSpA) represents a subtype of axial spondyloarthritis (axSpA) with no significant structural damage in sacroiliac joints and spine. In addition, patients with nr-axSpA demonstrate a substantial burden of illness, and a considerable share of them might progress to radiographic axSpA (r-axSpA) over time. The amount and quality of published data allows crude estimation of progression rate and factors related to a higher risk of progression. Areas covered: This review discusses the available data reporting the rates and predictors of radiographic progression in the sacroiliac joints and in the spine in patients with nr-axSpA as well as predisposing factors for such a progression. Expert commentary: Most of the studies report about 10-40% of patients with nr-axSpA to progress to r-axSpA over a period of 2-10 years. Multiple risk factors for the radiographic sacroiliitis progression are outlined and explored. There are not enough data to presume that any treatment modality may influence progression from nr-axSpA to r-axSpA, with TNFi showing some promising results. Radiographic progression in the spine is in general low in nr-axSpA; thus, long-term studies are required to investigate the natural course of the progression and possible treatment effects.

Background:There are inconclusive data on the effect of tumor necrosis factor inhibitors (TNFi) on radiographic spinal progression in axial spondyloarthritis (axSpA). Although inflammation and new bone formation are linked in axSpA, TNFi failed to show inhibition of radiographic spinal progression over two years compared to historical cohorts in pivotal studies in radiographic axSpA. Subsequent observational studies suggested that a longer treatment duration, earlier treatment initiation and effective inflammation suppression might be required to achieve inhibition of radiographic progression.Objectives:The aim of the current study was to evaluate the effect of TNFi on radiographic spinal progression in patients with early axSpA in a long-term inception cohort.Methods:A total of 266 patients with early axSpA (with r-axSpA with symptom duration ≤10 years and nr-axSpA with symptom duration ≤5 years) from the German Spondyloarthritis Inception Cohort (GESPIC) with at least two sets of spinal radiographs obtained at least 2 years apart during a 10-year follow-up were included. These patients contributed with a total of 542 2-year radiographic intervals. Spinal radiographs were evaluated by three trained and calibrated readers according to the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). The final mSASSS was calculated as a mean of three reader scores. The association between the current TNFi, previous TNFi and radiographic spinal progression defined as the absolute mSASSS change score over 2 years was analyzed using longitudinal generalized estimating equations (GEE) analysis.Results:Only 9 patients were treated with a tumor necrosis factor inhibitor (TNFi) at baseline, and a total of 77 patients received TNFi during the entire follow-up period that gave 103 2-year intervals covered by TNFi of any duration, and 78 intervals covered by TNFi with treatment duration of at least 12 months. Radiographic spinal progression in axSpA patients receiving TNFi in the current 2-year interval was not different from progression in patients not treated with TNFi, while TNFi in the previous 2-year interval was associated with lower progression compared to patients without TNFi in this interval (Figure 1). The latter was also evident for patients who received TNFi in both previous and current 2-year intervals, i.e. patients treated with TNFi over 4 years. The longitudinal GEE analysis confirmed no significant association between current TNFi treatment and radiographic spinal progression but a significant association between TNFi in the previous 2-year interval (especially if this was continued also in the current interval giving 4 years in total) and the progression in the current one (Table 1).Table 1.The association between the change of the mSASSS over two years and current and/or previous treatment with TNFi in the longitudinal generalized estimation equation analysis.TNFi treatment definitionReferenceβ*(95% CI)TNFi for ≥12 months in the previous 2-year intervalTNFi for ≥12 months in the current 2-year intervalYesNo TNFi for ≥12 months in the current 2-year interval-0.19(-0.56 to 0.18)YesNo TNFi for ≥12 months in the previous 2-year interval-0.56(-0.95 to -0.17)YesYesNo TNFi for ≥12 months in the current and previous 2-year intervals-0.59(-1.03 to -0.15)*Parameter estimates from the multivariable models adjusted for sex, symptom duration at the beginning of the current 2-year interval, time-averaged ASDAS in the current 2-year interval, smoking in the current 2-year interval, classification as non-radiographic or radiographic axSpA, and mSASSS at the beginning of the current 2-year interval.Conclusion:TNFi treatment exhibits a time-shifted inhibitory effect on radiographic spinal progression in axSpA that becomes evident only in the second 2-year interval after treatment initiation.Acknowledgements:GESPIC was initially supported by the BMBF. As consequence of the funding reduction by BMBF according to schedule in 2005 and stopped in 2007, complementary financial support has been obtained also from Abbott, Amgen, Centocor, Schering–Plough, and Wyeth. Starting from 2010, the core GESPIC cohort was supported by AbbVie.Disclosure of Interests:Denis Poddubnyy Speakers bureau: AbbVie, Bristol-Myers Squibb, Lilly, MSD, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Biocad, Gilead, GlaxoSmithKline, Eli Lilly, MSD, Novartis, Pfizer, Samsung Bioepis, and UCB, Grant/research support from: AbbVie, MSD, Novartis, and Pfizer, Valeria Rios Rodriguez: None declared, Murat Torgutalp: None declared, Ani Dilbaryan: None declared, Maryna Verba: None declared, Fabian Proft: None declared, Mikhail Protopopov: None declared, Judith Rademacher: None declared, Hildrun Haibel: None declared, Joachim Sieper: None declared, Martin Rudwaleit Consultant of: AbbVie, BMS, Celgene, Janssen, Eli Lilly, MSD, Novartis, Pfizer, Roche, UCB Pharma

Background:Psoriatic arthritis (PsA) is a heterogeneous disease with multiple musculoskeletal and dermatological manifestations. Due to this multifaceted clinical appearance, international guidelines do not provide a clear recommendation for one specific score to assess disease activity in PsA [1]. The Disease Activity Index for Psoriatic Arthritis (DAPSA), a validated, unidimensional score focusing on joint involvement, is one of the recommended options [1]. However, routine determination of C-reactive protein (CRP) to calculate DAPSA values takes hours to days. In contrast, quick quantitative CRP (qCRP) tests require only a few minutes and might facilitate regular assessment of the DAPSA (as Q-DAPSA) in clinical routine.Objectives:To validate the Q-DAPSA in a prospective, multicenter study of PsA patients. Since the Disease Activity Score 28 (DAS28) is not only used in rheumatoid arthritis, but also in PsA patients, the study also investigated the performance of a qCRP based DAS28 (DAS28-qCRP) in a PsA cohort.Methods:The study was conducted in five centers in Berlin, Germany. Consecutive adult (≥ 18 years) PsA patients were included. In addition to a rheumatological assessment, including patient reported outcomes (PROs), routine CRP and erythrocyte sedimentation rate (ESR) were measured in the local labs. Additionally, a qCRP testing with the „QuikRead go instrument“ (Aidian Oy, Finland) was performed locally at the study center (measurement range 0.5 - 200 mg/l for hematocrit concentrations of 40 – 45%). Statistical analysis included descriptive statistics, cross tabulation and weighted Cohen´s kappa comparing disease activity categories, Bland-Altman plots and intraclass correlation coefficient (ICC) for DAPSA, Q-DAPSA, DAS28-CRP and DAS28-qCRP.Results:In this study 104 patients were included between January and October 2020 (mean age: 51.2 years, mean disease duration: 7.1 years, 49 patients (47.1%) were male). 53 patients (51.0%) were treated with a bDMARD and 37 patients (35.6%) with csDMARDs. CRP and qCRP showed mean values of 5.20 and 6.17 mg/l, respectively. With the Q-DAPSA, 103 patients (99.0%) were assigned to the same disease activity category when compared to DAPSA (Table 1). Weighted Cohen´s kappa was 0.990 (95%CI 0.970; 1.000). ICC for numerical values of DAPSA and Q-DAPSA was 1.000 (95%CI 0.999; 1.000). The agreement of Q-DAPSA and DAPSA is shown in a Bland-Altman plot (Figure 1). DAS28-CRP and -qCRP were available for 103 patients; 101 patients (98.1%) showed the same disease activity category in the DAS28-qCRP and weighted Cohen´s kappa was 0.951 (95%CI 0.886; 1.000).Conclusion:The Q-DAPSA and DAPSA showed an almost perfect agreement on the assignment to disease activity categories (99%) with the important advantage of time. With Q-DAPSA, rheumatologists could base their clinical decision-making on a disease activity measurement by using a composite score immediately. Consequently, Q-DAPSA can be integrated in clinical routine and clinical trials and could be implemented into the treat-to-target concept in PsA patients. For rheumatologists who prefer DAS28-CRP for assessing disease activity in PsA patients, DAS28-qCRP may serve as a suitable alternative.References:[1]Smolen JS, et al. Ann Rheum Dis. 2018 Jan; 77(1):3-17.Table 1.Disease activity categories by Q-DAPSA vs. DAPASQ-DAPSA (n = 104)Remission (≤ 4)Low Disease Activity (> 4 and ≤ 14)High Disease Activity (> 14 and≤ 28)Very high Disease Activity (> 28)DAPSARemission (≤ 4)36 (34.6%)1 (1.0%)Low Disease Activity (> 4 and ≤ 14)39 (37.5%)High Disease Activity (> 14 and ≤ 28)22 (21.2%)Very high Disease Activity (> 28)6 (5.8%)The fields highlighted in red indicate that disease activity categories do not match. DAPSA = Disease activity index for Psoriatic Arthritis, Q-DAPSA = DAPSA calculated based on a quick quantitative CRPFigure 1.Bland-Altman plot for Q-DAPSA and DAPSAAcknowledgements:The authors would like to deeply thank Braun T, Doerwald C, Deter N, Höppner C, Lackinger J, Lorenz C, Lunkwitz K, Mandt B, Sron S and Zernicke J for their practical support and coordinating the study.Funding statement:The AQUA study was supported by an unrestricted research grant from Novartis. Testing kits were provided free of charge from Aidian Oy, Finland.Disclosure of Interests:None declared.

Background:The diagnostic approach in axial spondyloarthritis (SpA) relies on a estimation of the post-test disease probability that is based on evaluation of positive and negative results of diagnostic tests in the context of the pre-test disease probability.Objectives: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 as a part of the OptiRef study [1], 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 (LRs) 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 – see the online disease probability calculator http://www.axspa.de/calculator.html. It can be seen that the diagnostic values of the SpA parameters vary substantially between the groups. 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. Furthermore, 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%). Furthermore, combinations of parameters performed differently in the studied subgroups. Figure 1 illustrates that the observed differences in the diagnostic values of the SpA parameters in different subgroups were only clinically relevant in the presence of a low number of positive test results. For instance, combining IBP with anterior uveitis increased the post-test probability for axial SpA to 78% in the online screening group and to 87% in the physician-referred group, whereas using HLA-B27 positivity and active sacroiliitis on MRI in combination with IBP resulted in a surge in the post-test probability of the presence of axial SpA to around 95% in both groups.Conclusion:The diagnostic value of a single diagnostic test in the clinical practice is not fixed and a number of factors including the referral pathway can affect it. Fluctuation of the diagnostic values is especially relevant when the number of positive parameters is low (1-2).References:[1]Proft F, et al. Semin Arthritis Rheum. 2020;50:1015-1021.Acknowledgements:The OptiRef study was supported by a research grant from Novartis.Disclosure of Interests:None declared

Background:Diet has been previously described as an impact factor on the course of rheumatic diseases, such as rheumatoid arthritis and systemic lupus erythematosus (SLE). It has been previously reported that dietary sugar intake may contribute to subclinical inflammation and disease activity in SLE. However, there is very little investigation on the possible association between nutritional parameters and their influence on spondyloarthritis (SpA).Objectives:To investigate the possible impact of nutritional parameters on the disease activity in patients with SpA.Methods:Patients with radiographic axial SpA and starting a biological therapy were recruited between 2015 and 2019 in an extension of the prospective German Spondyloarthritis Inception Cohort (GESPIC). Dietary habits were collected at baseline using the country-specific validated food frequency questionnaire (FFQ) developed for the use in the German Health examination Survey for Adults 2008-2011. The FFQ includes questions about the frequency and amount of 53 food items, consumed during the past 4 weeks, and enabled to compute individual mean consumptions of foods in grams per day. Total energy intake (in Kcal per day) and nutritional parameters: carbohydrates, free sugars, total fats, saturated fats, mono and poly-unsaturated fats, proteins and dietary fiber, were calculated for each patient using a nutrition organization software and the database of Federal Food Code (Bundeslebensmittelschlüssel), version 3.02. Disease activity measures (BASDAI, CRP and ASDAS), as well as height, weight and body mass index (BMI) were assessed at baseline before starting the biological treatment.Results:A total of 104 patients from 129 patients with axial SpA enrolled in the cohort were included in this nutritional analysis. The mean age (mean±SD) was 37.0±11.0 years old with symptoms duration of 11.3±9.9 years, 68.3% were males, and 86.5% were HLA-B27 positive. Patients presented BMI of 25.1±4.3 kg/m2, BASDAI 5.6±1.4, CRP 14.0±18.2 mg/l, and ASDAS 3.5±1.0.In the univariable and multivariable regression analysis, a higher energy intake and carbohydrates were associated with higher disease activity, measured by ASDAS, BASDAI and CRP. This association was attributable to the full intake of carbohydrates and specifically to the total of free sugars (monosaccharides and disaccharides) and the decrease of dietary fiber as shown in the multivariable analyses (Figure 1). This effect was independent of age, sex, smoker status and BMI.Conclusion:A higher intake of carbohydrates and a higher consumption of free sugars are associated with higher disease activity in patients with AS.Figure 1.Multivariable linear regression analysis of the association between CRP and nutritional parameters in patients with radiographic axial SpA (n=104), adjusted for age, sex, body mass index and smoker status. Model 1 included variable of total energy intake, model 2 included variable of total intake of carbohydrates (CH) and model 3 included variable of free-sugar (monosaccharides and disaccharides).B, linear regression coefficient; CH, carbohydrates; CI, confidence interval; MS-FA, monosaturated fatty acids; PuS-FA, polyunsaturated fatty acids, S-FA, saturated fatty acids.Disclosure of Interests:None declared.

Background:Disease flares in axial spondyloarthritis (axSpA) might occur even in patients with otherwise stable disease receiving highly effective anti-inflammatory therapy such as TNF inhibitors. The frequency of disease flares, especially in patients with axSpA receiving long-term stable therapy, and factors associated with flares are not sufficiently investigated.Objectives:The objective was to assess the frequency of disease flares and to identify factors associated with flares in patients with early axSpA receiving continuous long-tem (up to 10 years) treatment with a TNF inhibitor etanercept.Methods:In the ESTHER (etanercept versus sulfasalazine in early axial spondyloarthritis trial), patients with early axSpA (symptom duration ≤5 years) were treated with ETN (n=40) versus sulfasalazine (n=36) for 48 weeks [2]. After one year all patients were treated continuously with etanercept (n=17 patients temporarily interrupted treatment in the 2nd year to assess time to flare and were then (re-)treated with etanercept, except 4 patients who completed the study in sustained remission) for up to 10 years in total. Only patients who were continuously treated with etanercept for at least 6 months were included in the current analysis. The disease flare was defined as a worsening of the ASDAS by ≥0.9 as compared to the value obtained at the previous visit. Univariate and multivariable cox-regression analyses were performed to analyze the predictors of flares.Results:Out of 76 patients who entered the study at baseline, 62 patients (n=32 with radiographic (r-) axSpA and n=30 with non-radiographic (nr-) axSpA) fulfilled the criterion of the continuous etanercept treatment. A total of 22 patients (35%) experienced at least one flare over the entire treatment period 10 patients (31.3%) in the r-axSpA and 12 patients (40%) in the nr-axSpA subgroup) - figure. A total of 81 flares occurred (33 and 48 in the r- and nr-axSpA subgroups, respectively) in the 10 years of follow-up. None of the documented disease flares resulted in a direct study withdrawal. The majority of flares occurred within first 4 years of treatment (figure). There were also no statistically significant differences between nr- and r-axSpA in the time until the first flare (p=0.4, Log-rank test). In the multivariable Cox regression analysis normal CRP values (≤5mg/l), HLA-B27 negativity, higher physician global assessment, a longer symptom duration at study entry, higher spinal ankylosis and higher fatty degeneration in the sacroiliac joints but lower spinal osteitis scores and lower ankylosis scores in the sacroiliac joints at baseline MRI were associated with a higher risk for flares.Conclusion:Disease flares according to the ASAS definition of clinically important worsening in axSpA based on ASDAS occurred ~1/3 of patients with early axSpA who received a treatment with etanercept for up to 10 years without major differences between r- and nr- forms of axSpA. HLA-B27 negativity, normal CRP, higher spinal ankylosis scores, higher fatty degeneration scores but lower ankylosis scores in the SIJ´s at baseline MRI were associated with a higher risk for flares.Figure 1.Baseline characteristics of all patients with with continous ETC treatment.all≥1 flareno flarepatientsn (%)62 (100)22 (35.5)40 (64.5)malen (%)38 (61.3)16 (72.7)22 (55)agemean (SD)34.1 (8.3)32.6 (7.8)35 (8.6)BASDAImean (SD)2.7 (2)1.8 (1.8)3.2 (1.9)ASDASmean (SD)1.6 (0.8)1.3 (0.7)1.7 (0.8)Figure 2.Kaplan-Meier curves indicating time to first flare and flare free survival propability.Acknowledgments:The ESTHER study was supported by an unrestricted research grant from Pfizer. Murat Torgutalp’s (MT) work at Charité - Universitätsmedizin was supported by an award from the Scientific and Technological Research Council of Turkey (TUBITAK).Disclosure of Interests:Fabian Proft Grant/research support from: Novartis Pharma GmbH, Consultant of: Consultancy / speaker fees from: Abbvie, BMS, Celgene, Lilly, MSD, Novartis, Pfizer, Roche, UCB, Speakers bureau: Consultancy / speaker fees from: Abbvie, BMS, Celgene, Lilly, MSD, Novartis, Pfizer, Roche, UCB, Murat Torgutalp: None declared, Anja Weiß: None declared, Mikhail Protopopov Consultant of: Novartis, Valeria Rios Rodriguez Consultant of: Abbvie, Novartis, Hildrun Haibel Consultant of: Abbvie, Jansen, MSD, and Novartis, Speakers bureau: Abbvie, Jansen, MSD, and Novartis, Kay Hermann: None declared, Christian Althoff: None declared, Olaf Behmer Employee of: Pfizer Pharma GmbH, Joachim Sieper Consultant of: AbbVie, Boehringer Ingelheim, Eli Lilly and Company, Janssen, Merck, Novartis, Pfizer, Roche, and UCB Pharma, Speakers bureau: AbbVie, Boehringer Ingelheim, Eli Lilly and Company, Janssen, Merck, Novartis, Pfizer, Roche, and UCB Pharma, Denis Poddubnyy Grant/research support from: AbbVie, MSD, Novartis, and Pfizer, Consultant of: AbbVie, Bristol-Myers Squibb, Eli Lilly, MSD, Novartis, Pfizer, Roche, UCB, Speakers bureau: AbbVie, Bristol-Myers Squibb, Eli Lilly, MSD, Novartis, Pfizer, Roche, UCB

Background:Inflammatory bowel disease (IBD) and specifically Crohn’s disease (CD) is known to be associated with spondyloarthritis (SpA). However, only little is known about factors associated with the development of spondyloarthritis in CD.Objectives:To identify factors associated with the presence of SpA in a cohort of patients with CD.Methods:Patients with a definite diagnosis of CD naïve to or not being treated with biological agents for at least 3 months were included in a CD-arm of the German Spondyloarthritis Inception Cohort (GESPIC-Crohn). Gastroenterologists were encouraged to include consecutively recently diagnosed CD patients. Patients were classified according to the Montreal classification including location and behavior of CD. Patients received a structured assessment of SpA manifestations (including magnetic resonance imaging of sacroiliac joints and spine) by a rheumatologist who was responsible for the final diagnosis of SpA / no SpA. Clinical activity of CD was assessed by the Harvey-Bradshaw Index (HBI). In addition, colonoscopy was performed, Simple endoscopic Score for Crohn’s Disease (SES-CD) was determined and fecal calprotectin was measured.Results:A total of 108 patients with CD were enrolled. The mean (mean ± SD) age was 36.6 ± 12.7 years, and CD symptom duration was 5.3 ± 7.4 years. At baseline, 44 (40.7%) patients were treated with non-biologic immunomodulating drugs: 16 (14.8%) patients received mesalazine, 27 (25.0%) azathioprine, and 1 (0.9%) methotrexate. Oral steroids were given to 38 (35.2%) patients. A total of 103 (96.3%) patients were biologics naïve. SpA was diagnosed in 23 (21.3%) patients: 12 had axial SpA and 11 peripheral SpA. Patients with SpA had higher prevalence of HLA-B27, of clinical SpA features (back pain, inflammatory back pain, peripheral arthritis, enthesitis), higher level of CRP and higher activity of CD as measured by the HBI. There were not substantial differences between SpA vs. non-SpA patients in terms of CD duration, endoscopic activity, disease location or behavior, or treatment, except for mesalazine, which was more frequently administered in patients with SpA than non-SpA (39.1% vs. 8.2%, p=0.001, respectively).Conclusion:SpA was present in 21% of patients with CD in this early cohort with almost equal proportions of axial and peripheral forms. Presence of HLA-B27 and higher clinical activity of CD were associated with the presence of SpA.TABLE.Baseline demographic and clinical characteristics of the included patients with Crohn’s disease with or without spondyloarthritis.VARIABLETOTALn=108SpAn=23No SpAn=85PAge, years, mean ± SD36.6 ± 12.737.5 ± 11.336.3 ± 13.10.44Male sex, n (%)50 (46.3)10 (43.5)40 (47.1)0.82CD symptom duration, years, mean ± SD5.3 ± 7.45.4 ± 7.25.1 ± 7.50.63HLA-B27 positive, n (%)13 (12.0)6 (26.1)7 (8.2)0.03Montreal classification Location: L1 - ileal68 (63.0)13 (56.5)55 (64.7)0.48 L2 - colonic000 L3 - ileocolonic39 (36.1)7 (30.4)32 (37.6)0.63 L4 – isolated upper disease10 (9.3)3 (13.0)7 (8.2)0.44Behavior:B1 – non-stricturing, non-penetrating69 (63.9)15 (65.2)54 (63.5)1.00 B2 - stricturing19 (17.6)4 (17.4)15 (17.6)1.00 B3 - penetrating6 (5.6)06 (7.1)0.34 Peri-anal disease7 (6.5)2 (8.7)5 (5.9)0.64 C-reactive protein, mg/l, mean ± SD10.7 ± 24.813.6 ± 23.210.0 ± 25.30.02 Harvey-Bradshaw Index, mean ± SD3.6 ± 4.05.5 ± 4.73.1 ± 3.60.01 Fecal calprotectin, mcg/d, mean ± SD185.9 ± 213.7211.7 ± 243.8179.5 ± 207.90.43Treatment of CD Mesalazine, n (%)16 (14.8)9 (39.1)7 (8.2)0.001 Methotrexate, n (%)27 (25.0)3 (13.0)24 (28.2)0.18 Azathioprine, n (%)1 (0.9)01 (1.2)1.00 Biologics naive, n (%)103 (96.3)22 (95.7)81 (96.4)1.00Disclosure of Interests:Valeria Rios Rodriguez Consultant of: Abbvie, Novartis, Mikhail Protopopov Consultant of: Novartis, Fabian Proft Grant/research support from: Novartis Pharma GmbH, Consultant of: Consultancy / speaker fees from: Abbvie, BMS, Celgene, Lilly, MSD, Novartis, Pfizer, Roche, UCB, Speakers bureau: Consultancy / speaker fees from: Abbvie, BMS, Celgene, Lilly, MSD, Novartis, Pfizer, Roche, UCB, Susanne Lüders: None declared, Judith Rademacher: None declared, Hildrun Haibel Consultant of: Abbvie, Jansen, MSD, and Novartis, Speakers bureau: Abbvie, Jansen, MSD, and Novartis, Maryna Verba: None declared, Joachim Sieper Consultant of: AbbVie, Boehringer Ingelheim, Eli Lilly and Company, Janssen, Merck, Novartis, Pfizer, Roche, and UCB Pharma, Speakers bureau: AbbVie, Boehringer Ingelheim, Eli Lilly and Company, Janssen, Merck, Novartis, Pfizer, Roche, and UCB Pharma, Elena Sonnenberg: None declared, Michael Schumann: None declared, Lea Isabell Kredel: None declared, Britta Siegmund Consultant of: Abbvie, Boehringer, Celgene, Falk, Janssen, Lilly, Pfizer, Prometheus, Takeda, Speakers bureau: Abbvie, CED Service GmbH, Falk, Ferring, Janssen, Novartis, Takeda (BS served as representative of the Charité), Denis Poddubnyy Grant/research support from: AbbVie, MSD, Novartis, and Pfizer, Consultant of: AbbVie, Bristol-Myers Squibb, Eli Lilly, MSD, Novartis, Pfizer, Roche, UCB, Speakers bureau: AbbVie, Bristol-Myers Squibb, Eli Lilly, MSD, Novartis, Pfizer, Roche, UCB

Background: One of the major reasons for a long diagnostic delay in axial spondyloarthritis (axSpA) is the late referral of patients by primary care physicians dealing with patients with chronic back pain. We developed and implemented an online self-referral tool (www.bechterew-check.de), which gave access to a rheumatological consultation if patients declared suffering from chronic back pain (≥ 3 months) with a symptom onset ≤ 45 years of age, and at least one feature indicative of SpA. In the prospective “Identification of the Optimal Referral Strategy for Early Diagnosis of Axial Spondyloarthritis (OptiRef) Study” we could diagnose axSpA in 19% of the self-referred patients [1]. Objectives: To optimize the online-self-referral tool for recognition of patients with high suspicion of axSpA in order to increase the specificity by keeping the high level of sensitivity. Methods: 181 patients who had fulfilled the online self-referral strategy were included and underwent a standardized rheumatology examination. The final diagnosis of axial SpA/no axial SpA by the rheumatologist served as the gold standard. The performance of all possible combinations of the referral parameters (13 parameters in total including 5 features of inflammatory back pain (IBP) and 8 other SpA features) added to both stem parameters (chronic back pain starting at age of ≤45 years) was tested. In addition, the following pre-specified combinations were evaluated: 1) ≥1 IBP parameter AND ≥1 other SpA parameter, 2) ≥1 IBP parameter OR ≥1 other SpA parameter. For all combinations, a sensitivity, a specificity, positive and negative predictive values (PPV and NPV), as well as a positive and negative likelihood ratio (LR+ and LR-) were calculated. We targeted the maximal specificity by acceptable sensitivity (defined as ≥90% of the original strategy). Results: For 163 of the included patients, full data of the online questionnaire as well as of rheumatology examination including the final diagnosis was available. 31 (19%) of them were diagnosed with axial SpA. Raising the threshold of the number of positive parameters (table 1) resulted in a quick drop of the sensitivity. According to the pre-defined selection criterion, only a strategy with any four positive parameters would be acceptable. An analysis of combined strategies (IBP parameters and/or other SpA parameters) resulted into identification of a strategy with an improved performance: a combination of ≥2 IBP parameters with ≥1 other SpA parameters (in addition to both stem parameters) showed a sensitivity of 90% (28/31), a specificity of 27% (35/132), a PPV of 22% (28/125), a NPV of 92% (35/38), LR+ of 1.23 and LR- of 0.36. Thus, identifying 28 of 31 patients with axSpA would have been possible after the assessment of 125 patients instead of 163. Conclusion: The data-driven optimized online self-referral tool (figure 1) requires the following parameters to be positive: chronic back pain (≥3 months) plus back pain onset before 45 years of age plus ≥2 IBP parameters plus ≥1 other SpA feature. The performance of this tool should be confirmed in a prospective study. Acknowledgements: The OptiRef project was supported by an unrestricted research grant from Novartis. References: 1.Proft F, et al. EULAR 2018, Abstract THU0230. Disclosure of Interests: Fabian Proft Grant/research support from: Novartis, Consultant for: yes but less than 10.000, Paid instructor for: yes but less than 10.000, Speakers bureau: yes but less than 10.000, Laura Spiller: None declared, Mikhail Protopopov: None declared, Valeria Rios Rodriguez: None declared, Burkhard Muche Speakers bureau: Yes less than 10.000, Judith Rademacher: None declared, Susanne Luders: None declared, Anne Katrin Weber: None declared, Imke Redeker: None declared, Denis Poddubnyy Grant/research support from: AbbVie, Merck Sharp & Dohme, Novartis, Consultant for: AbbVie, Bristol-Myers Squibb, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, UCB Pharma, Speakers bureau: AbbVie, Bristol-Myers Squibb, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, Roche, UCB Pharma

Background: Overlap between psoriasis and axial spondyloarthritis (axSpA) is common, as psoriasis occurs in approximately 10% of patients with axSpA. It has been noted that such an association may result in a particular phenotype of the disease, which has not been extensively investigated so far. Objectives: To analyze the association between skin psoriasis and clinical and radiographic characteristics of axSpA. Methods: Altogether 210 patients with definite axSpA (115 with radiographic and 95 with non-radiographic axSpA) from the German Spondyloarthritis Inception Cohort (GESPIC) were included in the current study. Information on the presence of psoriasis, clinical features, parameters of disease activity, and treatment were collected at baseline and every 6 months thereafter. Radiographs of sacroiliac joints and spine were obtained at baseline and after 2 years of follow-up and were scored by two trained readers according to the conventional grading system of the modified New York criteria (grade 0 to 4 per joint) and mSASSS (score 0-72). Group comparison was performed using Mann-Whitney U-Test for continuous variables and Fisher exact test for binary variables. A logistic regression model was constructed to assess the association of the psoriasis with radiographic progression in the sacroiliac joints and in the spine. Results: Overall, 28 patients (13.3%) with axSpA had skin psoriasis. Patients with psoriasis were less frequently HLA-B27 positive in comparison with patients with no skin symptoms (57.1% and 82,9% respectively, p=0.004), had more frequently a history of peripheral arthritis (57.1% and 31.9%, p= 0.01), had higher disease activity (BASDAI baseline 5.0 ± 2.2 and 3.8 ± 2.1, respectively, p=0.01) and worse physical function (BASFI at baseline 3.8 ± 2.3 and 2.8 ± 2.3, respectively, p=0.02) (Table 1). They were also more frequently treated with DMARDs (57.1% and 24.7%, respectively, p=0.001). Baseline radiographic characteristics were comparable between the groups. There was no statistically significant difference in rates of radiographic spinal progression and progression of radiographic sacroiliitis in patients with vs. without psoriasis (Table 2). In the multivariable logistic regression analysis, adjusted for the smoking status, sex, NSAID intake, presence of syndesmophytes at baseline and time-averaged ASDAS, skin psoriasis showed no significant association with radiographic spinal progression (OR 2.93, 95% CI 0.81 to 10.58) nor with progression of radiographic sacroiliitis by at least 1 grade (OR 1.98, 95% CI 0.72 to 5.43) Conclusion: Presence of skin psoriasis in patients with axSpA was associated with HLA-B27 negativity, peripheral arthritis, higher disease activity and worse functional status, but had no significant impact on radiographic characteristics of the disease. References: none Acknowledgement: GESPIC has been financially supported by the German Federal Ministry of Education and Research (BMBF). As funding by BMBF was reduced in 2005 and stopped in 2007, complementary financial support has been obtained also from Abbott/Abbvie, Amgen, Centocor, Schering-Plough, and Wyeth. Since 2010 GESPIC is supported by Abbvie. Disclosure of Interests: Mikhail Protopopov: None declared, Fabian Proft Grant/research support from: Novartis, Consultant for: yes but less than 10.000, Paid instructor for: yes but less than 10.000, Speakers bureau: yes but less than 10.000, Joachim Sieper Consultant for: Abbvie, Bohringer Ingelheim, Janssen, Lilly, Merck, Mylan, Novartis, Pfizer, UCB., Speakers bureau: Abbvie, Bohringer Ingelheim, Janssen, Lilly, Merck, Mylan, Novartis, Pfizer, UCB., Hildrun Haibel: None declared, Martin Rudwaleit Consultant for: AbbVie, BMS, Celgene, Janssen, Eli Lilly, MSD, Novartis, Pfizer, Roche, UCB Pharma, Consultant for: AbbVie, BMS, Celgene, Janssen, Eli Lilly, MSD, Novartis, Pfizer, Roche, UCB Pharma, Denis Poddubnyy Grant/research support from: AbbVie, Merck Sharp & Dohme, Novartis, Consultant for: AbbVie, Bristol-Myers Squibb, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, UCB Pharma, Speakers bureau: AbbVie, Bristol-Myers Squibb, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, Roche, UCB Pharma