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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.

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.

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.

Funder: AbbVie; FundRef: https://doi.org/10.13039/100006483, Funder: Galapagos Conservancy; FundRef: https://doi.org/10.13039/100012525, Funder: Janssen Pharmaceuticals; FundRef: https://doi.org/10.13039/100008897, Funder: Novartis; FundRef: https://doi.org/10.13039/100004336, Funder: Pfizer; FundRef: https://doi.org/10.13039/100004319, Funder: UCB; FundRef: https://doi.org/10.13039/100011110, Funder: Eli Lilly and Company; FundRef: https://doi.org/10.13039/100004312, Background:: Involvement of the axial skeleton (sacroiliac joints and spine) is a relatively frequent manifestation associated with psoriatic skin disease, mostly along with involvement of peripheral musculoskeletal structures (peripheral arthritis, enthesitis, dactylitis), which are referred to as psoriatic arthritis (PsA). Data suggest that up to 30% of patients with psoriasis have PsA. Depending on the definition used, the prevalence of axial involvement varies from 25% to 70% of patients with PsA. However, there are currently no widely accepted criteria for axial involvement in PsA.Objective: The overarching aim of the Axial Involvement in Psoriatic Arthritis (AXIS) study is to systematically evaluate clinical and imaging manifestations indicative of axial involvement in patients with PsA and to develop classification criteria and a unified nomenclature for axial involvement in PsA that would allow defining a homogeneous subgroup of patients for research. Design:: Prospective, multicenter, multinational, cross-sectional study. Methods and analyses:: In this multicenter, multinational, cross-sectional study, eligible patients [adult patients diagnosed with PsA and fulfilling Classification Criteria for Psoriatic Arthritis (CASPAR) with musculoskeletal symptom duration of ���10 years not treated with biological or targeted synthetic disease-modifying anti-rheumatic drugs] will be recruited prospectively. They will undergo study-related clinical and imaging examinations. Imaging will include radiography and magnetic resonance imaging examinations of sacroiliac joints and spine. Local investigators will evaluate for the presence of axial involvement based on clinical and imaging information which will represent the primary outcome of the study. In addition, imaging will undergo evaluation by central review. Finally, the central clinical committee will determine the presence of axial involvement based on all available information. Ethics:: The study will be performed according to the ethical principles of the Declaration of Helsinki and International Council for Harmonisation Good Clinical Practice guidelines. The study protocol will be approved by the individual Independent Ethics Committee / Institutional Review Board of participating centers. Written informed consent will be obtained from all included patients.Registration: ClinicalTrials.gov ID: NCT04434885.

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.

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.

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.

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 …

Objectives: The Simplified Disease Activity Index (SDAI) is a recommended composite score for assessing the remission status in patients with rheumatoid arthritis (RA). However, determination of C-reactive protein (CRP) levels takes several hours and sometimes days and limits the use of the SDAI in the clinical setting. The aim of this study was to validate the SDAI using a quick quantitative C-reactive protein (qCRP) assay (as SDAI-Q) in RA patients. Design: This is a multicenter, prospective, cross-sectional pilot study in RA patients. Methods: Adult patients (⩾18 years) with a clinical diagnosis of RA were recruited between January 2020 and September 2020 from five rheumatologic centers located in Berlin, Germany. SDAI, SDAI-Q, Clinical Disease Activity Index (CDAI), and DAS28 scores comprising CRP, qCRP, or erythrocyte sedimentation rate (ESR) were calculated. The agreement of disease activity categories was analyzed using cross tabulations and weighted Cohen’s kappa. The agreement of numerical values was analyzed with Bland–Altman plots and intraclass correlation coefficients (ICCs). Results: Overall, 100 RA patients were included in the statistical analysis. The mean value of qCRP (7.89 ± 16.98 mg/l) was slightly higher than that of routine laboratory CRP (6.97 ± 15.02 mg/l). Comparing SDAI and SDAI-Q, all patients were assigned to identical disease activity categories. Agreement of disease activity categories by CDAI and SDAI/SDAI-Q was observed in 93% with a weighted Cohen’s kappa of 0.929 (95% confidence interval (CI) = 0.878; 0.981). Conclusion: The SDAI-Q showed an absolute agreement regarding the assignment of disease activity categories in comparison with the conventional SDAI. Therefore, the SDAI-Q may facilitate the application of a treat-to-target concept in clinical trials and clinical routine as a quickly available disease activity score incorporating CRP as an objective parameter.

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 most important prerequisites for a timely diagnosis of axial spondyloarthritis (axSpA) is the early referral of a patient with back pain to a rheumatologist. In the past years a number of referral strategies has been proposed, most of them in line with the ASAS referral recommendations [1] and with a similar performance – about 30-40% of the referred patients can be diagnosed with axSpA after examination by a rheumatologist. In addition to physician-based strategies, an online self-referral (OSR) strategy has been recently proposed and evaluated about 20% of the patients being diagnosed with axSpA after rheumatologic evaluation [2].Objectives:The objective of the current analysis was to investigate the role of age and symptom duration for the optimization of a physician-based and an OSR strategy for axSpA.Methods:In the OptiRef study, patients with chronic back pain and suspicion of axSpA either referred by primary care physicians /orthopedists using the Berlin referral tool (=physician based) or based on a referral recommendation of an OSR were evaluated by rheumatologists in a specialized center [2]. All patients underwent a structured examination including imaging that resulted into the final diagnosis of axSpA or no axSpA. The relationship between age, symptom duration and the likelihood of axSpA diagnosis was evaluated in this analysis.Results:A total of 360 patients (180 presented via the OSR and 180 referred by the physician based referral strategy) were included in this analysis. Patient’s characteristics are shown in Table 1. A total of 71 patients (39.4%) in the physician-based group and 35 patients (19.4%) in the OSR group were finally diagnosed with axSpA. The heatmaps depicting the relationship between the proportions of patients diagnosed with axSpA and age plus symptom duration (Figure 1) showed a clear decline of the axSpA probability with increasing age. In the physician-referred group, however, axSpA was diagnosed even in patients who were above 50 years at the time-point of the examination, while there were only few patients with axSpA in the self-referred group aged 40-49 years, and none in the age group ≥50 years. Interestingly, there was no clear relationship between symptom duration and probability of the diagnosis: axSpA was diagnosed in a substantial proportion of patients even with a long history of back pain (>12 years) in both subgroups.Conclusion:The probability of axSpA is high in patients suffering from back pain and aged References:[1]Poddubnyy D, et al. Ann Rheum Dis 2015 Aug; 74(8):1483-1487.[2]Proft F, et al. Semin Arthritis Rheum. 2020; 50(5):1015-1021.Table 1.Patient characteristicsTotalN=360Berlin toolN=180Self-referralN=180p-valueDiagnosis of axial SpA, n (%)106 (29.4%)71 (39.4%)35 (19.4%)Age, years, mean (SD)36.9 (10.4)37.2 (11.5)36.6 (9.2)>0.99Male sex, n (%)177 (49.2%)100 (55.6%)77 (42.8%)0.02Back pain duration, years, mean (SD)7.9 (7.6)6.5 (6.9)9.2 (8.1)HLA-B27 positive, n (%)141 (40.9%)104 (59.8%)37 (21.6%)CRP elevation, n (%)52 (14.8%)34 (19.4%)18 (10.2%)0.02Inflammatory back pain, n (%)204 (56.7%)103 (57.2%)101 (56.1%)0.92Figure 1.Heatmaps depicting the proportions of patients diagnosed with axSpA in relation to age and symptom duration in the physician-based (A) and OSR (B) groups.Acknowledgements:We would like to thank all orthopaedists and primary care physicians who referred their patients. Further, we thank Dr. Anne-Katrin Weber and Dr. Susanne Lüders for the data collection support, Annegret Langdon for the data management support and Torsten Karge for set-up and support of the online screening tool.Funding statementThe OptiRef study was supported by an unrestricted research grant from Novartis.Disclosure of Interests:None declared.

Background:According to international recommendations, the Ankylosing Spondylitis Disease Activity Score (ASDAS) is the preferred score for assessing disease activity in axial spondyloarthritis (axSpA) [1]. However, routine determination of C-reactive protein (CRP) to calculate ASDAS values takes hours to days. This limits the use of ASDAS in clinical routine and clinical trials and hinders the implementation of treat-to-target approaches in axSpA. Whereas quick quantitative CRP (qCRP) tests allow CRP assessment within a few minutes. In a pilot project the performance of qCRP-based ASDAS assessment (ASDAS-qCRP) was already investigated in a single center study of 50 newly diagnosed, bDMARD-naïve axSpA patients with promising results [2].Objectives:To validate the ASDAS-qCRP in a prospective, multicenter study of axSpA patients in a typical axSpA cohort with an appropriate sample size.Methods:The study was conducted in five centers in Germany. Consecutive adult (≥ 18 years) axSpA 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 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 ASDAS-CRP and ASDAS-qCRP.Results:In this study 251 axSpA patients were included between January and September 2020 (mean age: 38.4 years; mean disease duration: 6.2 years, 159 patients (63.3%) were male, 211 (84.1%) HLA-B27 positive and 195 (77.7%) were classified as radiographic axSpA). 143 patients (57.0%) were treated with bDMARDs. CRP and qCRP showed mean values of 2.12 and 2.17 mg/l, respectively. With the ASDAS-qCRP, 242 patients (96.4%) were assigned to the same disease activity category as compared to the ASDAS based on the conventional lab CRP measurement (Table 1). Weighted Cohen´s kappa was 0.966 (95%CI: 0.943; 0.988). ICC for ASDAS-CRP- and ASDAS-qCRP-values was 0.997 (95%CI: 0.994; 0.999). The agreement of ASDAS-qCRP and ASDAS-CRP is shown in a Bland-Altman plot (Figure 1).Table 1.Disease activity categories by ASDAS-qCRP vs. ASDAS-CRPASDAS-qCRP (n = 251)Inactive Disease(< 1.3)Low Disease Activity (1.3 - < 2.1)High Disease Activity (2.1 - 3.5)Very high Disease Activity (> 3.5)ASDAS-CRPInactive Disease(< 1.3)56 (22.3%)2 (0.8%)Low Disease Activity (1.3 - < 2.1)62 (24.7%)7 (2.8%)High Disease Activity (2.1 - 3.5)97 (38.6%)Very high Disease Activity (> 3.5)27 (10.8%)The fields highlighted in red indicate that disease activity categories do not match.ASDAS = Ankylosing Spondylitis Disease Activity Score, CRP = C-reactive protein, qCRP = quick quantitative CRPConclusion:The ASDAS-qCRP and ASDAS-CRP showed an almost perfect agreement on the assignment to disease activity categories (96%) with the important advantage of time. With ASDAS-qCRP, rheumatologists could base their clinical decision-making on a disease activity measurement by using a composite score immediately. ASDAS-qCRP, therefore, can be integrated in clinical routine and clinical trials in the future and may facilitate implementation of the treat-to-target concept in axial SpA.References:[1]Smolen JS, et al. Ann Rheum Dis. 2018 Jan; 77(1):3-17.[2]Proft F, et al. Joint Bone Spine. 2019 Jul 29.Figure 1.Bland-Altman plot for ASDAS-qCRP and ASDAS-CRPAcknowledgements: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:Therapeutic decisions in RA patients should be based on regular disease activity assessment using scores like the Simplified Disease Activity Index (SDAI) or the Clinical Disease Activity Index (CDAI) [1]. The CDAI has the benefit of being immediately available, while the SDAI encompasses with the C-reactive protein (CRP) an acute phase reactant and therefore is the recommended score for the use in clinical trials. However, CRP determination takes hours to days, thus hindering the treat-to-target concept using the SDAI. Quick quantitative CRP (qCRP) tests allow CRP measurement within a few minutes. Therefore, qCRP based SDAI (SDAI-Q) could combine the advantages of both scores.Objectives:To validate the SDAI-Q in a prospective, multicenter study of RA patients.Methods:The study was conducted in five centers in Berlin, Germany. Consecutive adult (≥ 18 years) RA patients were included. In addition to a rheumatological assessment, including patient reported outcomes, routine CRP was measured in the local labs. Additionally, a qCRP testing with the „QuikRead go instrument“ (Aidian Oy, Finland) was performed locally (measurement range 0.5 - 200 mg/l). 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 CRP, qCRP, SDAI, SDAI-Q and CDAI.Results:In this study 100 RA patients were included (mean age: 60.9 years, mean disease duration: 11.4 years, 73.0% were female, 63.0% RF positive, 57.0% ACPA positive, 49.0% positive and 29% negative for both parameters). 75.0% were treated with csDMARD, 15% with tsDMARDs, 39.0% with bDMARDs and 40% with glucocorticoids (mean prednisolone equivalent: 5.4 mg prednisolone/d). Mean CRP and qCRP-levels were 6.97 and 7.89 mg/l, respectively (ICC 0.992; 95%CI: 0.987; 0.995). Comparing SDAI-Q and SDAI, all patients (100%) achieved the same disease activity status (Table 1A); weighted Cohen´s kappa was 1.000 (95%CI: 1.000; 1.000). ICC for SDAI-Q- and SDAI-values was 1.000 (95%CI: 1.000; 1.000). The agreement of SDAI-Q and SDAI is shown in a Bland-Altman plot (Figure 1). When comparing the CDAI with the SDAI-Q 93 patients (93%) were assigned to the same disease activity category (Table 1B); weighted Cohen´s kappa was 0.929 (95%CI: 0.878; 0.981). ICC for numerical values of SDAI-Q and CDAI was 0.989 (95%CI: 0.978; 0.994).Conclusion:SDAI-Q showed an absolute agreement with SDAI on the assignment to disease activity categories with the important advantage of time. With SDAI-Q, rheumatologists could base their clinical decision-making immediately on an index-based disease activity measurement by using a composite score considering acute phase reactants. Consequently, SDAI-Q can be integrated in clinical routine and clinical trials and could be implemented into the treat-to-target concept in RA patients.References:[1]Smolen JS, et al. Ann Rheum Dis. 2016 Jan; 75(1):3-15.Table 1.A) Disease activity categories by SDAI-Q vs. SDAI; B) Disease activity categories by SDAI-Q vs. CDAIASDAI-Q (n = 100)Remission (≤ 3.3)Low Disease Activity (> 3.3 and ≤ 11)Moderate Disease Activity (> 11 and ≤ 26)High Disease Activity (> 26)SDAIRemission (≤ 3.3)28 (28.0%)Low Disease Activity (> 3.3 and ≤ 11)31 (31.0%)Moderate Disease Activity (> 11 and ≤ 26)35 (35.0%)High Disease Activity (> 26)6 (6.0%)BSDAI-Q (n = 100)Remission (≤ 3.3)Low Disease Activity (> 3.3 and ≤ 11)Moderate Disease Activity (> 11 and ≤ 26)High Disease Activity (> 26)CDAIRemission (≤ 2.8)26 (26.0%)Low Disease Activity (> 2.8 and ≤ 10)2 (2.0%)28 (28.0%)2 (2.0%)Moderate Disease Activity (> 10 and ≤ 22)3 (3.0%)33 (33.0%)High Disease Activity (> 22)6 (6.0%)Fields highlighted in red indicate that disease activity categories do not match.SDAI = Simplified Disease Activity Index;SDAI-Q = SDAI calculated with a quick quantitative CRP assay;CDAI = Clinical Disease Activity Index.Figure 1.Bland-Altman plot for SDAI and SDAI-Q AcknowledgementsThe 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:Spondyloarthritides (SpA) are characterized by frequent extra-musculoskeletal manifestations (EMM) among them acute anterior uveitis (AAU) and Crohn’s disease (CD). Vice versa, about 50% of AAU and 20% of CD patients have concomitant SpA. SpA patients show gut dysbiosis together with frequent subclinical gut inflammation. Biomarkers reflecting disturbed gut barrier (intestinal-fatty acid binding protein (iFABP), lipopolysaccharide binding protein (LBP) and zonulin) were previously found to be elevated in patients with radiographic axial SpA (r-axSpA) (1).Objectives:To evaluate whether biomarkers reflecting leaky gut are altered in patients with AAU, CD and SpA compared to healthy controls and whether they differ between patients with EMM with and without concomitant SpA.Methods:A total of 100 patients from the German Spondyloarthritis Inception Cohort (GESPIC) were included – among them 20 patients with r-axSpA without EMM, 40 patients with CD and 40 patients with non-infectious AAU – out of which 19 and 20 patients, respectively, had concomitant SpA (11/8 and 20/0 axial/peripheral SpA, respectively). The GESPIC patients were compared to 20 age- and sex-matched healthy donors (HD). The following five serum biomarkers were analyzed with ELISA: calprotectin, iFABP, LBP, soluble CD14 (sCD14) and zonulin.Results:Patient characteristics are shown in Table 1. Serum levels of calprotectin, LBP, sCD14 and zonulin differed significantly between patients with r-axSpA, AAU and CD with and without concomitant SpA and HD (Figure 1). When comparing patients with EMM with and without underlying SpA, calprotectin serum levels were significantly elevated in CD patients with SpA (8.6µg/ml (SD 5.5µg/ml)) compared to CD patients without SpA (5.7µg/ml (SD 4.1µg/ml); Mann-Whitney U Test, p=0.031). Serum levels of the analyzed biomarkers did not differ between AAU patients with and without axSpA. Spearman rank correlation revealed a significant association between CRP and calprotectin (correlation coefficient r=0.230; p=0.012), LBP (r=0.596; pTable 1.Patient characteristics. Mean values (standard deviation) or absolute numbers are shown.CD + SpACDr-axSpAAAU + axSpAAAUHDN192120202020Age39.1 (11.3)38.7 (14.4)38.4 (10.3)39.6 (12.0)39.2 (12.5)38.6 (12.9)Male (%)9 (47%)9 (43%)9 (45%)9 (45%)9 (45%)9 (45%)HLA-B27 positive (%)5 (26%)3 (14%)17 (85%)17 (85%)13 (65%)2 (10%)CRP in mg/l14.3 (25.6)18.0 (41.8)9.1 (11.3)6.7 (9.9)2.3 (3.4)0.6 (0.7)ASDAS2.8 (1.1)3.2 (0.6)2.2 (1.0)BASDAI4.1 (2.2)5.4 (1.2)3.2 (2.4)Figure 1.Biomarkers reflecting disturbed gut barrier show distinct signatures in patients with acute anterior uveitis, Crohn’s disease and axial Spondyloarthritis. Kruskal Wallis Test; p values shown. Dunn-Bonferroni Post-Hoc analyses, significant pairwise differences are marked; * pWe found substantial differences in biomarkers reflecting disturbed gut barrier between with SpA, CD, AAU and healthy controls. The presence of SpA was associated with higher calprotectin serum levels in CD as compared to CD without SpA.References:[1]Ciccia F, et al. Dysbiosis and zonulin upregulation alter gut epithelial and vascular barriers in patients with ankylosing spondylitis. 2017.Acknowledgements:Dr. Judith Rademacher is participant in the BIH-Charité Clinician Scientist Program funded by the Charité –Universitätsmedizin Berlin and the Berlin Institute of Health.Disclosure of Interests:None declared

Background:Radiographs of the sacroiliac joints are commonly used as the first imaging method for the diagnosis of axial spondyloarthritis (axSpA), but the reliability of sacroiliitis detection is usually low. Recently we developed a deep convolutional neural network (CNN) that can detect radiographic sacroiliitis with expert-like accuracy in patients with axSpA, i.e., classification as radiographic or non-radiographic [1]. There is frequent criticism that many artificial intelligence algorithms for diagnostic analysis of medical images lack robust validation in real-world clinical applications.Objectives:The aim of this study was to evaluate the performance of our deep CNN in detecting definite radiographic sacroiliitis in the diagnostic setting.Methods:In this study, we included a total of 361 patients with chronic back pain who presented to a rheumatologist in a specialized SpA center with a suspicion of axSpA within the OptiRef project [2]. All patients received a structured rheumatologic diagnostic work-up that resulted in the final diagnosis of axial SpA/no axial SpA. Radiographs of sacroiliac joints were evaluated by a rheumatologist and radiologist according to the modified New York criteria; the consensus judgement of the presence of definite radiographic sacroiliitis (>=grade 2 bilaterally or >=grade 3 unilaterally) was used as a reference. The predictions of the deep CNN’s inference (with a balanced cutoff of 0.724 for the predictions of the model that was derived from the training and validation steps [1]) on all available pelvic radiographs was compared to this reference judgement.Results:Pelvic radiographs of 340 patients (110 with axSpA including 61 patient with radiographic and 49 with non-radiographic axSpA, and 230 without SpA) were available for the CNN evaluation. The deep CNN achieved a sensitivity of 79% for the diagnosis of radiographic axSpA. The specificity of radiographic sacroiliitis detection was 94% (Table 1). The area under the receiver operating characteristics curve for the prediction of the presence of definite radiographic sacroiliitis was 88%. Figure 1 shows an exemplary class activation map of our CNN.Table 1.Convolutional neural network predictions of the presence of radiographic sacroiliitis in patients with suspected axSpA according to the final diagnosis by rheumatologist in OptiRef (N=340).Clinical diagnosisCNN’s prediction on the presence of definite radiographic sacroiliitisPresentNot presentRadiographic axial SpA48/61 (78.7%)13/61 (21.3%)Non-radiographic axial SpA4/49 (8.2%)45/49 (91.8%)No SpA (other diagnosis)14/230 (6.1%)216/230 (93.9%)Conclusion:The artificial neural network showed good generalizability and a high specificity with acceptable sensitivity in the detection of radiographic sacroiliitis when applied in the diagnostic setting of patients with chronic back pain and suspicion of axSpA. This algorithm can therefore be used to aid the detection of radiographic sacroiliitis as a part of the diagnostic approach.References:[1]Bressem KK, et al. medRxiv. 2020:2020.05.19.20105304.[2]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:Observational cohort studies have shown that there is low, but still detectable progression level in radiographic sacroiliitis, which might also have an impact on the function in patients with axial spondyloarthritis (axSpA). Recent data showed that tumor necrosis factor inhibitors (TNFi) might retard spinal progression when initiated earlier and taken longer in patients with axSpA. However, the question of whether they also have such an effect on radiographic progression in sacroiliac joints (SIJs) is still unclear.Objectives:To investigate the longitudinal association between radiographic sacroiliitis progression and treatment with TNFi in patients with early axial SpA in a long-term inception cohort.Methods:Based on the availability of at least two sets of SIJ radiographs, 301 patients (166 with nr-axSpA, symptom duration ≤5 years and 135 with r-axSpA, symptom duration ≤10 years) from the German Spondyloarthritis Inception Cohort (GESPIC) were included in this analysis. These patients contributed with a total of 737 2-year radiographic intervals. Two trained and calibrated central readers scored the radiographs according to the modified New York criteria. If both scored an image as definite radiographic sacroiliitis, the patient was classified as having r-axSpA. The sacroiliac sum score was calculated as a mean of both readers. The association between previous as well as current TNFi use and radiographic sacroiliitis progression, which was defined as the change in the sacroiliitis sum score over 2 years, was analysed using longitudinal generalized estimating equations (GEE) analysis.Results:At baseline, 9 (3.0%) patients were treated with a TNFi, and 87 (28.9%) patients received at least one TNFi during the entire follow-up period. A total of 141 of the radiographic intervals were covered with TNFi of any duration, while 109 of them were covered with a TNFi of at least 12 months. While receiving ≥12 months TNFi in the previous interval was associated with a lower progression of the sacroiliitis sum score compared to not receiving TNFi in the previous interval, this was not the case in patients who received TNFi ≥12 months in the current 2-year interval (Figure 1). The significant association between TNF ≥12 months in the previous interval and progression in the sacroiliitis sum score were confirmed in the adjusted multivariable longitudinal GEE analysis. In addition, a similar trend for the beneficial effects was observed in different models, which included other treatment definitions with TNFi in the previous 2-year interval (Table).Table 1.The longitudinal GEE analysis of the association between progression in the sacroiliitis sum score and TNFi use.TNFi treatment definitionReferenceβ* (95% CI)TNFi for ≥ 12 months in the previous 2-year intervalNo TNFi for ≥ 12 months in the previous 2-year interval-0.09 (-0.18, -0.003)Any TNFi use in the previous 2-year intervalNo TNFi use in the previous 2-year interval-0.09 (-0.17, 0.002)TNFi for ≥ 12 months in the current 2-year intervalNo TNFi for ≥ 12 months in the current 2-year interval-0.03 (-0.11, 0.06)Any TNFi use in the current 2-year intervalNo TNFi use in the current 2-year interval0.05 (-0.05, 0.14)TNFi for ≥ 12 months in the previous and ≥ 12 months in the current 2-year intervalNo TNFi for ≥ 12 months in the previous and ≥ 12 months in the current 2-year interval-0.08 (-0.17, 0.004)* Parameter estimates from the multivariable models adjusted for sex, age at the beginning of the current 2-year interval, HLA-B27 positivity, symptom duration at the beginning of the current 2-year interval, time-averaged elevated CRP, time-averaged BASDAI, and time-averaged NSAID intake score in the current 2-year interval.Conclusion:Treatment with TNFi was associated with retardation of radiographic sacroiliitis progression in patients with axSpA. This effect becomes evident between 2 and 4 years after treatment initiation.References:Acknowledgements:GESPIC was initially supported by the BMBF. As a 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:Murat Torgutalp: None declared, Valeria Rios Rodriguez: None declared, Maryna Verba: None declared, Mikhail Protopopov: None declared, Fabian Proft: None declared, Judith Rademacher: None declared, Hildrun Haibel: None declared, Martin Rudwaleit Consultant of: AbbVie, BMS, Celgene, Janssen, Eli Lilly, MSD, Novartis, Pfizer, Roche, UCB Pharma, Joachim Sieper: None declared, 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

Objective The aim of this work was to investigate the association between disease activity measured by the Ankylosing Spondylitis Disease Activity Score (ASDAS) and radiographic spinal progression in patients with early axial spondyloarthritis (axSpA). Methods Altogether, 178 patients with definite axSpA (100 with ankylosing spondylitis and 78 with non-radiographic axSpA) were included. Spinal radiographs (baseline and year 2) were assessed according to the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) and for the presence of syndesmophytes. Clinical and lab data were collected at baseline and every 6 months thereafter. Time-averaged (over 2 years) values of the C-reactive protein based ASDAS were calculated. Results There was a clear positive association between disease activity according to ASDAS and radiographic spinal progression. In the logistic regression analysis, mSASSS progression by ≥2 points over 2 years was significantly associated with the time-averaged ASDAS: unadjusted OR=1.64 (95% CI 1.03 to 2.62), adjusted (for presence of syndesmophytes at baseline, smoking status and intake of non-steroidal anti-inflammatory drugs) OR=1.80 (95% CI 1.04 to 3.13). Syndesmophyte formation/progression demonstrated an even stronger association with the time-averaged ASDAS: unadjusted OR=2.62 (95% CI 1.46 to 4.68), adjusted OR=2.45 (95% CI 1.26 to 4.77). Conclusions Persisting high disease activity according to the ASDAS is associated with accelerated radiographic spinal progression in early axSpA.

Background:Previous studies showed that patients with non-radiographic and radiographic axial spondyloarthritis (nr- and r-axSpA) have similar disease burden and similar response to anti-inflammatory therapy given similar level of inflammatory activity. Only little is known, however, about long-term disease course in patients with early axSpA.Objectives:To investigate the long-term (up to 10 years) clinical course of patients with early axSpA.Methods:In total, 525 patients with early axSpA (r-axSpA with symptom duration ≤10 years and nr-axSpA with symptom duration ≤5 years) from the German Spondyloarthritis Inception Cohort (GESPIC) were included. The final patient classification was based on central reading results in 458 patients with available pelvic X-rays, and on local rheumatologist judgement in 67 patients. A total of 251 patients were finally classified as r-axSpA and 274 as nr-axSpA. Clinical evaluation, which included disease activity (BASDAI, C-reactive protein – CRP, ASDAS) as well as therapy recording, was performed at baseline and every 6 months thereafter until year 2 and annually thereafter till year 10. Treatment was conducted at the discretion of the local rheumatologist.Results:Since the cohort has started prior to introduction of TNF inhibitors (TNFi), only 2% patients received TNFi at baseline that increased to 23% at year 10 (15% in nr-axSpA and 31% in r-axSpA) – Figure 1. The use of NSAIDs and csDMARDs decreased in both groups (Figure 1), while use of systemic steroids did not change substantially (9% at baseline, 8% at year 10). The proportion of patients with low disease activity according to BASDAI (Conclusion:Patients with nr-axSpA and r-axSpA showed a similar disease course in terms of disease activity on the group level. The drop-out rate in this observational cohort was overall high, but comparable between groups. The lower proportion of patients with nr-axSpA being treated with TNFi might reflect a later introduction of TNFi for this indication.Acknowledgments:GESPIC has been financially supported by the German Federal Ministry of Education and Research as well as by Abbott, Amgen, Centocor, Schering–Plough, and Wyeth. From 2010 till 2019 GESPIC has been supported by Abbvie.Disclosure of Interests: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, Valeria Rios Rodriguez Consultant of: Abbvie, Novartis, Murat Torgutalp: None declared, Maryna Verba: None declared, Johanna Callhoff: None declared, 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, Judith Rademacher: None declared, Hildrun Haibel Consultant of: Abbvie, Jansen, MSD, and Novartis, Speakers bureau: Abbvie, Jansen, MSD, and Novartis, 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, Martin Rudwaleit Consultant of: AbbVie, BMS, Celgene, Janssen, Eli Lilly, MSD, Novartis, Pfizer, Roche, UCB Pharma

Background:Peripheral symptoms (PS), such as arthritis, enthesitis, and dactylitis, are common in axial spondyloarthritis (axSpA); data showing the association of PS and spinal radiographic progression in axSpA are controversial.Objectives:To analyze the association of PS and spinal radiographic progression in patients with axSpA.Methods:A total of 210 patients with axSpA (115 with radiographic and 95 with non-radiographic axSpA) were selected for analysis. Spinal radiographs were scored by two readers in a random order according to the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). Pelvic radiographs were scored according to the grading system of the modified New York criteria; a sacroiliitis sum score was calculated as a sum of the grades for both sacroiliac joints. Mann-Whitney and Fisher exact tests were performed for group comparisons. A multivariable regression analysis was performed to analyze the influence of PS on radiographic progression.Results:Of the 101 (48.1%) patients with PS, 78 had peripheral arthritis, 48 - enthesitis, 12 - dactylitis. 32 patients had ≤1 PS. Patients with PS were older, less frequently HLA-B27 positive, compared with patients with no PS (73 (73.0%) vs. 93 (85.3%), p=0.028), had higher disease activity (time-averaged ASDAS over 2 years 2.6 ± 0.9 vs. 2.3 ± 0.9; p=0.032), worse physical function (BASFI 3.5 ± 2.3 vs. 2.3 ± 2.2, pTable 1.Association of peripheral symptoms with radiographic progression in axial spondyloarthritis after 2 years of follow-up.Multivariable linear regression analysisOutcomeβ (95 %CI)mSASSS change score−0.98 (-1.68 to -0.28)*Change of the sacroiliitis sum score−0.06 (-0.32 to 0.20)**Multivariable logistic regression analysisOutcomeOdds ratio (95 %CI)Progression of mSASSS by ≥2 points0.33 (0.12 to 0.91)*Progression of sacroiliitis by at least 1 grade in opinion of both readers0.84 (0.33 to 2.09)**mSASSS - modified Stoke Ankylosing Spondylitis Spine Score.*Adjusted for the smoking status, HLA-B27 status, NSAIDs intake, baseline syndesmophytes, and time-averaged ASDAS.**Adjusted for the smoking status, HLA-B27 status, NSAIDs intake, sacroiliitis sum score at baseline, and time-averaged ASDAS.Conclusion:Presence of PS is associated with distinct characteristics of SpA including slower radiographic spinal progression which might be explained partly by the numerically lower mSASSS score at baseline.Acknowledgments: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, financial support has been obtained from Abbott / Abbvie, Amgen, Centocor, Schering-Plough, and Wyeth. Since 2010 GESPIC is supported by Abbvie.Dr. Murat Torgutalp was supported by the Scientific and Technological Research Council of Turkey (TUBITAK).Disclosure of Interests:Murat Torgutalp: None declared, 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, 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, Valeria Rios Rodriguez Consultant of: Abbvie, Novartis, Hildrun Haibel Consultant of: Abbvie, Jansen, MSD, and Novartis, Speakers bureau: Abbvie, Jansen, MSD, and Novartis, Martin Rudwaleit Consultant of: AbbVie, BMS, Celgene, Janssen, Eli Lilly, MSD, Novartis, Pfizer, Roche, 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:Long-term data on anti-TNF treatment in patients with early axial spondyloarthritis (SpA) is scarce.Objectives:The objective of this analysis was to assess the long-term clinical efficacy (up to 10 years of treatment) of a tumor necrosis factor (TNF) inhibitor etanercept (ETN) in patients with early axial spondyloarthritis, who participated in the long-term (until year 10) extension of the ESTHER (Etanercept vs. Sulfasalazine in Early Axial Spondyloarthritis Trial) trial.Methods:In the previously reported ESTHER trial, patients with early active axial SpA [including both non-radiographic axial SpA (nr-axSpA) and radiographic axial SpA (r-axSpA)/ankylosing spondylitis (AS)] with a symptom duration of Results:Out of 76 initial patients, 25% (n=19, 12 with r-axSpA and 7 with nr-axSpA) completed year 10 of the study. At baseline, completers were significantly more often male and showed lower values of patient (PGA) and physician global assessments of disease activity (PhGA), ASDAS (Ankylosing Spondylitis Disease Activity Score), BASMI (Bath Ankylosing Spondylitis Metrology Index), and AS-QoL (Ankylosing Spondylitis Quality of Life Questionnaire) as compared to non-completers (Table 1). When analyzing clinical data of the completers, mean BASDAI, BASFI and ASDAS values were constantly Conclusion:A sustained clinical response was shown over the 10 years of the study for the completers with comparable rates between r-axSpA and nr-axSpA. ETN was well tolerated across the entire treatment period and showed a good safety profile with no new safety signals.Table 1.Baseline characteristics of patients with axial spondyloarthritis who completed the study as compared to patients who dropped out.Completer(n=19)Non-Completer(n=57)p valueAge, years32.5 (7.4)32.8 (8.9)0.91Male patients, n (%)15 (78.9)29 (50.9)0.034Symptomduration, years1.1 (1.2)1 (1.7)0.81HLA-B27 positivity, n (%)18 (94.7)44 (77.2)0.091Elevated CRP (CRP>5mg/l), n (%)7 (38.9)33 (62.3)0.088Fulfilled New York criteria, n (%)12 (63.2)27 (47.4)0.24Patient global (0-10)6.1 (1.9)7.2 (1.7)0.025Physician global (0-10)5.5 (1.5)6.5 (1.2)0.007ASDAS3 (0.7)3.5 (0.8)0.042BASDAI (0-10)5.4 (1.1)5.8 (1.3)0.27BASFI (0-10)4 (2.1)4.4 (2)0.41BASMI (0-10)1.2 (1.3)2 (1.6)0.039AS-QoL (0-18)7.6 (3.9)10.1 (3.9)0.019Acknowledgments:The ESTHER study was supported by an unrestricted research grant from Pfizer.Murat Torgutalp’s work at Charité was supported by an award from the Scientific and Technological Research Council of Turkey.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, 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:It is presumed that the phenotype of the axial spondyloarthritis (axSpA) may differ in females and males; the published data are controversial.Objectives:To explore the sex differences in disease features and radiographic progression in axSpA.Methods:A total of 210 patients with axSpA (115 with radiographic and 95 with non-radiographic axSpA) were selected for analysis. Spinal radiographs were scored by two readers in a random order according to the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). Pelvic radiographs were scored according to the grading system of the modified New York criteria; a sacroiliitis sum score was calculated as a sum of the grades for both sacroiliac joints. Mann-Whitney and Fisher exact tests were performed for group comparisons. A multivariable regression analysis was performed to analyze the influence of gender on radiographic progression.Results:Males (n=107; 51%) were significantly younger at disease onset (34.8 ± 10.3 vs. 31.5 ± 11.2 years, p=0.008) and at diagnosis (37.5 ± 10.2 vs. 34.1 ± 11.2 years, p=0.006); symptom duration at baseline was similar (4.1 ± 2.6 vs. 4.3 ± 2.8 years, p=0.66). Females were less often HLA-B27 positive (74 (72.5%) vs. 92 (86.0%), p=0.02), had higher baseline disease activity (BASDAI 4.3±2.2 vs 3.7±2.0; p=0.05), but lower baseline C-reactive protein level (7.1 ± 10.9 vs. 12.3 ±18.2 mg/l, p=0.08), and similar time-averaged ASDAS (2.5±0.8 vs 2.4±1.0; p=0.385). Males more frequently had definite radiographic sacroiliitis (70.1% vs. 38.8%; pTable 1.Conclusion:There was a trend for male patients to have more radiographic damage at the baseline and more progression after two years, as reflected by the percentage of patients with new syndesmophytes.:Table 1.Association of sex with radiographic progression in spine and sacroiliac joints after 2 years of follow-up.Parameter, n (%) or mean±SDFemale(n=103)Male(n=107)PSpinal radiographic progressionmSASSS change0.46 ± 1.631.00 ± 2.850.25Progression of mSASSS by ≥2 points10 (9.7)20 (18.7)0.08New syndesmophytes or progression of syndesmophytes10 (9.7)23 (21.5)0.02Progression of radiografic sacroiliitisChange of the sacroiliitis sum score0.14 ± 0.940.13 ± 0.730.58Progression of sacroiliitis by at least 1 grade in opinion of both readers17 (16.5)9 (8.4)0.09mSASSS – modified Stoke Ankylosing Spondylitis Spine Score;Acknowledgments: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, financial support has been obtained from Abbott / Abbvie, Amgen, Centocor, Schering-Plough, and Wyeth. Since 2010 GESPIC is supported by Abbvie.Dr. Murat Torgutalp was supported by the Scientific and Technological Research Council of Turkey (TUBITAK).Disclosure of Interests:Mikhail Protopopov Consultant of: Novartis, Murat Torgutalp: 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, Hildrun Haibel Consultant of: Abbvie, Jansen, MSD, and Novartis, Speakers bureau: Abbvie, Jansen, MSD, and 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, Valeria Rios Rodriguez Consultant of: Abbvie, Novartis, Martin Rudwaleit Consultant of: AbbVie, BMS, Celgene, Janssen, Eli Lilly, MSD, Novartis, Pfizer, Roche, 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:There is few data available regarding differences in body composition and its possible changes in patients with ankylosing spondylitis (AS) treated with biological disease-modifying anti-rheumatic drugs (bDMARDs). An increase of body weight and lean mass in patients receiving TNF inhibitors, as well as a possible muscle wasting by high disease activity have been previously described. Bioelectrical impedance analysis (BIA) is a valid method to assess body composition and allows to distinguish between fat, fat-free mass and skeletal muscle mass.Objectives:To evaluate changes in body composition in patients with AS after 6 months of treatment with bDMARDs.Methods:Patients with a diagnosis of AS, fulfilling the modified New York criteria and starting a bDMARD therapy were included in the extension of the prospective German Spondyloarthritis Inception Cohort (GESPIC). All patients had high disease activity (BASDAI >=4 and/or ASDAS >=2.1) despite previous treatment with nonsteroidal anti-inflammatory drugs. Disease activity and body composition were assessed at baseline and after 6 months of bDMARD treatment. Body composition was assessed by the BIA with the seca© mBCA 515 device (SECA Deutschland GmbH, Hamburg/Germany) and included the following parameters: weight, body mass index (BMI), fat mass index (FMI), fat free mass index (FFMI), skeletal muscle mass value (SMM), and visceral adipose tissue value (VAT). Response to a bDMARD therapy was defined as achievement of clinically important improvement of ASDAS (>=1.1).Results:A total of 129 patients (66.7% male) with AS were recruited in this cohort extension between 2015 and 2019. The mean (mean ± SD) age was 36.2 ± 10.3 years, and symptom duration was 10.7 ± 9.1 years. HLA-B27 test was positive in 89.1% patients. BIA was assessed in 77 patients; the baseline characteristics of these patients were similar to those of the whole cohort. Of these, 75 patients were treated with TNF inhibitors and 2 patients were treated with an IL-17A inhibitor.After 6 months of a bDMARD treatment, body composition changed significantly with an increase of weight and BMI due to the gain of FMI but also of FFMI and SMM, while there was no increase of the visceral fat – table. In responders (improvement of ASDAS>=1.1 after 6 months) the results were similar to the whole group with a significantly gain (mean±SD) on BMI, FMI, FFMI and SMM (0.3 ± 1.4 kg/m2, 0.3 ± 1.0 kg/m2, 0.2 ±0.5 kg/m2, 0.5 ± 1.2 kg, pConclusion:Treatment with bDMARDs is associated with favorable changes of the body composition with increase of the muscle mass but not of the visceral fat. These changes were evident in treatment responders only.TABLE 1.Body composition parameter at baseline and after 6 months of treatment with a bDMARDs in patients with AS (n=77)Mean±SDDifference, mean±SD95% CIP*LowerUpperWeight at baseline, kg77.19±15.710.75±3.800.041.470.04Weight at 6 months, kg77.94±16.25BMI at baseline, kg/m225.03±4.320.30±1.290.060.550.02BMI at 6 months, kg/m225.33±4.43FMI at baseline, kg/m26.74±3.390.31±0.970.070.540.01FMI at 6 months, kg/m27.05±3.42FFMI at baseline, kg/m218.27±2.180.15±0.480.040.270.01FFMI at 6 months, kg/m218.42±2.27SMM at baseline, kg27.40±5.850.32±1.110.050.590.02SMM at 6 months, kg27.73±5.90VAT at baseline, liters1.94±1.62-0.12±0.63-0.270.040.14VAT at 6 months, liters1.82±1.56BMI: Body Mass Index; FMI: Fat Mass Index; FFMI: Free Fat Mass Index; SMM: Skeletal Muscle mass; VAT: Visceral Adipose Tissue.*Wilcoxon testAcknowledgments:GESPIC has been financially suported by ArthroMark and METARTHROS projectsDisclosure 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, Judith Rademacher: None declared, Burkhard Muche: None declared, Anne Katrin Weber: None declared, Susanne Lüders: 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, 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:Data on the impact of body weight and body mass index (BMI) on the response to biological disease-modifying anti-rheumatic drugs (bDMARDs) in axial spondyloarthritis (axSpA) including ankylosing spondylitis (AS) are still contradictory. Data on the impact of different components of the body composition on the treatment response are lacking.Objectives:To investigate the impact of body composition on the response to biological disease-modifying anti-rheumatic drugs (bDMARD) in patients with AS after 6 months of treatment.Methods:Patients with AS (radiographic axSpA), fulfilling the modified New York criteria and starting a bDMARD therapy were recruited between 2015 and 2019 in an extension of the prospective German Spondyloarthritis Inception Cohort (GESPIC-AS). All patients were required to be candidates for bDMARD therapy at baseline with high disease activity (BASDAI >=4 and/or ASDAS >=2.1) despite previous treatment with nonsteroidal anti-inflammatory drugs. Disease activity measures (BASDAI, CRP, ASDAS), as well as body composition parameters were assessed at baseline and after 6 months of bDMARD treatment. Body composition was assessed by the bioelectrical impedance analysis (BIA). Weight, body mass index (BMI), fat mass index (FMI), fat free mass index (FFMI), skeletal muscle mass value (SMM), visceral adipose tissue (VAT), total body water (TBW), and extracellular water (ECW) values were collected. The primary measure of the treatment response was ASDAS change at month 6 as compared to baseline.Results:A total of 129 patients with AS were included in this cohort. BIA was performed in 77 patients. There were 71.4% males, and 85.7% were HLA-B27 positive. At baseline, BASDAI was 5.4±1.4, CRP was 12.8±16.5 mg/l, and ASDAS - 3.0±1.0. The baseline BMI was 25.0±4.3 kg/m2. A total of 75 patients were treated with TNFi, 2 patients received an IL-17 inhibitor.A higher BMI at baseline was associated with a worse response to bDMARD therapy that was attributable to both, the fat mass as reflected by FMI and to the fat-free mass reflected by FFMI, but not to SMM or VAT or water components – Table. This effect was independent of age, sex, symptom duration, HLA-B27 status and ASDAS at baseline.Table.Univariable and multivariable linear regression analysis of the association between response to bDMARD treatment (change in the ASDAS score after 6 months) and body composition parameters in patients with AS (n=77)VariablesUnivariableMultivariable analysis*Analysisß (95%CI)Model 1ß (95%CI)Model 2ß (95%CI)Model 3ß (95%CI)Model 4ß (95%CI)Model 5ß (95%CI)Model 6ß (95%CI)Model 7ß (95%CI)BMI, kg/m2-0.016(-0.063; 0.031)-0.043(-0.079;-0.006)------FMI, kg/m2-0.024(-0.103; 0.054)--0.065(-0.128;-0.003)-----FMMI,kg/m2-0.010(-0.133; 0.112)---0.138(-0.253;-0.022)----SMM, kg0.026(-0.020; - 0.071)---0.012(-0.044; 0.069)---VAT, liters0.069(-0.099; 0.238)-----0.095(-0.248; 0.057)--TBW, liters0.020(-0.016; 0.056)-----0.007(-0.036; 0.051)-ECW, liters0.054(-0.43; 0.150)------0.005(-0.98; 0.107)*Adjusted for age, sex, HLA-B27 status, symptom duration, and ASDAS at baseline.BMI: Body Mass Index; FMI: Fat Mass Index; SMM: Skeletal Muscle mass; VAT: Visceral Adipose Tissue; AS: ankylosing spondylitis; bDMARD: biological disease-modifying anti-rheumatic drug; CI: 95% confidence interval.Conclusion:Both fat mass and fat free mass have an impact on the response to bDMARDs after 6 months of treatment in patients with AS. Interestingly, skeletal muscle mass, visceral fat as well as water components showed no association with treatment response.Acknowledgments:GESPIC has been financially supported by ArthroMark and METARTHROS projects.Disclosure 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, Judith Rademacher: None declared, Burkhard Muche: None declared, Anne Katrin Weber: None declared, Susanne Lüders: 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, 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

We read with interest the letter by Wallman et al , that reported the prevalence of irritable bowel syndrome (IBS) in patients with axial spondyloarthritis (axial SpA).1 The authors present data from the population based SPondylARtrit TvArsnittsKohort Universitetssjukhuset i Skane (SPARTAKUS) study,2 showing that symptoms meeting IBS criteria were significantly more frequent among patients with axial SpA without known inflammatory bowel diseases (IBD) (30%), than in controls (16%; OR: 2.5 (95% CI 1.1 to 5.7)). Authors conclude that IBS may be an overlooked frequent comorbidity of axial SpA warranting further research and increased awareness. In our view, this suggested high prevalence of IBS in patients with axial SpA might be …

Background Functional status and spinal mobility in patients with axial spondyloarthritis (axSpA) are known to be determined both by disease activity and by structural damage in the spine. The impact of structural damage in the sacroiliac joints (SIJ) on physical function and spinal mobility in axSpA has not been studied so far. The objective of the study was to analyze the impact of radiographic sacroiliitis on functional status and spinal mobility in patients with axSpA. Methods In total, 210 patients with axSpA were included in the analysis. Radiographs of SIJ obtained at baseline and after 2 years of follow up were scored by two trained readers according to the modified New York criteria grading system (grade 0–4). The mean of two readers’ scores for each joint and a sum score for both SIJ were calculated for each patient giving a sacroiliitis sum score between 0 and 8. The Bath Ankylosing Spondylitis Functional Index (BASFI) and Bath Ankylosing Spondylitis Metrology Index (BASMI) at baseline and after 2 years were used as outcome measures. Results Longitudinal mixed model analysis adjusted for structural damage in the spine (modified Stoke Ankylosing Spondylitis Spine Score - mSASSS), disease activity (Bath Ankylosing Spondylitis Disease Activity Index - BASDAI and C-reactive protein level) and gender, revealed an independent association of the sacroiliitis sum score with the BASFI: b = 0.10 (95% CI 0.01–0.19) and the BASMI: b = 0.12 (95% CI 0.03–0.21), respectively, indicating that change by one radiographic sacroiliitis grade in one joint is associated with BASFI/BASMI worsening by 0.10/0.12 points, respectively, independently of disease activity and structural damage in the spine. Conclusion Structural damage in the SIJ might have an impact on functional status and spinal mobility in axSpA independently of spinal structural damage and disease activity. Trial registration ClinicalTrials.gov, NCT01277419 . Registered on 14 January 2011.

Background It has been shown in the past that elevated C-reactive protein (CRP) [1] and the composite Ankylosing Spondylitis Disease Activity Score (ASDAS) [2,3] are associated with radiographic spinal progression in axial spondyloarthritis (axSpA). It is not clear, however, whether patient-reported measures of disease activity might also play a predictive role. Objectives To investigate the association between patient-reported measures of disease activity and radiographic spinal progression over two years in early axSpA. Methods Altogether 178 patients with definite axSpA (100 with ankylosing spondylitis and 78 with non-radiographic axSpA) from the German Spondyloarthritis Inception Cohort (GESPIC) were included in the current study. Spinal radiographs (cervical spine lateral views, lumbar spine lateral and anteroposterior views) were scored according to the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) system and for the presence of syndesmophytes. Clinical and lab data were collected at baseline and every 6 months thereafter. Time-averaged values (over 2 years) of the patient global assessment of disease activity (PG), BASDAI and its components, CRP and CRP-based ASDAS, were calculated. Results In the logistic regression analysis there was a significant association between time-averaged patient global and syndesmophyte formation (table): the adjusted odds ratio (OR) was 1.30 (1.01–1.69) meaning a 30% increase of the chance for new syndesmophytes formation over two years with an increase of PG by 1 point (on a 0–10 scale). The time-averaged BASDAI demonstrated no significant association with radiographic spinal progression, but duration and severity of morning stiffness were both significantly associated with syndesmophytes formation with a similar strength of association as the patient global (table). Similar trends although not always significant were observed for the mSASSS worsening by 2 points and more after two years. CRP and ASDAS did show an already known association with radiographic spinal progression in early axial SpA. Conclusions Higher patient global assessment of disease activity, duration and severity of morning stiffness are clinical parameters, which are associated with more radiographic spinal progression (syndesmophytes formation) in patients with early axial spondyloarthritis. References Poddubnyy D, et al. Arthritis Rheum 2012;64:1388–98. Ramiro S, et al. Ann Rheum Dis. 2014;73(8):1455–61. Poddubnyy D, eta l. Ann Rheum Dis 2014;73(Suppl2):422. Disclosure of Interest None declared