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Objectives To investigate whether meticulously following a treat-to-target (T2T)-strategy in daily clinical practice will lead to less radiographic progression in patients with active RA who start (new) DMARD-therapy. Methods Patients with RA from 10 countries starting/changing conventional synthetic or biologic DMARDs because of active RA, and in whom treatment intensification according to the T2T principle was pursued, were assessed for disease activity every 3 months for 2 years (RA-BIODAM cohort). The primary outcome was the change in Sharp-van der Heijde (SvdH) score, assessed every 6 months. Per 3-month interval DAS44-T2T could be followed zero, one or two times (in a total of two visits). The relation between T2T intensity and change in SvdH-score was modelled by generalized estimating equations. Results In total, 511 patients were included [mean (s.d.) age: 56 (13) years; 76% female]. Mean 2-year SvdH progression was 2.2 (4.1) units (median: 1 unit). A stricter application of T2T in a 3-month interval did not reduce progression in the same 6-month interval [parameter estimates (for yes vs no): +0.15 units (95% CI: −0.04, 0.33) for 2 vs 0 visits; and +0.08 units (−0.06; 0.22) for 1 vs 0 visits] nor did it reduce progression in the subsequent 6-month interval. Conclusions In this daily practice cohort, following T2T principles more meticulously did not result in less radiographic progression than a somewhat more lenient attitude towards T2T. One possible interpretation of these results is that the intention to apply T2T already suffices and that a more stringent approach does not further improve outcome.

Magnetic resonance imaging (MRI) features of active sacroiliac joint inflammation include joint space fluid and enhancement, but it is unclear to what extent these are present in normal children. To describe normal MRI appearances of pediatric sacroiliac joint spaces in boys and girls of varying ages. In this ethics-approved prospective study, 251 children (119 boys, 132 girls; mean age: 12.4 years, range: 6.1–18.0 years), had both oblique-coronal T1-weighted and short tau inversion recovery (STIR) sacroiliac joint MRI. Of these, 127 were imaged for other reasons and had asymptomatic sacroiliac joints (“normal cohort”) while 124 had low back pain with no features of sacroiliitis on initial clinical MRI review (“low-back-pain cohort”). Post-gadolinium T1-weighted sequences were available in 16/127 normal and 124/124 low-back-pain subjects. Three experienced radiologists scored high signal in the sacroiliac joint space on STIR (score 0=absent; 1=high signal compared to normal bone marrow present anywhere in the joint but not as bright as fluid [compared to vessels, cerebrospinal fluid]; 2=definite fluid signal in part of the joint; 3=definite fluid signal, entire vertical height, majority of slices) and, when available, joint space post-contrast enhancement (0=no high signal/enhancement; 1=thin, symmetrical, mildly increased linear high signal present in the joint space; 2=focal, thick or intense enhancement). Associations between joint signal scores, age, gender and sacral apophyseal closure were analysed. Increased signal on STIR (score 1–3) was present in 74.7% of pediatric sacroiliac joint spaces, as intense as fluid in 18.4%. There was no significant difference in proportion by gender, side or cohort, but girls showed peak signal earlier than boys (10 years old vs. 12 years old, respectively). On post-gadolinium T1-weighted sequences, a thin rim of increased signal was nearly universally seen in sacroiliac joint spaces without focal, intense or thick post-contrast enhancement. Sacroiliac joint spaces of most children demonstrate mildly increased signal on STIR, compared to normal bone marrow, and thin rim-like enhancement on post-contrast T1 images, likely related to cartilage. These findings should not be confused with sacroiliitis.

Objective To perform region-based development of whole-body MRI through validation of knee region scoring systems in spondyloarthritis (SpA). Methods Assessment of knee inflammatory pathologies using 2 systems, OMERACT MRI Whole-body score for Inflammation in Peripheral joints and Entheses (MRI-WIPE) and Knee Inflammation MRI Scoring System (KIMRISS), in 4 iterative multi-reader exercises. Results In the final exercise, reliability was mostly good for readers with highest agreement in previous exercise. Median pairwise single-measure ICCs for osteitis and synovitis/effusion status/change were 0.71/0.48 (WIPE-osteitis), 0.48/0.77 (WIPE-synovitis/effusion), 0.59/0.91 (KIMRISS-osteitis) and 0.92/0.97 (KIMRISS-synovitis/effusion). SRMs were 0.74 (WIPE-synovitis/effusion) and 0.78 (KIMRISS-synovitis/effusion). Conclusion MRI-WIPE and KIMRISS may both be useful in SpA whole-body evaluation studies.

Objective To investigate whether tumor necrosis factor inhibitors (TNFi) impact spinal radiographic progression in patients with axial spondyloarthritis (SpA) and whether this is coupled to their effect on inflammation.Methods Patients with axial SpA fulfilling the modified New York criteria were included in a prospective cohort (the ALBERTA Follow Up Research Cohort in Ankylosing Spondylitis Treatment). Spine radiographs, performed every 2 years for up to 10 years, were scored by 2 central readers, using the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). The indirect effect of TNFi on mSASSS was evaluated with generalized estimating equations by testing the interaction between TNFi and Ankylosing Spondylitis Disease Activity Score (ASDAS) at the start of each 2-year interval (t). If significant, the association between ASDAS at t and mSASSS at the end of the interval (t+1) was assessed in 1) patients treated with TNFi at all visits, 2) patients treated with TNFi at some visits, and 3) patients who were never treated with TNFi. In addition, the association between TNFi at t and mSASSS at t+1 (adjusting for ASDAS at t) was also tested (direct effect).Results In total, 314 patients were included. A gradient was seen for the effect of ASDAS at t on mSASSS at t+1 (interaction P = 0.10), with a higher progression in patients never treated with TNFi (beta = 0.41 [95% confidence interval (95% CI) 0.13, 0.68]) compared to those continuously treated (beta = 0.16 [95% CI 0.00, 0.31]) (indirect effect). However, TNFi also directly slowed progression, as treated patients had on average an mSASSS 0.85 units lower at t+1 compared to untreated patients (beta = -0.85 [95% CI -1.35, -0.35]).Conclusion Our findings indicate that TNFi reduce spinal radiographic progression in patients with radiographic axial SpA, which might be partially uncoupled from their effects on inflammation as measured by the ASDAS.

To determine patterns of variation of subchondral T2 signal changes in pediatric sacroiliac joints (SIJ) by location, age, sex, and sacral apophyseal closure. MRI of 502 SIJ in 251 children (132 girls), mean age 12.4 years (range 6.1–18.0), was obtained with parental informed consent. One hundred twenty-seven out of 251 had asymptomatic joints and were imaged for non-rheumatologic reasons, and 124 had low back pain but no sign of sacroiliitis on initial clinical MRI review. After calibration, three subspecialist radiologists independently scored subchondral signal changes on fat-suppressed fluid-sensitive sequences from 0 to 3 in 4 locations, and graded the degree of closure of sacral segmental apophyses. Associations between patient age, sex, signal changes, and apophyseal closure were analyzed. Rim-like subchondral increased T2 signal or “flaring” was much more common at sacral than iliac SIJ margins (72% vs 16%, p 90% of children. Iliac flaring scores were always lower than sacral, except for 1 child. Signal changes decreased as sacral apophyses closed, and were seen in

Resume Objectif Evaluer les facteurs predictifs de reponse selon un score IRM d’inflammation de la hanche (HIMRISS) dans un echantillon de patients atteints de coxarthrose recevant une injection d’acide hyaluronique (AH). Methodes Au total, 60 patients atteints de coxarthrose ont ete inclus. Les resultats cliniques ont ete evalues par le score WOMAC a l’inclusion, puis trois mois apres une injection d’AH. Quatre lecteurs ont evalue les lesions medullaires osseuses (LMO) et la synovite avant l’injection par le score HIMRISS sur les IRM de hanche. La fiabilite interlecteur du score HIMRISS etait de 0,86 pour le HIMRISS total, 0,64 pour celui des LMO acetabulaires, 0,83 pour les LMO femorales et 0,78 pour le score de synovite-epanchement. Les associations entre les caracteristiques a l’IRM et les donnees cliniques ont egalement ete evaluees. Les associations entre caracteristiques a l’IRM et reponse a l’injection d’AH ont ete analysees par regression logistique (univariee et multivariee) selon la reponse WOMAC50 a trois mois. Resultats Une reponse WOMAC50 a ete obtenue chez 45,5 % des patients. Cinq effets indesirables ont ete signales. A l’inclusion, on a observe une correlation significative entre le score WOMAC fonctionnel et le score HIMRISS de synovite-epanchement (r = 0,27, p = 0,03). Dans l’analyse univariee, les LMO femorales selon l’evaluation binaire (p = 0,025), le score HIMRISS des LMO femorales (p = 0,0038), le score HIMRISS des LMO acetabulaires (p = 0,042) et le score HIMRISS total (p = 0,0092) ont ete associes negativement a la reponse WOMAC50. Dans l’analyse multivariee ajustee selon l’âge et l’IMC, les scores HIMRISS des LMO femorales (p = 0,02) et total (p = 0,016) ont ete associes negativement a la reponse. A un seuil HIMRISS Conclusion Les scores HIMRISS, total et en sous-domaines, constituent une methode fiable permettant d’identifier les patients atteints de coxarthrose repondeurs aux injections d’AH.

OBJECTIVE: Prevalence of sacroiliitis in Crohn’s disease (CD) is variable depending on defining criteria. This study utilized standardized sacroiliac joint (SIJ) MRI to identify sacroiliitis in CD patients and its association with clinical and serological markers. METHODS: In this cross-sectional study, consecutive adult subjects with CD were prospectively enrolled from an inflammatory bowel disease clinic. All subjects underwent SIJ MRI. Data collected included CD duration, history of joint/back pain, HLA-B27 status, Bath Ankylosing Spondylitis Metrology Index (BASMI), Bath Ankylosing Spondylitis Disease Activity Index, Harvey-Bradshaw Index (HBI) for activity of CD, Ankylosing Spondylitis Disease Activity Score, C-reactive protein, and various serologic markers of inflammation. Three blinded readers reviewed MRIs for active and/or structural lesions according to the Spondyloarthritis Research Consortium of Canada modules. RESULTS: 33 CD patients were enrolled: 76% female, 80% white, median age 36.4 years (IQR 27.2–49.0), moderate CD activity (mean HBI 8.8±SD 4.5). 19 subjects (58%) reported any back pain, 13 of whom met ASAS inflammatory back pain criteria. 4 subjects (12%) showed sacroiliitis using global approach and 6 (18%) met ASAS imaging criteria of sacroiliitis. Older age (mean 51.2 ± SD 12.5 vs 37.2 ± 14; p=0.04), history of dactylitis (50.0% vs 3.4%, p=0.03) and worse BASMI (4.1 ± 0.7 vs 2.4 ± 0.8, p=

Objective To validate a revised version of the KIMRISS method for quantification of BML and synovitis-effusion in the knee by comparison with an established method, MOAKS. Methods Novel calibration tools were developed for both methods. We compared reliability for status and change scores of BML and synovitis-effusion on baseline and one-year MRI scans. Results Significant increase in both BML and synovitis-effusion was evident using KIMRISS but only for synovitis-effusion using MOAKS. Pre-specified targets for acceptable reliability (≥0.80 and ≥0.70 for status and change scores, respectively) were achieved more frequently for KIMRISS for both BML and synovitis. Conclusion Per OFISA criteria, KIMRISS should progress to assessment of discrimination.

Magnetic resonance imaging (MRI) features of active sacroiliac joint inflammation include joint space fluid and enhancement, but it is unclear to what extent these are present in normal children.To describe normal MRI appearances of pediatric sacroiliac joint spaces in boys and girls of varying ages.In this ethics-approved prospective study, 251 children (119 boys, 132 girls; mean age: 12.4 years, range: 6.1-18.0 years), had both oblique-coronal T1-weighted and short tau inversion recovery (STIR) sacroiliac joint MRI. Of these, 127 were imaged for other reasons and had asymptomatic sacroiliac joints ("normal cohort") while 124 had low back pain with no features of sacroiliitis on initial clinical MRI review ("low-back-pain cohort"). Post-gadolinium T1-weighted sequences were available in 16/127 normal and 124/124 low-back-pain subjects. Three experienced radiologists scored high signal in the sacroiliac joint space on STIR (score 0=absent; 1=high signal compared to normal bone marrow present anywhere in the joint but not as bright as fluid [compared to vessels, cerebrospinal fluid]; 2=definite fluid signal in part of the joint; 3=definite fluid signal, entire vertical height, majority of slices) and, when available, joint space post-contrast enhancement (0=no high signal/enhancement; 1=thin, symmetrical, mildly increased linear high signal present in the joint space; 2=focal, thick or intense enhancement). Associations between joint signal scores, age, gender and sacral apophyseal closure were analysed.Increased signal on STIR (score 1-3) was present in 74.7% of pediatric sacroiliac joint spaces, as intense as fluid in 18.4%. There was no significant difference in proportion by gender, side or cohort, but girls showed peak signal earlier than boys (10 years old vs. 12 years old, respectively). On post-gadolinium T1-weighted sequences, a thin rim of increased signal was nearly universally seen in sacroiliac joint spaces without focal, intense or thick post-contrast enhancement.Sacroiliac joint spaces of most children demonstrate mildly increased signal on STIR, compared to normal bone marrow, and thin rim-like enhancement on post-contrast T1 images, likely related to cartilage. These findings should not be confused with sacroiliitis.

Background:Inflammation in peripheral joints and entheses is common in spondyloarthritis (SpA). Whole-body magnetic resonance imaging (WB-MRI) allows assessment of the overall inflammatory status of arthritis patients including joints and entheses. The OMERACT MRI Whole-body scoring system for Inflammation in Peripheral joints and Entheses (MRI-WIPE) [1] has been developed and validated for the entire body assessment, including the knee, but not separately validated for the knee joint region. Detailed MRI scoring systems exist for heels, hands and feet, but although knee arthritis is a key cause of functional impairment, no detailed scoring system has been validated for inflammatory arthritides. The Knee Inflammation MRI Scoring System (KIMRISS) [2] was developed and validated in osteoarthritis and demonstrated good reliability.Objectives:To perform region-based development of whole-body MRI through validation of two knee region scoring systems in SpA.Methods:Assessment of inflammation was performed in the knee region on sagittal WB-MRIs using 2 scoring systems, MRI-WIPE and KIMRISS (Figure 1), in 4 iterative multi-reader exercises. In the final exercise, images (psoriatic arthritis, axial and peripheral SpA) were obtained before and after TNF-inhibitor.Results:In the final exercise (exercise 4), reliability was mostly good for experienced readers with the overall highest interreader agreement in the previous exercise (exercise 3). Median pairwise single measure intraclass correlation coefficients for osteitis and synovitis/effusion for status/change were 0.71/0.48 (WIPE osteitis), 0.48/0.77 (WIPE synovitis/effusion), 0.59/0.91 (KIMRISS osteitis) and 0.92/0.97 (KIMRISS synovitis/effusion) (Table 1). Wilcoxon signed-rank test showed significant change in synovitis/effusion for both methods and they correlated significantly regarding status in osteitis (0.92, pTable 1.MRI-WIPE knee and KIMRISS interreader reliability for OMERACT exercises 3 and 4MRI-WIPE KneeKIMRISSOsteitisSynovitis/effusionOsteitisSynovitis/effusionVariablesNo. patientsType of scoreMean scoreICCMean scoreICCMean scoreICCMean scoreICCExercise 39 readers11Status3.6 (0-16)0.57 (-0.06-0.98)1.8 (0-4)0.47 (0.05-0.85)32.3 (1-224)0.87 (0.66-0.99)29.9 (11-60)0.34 (-0.62-0.87)11Change1.1 (-2-6)0.53 (0.03-0.90)0 (-2-1)0.32 (-0.13-0.76)27.7 (-9-131)0.58 (-0.30-0.96)-1.6 (-33-11)0.48 (-0.32-0.95)Exercise 33 readers11Status3.1 (0-16)0.83 (0.71-0.97)2.5 (0-5)0.59 (0.51-0.71)34.4 (0-233)0.89 (0.83-0.99)36.5 (16-78)0.59 (0.08-0.86)11Change0.9 (-3-6)0.72 (0.57-0.83)0 (-2-1)0.63 (0.49-0.76)19.3 (-23-86)0.46 (0.18-0.83)-1.8 (-45-17)0.89 (0.82-0.95)Exercise 49 readers10Change-0.25 (-4-5)0.38 (-0.35-0.94)-1.0 (-3-1)0.30 (-0.43-0.89)-0.45 (-37-65)0.26 (-0.86-0.97)-14.7 (-48-0.20)0.48 (-0.39-0.99)20Status2.9 (0-7)0.50 (-0.01-0.84)2.1 (0-4)0.44 (-0.21-0.79)15.2 (0-66)0.35 (-0.04-0.89)55.6 (1-122)0.54 (0.01-0.96)Exercise 43 readers10Change0.2 (-2-6)0.48 (0.16-0.66)-1.4 (-5-0)0.77 (0.70-0.82)5.8 (-27-111)0.92 (0.90-0.94)-20.7 (-65-28)0.97 (0.96-0.98)20Status2.3 (0-6)0.71 (0.60-0.80)2.7 (0-5)0.48 (0.42-0.57)11.4 (0-36)0.59 (0.39-0.71)69.4 (1-153)0.91 (0.87-0.93)Sum scores are mean (range) of the patients scores. ICC values are mean (range). ICC is 2-way mixed model, single measure, by absolute agreement.Conclusion:MRI-WIPE and KIMRISS may both be useful as part of modular whole-body evaluation in clinical studies.References:[1]Krabbe S et al. J Rheum. 2019;46(9):1215-21[2]Jaremko JL et al. RMD Open. 2017;3(1):e000355Acknowledgements:We thank CARE Aarthritis Limited (carearthritis.com) for help with setting up the web-based scoring interface, the scoring exercises, and the web-based meetings. We thank all who participated in the SIG (Special Interest Group) virtual OMERACT meeting 29 October 2020. HMO, GDM and PGC are supported in part by the National Institute for Health Research (NIHR) Leeds Biomedical Research Centre, United Kingdom. The views expressed in this study are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health.Disclosure of Interests:Marie Wetterslev: None declared, Walter P Maksymowych Speakers bureau: AbbVie, Janssen, Novartis, Pfizer and UCB, Consultant of: AbbVie, Boehringer Ingelheim, Celgene, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer and UCB, Grant/research support from: AbbVie, Novartis, Pfizer and UCB, Robert G Lambert Consultant of: Parexel and Pfizer, Iris Eshed: None declared, Susanne Juhl Pedersen Speakers bureau: MSD, Pfizer, AbbVie, Novartis and UCB, Consultant of: AbbVie and Novartis, Grant/research support from: AbbVie, MSD, and Novartis, Maria Stoenoiu: None declared, Simon Krabbe: None declared, Paul Bird Speakers bureau: Janssen, Abbvie, UCB, Celgene, BMS, Novartis, Pfizer, Gilead, Eli-Lilly, Consultant of: Janssen, Abbvie, UCB, Celgene, BMS, Novartis, Pfizer, Gilead, Eli-Lilly, Violaine Foltz: None declared, Ashish Jacob Mathew: None declared, Frederique Gandjbakhch: None declared, Joel Paschke: None declared, Philippe Carron Speakers bureau: Pfizer, MSD, Novartis, BMS, AbbVie, UCB, Eli Lilly, Gilead and Celgene, Consultant of: Pfizer, MSD, Novartis, BMS, AbbVie, UCB, Eli Lilly, Gilead and Celgene, Grant/research support from: UCB, MSD and Pfizer, Gabriele De Marco: None declared, Helena Marzo-Ortega Speakers bureau: AbbVie, Celgene, Janssen, Lilly, Novartis, Pfizer, Takeda and UCB, Grant/research support from: Janssen and Novartis, Anna Enevold Fløistrup Poulsen: None declared, Jacob L Jaremko: None declared, Philip G Conaghan Speakers bureau: AbbVie, AstraZeneca, BMS, Eli Lilly, EMD Serono, Flexion Therapeutics, Galapagos, Gilead, Novartis, Pfizer and Stryker, Consultant of: AbbVie, AstraZeneca, BMS, Eli Lilly, EMD Serono, Flexion Therapeutics, Galapagos, Gilead, Novartis, Pfizer and Stryker, Mikkel Østergaard Speakers bureau: Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli-Lilly, Hospira, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sandoz, Sanofi and UCB, Consultant of: Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli-Lilly, Hospira, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sandoz, Sanofi and UCB, Grant/research support from: Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli-Lilly, Hospira, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sandoz, Sanofi and UCB

Objective.Compelling evidence supports a treat-to-target (T2T) strategy for optimal outcomes in rheumatoid arthritis (RA). There is limited knowledge regarding the factors that impede implementation of T2T, particularly in a setting where adherence to T2T is protocol-specified. We aimed to assess clinical factors that associate with failure to adhere to T2T.Methods.Patients with RA from 10 countries who were starting or changing conventional synthetic disease-modifying antirheumatic drugs and/or starting tumor necrosis factor inhibitors were followed for 2 years. Participating physicians were required per protocol to adhere to the T2T strategy. Factors influencing adherence to T2T low disease activity (T2T-LDA; 44-joint count Disease Activity Score ≤ 2.4) were analyzed in 2 types of binomial generalized estimating equations models: (1) including only baseline features (baseline model); and (2) modeling variables that inherently vary over time as such (longitudinal model).Results.A total of 571 patients were recruited and 439 (76.9%) completed 2-year followup. Failure of adherence to T2T-LDA was noted in 1765 visits (40.5%). In the baseline multivariable model, a high number of comorbidities (OR 1.10, 95% CI 1.02–1.19), smoking (OR 1.32, 95% CI 1.08–1.63) and high number of tender joints (OR 1.03, 95% CI 1.02–1.04) were independently associated with failure to implement T2T, while anticitrullinated protein antibody/rheumatoid factor positivity (OR 0.63, 95% CI 0.50–0.80) was a significant facilitator of T2T. Results were similar in the longitudinal model.Conclusion.Lack of adherence to T2T in the RA BIODAM cohort was evident in a substantial proportion despite being a protocol requirement, and this could be predicted by clinical features. [Rheumatoid Arthritis (RA) BIODAM cohort; ClinicalTrials.gov: NCT01476956].

ObjectivesTo investigate whether following a treat-to-target (T2T)-strategy in daily clinical practice leads to more patients with rheumatoid arthritis (RA) meeting the remission target.MethodsRA patients from 10 countries starting/changing conventional synthetic or biological disease-modifying anti-rheumatic drugs were assessed for disease activity every 3 months for 2 years (RA BIODAM (BIOmarkers of joint DAMage) cohort). Per visit was decided whether a patient was treated according to a T2T-strategy with 44-joint disease activity score (DAS44) remission (DAS44 ResultsIn total 4356 visits of 571 patients (mean (SD) age: 56 (13) years, 78% female) were included. Appropriate application of T2T was found in 59% of the visits. T2T (vs no T2T) did not yield a higher likelihood of DAS44 remission 3 months later (OR (95% CI): 1.03 (0.92 to 1.16)), but sustained T2T resulted in an increased likelihood of achieving DAS44 remission (OR: 1.19 (1.03 to 1.39)). Similar results were seen with DAS28-ESR remission. For more stringent definitions (CDAI, SDAI and ACR/EULAR Boolean remission), T2T was consistently positively associated with remission (OR range: 1.16 to 1.29), and sustained T2T had a more pronounced effect on remission (OR range: 1.49 to 1.52).ConclusionIn daily clinical practice, the correct application of a T2T-strategy (especially sustained T2T) in patients with RA leads to higher rates of remission.

Objective.The Outcome Measures in Rheumatology Soluble Biomarker Working Group initiated an international, multicenter, prospective study, the Rheumatoid Arthritis (RA) BIODAM cohort, to generate resources for the clinical validation of candidate biomarkers predictive of radiographic progression. This first report describes the cohort, clinical outcomes, and radiographic findings.Methods.Patients with RA from 38 sites in 10 countries starting or changing conventional synthetic disease-modifying antirheumatic drugs and/or starting tumor necrosis factor inhibitors were followed for 2 years. Participating physicians were required to adhere to a treat-to-target strategy. Biosamples (serum, urine) were acquired every 3 months, radiography of hands and feet every 6 months, and ultrasound of hands and feet every 3 months in a subset. Primary endpoint was radiographic progression by the Sharp/van der Heijde score.Results.A total of 571 patients were recruited and 439 (76.9%) completed 2-year followup. At baseline, the majority was female (76%), mean age 55.7 years, and mean disease duration 6.5 years. Patients had a mean of 8.4 swollen and 13.6 tender joints, 44-joint count Disease Activity Score (DAS44) 3.8, 77.7% rheumatoid factor–positive or anticitrullinated protein antibody–positive. Percentage of patients in DAS and American College of Rheumatology remission at 2 years was 52.2% and 27.1%, respectively. Percentage of patients with radiographic progression (> 0.5) at 1 and 2 years was 38.2% and 59.9%, respectively.Conclusion.The RA BIODAM prospective study succeeded in generating an extensive list of clinical, imaging (2343 radiographs), and biosample (4638 sera) resources that will be made available to expedite the identification and validation of biomarkers for radiographic damage endpoints. (Clinicaltrials.gov: NCT01476956, clinicaltrials.gov/ct2/show/NCT01476956)

OBJECTIVE: To assess predictors of response, according to hip MRI inflammatory scoring system (HIMRISS), in a sample of patients with hip osteoarthritis (OA) treated by hyaluronic acid (HA) injection.METHOD: Sixty patients with hip OA were included. Clinical outcomes were assessed at baseline and three months after HA injection by WOMAC. On hip MRI performed before HA injection, bone marrow lesion (BML) and synovitis were assessed by HIMRISS by four readers. The inter-reader reliability of HIMRISS was for HIMRISS total, acetabular BML, femoral BML and synovitis-effusion respectively 0.86, 0.64, 0.83 and 0.78. Associations between MRI features and clinical data were assessed. Logistic regression (univariate and multivariate) was used to explore associations between MRI features and response to HA injection, according to WOMAC50 response at three months.RESULTS: In total, 45.5% of patients met WOMAC50 response. Five adverse events were reported. At baseline, WOMAC function correlated significantly to HIMRISS synovitis-effusion (r=0.27, P=0.03). In univariate analysis, BML femoral according to binary assessment (P=0.025), HIMRISS BML femoral (P=0.0038), HIMRISS BML acetabular (P=0.042), HIMRISS total (P=0.0092) were associated negatively with WOMAC50 response. In multivariate analysis, adjusted for age and BMI, HIMRISS femoral BML (P=0.02) and HIMRISS total (P=0.016) were negatively associated with response. At a HIMRISS threshold ofCONCLUSION: HIMRISS is reliable for total scores and sub-domains. It permits identification of responders to HA injection in hip OA patients.

Background Published methods for quantification of magnetic resonance imaging (MRI) evidence of inflammation in the sacroiliac joint lack validation in pediatric populations. We evaluated the reliability and construct validity of the Spondyloarthritis Research Consortium of Canada (SPARCC) sacroiliac joint inflammation score (SIS) in children with suspected or confirmed juvenile spondyloarthritis (JSpA). Methods The SPARCC SIS measures the presence, depth, and intensity of bone marrow inflammation on MRI through the cartilaginous part of the joint. Six readers blinded to clinical details except age, participated in two reading exercises, each preceded by a calibration exercise. Inter-observer reliability was assessed using intraclass correlation coefficients (ICCs) and for pre-specified acceptable reliability the inraclass correlation coefficient (ICC) was > 0.8. Results The SPARCC SIS had face validity and was feasible to score in pediatric cases in both reading exercises. Cases were mostly male (64%) and the median age at the time of imaging was 14.9 years. After calibration, the median ICC across all readers for the SIS total score was 0.81 (IQR 0.71–0.89). SPARCC SIS had weak correlation with disease activity (DA) as measured by the JSpADA (r = − 0.12) but discriminated significantly between those with and without elevated C-reactive protein (p = 0.03). Conclusion The SPARCC SIS was feasible to score and had acceptable reliability in children. The ICC improved with additional calibration and reading exercises, for both experienced and inexperienced readers.

This study reports the reliability of the juvenile idiopathic arthritis magnetic resonance imaging scoring system (JAMRIS-SIJ). The study comprised of eight raters—two rheumatologists and six radiologists—and 30 coronal T1 and Short-Tau Inversion Recovery (STIR) MRI scans of patients with enthesitis-related juvenile spondylarthritis. The median age of patients was 15 years with a mean disease duration of 5 years and 22 (73.3%) of the sample were boys. The inter-rater agreement of scores for each of the JAMRIS-SIJ items was calculated using a two-way random effect, absolute agreement, and single rater intraclass correlation coefficient (ICC 2.1). The ICC was interpreted together with kurtosis, since the ICC is also affected by the distribution of scores in the sample. The eight-rater, single measure inter-rater ICC (and kurtosis) values for JAMRIS-SIJ inflammation and damage components were the following: bone marrow edema (BME), 0.76 (1.2), joint space inflammation, 0.60 (1.8), capsulitis, 0.58 (9.2), enthesitis, 0.20 (0.1), ankylosis, 0.89 (35), sclerosis, 0.53 (4.6), erosion, 0.50 (6.5), fat lesion, 0.40 (21), backfill, 0.38 (38). The inter-rater reliability for BME and ankylosis scores was good and met the a priori set ICC threshold, whereas for the other items it was variable and below the selected threshold. Future directives should focus on refinement of the scores, definitions, and methods of interpretation prior to validation of the JAMRIS-SIJ through the assessment of its measurement properties.

Background:Whole-body MRI (WB-MRI) allows assessment of the overall inflammation in arthritis patients, including joint and entheses. To enhance the use of WB-MRI in clinical trials, the OMERACT MRI in Arthritis Working Group developed the OMERACT MRI Whole-body score for Inflammation in Peripheral joints and Entheses in inflammatory arthritis (MRI-WIPE) [1]. This has been validated for the entire body, including the hip/pelvis region, but not for each individual region. More detailed scoring systems exist for heels, hands and feet but although hip arthritis is a key cause of functional impairment in spondyloarthritis (SpA), no detailed scoring system has been published for use in SpA. The Hip Inflammation Magnetic Resonance Imaging Scoring System (HIMRISS) was developed and validated in osteoarthritis showing good reliability.Objectives:To validate reliability, correlation and responsiveness of two WB-MRI scores for the hip/pelvis region in SpA.Methods:Inflammation in the hip/pelvis region was assessed on coronal WB-MRIs in 4 iterative multi-reader exercises using MRI-WIPE for the hip/pelvis region and HIMRISS (Figure 1). In final exercises, images (axial/peripheral SpA and psoriatic arthritis) were obtained before and after TNF-inhibitor.Results:In final exercises reliability was mostly good for the best calibrated readers. Median single-measure intraclass correlation coefficients were 0.58-0.65 (WIPE osteitis), 0.10-0.88 (HIMRISS osteitis), 0.38-0.72/0.52-0.60 (WIPE synovitis/effusion) and 0.68-0.89/0.78-0.85 (HIMRISS synovitis/effusion) (Table 1). The methods correlated significantly for status in osteitis (0.72, p=0.019) and for synovitis/effusion status (0.83, p=0.003) and change (0.73, p=0.017) (Table 1). In exercise 4 Wilcoxon signed-rank test showed significant change in osteitis between timepoints using WIPE hip/pelvis and SRM was large (1.23), while lower for WIPE synovitis/effusion and HIMRISS.Table 1.MRI-WIPE hip/pelvis and HIMRISS interreader reliability for OMERACT exercises 3-4MRI-WIPE hip/pelvisHIMRISSOsteitisSynovitis/effusionOsteitisSynovitis/effusionVariablesNo. patients(cases)Type of scoreMeanscoreICCMeanscoreICCMeanscoreICCMeanscoreICCExercise 39 readers11Status2.3 (0-10)0.69 (0.23-0.93)1.4 (0-4)0.58 (-0.06-0.96)8.2 (1-60)0.84 (0.56-0.99)12.8 (3-25)0.52 (0.00-.91)11Change-0.2 (-1-1)NA-0.2 (-3-1)0.50 (0.10-0.87)-0.35 (-3-1)NA-1.8 (-17-10)0.50 (-0.05-0.89)Exercise 33 readers11Status1.8 (0-10)0.63 (0.46-0.93)1.7 (0-5)0.60 (0.34-0.80)6.6 (0-65)0.88 (0.77-0.94)12.8 (2-28)0.89 (0.87-0.91)11Change-0.12 (-1-1)NA-0.12 (-3-2)0.60 (0.48-0.83)-0.7 (-7-0)NA-1.6 (-21-8)0.78 (0.70-0.87)Exercise 49 readers10 (1-10)Status1.2 (0-4)0.21 (-0.39-0.91)1.1 (0-2)0.19 (-0.31-0.69)1.8 (0-6)0.07 (-0.17-0.83)16.4 (9-23)0.31 (0.00-0.89)10 (11-20)Status1.6 (0-6)0.51 (-0.08-0.99)1 (0-3)0.40 (-0.17-0.88)3.5 (1-8)0,08 (-0.21-0.95)11.2 (5-24)0.49 (0.00-0.94)10 11-20)Change-0.4 (-2-0)NA-0.39 (-2-0)0.22 (-0.68-0.83)-2.2 (-7-2)NA-5.2 (-18-0)0.57 (0.02-0.92)20 (1-20)Status1.4 (0-6)0.41 (-0.35-0.92)1.0 (0-3)0.27 (-0.07-0.75)2.7 (0-9)0.09 (-0.17-0.85)13.8 (5-25)0.45 (0.01-0.90)Exercise 43 readers10 (1-10)Status0.8 (0-4)0.29 (0.01-0.78)1.3 (0-2)-0.02 (-0.29-0.12)0.4 (0-2)-0.04 (-0.04-0.04)15.8 (5-26)0.73 (0.59-0.89)10 (11-20)Status1.8 (0-9)0.65 (0.52-0.76)1.2 (0-4)0.72 (0.62-0.81)1.7 (0-5)0.06 (-0.17-0.35)9.2 (2-26)0.68 (0.53-0.88)10 (11-20)Change-0.6 (-2-0)NA-0.5 (-3-1)0.52 (0.49-0.55)-0.2 (-2-1)NA-2.8 (-19-6)0.85 (0.82-0.88)20 (1-20)Status1.3 (0-9)0.58 (0.43-0.69)1.2 (0-4)0.38 (0.31-0.44)1.0 (0-5)0.10 (-0.09-0.33)12.5 (2-26)0.73 (0.69-0.77)Sum scores and ICCs are mean (range). ICC is 2-way mixed, single measure, by absolute agreement.Conclusion:MRI-WIPE and HIMRISS may be useful tools in modular WB-MRI evaluation of hip/pelvis inflammation in clinical trials in SpA.References:[1]Krabbe S et al. J Rheum. 2019;46(9):1215-21[2]Jaremko JL et al. J Rheum. 2019;46(9)1239-42Acknowledgements:We thank CARE Arthritis Limited (carearthritis.com) for help with setting up the web-based scoring interface, scoring exercises, and the web-based meetings. We acknowledge the contribution of SIG (Special Interest Group) participants at the virtual OMERACT meeting October 29, 2020. HMO, GDM and PGC are supported in part by the National Institute for Health Research (NIHR) Leeds Biomedical Research Centre, United Kingdom. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health.Disclosure of Interests:Marie Wetterslev: None declared, Robert G Lambert Consultant of: Parexel and Pfizer, Walter P Maksymowych Speakers bureau: AbbVie, Janssen, Novartis, Pfizer and UCB, Consultant of: AbbVie, Boehringer Ingelheim, Celgene, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer and UCB, Grant/research support from: AbbVie, Novartis, Pfizer and UCB, Iris Eshed: None declared, Susanne Juhl Pedersen Speakers bureau: MSD, Pfizer, AbbVie, Novartis and UCB, Consultant of: AbbVie and Novartis, Grant/research support from: AbbVie, MSD, and Novartis, Paul Bird Speakers bureau: Janssen, Abbvie, UCB, Celgene, BMS, Novartis, Pfizer, Gilead, Eli-Lilly, Consultant of: Janssen, Abbvie, UCB, Celgene, BMS, Novartis, Pfizer, Gilead, Eli-Lilly, Maria Stoenoiu: None declared, Simon Krabbe: None declared, Ashish Jacob Mathew: None declared, Violaine Foltz: None declared, Frederique Gandjbakhch: None declared, Joel Paschke: None declared, Gabriele De Marco: None declared, Helena Marzo-Ortega Speakers bureau: AbbVie, Celgene, Janssen, Lilly, Novartis, Pfizer, Takeda and UCB, Grant/research support from: Janssen and Novartis, Philippe Carron Speakers bureau: Pfizer, MSD, Novartis, BMS, AbbVie, UCB, Eli Lilly, Gilead and Celgene, Consultant of: Pfizer, MSD, Novartis, BMS, AbbVie, UCB, Eli Lilly, Gilead and Celgene, Grant/research support from: UCB, MSD and Pfizer, Anna Enevold Fløistrup Poulsen: None declared, Jacob L Jaremko: None declared, Philip G Conaghan Speakers bureau: AbbVie, BMS, Eli Lilly, Flexion Therapeutics, Galapagos, Gilead, Novartis, Pfizer, Regeneron, Stryker, Consultant of: AbbVie, BMS, Eli Lilly, Flexion Therapeutics, Galapagos, Gilead, Novartis, Pfizer, Regeneron, Stryker, Mikkel Østergaard Speakers bureau: Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli-Lilly, Hospira, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sandoz, Sanofi and UCB, Consultant of: Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli-Lilly, Hospira, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sandoz, Sanofi and UCB, Grant/research support from: Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli-Lilly, Hospira, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sandoz, Sanofi and UCB

Background:There is no international consensus on the optimal number of slices for evaluation of MRI structural lesions in the SIJ. An “all slice” method evaluates lesions from the most anterior slice, defined as the first slice with vertical height of ≥1cm of the SIJ joint cavity, up to the most posterior slice, defined as the most posterior slice where ≥1cm vertical height of the cartilaginous portion is still visible. The SPARCC method scores the transitional slice between cartilaginous and ligamentous compartments as the first slice and then an additional 4 slices anterior to the transitional slice.Objectives:We aimed to investigate inter-reader reliability, the extent of detection of lesions, and frequency of cases with a positive MRI for structural lesions when using an “all slice” approach versus the SPARCC scoring of 5 central slices.Methods:MRI T1W images with DICOM series were available from 148 cases who had MRI performed in the ASAS-Classification Cohort. Seven central readers recorded MRI lesions in an eCRF that recorded global assessments of presence/absence of changes suggestive of axSpA and structural lesions typical of axSpA. Structural lesions per the ASAS definitions were also recorded in consecutive semicoronal slices using the “all slice” approach, but also recording the transitional slice, according to their presence/absence in SIJ quadrants (erosion, fat lesion, sclerosis) or halves (backfill, ankylosis). Structural lesion frequencies were assessed descriptively according to majority agreement (≥4/7) of central readers and also any 2 central readers. Reliability for detection of MRI lesions was compared between central and local readers using the ICC.Results:The mean (SD) (range) number of anterior and posterior slices peripheral to the 5 central slices was 1.0 (1.0) (0-4) and 2.2 (1.8) (0-6) per case, respectively. There were 2 cases (1.4%) where ≥2 readers scored structural lesions in peripheral slices but not in the 5 central slices. The mean percentage of the total structural lesion score that was captured by the 5 central slices was >75% for all types of lesions except ankylosis (59%) (Table 1). Inter-reader reliability was greater for all lesions when assessing the 5 central slices and especially for erosion and backfill (Table 1).Conclusion:The major component of structural lesion data is captured by assessment of 5 slices, which includes the transitional slice and the subsequent 4 anterior slices. Moreover, reliability for detection of structural lesions is substantially worse in peripheral slices.MRI Lesion“All slice”Central 5 slicesPeripheral slicesP value central vs peripheral slicesP value“all slice” vs central slicesMean (SD) Lesion Score Per CaseErosion2.4 (4.5) (0-22.9)1.8(3.4) (0-17.1)0.6 (1.4) (0-10.1)< 0.001Fat lesion2.5 (5.9) (0-34.0)1.8 (4.5) (0-25.1)0.7 (1.8) (0-9.9)< 0.001Sclerosis2.0 (4.9) (0-39.0)1.5 (3.6) (0-26.1)0.5 (1.5) (0-12.9)< 0.001Backfill0.5 (1.5) (0-12)0.4 (1.2) (0.0-9.3)0.1 (0.4) (0-2.7)< 0.0010.84Ankylosis0.5 (3.4) (0-30.7)0.3 (2.3) (0-20.0)0.2 (1.2) (0-11.3)0.100.18Mean (SD) (Range) % of Total Lesion Score in Central vs Peripheral slicesErosion100%76.4% (28.9%) (0-100%)23.6% (28.9%) (0-100%)NAFat lesion100%75.4% (26.5%) (0-100%)24.6% (26.5%) (0-100%)NASclerosis100%79.5% (22.9%) (0-100%)20.5% (22.9%) (0-100%)NABackfill100%86.0% (20.2%) (0-100%)14.0% (20.2%)(0-100%)NAAnkylosis100%59.0% (36.4%) (0-100%)41.0% (36.4%) (0-100%)0.56NAICC of 7 readers (Mean (SD) (Range))MRI lesionAll slicesCentral 5 slicesPeripheral slicesErosion0.54 (0.15) (0.28-0.84)0.58 (0.13) (0.34-0.85)0.40 (0.17) (0.10-0.66)Fat lesion0.61 (0.18) (0.30-0.89)0.63 (0.16) (0.35-0.88)0.52 (0.20) (0.19-0.82)Sclerosis0.73 (0.18) (0.36-0.94)0.73 (0.16) (0.36-0.91)0.67 (0.19) (0.27-0.94)Backfill0.37 (0.21) (0.10-0.85)0.39 (0.19) (0.14-0.83)0.18 (0.23) (0.0-0.80)Ankylosis0.97 (0.02) (0.91-0.99)0.99 (0.01) (0.97-1.0)0.85 (0.10) (0.62-0.98)Disclosure of Interests:None declared.

Background:Axial spondyloarthritis (axSpA) presents diagnostic challenges incurring a delay of up to a decade and relies considerably on radiographic and MRI evidence of sacroiliitis which has led to the development of classification criteria which also rely on imaging. However, it has been suggested that such criteria may not be appropriate for axSpA patients presenting with other forms of SpA, especially psoriatic, because imaging features may vary in frequency and/or may be atypical. This hypothesis has never been tested in a prospective inception cohort of patients presenting with undiagnosed back pain.Objectives:We aimed to compare the spectrum of radiographic and MRI abnormalities in the sacroiliac joint (SIJ) of an inception cohort of patients presenting with undiagnosed back pain and psoriasis, iritis, and colitis.Methods:We used data from the prospective multicenter Screening for Axial Spondyloarthritis in Psoriasis, Iritis, and Colitis (SASPIC) Study, which is aimed at early detection of axial SpA in patients referred by the respective specialist after first presenting with these disorders. Consecutive patients ≤45 years of age with ≥3 months undiagnosed back pain with any one of psoriasis, AAU, or colitis undergo routine clinical evaluation by a rheumatologist for axial SpA followed by imaging. In SASPIC I, MRI evaluation of the SIJ was ordered per rheumatologist decision. In SASPIC II, MRI evaluation was ordered for all patients. Radiographs and MRI scans were assessed by two central readers and comparisons of the three groups were based on concordant assessments of imaging features. Evaluation of MRI scans included both global assessment for presence/absence of axSpA with confidence scale (-10 to +10), active and structural lesions typical of axSpA per recent ASAS definitions, and granular assessment of individual lesions according to SIJ quadrants and halves in consecutive semicoronal slices through the SIJ. Groups were compared by ANOVA and the chi-square test.Results:A total of 240 patients were recruited, 143 from SASPIC I and 97 from SASPIC II, 101 (42.1%) being diagnosed with axSpA (65.3% male, mean age 34.4 years, mean symptom duration 8.7 years, B27 positive 55.4%). Mean age of colitis (N=101), psoriasis (N=61), iritis (N=78) patients were 33.4, 36.6, 34.3 years, respectively, mean symptom duration was 6.8, 7.2, 9.4 years, respectively, and % males were 45.5%, 52.5%, 51.3%, respectively. There were no significant group differences for unilateral versus bilateral radiographic sacroiliitis and no significant differences in the frequencies, type, or distribution of MRI lesions (Table 1).Conclusion:Data from the SASPIC prospective inception cohort does not support the view that imaging of the SIJ differs in psoriatic axSpA, which appears similar to axSpA associated with iritis or colitis. These data support the umbrella concept of axSpA.Imaging FeatureColitis (n=30)Psoriasis (n=19)Iritis (n=52)P valueUnilateral sacroiliitis (grade ≥2), N(%)1 (3.3%)0 (0%)2 (3.8%)0.69mNY criteria +, N(%)5 (16.7%)6 (31.2%)15 (28.8%)0.39Grade of sacroiliitis, mean(SD)1.8 (2.2)2.1 (2.7)2.2 (2.4)0.76MRI indicative of axSpA, N(%)15 (50.0%)11 (57.9%)32 (61.5%)0.60MRI indicative of axSpA (confidence ≥5/10), N(%)14 (46.7%)10 (52.6%)30 (57.7%)0.63MRI active lesion typical of axSpA, N(%)6 (20.0%)6 (31.6%)18 (34.6%)0.37MRI structural lesion typical of axSpA, N(%)11 (36.7%)7 (36.8%)18 (34.6%)0.98MRI with unilateral lesion (any)2 (6.7%)3 (15.8%)11 (21.2%)0.22MRI with unilateral lesion (BME)1 (3.3%)2 (10.5%)5 (9.6%)0.54MRI with unilateral lesion (Erosion)0 (0%)0 (0%)3 (5.8%)0.23MRI with unilateral lesion (Sclerosis)1 (3.3%)1 (5.3%)3 (5.8%)0.89MRI with unilateral lesion (Fat)0 (0%)0 (0%)0 (0%)NAMRI with iliac lesion17 (56.7%)12 (63.2%)32 (61.5%)0.88MRI with sacral lesion12 (40.0%)11 (57.9%)31 (59.6%)0.21Disclosure of Interests:Walter P Maksymowych Speakers bureau: Abbvie, Janssen, Novartis, Pfizer, UCB, Consultant of: Abbvie, BMS, Boehringer, Galapagos, Gilead, Lilly, Novartis, Pfizer, UCB, Grant/research support from: Abbvie, Novartis, Pfizer, Ulrich Weber: None declared, Jon Chan: None declared, Raj Carmona: None declared, James Yeung: None declared, Sibel Aydin: None declared, Jodie Reis: None declared, Liam Martin: None declared, Ariel Masetto: None declared, Olga Ziouzina: None declared, Dianne Mosher: None declared, Stephanie Keeling: None declared, Sherry Rohekar: None declared, Rana Dadashova: None declared, Joel Paschke: None declared, Amanda Carapellucci: None declared, Robert G Lambert: None declared.

Background:Randomized controlled trials have targeted reducing the size of BML and degree of synovitis for the treatment of OA. We have developed the OMERACT Knee Inflammation MRI Scoring System (KIMRISS) and have recently refined it to maximize reliability and sensitivity to change. Innovations include electronic overlays for assessment of BML in 500 subregions, a web-based interface with direct online scoring, and real-time iterative calibration (RETIC) prior to reading exercises. Synovitis-effusion (S-E) is also scored on all consecutive sagittal slices on a web-based interface.Objectives:We aimed to test the feasibility, reliability, and responsiveness of KIMRISS versus an established method, MOAKS, in two multi-reader exercises.Methods:KIMRISS incorporates web-based graphic overlays for each of femur, tibia, and patella (range 0-500). S-E is recorded as the largest diameter perpendicular to the longest axis of this feature (range 0-100). All scores are pro-rated for a standardized number of MRI slices. In a pre-reading exercise for KIMRISS, readers scored sufficient cases in RETIC to attain scoring proficiency, pre-specified as an ICC of ≥0.80 and ≥0.70 for status and change scores of BML and S-E compared to developer reads. A new web-based scoring platform with overlays designating different subregions for scoring BML was developed for MOAKS. We compared reliability for status and change scores of BML and S-E in 2 international multi-reader exercises of baseline and one-year MRI scans from the Osteoarthritis Initiative: A. 4 expert readers and an OMERACT fellow scored 38 cases selected for MOAKS BML score ≥1. B. 7 expert readers and an OMERACT fellow scored 60 cases selected for MOAKS BML ≥3 and Kellgren-Lawrence (K-L) grade Results:For exercises A/B, subjects were 55.3%/ 26.7% male, mean(±SD) age 61.7(±9.1)/61.9(8.8) years, and radiographic K-L grade ≤2 in 39.4%/100%. Change was small in both exercises (Table 1.KIMRISS and MOAKS scores in Two International Multi-reader ExercisesMethodMRI featureScores mean (SD)SDC(% of max)P valueSRMBaselineOne-year Follow upChangeEXERCISE AMOAKSBML3.6 (2.9)3.4 (2.3)-0.2 (1.9)1.0 (2.2%)0.72-0.11Synovitis-effusion1.3 (0.8)1.5 (0.8)0.2 (0.4)0.4 (13.3%)0.0170.5KIMRISSBML15.7 (13.3)21.2 (22.5)5.5 (15.3)5.6 (1.1%)0.0220.36Synovitis-effusion21.8 (12.0)24.3 (11.9)2.5 (7.4)2.8 (2.8%)0.0430.34EXERCISE BMOAKSBML4.2 (2.6)3.7 (2.4)-0.5 (2.1)1.1 (2.4%)0.083-0.24Synovitis-effusion1.2 (0.7)1.3 (0.8)0.0 (0.5)0.4 (13.3%)0.590.0KIMRISSBML18.0 (17.5)15.9 (14.3)-2.1 (12.3)5.9 (1.2%)0.19-0.17Synovitis-effusion21.8 (9.3)22.9 (10.8)1.1 (7.1)2.2 (2.2%)0.250.15Intra-class Correlation Coefficients (95%CI)MethodMRI featureExercise AExercise BKIMRISS statusKIMRISS changeBML0.86 (0.78-0.92)0.88 (0.81-0.93)0.80 (0.70-0.87)0.72 (0.64-0.80)MOAKS statusMOAKS changeBML0.71 (0.46-0.85)0.76 (0.64-0.85)0.67 (0.56-0.77)0.69 (0.60-0.78)KIMRISS statusKIMRISS changeSynovitis-effusion0.88 (0.81-0.93)0.87 (0.79-0.92)0.75 (0.52-0.86)0.87 (0.82-0.91)MOAKS statusMOAKS changeSynovitis-effusion0.66 (0.4-0.79)0.52 (0.36-0.67)0.65 (0.52-0.75)0.48 (0.37-0.60)Conclusion:The KIMRISS method for scoring BML and Synovitis-Effusion scores highly for feasibility and demonstrates consistently high reliability when compared to MOAKS. Further validation for responsiveness is necessary in cases with greater change in MRI features than in the OAI dataset.Disclosure of Interests:None declared.

Background:There is lack of international consensus as to what defines a structural lesion on MRI of the sacroiliac joints (SIJ) typical of axial spondyloarthritis (axSpA). The ASAS MRI group has generated updated consensus lesion definitions that describe each of the MRI lesions in the SIJ1. These definitions have been evaluated by 7 readers from the ASAS-MRI group on MRI images from the ASAS Classification Cohort.Objectives:We aimed to identify quantitative cut-offs based on numbers of slices and SIJ quadrants that define a positive MRI for structural lesions typical of axSpA, the gold standard being majority central reader decision as to the presence of a structural lesion typical of axSpA with high confidence.Methods:MRI structural lesions meeting ASAS definitions were recorded in an eCRF that comprises global assessment (structural lesion typical of axSpA present/absent and degree of confidence (-4 (absent) to +4 (present)), and detailed scoring of lesions per SIJ quadrant. Detailed scoring was based only on assessment of DICOM images (n =148). We calculated sensitivity and specificity for numbers of SIJ quadrants and consecutive slices with erosion, sclerosis, and fat lesions where a majority of readers (≥4/7) agreed as to the presence of a structural lesion typical of axSpA with high confidence (≥ +3). We tested candidate lesion definitions for predictive diagnostic utility in cases assessed after 4.4 years of follow up by the local rheumatologist.Results:Structural lesions typical of axSpA were observed by majority read in 33 (32.4%) of 102 cases diagnosed with axSpA, and 3 (6.8%) of 44 cases without axSpA and 29 cases were assigned a high degree of confidence (≥ +3) by a majority of readers. Cut-offs achieving specificity of 95% were erosion in ≥2 consecutive slices (sensitivity 83%), erosion ≥3 SIJ quadrants (sensitivity 90%), and fat lesion (≥1cm horizontal depth) in ≥1 SIJ quadrant (sensitivity 59%) (Table). These had very high positive predictive values (>95%) for diagnosis of axSpA in cases diagnosed by the rheumatologist after 4.4 years follow up.Conclusion:ASAS-defined erosion in ≥2 consecutive slices or in ≥3 SIJ quadrants and ASAS-defined fat lesion with depth >1cm in ≥1 SIJ quadrant are high priority candidates for defining an MRI structural lesion typical of axSpA. This will require similar assessment in additional axSpA cohorts.References:[1]Maksymowych et al. Ann Rheum Dis 2019; 78:1550-8.Table 1.Majority readers agree structural lesion indicative of axSpA is present with confidence ≥3/4 is the gold-standard external referenceSensitivitySpecificityErosion Score ≥1 SIJ qdr93.1 (77.2-99.2)80.6 (72.4-87.3)Erosion Score ≥2 SIJ qdr93.1 (77.2-99.2)90.8 (84.1-95.3)Erosion Score ≥3 SIJ qdr89.7 (72.6-97.8)95.8 (90.5-98.6)Erosion in 2 consecutive slices82.8 (64.2-94.2)95.0 (89.3-98.1)Fat lesion ≥1 SIJ qdr82.8 (64.2-94.2)81.5 (73.4-88.0)Fat lesion ≥2 SIJ qdr69.0 (49.2-84.7)86.6 (79.1-92.1)Fat lesion ≥3 SIJ qdr62.1 (42.3-79.3)91.6 (85.1-95.9)Fat lesion in 2 consecutive slices55.2 (35.7-73.6)93.3 (87.2-97.1)Fat lesion (>1cm depth) ≥158.6 (38.9-76.5)95.0 (89.3-98.1)Fat lesion (>1cm depth) ≥255.2 (35.7-73.6)95.8 (90.5-98.6)Fat lesion (>1cm depth) ≥351.7 (32.5-70.6)97.5 (92.8-99.5)Fat lesion (>1cm depth) in 2 consecutive slices48.3 (29.4-67.5)97.5 (92.8-99.5)Table. SIJ qdr: sacroiliac joint quadrantDisclosure of Interests:Walter P. Maksymowych Grant/research support from: AbbVie, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Boehringer Ingelheim, Celgene, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer, and UCB, Employee of: Chief Medical Officer of CARE Arthritis Limited, Speakers bureau: AbbVie, Janssen, Novartis, Pfizer, and UCB, Xenofon Baraliakos: None declared, Ulrich Weber: None declared, Pedro M Machado Consultant of: PMM: Abbvie, Celgene, Janssen, Lilly, MSD, Novartis, Pfizer, Roche and UCB, Speakers bureau: PMM: Abbvie, BMS, Lilly, MSD, Novartis, Pfizer, Roche and UCB, Susanne Juhl Pedersen Grant/research support from: 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, Stephanie Wichuk: None declared, 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, Martin Rudwaleit Consultant of: AbbVie, BMS, Celgene, Janssen, Eli Lilly, MSD, Novartis, Pfizer, Roche, UCB Pharma, Désirée van der Heijde Consultant of: AbbVie, Amgen, Astellas, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Cyxone, Daiichi, Eisai, Eli-Lilly, Galapagos, Gilead Sciences, Inc., Glaxo-Smith-Kline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, UCB Pharma; Director of Imaging Rheumatology BV, Robert B.M. Landewé Consultant of: AbbVie; AstraZeneca; Bristol-Myers Squibb; Eli Lilly & Co.; Galapagos NV; Novartis; Pfizer; UCB Pharma, Joel Paschke: None declared, Robert G Lambert: None declared, Mikkel Ǿstergaard Grant/research support from: AbbVie, Bristol-Myers Squibb, Celgene, Merck, and Novartis, Consultant of: AbbVie, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Hospira, Janssen, Merck, Novartis, Novo Nordisk, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi, and UCB, Speakers bureau: AbbVie, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Hospira, Janssen, Merck, Novartis, Novo Nordisk, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi, and UCB

Background: Several cohorts have reported the performance of the aSAS classification criteria in settings where clinical, radiographic, and MRI features have been simultaneously incorporated into the diagnostic evaluation in arriving at a gold standard for the testing of the criteria. MRI improves diagnostic precision but access is limited and it is therefore still important to understand how the criteria perform in a setting where diagnostic evaluation can be conducted sequentially before and after MRI assessment. We hypothesized that the aSAS criteria would demonstrate enhanced specificity when MRI is available due to enhanced diagnostic precision. Objectives: We aimed to test the impact of adding MRI to the diagnostic evaluation on the performance of the classification criteria in unselected patients referred with undiagnosed back pain who have presented with acute anterior uveitis (AAU), psoriasis, or colitis to their respective specialists. Methods: Consecutive patients ≤45 years of age with ≥3 months undiagnosed back pain with any one of psoriasis, acute anterior uveitis (AAU), or colitis undergo routine clinical evaluation by a rheumatologist for axial SpA and MRI evaluation is ordered per rheumatologist decision. The rheumatologist determines the presence or absence of axial SpA and the degree of confidence in the diagnosis (-10 (definitely not SpA) to +10 (definite SpA)) at 3 consecutive stages: 1. After the clinical evaluation; 2. After the results of labs (B27, CRP) and radiography; 3. After the results of MRI evaluation. We calculated the sensitivity and specificity of the aSAS criteria and the component imaging and clinical arms using the stage 2 and 3 diagnostic assessments by the local rheumatologist as gold standard. Results: A total of 246 patients were recruited, 47.6% being diagnosed with axSpA (61.5% male, age 33.7 years, symptom duration 7.6 years, B27 positive 52.1%), after final diagnostic evaluation. Sensitivity/specificity of the aSAS criteria, imaging arm, clinical arm after stage 2 diagnostic evaluation for the entire cohort were 67.4/85.7%, 39.7/95.2%, 48.9/87.6%, respectively (Table). For the subset of 146 patients who had MRI and had diagnostic evaluation at both stage 2 (pre-MRI) and stage 3 (post-MRI), sensitivity of the criteria was greater but specificity was lower when tested against the stage 3 diagnosis. This was particularly apparent in the clinical arm. Conclusion: The aSAS criteria were less specific when MRI assessment was added to the process of diagnostic evaluation, which could reflect rheumatologist over-interpretation of both clinical and radiographic findings in this population with higher pre-test probability of axSpA. Disclosure of interests: Walter P Maksymowych Grant/research support from: abbVie, Pfizer, Janssen, Novartis, Consultant for: abbVie, Eli Lilly, Boehringer, Galapagos, Janssen, Novartis, Pfizer and UCB Pharma; Chief Medical officer for Canadian Research and Education arthritis, Raj Carmona Grant/research support from: amgen, abbvie, Jannsen, Consultant for: amgen, abbvie, BMS, Eli Lilly, Merck, Novartis, Jannsen, Takeda, UCB, James Yeung: None declared, Jon Chan Grant/research support from: Janssen, UCB, Novartis, Pfizer, Celgene, Consultant for: amgen, Celgene, Eli Lilly, Janssen, amgen, abbvie, Novartis, Pfizer, UCB, Sandoz, Merck, Liam Martin: None declared, Sibel aydin Consultant for: abbvie, Celgene, UCB, Novartis, Jannsen, Sanofi, Dianne Mosher: None declared, ariel Masetto Grant/research support from: amgen, Sanofi, Consultant for: Sanofi, Pfizer, Bristol-Myers Squibb, Novartis, Boehringer ingelheim, Speakers bureau: Novartis, Stephanie Keeling Consultant for: abbVie. Pfizer, Eli Lily, Janssen, amgen, astrzeeneca, UCB., Olga Ziouzina: None declared, Sherry Rohekar Consultant for: abbvie, amgen, BMS, Celgene, Eli-Lilly, Janssen, Merck, Novartis, Pfizer, Roche, Sanofi, UCB, Joel Paschke: None declared, amanda Carapellucci: None declared, Robert G Lambert Consultant for: Bioclinica, Parexel, abbvie

Background: Early diagnosis of rheumatoid arthritis (RA) is hampered by suboptimal accuracy of currently available serological biomarkers. Recent advancements in metabolomic profiling include liquid chromatography mass spectrometry (LC-MS) and in-depth profiling of amine/phenol and carboxyl submetabolomes, resulting in 1000-fold increase in detection sensitivity, and universal metabolome-standard methodology to facilitate metabolome comparisons among different data sets. Objectives: We aimed to identify a metabolite signature with consistently high accuracy for RA. Methods: Sera from 2 RA cohorts were analyzed: Cohort A samples were from 50 RA patients, 39 female (mean age 49.9), 11 male (mean age 47.8), symptom duration 3.7, naive to b-DMARD, and 50 age and sex-matched healthy controls. Cohort B samples were from 50 RA patients, 40 female (mean age 53.4), 10 male (mean age 57.2), symptom duration Results: A total of 3415 amine/phenol and 2114 carboxyl metabolites were commonly detected in more than 80% of the samples. For amine/phenol submetabolome profiling, partial least squares discriminant analysis (PLSDA) showed a clear separation of the groups for each cohort (R2=0.98;Q2=0.92 for cohort A and R2=0.93;Q2=0.79 for cohort B). Similarly, for carboxyl submetabolome profiling, a clear separation between RA and controls was demonstrable (R2=0.93;Q2=0.80 for cohort A and R2=0.84;Q2=0.55 for cohort B). 13 positively identified amine/phenol-containing metabolites, including o-phosphoethanolamine and glycyl-valine, were both significant in cohort A and cohort B, and each of these metabolites showed similar fold changes between RA and controls for both cohorts. 5 carboxyl-containing metabolites, with 1 positively identified, azelaic acid, and 4 unidentified, were both significant in 2 cohorts. The ROC AUC (95%CI) of the 13 amine/phenol-containing metabolite panel were 0.99 (0.94-1.00), 0.98 (0.92-1.00) and 0.98 (0.95-1.00) for cohort A and cohort B (pre- and post-treatment), respectively, with sensitivity/specificity of 94%/96%, 94%/95%, 94%/94%. The ROC AUC (95%CI) of the 5 carboxyl metabolite panel were 0.92 (0.86-0.97), 0.96 (0.91-0.99), 0.89 (0.82-0.95), respectively, with sensitivity/specificity of 86%/86%, 90%/91%, 80%/80%. The combined panel of 18 metabolites demonstrated ROC AUC>0.99 with sensitivity and specificity>95% for each cohort. None of these biomarker metabolites correlated with age, gender, or symptom duration. Conclusion: Consistent discrimination in metabolite profiles between discovery and verification cohorts generated high priority candidates for further biomarker validation in RA. Disclosure of Interests: Xiaohang Wang: None declared, Joel Paschke: None declared, Rana Dadashova: None declared, Edna Hutchings: None declared, Liang Li: None declared, Walter P Maksymowych Grant/research support from: AbbVie, Pfizer, Janssen, Novartis, Consultant for: AbbVie, Eli Lilly, Boehringer, Galapagos, Janssen, Novartis, Pfizer and UCB Pharma; Chief Medical Officer for Canadian Research and Education Arthritis

Background Follow up of the ASAS Classification Cohort (CC) indicated a high positive predictive value for the ASAS classification criteria derived from baseline patient and imaging data1. Moreover, diagnosis of axSpA was changed by the rheumatologist in only 11.2% of patients after 4.4 years. This has raised potential concerns regarding diagnostic ascertainment bias. Objectives To determine the evolution of MRI features of axSpA in ASAS-CC cases by central readers, whether this reflects diagnostic assignment by the rheumatologist, and the predictive utility of baseline MRI features of axSpA. Methods MR images were available from 108 cases in the ASAS-CC at baseline and follow up (mean 4.4 years) and also had a rheumatologist diagnosis at both time points. Eight readers from the ASAS MRI group recorded MRI lesions that comprised global assessment (MRI indicative of axSpA (yes/no), active and/or structural lesion typical of axSpA (yes/no) according to ASAS definitions), ASAS definition of positive MRI, and detailed scoring of lesions per SIJ quadrant (SPARCC SIJ method). MRI data from ≥2 readers and from the majority of readers (≥5/8) was used to calculate positive and negative predictive values (PPV, NPV). Results MRI was considered diagnostic of axSpA in 52/108 (48.1%) cases at baseline and in 47/86 (54.7%) diagnosed at baseline as axSpA by the rheumatologist. Change in MRI diagnosis was recorded in 10/108 (9.3%) of cases (2 from yes to no, and 4 from no to yes for axSpA) according to agreement by ≥2 readers and in only 3 cases according to ≥5/8 readers (Table 1). Change in rheumatologist diagnosis was recorded in 9/108 (8.3%), 2 of which had a change in MRI diagnosis. Baseline MRI lesions considered typical of axSpA had very high PPV for follow up diagnosis of axSpA (Table 2). Conclusion The infrequent change in diagnostic ascertainment of rheumatologists over follow up of the ASAS-CC is supported by this central reader evaluation of MRI scans. A positive MRI at baseline had very high PPV for a follow up diagnosis of axSpA. Reference [1] Sepriano et al. ARD 2016;75:1034-42 Disclosure of Interests Walter P Maksymowych Grant/research support from: AbbVie, Pfizer, Janssen, Novartis, Consultant for: AbbVie, Eli Lilly, Boehringer, Galapagos, Janssen, Novartis, Pfizer and UCB Pharma; Chief Medical Officer for Canadian Research and Education Arthritis, Xenofon Baraliakos Grant/research support from: AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Centocor, Chugai, Janssen, MSD, Novartis, Pfizer Inc, Roche and UCB, Grant/research support from: AbbVie, Pfizer, Merck Sharp & Dohme, UCB Pharma, Novartis, Consultant for: AbbVie, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Chugai, Janssen Biologics, Novartis, Pfizer, UCB Pharma, Galapagos, Speakers bureau: AbbVie, Chugai, Janssen, Novartis, Pfizer, UCB Pharma, Manouk de Hooge: None declared, Iris Eshed: None declared, Susanne Juhl Pedersen: None declared, Ulrich Weber Consultant for: Abbvie, Joachim Sieper Consultant for: Abbvie, Bohringer Ingelheim, Janssen, Lilly, Merck, Mylan, Novartis, Pfizer, UCB., Speakers bureau: Abbvie, Bohringer Ingelheim, Janssen, Lilly, Merck, Mylan, Novartis, Pfizer, UCB., Stephanie Wichuk: None declared, Denis Poddubnyy Grant/research support from: AbbVie, Merck Sharp & Dohme, Novartis, Consultant for: AbbVie, Bristol-Myers Squibb, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, UCB Pharma, Speakers bureau: AbbVie, Bristol-Myers Squibb, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, Roche, UCB Pharma, Joel Paschke: None declared, Robert G Lambert Consultant for: Bioclinica, Parexel, Abbvie, Mikkel Ǿstergaard Grant/research support from: Abbvie, Celgene, Centocor, Merck, Novartis, Consultant for: Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli Lilly, Hospira, Janssen, Merck, Novartis, Novo, Orion, Pfizer, Regeneron, Roche, and UCB, Speakers bureau: Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli Lilly, Hospira, Janssen, Merck, Novartis, Novo, Orion, Pfizer, Regeneron, Roche, and UCB

Background The association between disease activity and spinal radiographic progression in radiographic axial spondyloarthritis (r-axSpA) has been previously shown in a cohort of patients (pts) not being treated with TNF inhibitors (TNFi).1 Objectives To test the possible association between disease activity and spinal radiographic progression in r-axSpA in a real-life cohort, also including patients treated with TNFi. Methods Pts with axial spondyloarthritis (axSpA) fulfilling the modified New York criteria (mNY) were included in this prospective, observational cohort (ALBERTA FORCAST). Clinical and imaging data were collected at baseline and every 2 years up to 10 years of follow-up. Radiographs of the spine were independently scored by 2 central readers and one adjudicator (if disagreement), with known chronological order but blinded to clinical data, using the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). To be included, pts had to have ≥ one 2-year interval with data on mSASSS from ≥1 reader available as well as complete data on ASDAS and TNFi exposure at the start of the interval. The association between ASDAS at the start of the interval (t) and mSASSS 2 years later (t+1) was tested in two types of longitudinal GEE models: i. multilevel (2 readers) model with the individual reader scores as outcome (2-level models); ii. Using as outcome averaged scores between readers (1-level models). Both type of models were adjusted for mSASSS at t (autoregression) and for a set of potential confounders defined a priori on clinical grounds (Figure). Results In total, 314 pts (442 intervals) were included [74% males, mean symptom duration 17.8 (SD 11.7) years, 83% HLA-B27 positive and 7% previously treated with ≥1 TNFi]. At baseline the mean ASDAS was 2.7 (1.3) and the mean mSASSS 13.8 (18.9). During follow-up 213 (68%) pts received treatment with TNFi in ≥1 visit. Overall, the average 2-year progression was 1.33 (2.68) mSASSS-units per 2-year interval. In the 2-level multivariable model, 1 ASDAS-unit increase at t was associated with an increase of 0.25 mSASSS-units at t+1 [β (95% CI): 0.25 (95%CI 0.10; 0.41)] (Figure). Results were similar using the averaged mSASSS as the outcome [β (95% CI): 0.25 (0.08; 0.43)]. Conclusion These data add to previous evidence by showing that a higher ASDAS is associated with higher spinal radiographic progression in pts with r-axSpA independent of prior treatment with TNFi. Reference [1] Ramiro S, et al. Ann Rheum Dis2014;73:1455–61. Disclosure of Interests Alexandre Sepriano: None declared, Sofia Ramiro Grant/research support from: MSD, Consultant for: AbbVie, Lilly, MSD, Novartis, Pfizer, Sanofi, Speakers bureau: AbbVie, Lilly, MSD, Novartis, Pfizer, Sanofi, Stephanie Wichuk: None declared, Praveena Chiowchanwisawakit: None declared, Terrie MacCosham: None declared, Joel Paschke: None declared, Desiree van der Heijde Consultant for: AbbVie, Amgen, Astellas, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Daiichi, Eli-Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, Union Chimique Belge, Robert B.M. Landewe: None declared, Walter P. Maksymowych Grant/research support from: Abbvie, Novartis, Pfizer, Consultant for: Abbvie, Boehringer, Celgene, Galapagos, Lilly, Novartis, Pfizer, UCB, Speakers bureau: Abbvie, Boehringer, Celgene, Galapagos, Lilly, Novartis, Pfizer, UCB

Background: Although MRI of the sacroiliac joints (SIJ) is the most sensitive imaging modality for early diagnosis of axial spondyloarthritis (axSpA) it is costly and not readily available. Therefore, clinicians still rely primarily on radiography. The relative degree to which radiography and MRI changes diagnostic ascertainment of axSpA in patients presenting with undiagnosed back pain has not been formally studied. Objectives: We aimed to assess the relative impact of radiography and MRI evaluation on diagnostic ascertainment of axial SpA in patients presenting with undiagnosed back pain to rheumatologists, and the impact of central evaluation. Methods: The multicenter Screening for Axial Spondyloarthritis in Psoriasis, Iritis, and Colitis (SASPIC) Study is aimed at early detection of axial SpA. Consecutive patients ≤45 years of age with ≥3 months undiagnosed back pain with any one of psoriasis, acute anterior uveitis (AAU), or colitis undergo routine clinical evaluation by a rheumatologist for axial SpA and MRI evaluation is ordered per rheumatologist decision. The rheumatologist determines the presence or absence of axial SpA at 3 consecutive stages: 1. After the clinical evaluation; 2. After the results of labs (B27, CRP) and radiography; 3. After the results of MRI evaluation. The eCRF, radiographs, and MRI scans were also assessed centrally. Results: The SASPIC cohort comprises 246 patients (52.4% male, mean age 34.5 years, mean symptom duration 7.3 years, mean back pain duration 7.1 years, B27+ 36.2%) referred with AAU (29.7%), psoriasis (18.7%), Crohn’s colitis (31.3%), ulcerative colitis (20.3%). MRI was conducted in 149 patients. The number of patients diagnosed with axSpA by the local rheumatologist decreased after radiography and then decreased further after MRI while confidence in the diagnosis progressively increased (Table 1). After central evaluation of all patient data, the number of patients diagnosed with axSpA decreased substantially compared to assessment by local readers (Table 2). Conclusion: In a setting of undiagnosed back pain and higher risk for axial SpA, imaging is primarily helpful in ruling out SpA and reducing false positives. Despite this, central evaluation raises concerns regarding ascertainment of false positive SpA in routine practice. Disclosure of Interests: Walter P Maksymowych Grant/research support from: AbbVie, Pfizer, Janssen, Novartis, Consultant for: AbbVie, Eli Lilly, Boehringer, Galapagos, Janssen, Novartis, Pfizer and UCB Pharma; Chief Medical Officer for Canadian Research and Education Arthritis, Raj Carmona Grant/research support from: Amgen, Abbvie, Jannsen, Consultant for: Amgen, Abbvie, BMS, Eli Lilly, Merck, Novartis, Jannsen, Takeda, UCB, James Yeung: None declared, Jon Chan Grant/research support from: Janssen, UCB, Novartis, Pfizer, Celgene, Consultant for: Amgen, Celgene, Eli Lilly, Janssen, Amgen, Abbvie, Novartis, Pfizer, UCB, Sandoz, Merck, Liam Martin: None declared, Sibel Aydin Consultant for: Abbvie, Celgene, UCB, Novartis, Jannsen, Sanofi, Dianne Mosher: None declared, Ariel Masetto Grant/research support from: Amgen, Sanofi, Consultant for: Sanofi, Pfizer, Bristol-Myers Squibb, Novartis, Boehringer Ingelheim, Speakers bureau: Novartis, Stephanie Keeling Consultant for: AbbVie. Pfizer, Eli Lily, Janssen, Amgen, Astrzeeneca, UCB., Olga Ziouzina: None declared, Sherry Rohekar Consultant for: Abbvie, Amgen, BMS, Celgene, Eli-Lilly, Janssen, Merck, Novartis, Pfizer, Roche, Sanofi, UCB, Joel Paschke: None declared, Amanda Carapellucci: None declared, Robert G Lambert Consultant for: Bioclinica, Parexel, Abbvie

Background Recent observational data suggest that TNFi reduce spinal radiographic progression in radiographic axial spondyloarthritis (r-axSpA) mostly by inhibiting disease activity1. Yet, resolution on the controversial effect of TNFi on structural progression is yet to be achieved. Objectives To investigate whether in r-axSpA TNFi have an indirect (through ASDAS) and/or direct effect on spinal radiographic progression. Methods Patients (pts) with axial spondyloarthritis (axSpA) fulfilling the modified New York criteria (mNY) were included in this prospective, observational cohort (ALBERTA FORCAST). Clinical and imaging data were collected at baseline and every 2 years up to 10 years of follow-up. Radiographs of the spine were independently scored by 2 central readers and one adjudicator (if disagreement), with known chronological order but blinded to clinical data, using the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). The indirect effect of TNFi on mSASSS progression was evaluated by testing the interaction between TNFi and ASDAS at the start of each 2-year interval (t). If significant (p Results In total, 314 pts were included [74% males, mean symptom duration 17.8 (SD 11.7) years, 83% HLA-B27 positive and 7% previously treated with ≥1 TNFi]. The interaction between ASDAS and TNFi at t was significant (p=0.10). A gradient was seen for the effect of ASDAS at t on mSASSS at t+1, which was more than 2 times higher in patients never treated with TNFi (β (95% CI): 0.41 (0.13; 0.68) compared to those always treated [β (95% CI): 0.16 (0.00; 0.31)] (Figure), showing that treatment with TNFi diminishes the effect of ASDAS on mSASSS. In addition to the indirect effect, TNFi also directly associated with less mSASSS progression: Pts receiving TNFi at t had on average 0.87 mSASSS-units less on t+1 compared to those not treated [β (95% CI): -0.85 (-1.35; -0.35)] and this was noted independently of ASDAS. Importantly, this effect remained significant after PS-adjustment [β (95% CI): -0.80 (-1.37; -0.22)]. Conclusion This data is in in agreement with previous evidence showing that treatment with TNFi limits spinal radiographic progression in pts with r-axSpA by decreasing disease activity. Additionally, a direct effect of TNFi reducing mSASSS progression, and independent of ASDAS inflammation, is also seen suggesting that other mechanisms also contribute to the structural effect of TNFi. References [1] Molnar C, et al. Ann Rheum Dis2018;77:63-69. Disclosure of Interests Alexandre Sepriano: None declared, Sofia Ramiro Grant/research support from: MSD, Consultant for: AbbVie, Lilly, MSD, Novartis, Pfizer, Sanofi, Speakers bureau: AbbVie, Lilly, MSD, Novartis, Pfizer, Sanofi, Stephanie Wichuk: None declared, Praveena Chiowchanwisawakit: None declared, Terrie MacCosham: None declared, Joel Paschke: None declared, Desiree van der Heijde Consultant for: AbbVie, Amgen, Astellas, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Daiichi, Eli-Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, Union Chimique Belge, Robert B.M. Landewe: None declared, Walter P. Maksymowych Grant/research support from: Abbvie, Novartis, Pfizer, Consultant for: Abbvie, Boehringer, Celgene, Galapagos, Lilly, Novartis, Pfizer, UCB, Speakers bureau: Abbvie, Boehringer, Celgene, Galapagos, Lilly, Novartis, Pfizer, UCB

Background: The ASAS MRI group has generated updated lesion definitions for MRI lesions in the SIJ. While the ASAS definition of a positive MRI for classification purposes remains unchanged, these additional ASAS definitions for active and structural lesions may also be of diagnostic value. It is important to understand their relative contribution and complementarity as diagnostic indicators. Objectives: To determine optimal cut-offs for the number of SIJ quadrants with MRI lesions reflecting diagnosis of axSpA in patients with undiagnosed back pain. Methods: MRI lesions on baseline scans from the ASAS Classification Cohort were recorded by 7 experienced readers from the ASAS-MRI group. Detailed scoring of lesions per SIJ quadrant (SPARCC SIJ quadrantic method) was available for assessment of bone marrow edema (BME) and structural lesions in 158 and 146 cases, respectively, who were diagnosed by the local rheumatologist at baseline. Of these, 86 and 79 cases with BME and structural lesion data, respectively, were also diagnosed by the local rheumatologist at follow up (mean 4.4 years). We calculated sensitivity and specificity for varying numbers of SIJ quadrants with MRI lesions with rheumatologist diagnosis of axSpA at baseline and follow up as gold standard. Results: Lesion cut-offs based on BME were most sensitive for diagnosis at baseline and follow up but erosion- and fatty-lesion cut-offs were more specific (Table). At least 2 SIJ quadrants with erosion or fat metaplasia were associated with >90% specificity for the diagnosis of axSpA. There was also a consistent improvement in the sensitivity and specificity performance of cut-offs based on erosions and fatty lesions according to diagnosis at baseline and at follow up after 4.4 years but not for cut-offs based on BME. Lesion cut-offs that combined BME and/or erosion enhanced sensitivity without compromising specificity. Conclusion: The updated ASAS definitions based on the presence of MRI lesions in 2-3 SIJ quadrants have comparable diagnostic performance. This performance improves for erosion and fatty lesion cut-offs after follow up. Disclosure of Interests: Walter P Maksymowych Grant/research support from: AbbVie, Pfizer, Janssen, Novartis, Consultant for: AbbVie, Eli Lilly, Boehringer, Galapagos, Janssen, Novartis, Pfizer and UCB Pharma; Chief Medical Officer for Canadian Research and Education Arthritis, Robert G Lambert Consultant for: Bioclinica, Parexel, Abbvie, Xenofon Baraliakos Grant/research support from: AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Centocor, Chugai, Janssen, MSD, Novartis, Pfizer Inc, Roche and UCB, Grant/research support from: AbbVie, Pfizer, Merck Sharp & Dohme, UCB Pharma, Novartis, Consultant for: AbbVie, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Chugai, Janssen Biologics, Novartis, Pfizer, UCB Pharma, Galapagos, Speakers bureau: AbbVie, Chugai, Janssen, Novartis, Pfizer, UCB Pharma, Susanne Juhl Pedersen: None declared, Pedro Machado Consultant for: Abbvie, BMS, Celgene, Janssen, MSD, Novartis, Pfizer, Roche and UCB, Speakers bureau: Abbvie, BMS, Celgene, Janssen, MSD, Novartis, Pfizer, Roche and UCB, Joachim Sieper Consultant for: Abbvie, Bohringer Ingelheim, Janssen, Lilly, Merck, Mylan, Novartis, Pfizer, UCB., Speakers bureau: Abbvie, Bohringer Ingelheim, Janssen, Lilly, Merck, Mylan, Novartis, Pfizer, UCB., Stephanie Wichuk: None declared, Denis Poddubnyy Grant/research support from: AbbVie, Merck Sharp & Dohme, Novartis, Consultant for: AbbVie, Bristol-Myers Squibb, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, UCB Pharma, Speakers bureau: AbbVie, Bristol-Myers Squibb, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, Roche, UCB Pharma, Joel Paschke: None declared, Mikkel Ǿstergaard Grant/research support from: Abbvie, Celgene, Centocor, Merck, Novartis, Consultant for: Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli Lilly, Hospira, Janssen, Merck, Novartis, Novo, Orion, Pfizer, Regeneron, Roche, and UCB, Speakers bureau: Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli Lilly, Hospira, Janssen, Merck, Novartis, Novo, Orion, Pfizer, Regeneron, Roche, and UCB, Ulrich Weber Consultant for: Abbvie

Background There has been no central reader evaluation of MRI scans from the ASAS Classification Cohort (ASAS-CC)1 to compare detection of lesions in the sacroiliac joints (SIJ) between central and ASAS-CC local site readers. Active MRI lesions typical of axSpA were reported in 61.6% and 2.2% of patients from this cohort diagnosed with axSpA and non-axSpA back pain, respectively1. Structural lesions were recorded but not reported in the literature. Objectives We aimed to compare detection of active and structural lesions on MRI images of the SIJ from the ASAS-CC between ASAS-CC local site readers and central readers from the ASAS-MRI group. Methods MRI images were available from 258 of the 495 cases who had MRI performed in the ASAS-CC and also had a local rheumatologist diagnosis. Seven central readers recorded MRI lesions in an eCRF that included wording of lesions defining active and structural lesions typical of axSpA that was exactly the same as in the original ASAS-CC eCRF permitting comparisons between central and local site readers. In addition, lesions that met the criteria for an ASAS positive MRI were recorded by central readers. Active and structural lesion frequencies were assessed descriptively according to majority agreement (=4/7) of central reader data and also any 2 central readers. Reliability of detection of MRI lesions was compared between central and local readers using the kappa coefficient. Results Significant differences in lesion frequencies were observed according to diagnostic category (Table 1). The frequency of active lesions reported by local readers (61%)was greater than for central readers that agreed on the presence of an active lesion (49.7%). Structural lesions were reported less frequently by local readers (44.0%) compared to central readers that agreed on the presence of a structural lesion (54.9%). Reliability of local readers for detection of active lesions was good but only fair for structural lesions (Table 2). Conclusion Local readers may have overestimated the presence of active lesions and underestimated the presence of structural lesions in the ASAS-CC. Their reliability for detection of structural lesions was limited which could reflect lack of awareness of structural lesions related to axSpA. References [1] Rudwaleit et al. Ann Rheum Dis 2009;68: 777-83 Disclosure of Interests Walter P Maksymowych Grant/research support from: AbbVie, Pfizer, Janssen, Novartis, Consultant for: AbbVie, Eli Lilly, Boehringer, Galapagos, Janssen, Novartis, Pfizer and UCB Pharma; Chief Medical Officer for Canadian Research and Education Arthritis, Xenofon Baraliakos Grant/research support from: AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Centocor, Chugai, Janssen, MSD, Novartis, Pfizer Inc, Roche and UCB, Grant/research support from: AbbVie, Pfizer, Merck Sharp & Dohme, UCB Pharma, Novartis, Consultant for: AbbVie, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Chugai, Janssen Biologics, Novartis, Pfizer, UCB Pharma, Galapagos, Speakers bureau: AbbVie, Chugai, Janssen, Novartis, Pfizer, UCB Pharma, Robert G Lambert Consultant for: Bioclinica, Parexel, Abbvie, Ulrich Weber Consultant for: Abbvie, Joachim Sieper Consultant for: Abbvie, Bhringer Ingelheim, Janssen, Lilly, Merck, Mylan, Novartis, Pfizer, UCB., Speakers bureau: Abbvie, Bhringer Ingelheim, Janssen, Lilly, Merck, Mylan, Novartis, Pfizer, UCB., Stephanie Wichuk: None declared, Denis Poddubnyy Grant/research support from: AbbVie, Merck Sharp & Dohme, Novartis, Consultant for: AbbVie, Bristol-Myers Squibb, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, UCB Pharma, Speakers bureau: AbbVie, Bristol-Myers Squibb, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, Roche, UCB Pharma, Mikkel ?stergaard Grant/research support from: Abbvie, Celgene, Centocor, Merck, Novartis, Consultant for: Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli Lilly, Hospira, Janssen, Merck, Novartis, Novo, Orion, Pfizer, Regeneron, Roche, and UCB, Speakers bureau: Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli Lilly, Hospira, Janssen, Merck, Novartis, Novo, Orion, Pfizer, Regeneron, Roche, and UCB, Joel Paschke: None declared, Susanne Juhl Pedersen: None declared, Pedro Machado Consultant for: Abbvie, BMS, Celgene, Janssen, MSD, Novartis, Pfizer, Roche and UCB, Speakers bureau: Abbvie, BMS, Celgene, Janssen, MSD, Novartis, Pfizer, Roche and UCB

Background: Classification criteria for axial spondyloarthritis (axSpA) that capture the spectrum of disease present challenges due to the frequency of back pain, the relative infrequency of axSpA, and limited physical and laboratory findings in early disease. Several cohorts have reported the performance of the ASAS classification criteria in settings where patients have been selected for certain features such as the presence of inflammatory back pain and/or short symptom duration. Objectives: We aimed to test the performance of the ASAS classification criteria in unselected patients referred with undiagnosed back pain who have presented with acute anterior uveitis (AAU), psoriasis, or colitis to their respective specialists and whether performance varied according to demographic factors and symptom severity. Methods: he multicenter Screening for Axial Spondyloarthritis in Psoriasis, Iritis, and Colitis (SASPIC) Study is aimed at early detection of axial SpA. Consecutive patients ≤45 years of age with ≥3 months undiagnosed back pain with any one of psoriasis, acute anterior uveitis (AAU), or colitis undergo routine clinical evaluation by a rheumatologist for axial SpA and MRI evaluation is ordered per rheumatologist decision. The rheumatologist determines the presence or absence of axial SpA and the degree of confidence in the diagnosis (-10 (definitely not SpA) to +10 (definite SpA)) at 3 consecutive stages: 1. After the clinical evaluation; 2. After the results of labs (B27, CRP) and radiography; 3. After the results of MRI evaluation. Assessment of imaging was conducted by local and central readers. We calculated the sensitivity and specificity of the ASAS criteria and the component imaging and clinical arms using the stage 3 diagnostic assessment by the local rheumatologist as gold standard. Results: A total of 246 patients were recruited, 47.6% being diagnosed with axSpA (61.5% male, age 33.7 years, symptom duration 7.6 years, B27 positive 52.1%), after stage 3 evaluation. Sensitivity/specificity of the ASAS criteria, imaging arm, clinical arm were 74.4/79.8%, 55.6/93.8%, 50.4/82.2%, respectively (Table). For patients diagnosed with a high degree of confidence sensitivity/specificity was 87.5/82.7%, 68.8/94.5%, 56.3/84.5%, respectively. Specificity, especially for the clinical arm, was notably higher in patients with a higher degree of back pain (≥5/10), and in those with longer symptom duration (≥5 years). Conclusion: The performance of the ASAS criteria in the SASPIC cohort is comparable to the findings in the original ASAS classification study. Performance may vary according to symptom duration and severity of symptoms which likely impacts diagnostic ascertainment. Disclosure of Interests: Walter P Maksymowych Grant/research support from: AbbVie, Pfizer, Janssen, Novartis, Consultant for: AbbVie, Eli Lilly, Boehringer, Galapagos, Janssen, Novartis, Pfizer and UCB Pharma; Chief Medical Officer for Canadian Research and Education Arthritis, Raj Carmona Grant/research support from: Amgen, Abbvie, Jannsen, Consultant for: Amgen, Abbvie, BMS, Eli Lilly, Merck, Novartis, Jannsen, Takeda, UCB, James Yeung: None declared, Jon Chan Grant/research support from: Janssen, UCB, Novartis, Pfizer, Celgene, Consultant for: Amgen, Celgene, Eli Lilly, Janssen, Amgen, Abbvie, Novartis, Pfizer, UCB, Sandoz, Merck, Liam Martin: None declared, Sibel Aydin Consultant for: Abbvie, Celgene, UCB, Novartis, Jannsen, Sanofi, Dianne Mosher: None declared, Ariel Masetto Grant/research support from: Amgen, Sanofi, Consultant for: Sanofi, Pfizer, Bristol-Myers Squibb, Novartis, Boehringer Ingelheim, Speakers bureau: Novartis, Stephanie Keeling Consultant for: AbbVie. Pfizer, Eli Lily, Janssen, Amgen, Astrzeeneca, UCB., Olga Ziouzina: None declared, Sherry Rohekar Consultant for: Abbvie, Amgen, BMS, Celgene, Eli-Lilly, Janssen, Merck, Novartis, Pfizer, Roche, Sanofi, UCB, Joel Paschke: None declared, Amanda Carapellucci: None declared, Robert G Lambert Consultant for: Bioclinica, Parexel, Abbvie

Background: There is limited prospective data as to the frequency of axial spondyloarthritis (axSpA) in unselected patients referred to rheumatologists with undiagnosed back pain. It is also unclear which clinical features discriminate between axSpA and non-specific causes of back pain that might inform the development of a screening strategy. Objectives: To determine the prevalence of axSpA in unselected patients referred with undiagnosed back pain presenting with AAU, psoriasis, or colitis and determine which clinical characteristics define patients with axSpA. Methods: The multicenter Screening for Axial Spondyloarthritis in Psoriasis, Iritis, and Colitis (SASPIC) Study is aimed at facilitating early detection of axial SpA. First and last patients were recruited on February 2013 and March 2018, respectively. Consecutive patients ≤45 years of age with ≥3 months undiagnosed back pain with any one of psoriasis, AAU, or colitis had routine clinical evaluation by a rheumatologist for axial SpA and MRI evaluation ordered per rheumatologist decision. Differences in clinical characteristics between those who were diagnosed as axSpA or non-specific back pain were analyzed using chi-squared and t-tests. Results: A total of 246 patients were recruited, 47.6% were diagnosed with axSpA, and these included 68.5% of B27 positive patients (Table 1). Diagnosis of axSpA was established in 45.7%, 61.6%, and 40.2% of patients, while ASAS classification criteria were met by 26.1%, 71.2%, and 27.6% of patients with psoriasis, AAU, and IBD, respectively. Features of inflammatory back pain, male gender, and B27 positivity, but not physical measures discriminated axSpA from other causes of back pain (Table 2). Conclusion: Patients with extra-articular manifestations and undiagnosed back pain have a high prevalence of axSpA and referral to a rheumatologist should constitute standard of care, especially if B27 positive. Disclosure of Interests: Walter P Maksymowych Grant/research support from: AbbVie, Pfizer, Janssen, Novartis, Consultant for: AbbVie, Eli Lilly, Boehringer, Galapagos, Janssen, Novartis, Pfizer and UCB Pharma; Chief Medical Officer for Canadian Research and Education Arthritis, Raj Carmona Grant/research support from: Amgen, Abbvie, Jannsen, Consultant for: Amgen, Abbvie, BMS, Eli Lilly, Merck, Novartis, Jannsen, Takeda, UCB, James Yeung: None declared, Jon Chan Grant/research support from: Janssen, UCB, Novartis, Pfizer, Celgene, Consultant for: Amgen, Celgene, Eli Lilly, Janssen, Amgen, Abbvie, Novartis, Pfizer, UCB, Sandoz, Merck, Liam Martin: None declared, Sibel Aydin Consultant for: Abbvie, Celgene, UCB, Novartis, Jannsen, Sanofi, Dianne Mosher: None declared, Ariel Masetto Grant/research support from: Amgen, Sanofi, Consultant for: Sanofi, Pfizer, Bristol-Myers Squibb, Novartis, Boehringer Ingelheim, Speakers bureau: Novartis, Stephanie Keeling Consultant for: AbbVie. Pfizer, Eli Lily, Janssen, Amgen, Astrzeeneca, UCB., Olga Ziouzina: None declared, Sherry Rohekar Consultant for: Abbvie, Amgen, BMS, Celgene, Eli-Lilly, Janssen, Merck, Novartis, Pfizer, Roche, Sanofi, UCB, Joel Paschke: None declared, Amanda Carapellucci: None declared, Robert G Lambert Consultant for: Bioclinica, Parexel, Abbvie

Objective.To develop and validate an enthesitis magnetic resonance imaging (MRI) scoring system for spondyloarthritis/psoriatic arthritis, using the heel as model.Methods.Consensus definitions of key pathologies and 3 heel enthesitis multireader scoring exercises were done, separated by discussion, training, and calibration.Results.Definitions for bone and soft tissue pathologies were agreed. In the final exercise, median pairwise single-measures intraclass correlation coefficients (ICC; patient-level) for entheseal inflammation status/change scores were 0.83/0.82 for all readers. For radiologists and selected rheumatologists, ICC were 0.91/0.84 and quadratic-weighted κ (lesion-level) 0.57–0.91/0.45–0.81.Conclusion.The proposed definitions and Heel Enthesitis Scoring System (HEMRIS) are reliable among trained readers and promising for clinical trials.

Background:Early diagnosis of rheumatoid arthritis (RA) is hampered by suboptimal accuracy of currently available serological biomarkers. Metabolomics may reveal promising biomarker candidates associated with the biomolecular processes of RA. In this work, we applied a high-performance chemical isotope labeling (CIL) LC-MS technique for in-depth profiling of the amine/phenol-submetabolome in serum samples. To avoid false positives and obtain high-confidence biomarker candidates, we analyzed three independent sets of serum samples collected from RA patients and healthy controls to examine the common effects.Objectives:We aimed to identify a metabolite signature with consistently high accuracy for RA.Methods:Serum samples were taken from 3 RA cohorts, which comprised 50, 49, and 131 RA patients, respectively. Within each cohort, there were sex/age-matched healthy controls: 50 in Cohort 1, 50 in Cohort 2, and 100 in Cohort 3. Among these 446 subjects, 75% were females and the average age was 52.5 years. Amine/phenol-containing metabolites were labeled by12C-dansyl chloride to improve the LC-MS detection. For each cohort, a pooled sample was prepared and labeled by13C-dansyl group to serve as the reference sample for relative quantification. Then the individual samples and the pooled sample were mixed 1:1. Finally, an LC-QTOF-MS platform analyzed the mixtures and output the intensity ratios of12C/13C peak pairs.Results:1,149 amine/phenol-containing metabolites were commonly detected across the three sample sets. Among them, 134 were positively identified by our dansyl-labeling standard library, and 141 were matched to predicted retention times and mass values of dansyl-labeled human metabolites. Visualized by the partial least squares discriminant analysis (PLS-DA), the overall amine/phenol-submetabolome demonstrated clear and consistent differences between healthy controls and the RA groups, with cross-validation Q2 = 0.765, 0.745, 0.793, respectively. The selection of significant metabolites was conducted according to the fold change and false-discovery-rate-adjusted Welch’s t-test. Cohort 1 demonstrated 85 metabolites having higher concentrations in the RA samples than the controls, and 89 metabolites with lowered concentrations. The numbers of increased/decreased metabolites in Cohort 2 and 3 were 87/26 and 90/53, respectively. Importantly, there were 59 significantly discriminatory metabolites commonly found in the three data sets (49 increased and 9 decreased). We picked the top three with the highest univariate classification performance to form a biomarker panel. We implemented the linear support vector machine (SVM) to build the classifier and the receiver operating characteristic (ROC) analysis to measure the performance. The area-under-the-curve (AUC) values (95% confidence interval) were 1.000 (1.000-1.000), 0.992 (0.967-1.000) and 0.902 (0.858-0.945) for the three cohorts, respectively. The results revealed the importance of examining multiple sample sets and even in the worst case (Cohort 3), our biomarker candidates could differentiate RA at 82.5% sensitivity and 82.5% specificity. Particularly, in Cohort 3, there were 30 RA patients negative for anti-cyclic citrullinated peptide and rheumatoid factor, and our metabolite panel demonstrated consistently high performance for differentiating these specific subjects from healthy controls.Conclusion:Metabolites showing significant and consistent changes associated with RA have been identified with high discriminative power.Disclosure of Interests:Wei Han: None declared, Xiaohang Wang: None declared, Liang Li: None declared, Stephanie Wichuk: None declared, Edna Hutchings: None declared, Rana Dadashova: None declared, Joel Paschke: None declared, Walter P Maksymowych Grant/research support from: Received research and/or educational grants from Abbvie, Novartis, Pfizer, UCB, Consultant of: WPM is Chief Medical Officer of CARE Arthritis Limited, has received consultant/participated in advisory boards for Abbvie, Boehringer, Celgene, Eli-Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, UCB, Speakers bureau: Received speaker fees from Abbvie, Janssen, Novartis, Pfizer, UCB.

Background:Active MRI lesions typical of axial spondyloarthritis (axSpA) were reported in 61.6% and 2.2% of axSpA and not-axSpA patients, respectively, from the ASAS classification cohort (ASAS-CC)1. Discrepancy between local and central reader evaluation of MRI scans could result in differences in numbers of patients fulfilling the imaging arm of the ASAS classification criteria. But final classification may not be impacted if discrepant patients still fulfill the clinical arm.Objectives:We aimed to assess the impact of reader discrepancy in detection of active MRI lesions on the number of patients classified as having axSpA in patients recruited to the ASAS-CC.Methods:MRI images of the sacroiliac joints (SIJs) were available from 252 cases in the ASAS-CC, and these also had clinical and radiographic data. Seven central readers from the ASAS-MRI group recorded MRI lesions in an eCRF that included active lesions typical of axSpA in the SIJ (MRI-active) that was worded exactly the same as in the original ASAS-CC eCRF permitting comparisons between central and local site readers. Active lesions were deemed to be present according to majority agreement (≥4/7) of central readers and also any 2 central readers. We calculated the number of patients that were classified differently after central evaluation for overall fulfilment of the ASAS criteria and for the imaging arm.Results:Discordance between central and local readers for detection of MRI-active was recorded in 45(17.8%) and 47(18.2%) of cases according to 2-reader and majority (≥4/7) central reader data, respectively (kappa (95%CI) of 0.64 (0.54-0.73) and 0.62 (0.53-0.72). With central reading as external standard the false-positive rate for active lesions was 26.9%% and 32.2% (‘local overcall’) for 2-reader and majority reader data, respectively. There were 159(63.1%) patients who fulfilled the ASAS axSpA criteria based on local-reading, and 148(58.7%) and 143(56.7%) patients based on 2-reader and majority central-reading, respectively (Table). When fulfillment of the imaging arm was the primary consideration (irrespective of the clinical arm), 126 (50%) patients fulfilled the criteria based on local-reading, and 111 (44%) and 102 (40.5%) patients based on 2-reader and majority central-reading, respectively.Conclusion:Despite substantial overcall for positive MRI SIJ inflammation by local readers, the number of patients classified as having axSpA did not change substantially. This is due to the alternate mechanism for classification through the clinical arm.References:[1]Rudwaleit et al. Ann Rheum Dis 2009;68: 777-83Impact of Central Vs. Local Reader SIJ MRI Inflammation Assessment on SpA Classification in cases with all clinical, radiographic, and central and local MRI inflammation data available (n=252)MRI assessment usedSpA Classification = Yes N(%)SpA Classification = No N(%)Imaging Arm SpA Classification = Yes N(%)Imaging Arm SpA Classification = No N(%)Local Reader MRI positive159 (63.1%)93 (36.9%)126 (50%)126 (50%)>2 Central Reader MRI positive148 (58.7%)104 (41.3%)111 (44.0%)141 (56.0%)Majority Central Reader (≥4/7) MRI positive143 (56.7%)109 (43.2%)102 (40.5%)150 (59.5%)Disclosure of Interests:Walter P. Maksymowych Grant/research support from: AbbVie, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Boehringer Ingelheim, Celgene, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer, and UCB, Employee of: Chief Medical Officer of CARE Arthritis Limited, Speakers bureau: AbbVie, Janssen, Novartis, Pfizer, and UCB, Susanne Juhl Pedersen Grant/research support from: Novartis, Ulrich Weber: None declared, Pedro M Machado Consultant of: PMM: Abbvie, Celgene, Janssen, Lilly, MSD, Novartis, Pfizer, Roche and UCB, Speakers bureau: PMM: Abbvie, BMS, Lilly, MSD, Novartis, Pfizer, Roche and UCB, Xenofon Baraliakos Grant/research support from: Grant/research support from: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB and Werfen, Consultant of: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB and Werfen, Speakers bureau: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB and Werfen, 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, Stephanie Wichuk: None declared, 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, Martin Rudwaleit Consultant of: AbbVie, BMS, Celgene, Janssen, Eli Lilly, MSD, Novartis, Pfizer, Roche, UCB Pharma, Désirée van der Heijde Consultant of: AbbVie, Amgen, Astellas, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Cyxone, Daiichi, Eisai, Eli-Lilly, Galapagos, Gilead Sciences, Inc., Glaxo-Smith-Kline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, UCB Pharma; Director of Imaging Rheumatology BV, Robert B.M. Landewé Consultant of: AbbVie; AstraZeneca; Bristol-Myers Squibb; Eli Lilly & Co.; Galapagos NV; Novartis; Pfizer; UCB Pharma, Joel Paschke: None declared, Mikkel Ǿstergaard Grant/research support from: AbbVie, Bristol-Myers Squibb, Celgene, Merck, and Novartis, Consultant of: AbbVie, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Hospira, Janssen, Merck, Novartis, Novo Nordisk, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi, and UCB, Speakers bureau: AbbVie, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Hospira, Janssen, Merck, Novartis, Novo Nordisk, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi, and UCB, Robert G Lambert: None declared

Background:Classification of axial spondyloarthritis (axSpA) is based on either an imaging or clinical arm. Radiographic or MRI evidence of sacroiliitis can be applied for the imaging arm. However, it is well-established that reliability and sensitivity of radiographic sacroiliitis is inadequate.Objectives:To assess the impact of replacing radiographic sacroiliitis with MRI structural lesions (MRI-S) typical of axSpA on the number of patients classified as having axSpA in patients with undiagnosed back pain recruited to the ASAS Classification Cohort (ASAS-CC).Methods:MRI images of the sacroiliac joint (SIJ) were available from 217 cases in the ASAS-CC, which also had clinical, laboratory, and radiographic data. Seven central readers from the ASAS-MRI group recorded MRI lesions in an eCRF that included active (MRI-A) and structural (MRI-S) lesions typical of axSpA. MRI-A was deemed to be present according to majority agreement (≥4/7) of central readers. MRI-S was deemed to be present according to the majority (majority reader MRI-S) and also according to at least 2 central readers (≥2-reader MRI-S). We calculated the number of patients that were classified differently after replacement of radiographs by MRI-S for overall fulfillment of the ASAS criteria and for the imaging arm.Results:In total, 119 (54.8%) cases fulfilled the axSpA criteria based on local reading of radiographic sacroiliitis and central reading of active inflammation on MRI. This changed to 125 (57.6%) and 118 (54.4%) of cases after replacement of radiographic sacroiliitis by ≥2-reader and majority reader MRI-S, respectively (Table). A total of 13 (6.0%) and 7 (3.2%) cases who were classified as not having axSpA were re-classified as having axSpA after replacing radiographic sacroiliitis with ≥2-reader and majority reader MRI-S, respectively. Conversely, 7 (3.2%) and 8 (3.7%) cases were re-classified as not having axSpA after substitution by ≥2-reader and majority reader MRI-S, respectively. When fulfillment of the imaging arm was the primary consideration (irrespective of the clinical arm), the number of patients reclassified from not axSpA to axSpA was 25 (11.5%) by ≥2-reader and 13 (6.0%) by majority reader MRI-S, while 8 (3.7%) and 11 (5.1%) were reclassified from axSpA to not axSpA.Conclusion:The number of patients classified as having axSpA does not change substantially when MRI-S replaces radiographic sacroiliitis. However, it remains possible that MRI structural lesions can influence the final diagnosis, the gold standard for assessment of the performance of the ASAS criteria.Impact of Replacement of Radiographic Sacroilitis by MRI Structural Lesions on SpA Classification in cases with all clinical, radiographic, and central and local MRI inflammation data available (n=217)MRI assessment usedSpA Classification=Yes N(%)SpA Classification=No N(%)Imaging Arm SpA Classification=Yes N(%)Imaging Arm SpA Classification=No N(%)Radiographic Sacroiliitis + Majority Central Reader MRI Inflammation Positive119 (54.8%)97 (44.7%)83(38.2%)134 (61.8%)Replace Radiographic Sacroiliitis with ≥2 Central Reader MRI Structural Positive125 (57.6%)92 (42.4%)100 (46.1%)117 (53.9%)Replace Radiographic Sacroiliitis with Majority Central Reader MRI Structural Positive118 (54.4%)99 (45.6%)85 (39.2%)132 (60.8%)Disclosure of Interests:Walter P. Maksymowych Grant/research support from: AbbVie, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Boehringer Ingelheim, Celgene, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer, and UCB, Employee of: Chief Medical Officer of CARE Arthritis Limited, Speakers bureau: AbbVie, Janssen, Novartis, Pfizer, and UCB, Pedro M Machado Consultant of: PMM: Abbvie, Celgene, Janssen, Lilly, MSD, Novartis, Pfizer, Roche and UCB, Speakers bureau: PMM: Abbvie, BMS, Lilly, MSD, Novartis, Pfizer, Roche and UCB, Robert G Lambert: None declared, Xenofon Baraliakos Grant/research support from: Grant/research support from: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB and Werfen, Consultant of: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB and Werfen, Speakers bureau: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB and Werfen, Mikkel Ǿstergaard Grant/research support from: AbbVie, Bristol-Myers Squibb, Celgene, Merck, and Novartis, Consultant of: AbbVie, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Hospira, Janssen, Merck, Novartis, Novo Nordisk, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi, and UCB, Speakers bureau: AbbVie, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Hospira, Janssen, Merck, Novartis, Novo Nordisk, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi, and 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, Stephanie Wichuk: None declared, 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, Martin Rudwaleit Consultant of: AbbVie, BMS, Celgene, Janssen, Eli Lilly, MSD, Novartis, Pfizer, Roche, UCB Pharma, Désirée van der Heijde Consultant of: AbbVie, Amgen, Astellas, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Cyxone, Daiichi, Eisai, Eli-Lilly, Galapagos, Gilead Sciences, Inc., Glaxo-Smith-Kline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, UCB Pharma; Director of Imaging Rheumatology BV, Robert B.M. Landewé Consultant of: AbbVie; AstraZeneca; Bristol-Myers Squibb; Eli Lilly & Co.; Galapagos NV; Novartis; Pfizer; UCB Pharma, Joel Paschke: None declared, Susanne Juhl Pedersen Grant/research support from: Novartis, Ulrich Weber: None declared

Background:Patients presenting with back pain and psoriasis, iritis, or colitis, represent a high-risk population for the presence of axial spondyloarthritis (axSpA). The Dublin Evaluation Tool (DUET)1, the Berlin algorithm2, and the ASAS modification of this algorithm3are recommended referral strategies aimed at early diagnosis of axSpA. DUET was developed for patients presenting with AAU. Validation of these algorithms in inception cohorts is limited.Objectives:1. To assess the performance of referral algorithms for diagnosis of axSpA when tested against the final local rheumatologist diagnosis in an inception cohort of patients presenting with undiagnosed back pain and extra-articular manifestations. 2. To determine whether different criteria for inflammatory back pain (IBP) impact the performance of the algorithms.Methods:The multicenter Screening for Axial Spondyloarthritis in Psoriasis, Iritis, and Colitis (SASPIC) Study at 11 sites is aimed at early detection of axial SpA in patients presenting with undiagnosed back pain to the rheumatologist. Consecutive patients ≤45 years of age with ≥3 months undiagnosed back pain with any one of psoriasis, acute anterior uveitis (AAU), or colitis diagnosed by the relevant specialist undergo routine clinical evaluation by a rheumatologist for axial SpA. The rheumatologist determines the presence or absence of axial SpA at 3 consecutive stages: 1. After the clinical evaluation; 2. After the results of labs (B27, CRP) and radiography; 3. After the results of MRI evaluation. Final diagnosis by the rheumatologist was used as external standard to test the performance of the algorithms. We tested the following criteria for IBP in the algorithm: ASAS, Berlin, rheumatologist global for likelihood of IBP >5 (0-10 scale), and DUET algorithm in AAU patients.Results:A total of 246 patients were recruited, 73 presented with iritis, 46 with psoriasis, and 127 with colitis, 47.6% were diagnosed with axSpA. The diagnosis of axSpA was established in 45.7%, 61.6%, and 40.2% of patients with psoriasis, AAU, and IBD, respectively. The performance of the ASAS-modification of the Berlin algorithm was superior to the original algorithm as reported previously3, primarily for enhanced sensitivity, and this was observed irrespective of the criteria used to define IBP (Table 1). Conversely, the performance of the Duet algorithm in the subset of patients with AAU was substantially worse than previously reported1.Conclusion:The ASAS modification of the Berlin algorithm is the preferred referral strategy for patients presenting with undiagnosed back pain to the rheumatologist.References:[1]Haroon M, et al. Ann Rheum Dis 2015; 74: 1990-5[2]Poddubnyy D, et al. J Rheumatol 2011; 38: 2452–60[3]Van den Berg R, et al. Ann Rheum Dis 2013;72:1646–53AlgorithmSensitivity (%)Specificity (%)Correct diagnosis (%)False negative (%)False positive (%)Original Berlin(ASAS criteria for IBP)65.376.671.116.712.2Original Berlin(Berlin criteria for IBP)64.476.670.717.112.2Original Berlin(IBP global >5)67.878.173.215.411.4ASAS Modification of Berlin algorithm (ASAS criteria for IBP)73.775.874.812.612.6ASAS Modification of Berlin algorithm (Berlin criteria for IBP)73.775.074.412.613.0ASAS Modification of Berlin algorithm(IBP global >5)76.377.376.811.411.8DUET84.450.071.29.619.2Disclosure of Interests:Ulrich Weber: None declared, Georg Kröber: None declared, Raj Carmona: None declared, James Yeung: None declared, Jon Chan: None declared, Sibel Aydin: None declared, Liam Martin: None declared, Ariel Masetto: None declared, Stephanie Keeling: None declared, Olga Ziouzina: None declared, Sherry Rohekar: None declared, Rana Dadashova: None declared, Amanda Carapellucci: None declared, Joel Paschke: None declared, Robert G Lambert: None declared, Walter P. Maksymowych Grant/research support from: AbbVie, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Boehringer Ingelheim, Celgene, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer, and UCB, Employee of: Chief Medical Officer of CARE Arthritis Limited, Speakers bureau: AbbVie, Janssen, Novartis, Pfizer, and UCB

Background:The ASAS classification criteria for axial spondyloarthritis (axSpA) have overall sensitivity/specificity of 82.9%/84.4% but component imaging and clinical arms differ in performance (66.2%/97.3% and 56.6%/83.3%, respectively)1.Objectives:We aimed to demonstrate that a data-driven elimination of SpA clinical features that were non-discriminatory in comparisons of patients diagnosed with and without axSpA in a prospective cohort of patients with undiagnosed back pain could enhance the performance of the criteria.Methods:We used data from the prospective multicenter Screening for Axial Spondyloarthritis in Psoriasis, Iritis, and Colitis (SASPIC) Study. Consecutive patients ≤45 years of age with ≥3 months undiagnosed back pain with any one of psoriasis, AAU, or colitis undergo routine diagnostic evaluation by a rheumatologist for axial SpA, including imaging assessed by central readers. Univariable and multivariable logistic regression analysis was performed to determine which clinical SpA features were/were not discriminatory for the final diagnosis of axSpA. We then compared the sensitivity and specificity of the ASAS criteria with and without these features.Results:A total of 246 patients were recruited, 47.6% being diagnosed with axSpA (61.5% male, age 33.7 years, symptom duration 7.6 years, B27 positive 52.1%). The following clinical SpA features were non-discriminatory between axSpA/not axSpA: NSAID response, family history of SpA, heel enthesitis, peripheral arthritis, dactylitis. Specificity of the clinical arm and the overall criteria increased from 82.2% to 86.8% without impacting sensitivity. This effect was particularly noteworthy in patients with lower degree of symptomatology (back pain severity Conclusion:In a prospective cohort with a high pre-test probability of axSpA certain clinical SpA features were not helpful in discriminating a diagnosis of SpA from not-SpA. Deletion of these features from the list of SpA features used in the ASAS classification criteria enhanced the performance of the criteria, especially in female patients and those with early disease.References:[1]Rudwaleit et al. Ann Rheum Dis 2009;68: 777-83Patient CategoryNumberASAS criteriaImaging armClinical armSenSpecSenSpecSensSpecAll patients2466582.236.897.750.482.2High confidence in diagnosis19073.884.547.598.256.384.5Patients with back pain ≥5/1016563.384.934.298.851.984.9Patients with back pain 8168.476.742.195.347.476.7Patients with symptom duration ≥5 years10371.285.735.697.156.285.7Patients with symptom duration 14354.57838.698.340.978Males12968.184.247.298.248.684.2Females1176080.62097.253.380.6After deletion of ‘NSAID response’, ‘Family Hx SpA’, ‘heel enthesitis’, ‘peripheral arthritis’, ‘dactylitis’ SpA featuresAll patients2466586.836.897.750.486.8High confidence in diagnosis19073.887.347.598.256.387.3Patients with back pain ≥5/1016563.384.934.298.851.984.9Patients with back pain 8168.490.742.195.347.490.7Patients with symptom duration ≥5 years10371.288.635.697.156.288.6Patients with symptom duration 14354.584.738.698.340.984.7Males12968.187.747.298.248.687.7Females1176086.12097.253.386.1Disclosure of Interests:Walter P. Maksymowych Grant/research support from: AbbVie, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Boehringer Ingelheim, Celgene, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer, and UCB, Employee of: Chief Medical Officer of CARE Arthritis Limited, Speakers bureau: AbbVie, Janssen, Novartis, Pfizer, and UCB, Raj Carmona: None declared, Jon Chan: None declared, James Yeung: None declared, Sibel Aydin: None declared, Liam Martin: None declared, Ariel Masetto: None declared, Olga Ziouzina: None declared, Stephanie Keeling: None declared, Sherry Rohekar: None declared, Rana Dadashova: None declared, Joel Paschke: None declared, Amanda Carapellucci: None declared, Robert G Lambert: None declared

Key messages #### What is already known about this subject? #### What does this study add? #### How might this impact on clinical practice? Entheses are sites where tendons, fascia, ligament or joint capsule attach to bones of the appendicular or axial skeleton.1 2 Inflammation at these sites, enthesitis, involves both soft tissue and bone, and is considered as a core pathological process in spondyloarthritis (SpA), including psoriatic arthritis (PsA).3 4 The prevalence of enthesitis in SpA, including PsA, has been reported to be 13.6%–35%, with Achilles tendon and plantar fascia insertion being the most common sites.5 6 Assessing enthesitis as primary or secondary outcome in clinical trials requires a comprehensive, sensitive and validated assessment method. Clinical examination using different enthesitis indices has been shown to have low sensitivity and specificity, with suboptimal reproducibility.7 8 MRI allows sensitive assessment of enthesitis,9–11 and the OMERACT MRI in Arthritis Working Group has recently developed and validated the OMERACT Heel Enthesitis MRI Scoring System (HEMRIS), along with consensus-based definitions of the MRI features to be scored.12 Thus, this method may facilitate a more reliable assessment of enthesitis in clinical trials. The exact area of assessment and the individual grades of HEMRIS may be difficult for new readers to conceptualise. Furthermore, the applicability and reproducibility of …

Background In current rheumatology practice, the circumstances that prompt clinicians to order MRI in patients with suspected axSpA are unclear. In addition, the manner and degree to which MRI changes diagnostic ascertainment of axSpA in patients presenting with undiagnosed back pain has not been formally studied. Objectives 1. To determine whether any particular patient demographic and/or disease characteristics are associated with rheumatologist ordering of MRI. 2. To assess the impact of MRI evaluation on diagnostic ascertainment of axial SpA in patients presenting with undiagnosed back pain. Methods The multicenter Screening for AxSpA in Psoriasis, Iritis, and Colitis (SASPIC) Study is aimed at early detection of axial SpA in consecutive patients presenting with undiagnosed back pain to the rheumatologist. Consecutive patients with any one of psoriasis, iritis, or colitis diagnosed by the relevant specialist undergo routine evaluation by a rheumatologist. The rheumatologist determines the presence/absence of axial SpA and the degree of confidence in the diagnosis (−10 (definitely not SpA) to +10 (definite SpA) on a NRS) at 3 consecutive stages: 1. After the clinical evaluation; 2. After the results of labs (B27, CRP) and radiography; 3. After the results of MRI. Differences in patient demographics and/or disease characteristics between those who did or did not have MRI were assessed by chi-square and t-tests. We assessed the degree of diagnostic reclassification after each step at the categorical level (axial SpA yes/no) and also according to the degree of confidence. Results 244 patients (51.6% male, mean age 34.6 years, mean age at symptom onset 27.4 years, mean back pain duration 7.1 years, B27 +37.2%) were referred with AAU (29.9%), psoriasis (21.7%), Crohn’s colitis (32.8%), ulcerative colitis (19.3%). A diagnosis of axSpA was made in 67.5% after stage 1 clinical evaluation and in 56.4% at stage 2 after review of the labs and radiography. MRI evaluation varied across sites (mean(range): 73% (16.7%>100%) of patients), ordered in 141 patients, and significantly more frequently in those with probable inflammatory type back pain (probability >5 (0–10 scale) (p=0.04), when radiography was mNY- (p=0.005) and in those without Crohn’s colitis (p=0.001). No differences in ordering of MRI were noted according to age, gender, disease duration, back pain severity, NSAID response, B27 status, or CRP level. In patients with completed MRI scans, a diagnosis of axSpA was made in 70.5% after stage 1 clinical evaluation, in 56.4% after review of the labs and radiography, and in 47.3% after MRI review. 24 (18.6%) were recategorized from SpA to non-SpA and 4 (3.1%) from non-SpA to SpA. Confidence in diagnostic categorization was increased after MRI. Conclusions In a setting of undiagnosed back pain and higher risk for axial SpA, use of MRI is primarily driven by negative radiography. MRI was primarily helpful in ruling out SpA and reducing false positives. Disclosure of Interest None declared

Background The application and appropriate use of imaging-based scoring instruments is usually based on passive learning from published manuscripts while real-time interaction with instrument developers is often non-feasible. Moreover, most instruments lack knowledge transfer tools that would facilitate attainment of pre-specified performance targets for reader reliability. Objectives 1. To develop a web-based calibration module for the SPARCC MRI SIJ Inflammation Score based on consensus scores from these instrument developers, experiential game psychology, and real-time iterative feedback. 2. To test the feasibility and attainment of pre-specified performance targets for reader reliability. Methods The scoring of inflammatory lesions of the SIJ on MRI using the SPARCC method is based on SIJ quadrants and the calibration module is comprised of 50 DICOM cases, each with scans from baseline and 12 weeks after the start of TNF inhibitor therapy. Scans are scored blinded-to-time-point. Continuous visual real-time feedback regarding concordance/discordance of scoring per SIJ quadrant with expert readers is provided by a color-coding scheme. Reliability is additionally assessed by real-time intra-class correlation coefficient with the first ICC data being provided after 20 cases. Accreditation for SPARCC BME score is achieved with status and change score ICC of >0.8 and>0.7 and is based on the final 20 cases. 26 readers scored the SPARCC BME module (7 rheumatology fellows, 2 chiropracters, 1 undergraduate, 8 rheumatologists, 8 radiologists) with 21 having no prior experience. Feasibility was assessed by 8-item survey. Results The majority of readers achieved accreditation for SPARCC BME score on the basis of sufficient reliability with instrument developers for both status and change scores, irrespective of prior experience (table 1). All readers who completed the module a second time, 6 months after the first exposure, achieved accreditation for SPARCC BME score. All readers rated the modules as easy and intuitive with average time for reading each case for SPARCC BME being 8 min. Conclusions Experiential web-based learning is an effective and feasible calibration tool to achieve proficiency targets in the scoring of MRI scans for SIJ inflammatory lesions. Disclosure of Interest W. Maksymowych Shareholder of: CaRE Arthritis, S. Krabbe: None declared, D. Biko: None declared, P. Weiss: None declared, M. Maksymowych: None declared, J. Cheah: None declared, G. Krober: None declared, U. Weber: None declared, K. Danebod: None declared, P. Bird: None declared, P. Chiowchanwisawakit: None declared, J. Moeller: None declared, M. Francavilla: None declared, J. Stimec: None declared, T. Kogay: None declared, V. Zubler: None declared, M. Battish: None declared, N. Winn: None declared, D. Rumsey: None declared, R. Guglielmi: None declared, S. Pedersen: None declared, H. Boutrup: None declared, S. Shafer: None declared, J. Jaremko: None declared, F. Malik: None declared, E. Heffernan: None declared, M. Johansson: None declared, B. Trinh: None declared, J. Paschke: None declared, R. Lambert: None declared

Objective.There is a critical need for measures to evaluate structural progression in the pediatric sacroiliac joint (SIJ). We aimed to evaluate the construct validity and reliability of the Spondyloarthritis Research Consortium of Canada SIJ Structural Score (SSS) in children with suspected or confirmed juvenile spondyloarthritis.Methods.The SSS assesses structural lesions of the SIJ on magnetic resonance imaging (MRI) through the cartilaginous part of the joint. We conducted 3 sequential reading exercises with 6 readers (1 adult and 3 pediatric radiologists, 1 adult and 1 pediatric rheumatologist). Each exercise was preceded by a calibration module. Interobserver reliability was assessed using intraclass correlation coefficients (ICC). Prespecified acceptable reliability thresholds were ICC > 0.5 for erosion, backfill, and sclerosis, and ICC > 0.7 for ankylosis and fat metaplasia.Results.The SSS had face validity and was feasible to score in pediatric cases for all 3 reading exercises. Of the cases used in the 3 exercises, 58% were male and the median age was 14 years (range 6.8–18.7 yrs). After calibration, median ICC across all readers for each SSS component were the following: erosion 0.67 (interquartile range 0.54–0.80), backfill 0.33 (0.19–0.52), fat metaplasia 0.74 (0.62–0.85), sclerosis 0.63 (0.48–0.77), and ankylosis 0.44 (0.28–0.62). Prespecified reliability thresholds were achieved in the third exercise for erosion, sclerosis, and fat metaplasia but not for backfill or ankylosis.Conclusion.The SSS was feasible to score and had acceptable reliability for pediatric SIJ MRI evaluation. The ICC improved with additional calibration and reading exercises, even for readers with limited experience.

Background Clinical trials in children with pediatric spondyloarthritis and axial disease are lacking. In order to assess the effectiveness of medications we need an objective measure to quantify severity of inflammation in the pediatric sacroiliac joint. Objectives We evaluated the reliability and construct validity of the Spondyloarthritis Research Consortium of Canada (SPARCC) sacroiliac joint inflammation score (SIS) in children with suspected or confirmed juvenile spondyloarthritis (SpA). Methods The SIS divides the joint into quadrants and scores the presence, depth, and intensity of bone marrow edema (BME) on short tau inversion recovery (STIR) magnetic resonance imaging (MRI). Six consecutive semicoronal slices through the cartilaginous portion of the joint are scored for BME (total score 0–72). We developed a pediatric training module that included scoring instructions and examples of bright subchondral signal on STIR scans easily confused with inflammation (Figure). After reviewing the module, 6 readers (1 adult and 3 pediatric radiologists, 1 adult rheumatologist, and 1 pediatric rheumatologist), blinded to clinical details except age, scored 30 studies that included semicoronal T1-weighted and STIR sequences. Pain was recorded on a visual analogue scale (0–10). Disease activity was evaluated using the juvenile SpA disease activity (JSpADA) index (range 0–8). Inter-observer reliability was assessed using intraclass correlation (ICC). Correlation (convergent validity) of the mean SPARCC SIS developers9 score with disease activity was tested using Spearman correlation. Discrimination was tested by comparing the mean SPARCC SIS developers9 score between children with and without inflammatory back pain using the Mann-Whitney test. Results The SIS had face validity and was feasible to score in the 30 pediatric cases. 21 (70%) were male. Median age at the time of imaging was 15.5 years (IQR: 12.7–16.8). Median pain score and JSpADA index were 2 (IQR 0.5–6) and 2 (IQR: 0.5–3), respectively. Of the 180 scores submitted by 6 readers, 140 (78%) of the studies had a SIS ≥2. Median SIS was 14 (IQR: 3–29). ICCs for all readers (N=6), SPARCC developers (N=2), rheumatologists (N=2), and pediatric radiologists (N=3) were 0.63 (95% CI: 0.45–0.78), 0.89 (95% CI: 0.75–0.95), 0.43 (95% CI: -0.02–0.71), and 0.85 (95% CI: 0.72–0.92), respectively. SIS had low correlation with disease activity as measured by the JSpADA (r=-0.08) and C-reactive protein (r=0.14). SIS score did not discriminate between those with and without inflammatory back pain (p=0.16). Conclusions The SIS was feasible to score and had near excellent reliability, even with limited calibration. SIS did not have convergent validity with clinical measures of disease activity, highlighting that imaging and clinical evaluations provide complimentary but non-overlapping information. Responsiveness of the SIS should be evaluated in a prospective cohort of children who start biologic therapy. Disclosure of Interest None declared

Background While, a Treat-to-Target strategy (T2T), treating patients with rheumatoid arthritis (RA) towards a certain target (eg. clinical remission; T2T-REM), is highly recommended, several patients in clinical remission often have residual synovitis on ultrasound-imaging (US). This may result in silent radiographic progression and clinical flare. It is arguable whether targeting US-synovitis may result in “deeper” remission in clinical practice. Objectives To assess whether using US in a T2T strategy leads to more patients meeting clinical remission than using only clinical information. Methods Patients with RA who started or changed csDMARD and/or anti-TNF treatment followed in centers with expertise in US and participating in BIODAM (2-year multicenter prospective observational cohort) were included. Clinical and US data [by the US7-score that includes 7 joints of the clinically dominant hand and foot for synovitis and tenosynovitis on gray-scale US (GSUS) and power-doppler US (PDUS) and erosions on GSUS] were collected every 3 months. Per visit was decided whether the patient was treated according to the clinical definition of T2T with remission as benchmark (T2T-CLIN-REM). Though not mandatory, US-data could also be used for this purpose. T2T-CLIN-REM was considered correctly applied if: either i) a patient already had a disease activity score below the remission target (i.e. ACR/EULAR boolean remission) or ii) if not, treatment was intensified. A T2T strategy taking also US data into account (T2T-CLIN-US-REM) was considered correctly applied if: either i) both clinical and US remission (all joints included in the US7-score with GSUS synovitis Results In total 963 visits of 130 patients were included. T2T-CLIN-US-REM was correctly followed in 33% of the visits, T2T-CLIN-REM in 14%, and any of these in 52%. Remission according to the ACR/EULAR-boolean definition was achieved in 19.6% of the visits. Compared to the conventional T2T-CLIN-REM strategy, using a combined clinical and US benchmark for T2T led to a lower – instead of higher - likelihood of ACR/EULAR-boolean remission 3 months later [OR (95% CI): 0.39 (0.24; 0.63] (table). Conclusions Our results, from a non-randomized study, did not suggest an advantage of using US of 7 joints in addition to clinical examination as a T2T benchmark as compared to clinical examination alone in getting RA patients into clinical remission. Disclosure of Interest None declared

Background Criteria for inflammatory back pain (IBP) in spondyloarthritis (SpA) include the Calin, Berlin, and Assessments in SpA International Society (ASAS) criteria, although no studies have undertaken comparative validation to determine which are optimal versus the rheumatologist expert opinion gold standard assessment. Objectives We aimed to compare IBP criteria in unselected patients presenting with undiagnosed back pain to rheumatology practice. Methods The Screening for Axial Spondyloarthritis in Psoriasis, Iritis, and Colitis (SASPIC) Study is aimed at the development and validation of a triage strategy for detection of axial SpA in patients presenting with undiagnosed back pain. Consecutive patients ≤45 years of age with ≥3 months undiagnosed back pain with any one of psoriasis, acute anterior uveitis, or colitis diagnosed by the relevant specialist undergo routine clinical evaluation by a rheumatologist for axial SpA. The rheumatologist determines the presence or absence of IBP (defined as 5 on 0–10 scale, respectively) and axial SpA (yes/no) after the clinical evaluation and review of labs (B27, CRP) and imaging (x-ray, MRI). Clinical and laboratory data, radiographs and MRI scans are also assessed centrally for diagnosis of axial SpA (yes/no). We assessed sensitivity and specificity of each of the IBP criteria for diagnosis of IBP according to the local rheumatologist, diagnosis of axial SpA by local rheumatologist, diagnosis of axial SpA by central assessment, and concordant diagnosis of axial SpA by both local and central assessment. Results We recruited 185 patients (48.6% male, mean age 27.6 years, mean back pain duration 7.0 years) with iritis (30.3%), psoriasis (17.3%), Crohn9s (38.4%) and ulcerative colitis (18.9%). IBP and/or axial SpA were considered present in 65.2% and 47.3%, respectively, of all patients by the local rheumatologist. By central assessment axial SpA was considered present in 32.7% while amongst patients with a concordant diagnosis by both local and central assessment 37.2% were considered to have axial SpA. Sensitivity was comparatively high for all IBP criteria but specificity was poor. The Berlin criteria consistently performed best while the Calin criteria consistently performed worst (Table). Conclusions IBP criteria lack specificity for rheumatologist diagnosed IBP or axial SpA but the Berlin criteria have consistently better performance. Disclosure of Interest None declared

Background MRI can detect both inflammatory and structural lesions in the sacroiliac joints (SIJ) of patients with axial SpA. However, standard MRI sequences do not directly depict bone and the appearance of erosion may vary according to the presence/absence of inflammation. Consequently, further validation using an accepted gold standard, namely, computed tomography (CT), is essential. Objectives We aimed to assess the detection of structural lesions in the SIJ by MRI using CT as the gold standard. Methods CT scans from 44 patients (26 females, mean age 49.4 years, mean symptom duration 9.1 years) were reconstructed in the semicoronal plane parallel to the superior border of the sacrum, as for conventional MRI evaluation of the SIJ, and scoring of lesions by CT was confined to this plane. Structural lesions were scored in consecutive slices in SIJ quadrants (erosion, sclerosis) or SIJ halves (ankylosis) on a dichotomous basis (present/absent) using the same anatomical principles for defining SIJ quadrants as developed for the SPARCC MRI SIJ inflammation and structural scores. T1W MRI scans of the SIJ from the same cases conducted at the same time as CT were assessed independently for structural lesions (erosion, fat, backfill, ankylosis, sclerosis) blinded to CT assessments using the SPARCC method. Agreement between CT and MRI was assessed by kappa statistics. Sensitivity/specificity of MRI for CT lesions was calculated. The primary analysis was based on lesions detected concordantly by both readers at the level of the individual iliac/sacral joint surface (erosion, sclerosis) or the individual joint (ankylosis, backfill). Results With CT as gold standard and a lesion defined as being present when recorded in the same location on at least 1 coronal slice by both readers, MRI-defined ankylosis had 56.3% sensitivity and 100% specificity for CT ankylosis (Table). For erosion, sensitivity and specificity of MRI was 81.3% and 96.2%, and for sclerosis, sensitivity and specificity of MRI was 50% and 97%, respectively. Agreement between CT and MRI for erosion increased when the cut-off for presence of a lesion was set at 2 slices but only marginally for sclerosis, even when the cut-off for presence of a lesion was set at 3 slices. Lesions observed on CT corresponding to backfill on MRI were ankylosis, erosion, and sclerosis, in 66.7%, 66.7%, and 80% of backfill lesions, respectively. Conclusions Ankylosis and erosion on MRI correspond closely with the same type of lesion observed on CT. Both new bone formation and erosion are frequently evident on CT at locations where backfill is observed on MRI supporting the hypothesis that backfill is an intermediary tissue between erosion and ankylosis. Disclosure of Interest None declared

Background Computed tomography (CT) is considered the imaging benchmark for the assessment of certain structural lesions in the sacroiliac joints (SIJ) of patients with axial spondyloarthritis (axSpA). Availability of low dose radiation techniques may lead to more widespread use, potentially as a structural endpoint in clinical trials research. Objectives We aimed to validate a new CT-based scoring method, the CT Sacroiliac Structural Score (CT-SSS), for assessing structural lesions in the SIJ. Methods CT scans of the SIJ from 44 patients (26 females, mean age 49.4 years, mean symptom duration 9.1 years) were reconstructed in the semicoronal plane parallel to the superior border of the sacrum and scoring of lesions was confined to this plane. Structural lesions were scored in consecutive slices in SIJ quadrants (erosion, sclerosis) or SIJ halves (ankylosis) on a dichotomous basis (present/absent) using the same anatomical principles as developed for the SPARCC MRI SIJ inflammation and structural scores. The most anterior slice is defined as visible joint ≥1cm vertical height and when Results Scoring was feasible (5–10 minutes per scan) and both ankylosis (ICC=0.95) and erosion (ICC=0.81) were reliably scored (Table). Sclerosis was less reliably scored (ICC=0.39). Presence/absence of ankylosis was reliably detected irrespective of whether this was based on a single slice (κ=0.77) or 3 consecutive slices (κ=0.81). Reliable detection was lower for erosion (κ=0.50 for 1 or 3 slices) and sclerosis (κ=0.44 and 0.48 for 1 and 3 slices, respectively). Bland-Altman graphs illustrate reliability across the range of scores for ankylosis and erosion. Conclusions The CT-SSS method is feasible and reliable for scoring ankylosis and erosion with minimal calibration. Sclerosis requires further standardization and calibration. Disclosure of Interest None declared