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ObjectiveWe aimed to compile evidence for the efficacy and safety of therapeutic options for the peripheral arthritis domain of psoriatic arthritis (PsA) for the revised 2021 Group in Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) treatment recommendations.MethodsA working group consisting of clinicians and patient research partners was convened. We reviewed the evidence from new randomized controlled trials (RCTs) for PsA treatment from February 19, 2013, to August 28, 2020. We used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE)-informed approach to derive evidence for the classes of therapeutic options for 3 patient groups: (1) naïve to treatment, (2) inadequate response to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), and (3) inadequate response to biologic DMARDs (bDMARDs). Recommendations were derived through consensus meetings.ResultsThe evidence review included 69 RCTs. We derived GRADE evidence for each class of therapeutic options and achieved consensus for the recommendations. For patients naïve to treatment, the working group strongly recommends csDMARDs (methotrexate, sulfasalazine, leflunomide) and phosphodiesterase 4 inhibitors, and emphasizes regular assessment and early escalation to achieve treatment target. bDMARDs (tumor necrosis factor inhibitors [TNFi], interleukin 17 inhibitors [IL-17i], IL-12/23i, IL-23i) and Janus kinase inhibitors (JAKi) are also strongly recommended. For patients with inadequate response to csDMARDs, we strongly recommend TNFi, IL-17i, IL-12/23i, IL-23i, and JAKi. For those who had prior experience with bDMARDs, we strongly recommend a second TNFi, IL-17i, IL-23i, and JAKi. The evidence supporting nonpharmacological interventions was very low. An expert panel conditionally recommends adequate physical activity, smoking cessation, and diet to control weight gain.ConclusionEvidence supporting optimal therapy for the peripheral arthritis domain of PsA was compiled for the revised 2021 GRAPPA treatment recommendations.

Objective To investigate the association between clinical joint tenderness and intra- and periarticular inflammation as assessed by ultrasound and MRI in patients with active PsA and to explore if the associations differ according to patient-reported outcomes (PROs) and structural damage. Methods Forty-one patients with active PsA and hand involvement had 76/78 joints examined for swelling/tenderness and ultrasound and MRI of 24 and 12 finger joints, respectively. Synovitis, tenosynovitis, periarticular inflammation and erosions were assessed using OMERACT definitions and scoring systems. Correlation between imaging inflammation sum-scores (intra-and periarticular) and tender/swollen joint counts were calculated using Spearman’s rho, agreement at joint level was examined using prevalence and bias adjusted kappa (PABAK). Subgroup analyses explored the influence of PROs and radiographic erosive disease on these associations. Results No significant correlations were found between tender or swollen joint counts and imaging inflammation sum-scores (rho = −0.31–0.38). In patients with higher level of overall pain, disability and lower self-reported mental health, a tendency towards negative correlations were found. At joint level, intra- and periarticular imaging inflammatory lesions had slight agreement with joint tenderness (PABAK = 0.02–0.19) and slight to moderate with swelling (PABAK = 0.16–0.54). For tender joints, agreement with imaging inflammation was even weaker in patients with either high overall pain scores, high disability scores, and/or non-erosive disease. Conclusion Joint tenderness had low association with imaging signs of inflammation in PsA patients, particularly in patients with high self-reported pain, disability and low mental health, indicating that tenderness is influenced by other parameters than local inflammation.

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.

Objectives To investigate SI joint MRI inflammation, structural and degenerative lesion characteristics in patients with axial spondyloarthritis (axSpA) and various control groups. Methods Patients with axSpA (n = 41) and lumbar disc herniation (n = 25), women with (n = 46) and without (n = 14) post-partum (childbirth within 4–16 months) buttock/pelvic pain, cleaning assistants (n = 26), long-distance runners (n = 23) and healthy men (n = 29) had MRI of the SI joints prospectively performed. MRI lesions were assessed on nine slices covering the cartilaginous compartment by two experienced readers according to the definitions of the Spondyloarthritis Research Consortium of Canada SI joint inflammation and structural scores, and were evaluated according to depth and extent. Other morphological characteristics were also analysed. Results Total depth scores for bone marrow oedema (BME) and fat lesion (FAT) and total extent score for erosion were statistically significantly highest in axSpA, while scores for sclerosis were numerically highest in women with post-partum pain. Maximum BME depth >10 mm was frequently and exclusively found in axSpA and post-partum women (39% vs 14–17%) while FAT depth >5 mm was predominantly found in axSpA (76% vs 0–10%). Erosions were primarily seen in axSpA, especially when extensive (≥4 or confluent; 17% vs 0%). Capsulitis was absent in non-axSpA groups. BME and FAT in the ligamentous compartment were primarily found in axSpA (17/22% vs 0/2% in non-axSpA groups). In non-axSpA, osteophytes (axSpA vs non-axSpA: 0% vs 3–17%) and vacuum phenomenon (7% vs 30–66%) were more frequent, and the joint space was wider [mean (s.d.) 1.5 (0.9) vs 2.2 (0.5) mm]. Conclusions FAT depth >5 mm, but not BME depth >10 mm, could almost differentiate axSpA patients from all other groups. When excluding post-partum women, BME >5 mm and erosion were highly specific for axSpA.

Objective To investigate the anatomic location and distribution of lesions on magnetic resonance imaging (MRI) in the sacroiliac (SI) joints in patients with axial spondyloarthritis (SpA), women with and without postpartum pain (childbirth within 4-16 months), patients with disc herniation, cleaning staff, runners, and healthy persons. Methods In a prospective cross-sectional study of 204 participants, MRI of the entire cartilaginous compartment of the SI joint was scored blindly by 2 independent, experienced readers, according to Spondyloarthritis Research Consortium of Canada definitions of SI joint inflammation and structural lesions in each SI joint quadrant or half and in each of 9 slices. The locations of the lesions (unilateral/bilateral, upper/lower, sacral/iliac, and anterior/central/posterior slices) were analyzed based on concordant reads. Results Bone marrow edema (BME) occurred in all quadrants in nearly all participant groups, but rarely bilaterally, except in patients with axial SpA and women with postpartum pain. Fat lesions were mainly found in axial SpA and occurred in all quadrants, but mostly bilaterally in sacral quadrants. Erosion was rare, except in axial SpA, where it was mainly iliac and often bilateral. Sclerosis was exclusively iliac and most frequent in women with postpartum pain. Conclusion The location and distribution of common SI joint lesions in axial SpA and non-axial SpA were reported, and group-specific patterns were revealed. BME distributed bilaterally or unilaterally, both locally and more widespread in the SI joint, is common in both postpartum women with pain and axial SpA patients, which limits the use of BME to differentiate these groups. This study indicates that the presence of fat lesions, especially when widespread, and/or erosion, particularly when located centrally or posteriorly, are diagnostically important and should be investigated further.

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

ObjectivesSpinal MRI is used to visualise lesions associated with axial spondyloarthritis (axSpA). The ASAS MRI working group (WG) updated and validated the definitions for inflammatory and structural spinal lesions in the context of axSpA.MethodsAfter review of the existing literature on all possible types of spinal MRI pathologies in axSpA, the group (12 rheumatologists and two radiologists) consented on the required revisions of lesion definitions compared with the existing nomenclature of 2012. In a second step, using 62 MRI scans from the ASAS classification cohort, the proposed definitions were validated in a multireader campaign by global (absent/present) and detailed (inflammation and structural) lesion assessment at the vertebral corner (VC), vertebral endplate, facet joints, transverse processes, lateral and posterior elements. Intraclass correlation coefficient (ICC) was used for analysis.ResultsRevisions were made for both inflammatory (bone marrow oedema, BMO) and structural (fat, erosion, bone spur and ankylosis) lesions, including localisation (central vs lateral), extension (VC vs vertebral endplate) and extent (minimum number of slices needed), while new definitions were suggested for the type of lesion based on lesion maturity (VC monomorphic vs dimorphic). The most reliably assessed lesions were VC fat lesion and VC monomorphic BMO (ICC (mean of all 36 reader pairs/overall 9 readers): 0.91/0.92; 0.70/0.67, respectively.ConclusionsThe lesion definitions for spinal MRI lesions compatible with SpA were updated by consensus and validated by a group of experienced readers. The lesions with the highest frequency and best reliability were fat and monomorphic inflammatory lesions at the VC.

Objectives In a 2-year follow-up study of patients with axial spondyloarthritis (axSpA) in clinical remission who tapered TNF inhibitor (TNFi) treatment according to a clinical guideline, we aimed to investigate the proportion who successfully tapered/discontinued therapy and baseline predictors thereof. The proportion regaining clinical remission after flare and the progression on MRI/radiography were also assessed. Methods One-hundred-and-nine patients (78 [72%]/31 [28%] receiving standard and reduced dose, respectively) in clinical remission (BASDAI < 40, physician global score < 40) and no signs of disease activity the previous year tapered TNFi as follows: to two-thirds of standard dose at baseline, half at week 16, one-third at week 32 and discontinuation at week 48. Patients experiencing clinical, BASDAI or MRI flare (predefined criteria) stopped tapering and escalated to previous dose. Prediction analyses were performed by multivariable regression. Results One hundred and six patients (97%) completed 2 years’ follow-up; 55 patients (52%) had successfully tapered: 23 (22%) receiving two-thirds, 15 (14%) half, 16 (15%) one-third dose and 1 (1%) discontinued. In patients at standard dose at baseline (n = 78), lower physician global score was the only independent predictor of successful tapering (odds ratio [OR] = 0.79 [95% CI: 0.64, 0.93]; P = 0.003). In the entire patient group lower physician global score (OR = 0.86 [0.75, 0.98]; P = 0.017), lower Spondyloarthritis Research Consortium of Canada (SPARCC) Sacroiliac Joint Erosion score (OR = 0.78 [0.57, 0.98]; P = 0.029) and current smoker (OR = 3.28 [1.15, 10.57]; P = 0.026) were independent predictors of successful tapering. At 2 years, 97% of patients were in clinical remission. Minimal changes in imaging findings were observed. Conclusion After 2 years following a clinical guideline, 52% of patients with axSpA in clinical remission had successfully tapered TNFi, only 1% discontinued. Baseline physician global score was an independent predictor of successful tapering.

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

Objective.In axial spondyloarthritis (axSpA), sacroiliac joint (SIJ) erosion is often followed by fat metaplasia in an erosion cavity (backfill), and subsequently ankylosis. We aimed to combine the Spondyloarthritis Research Consortium of Canada (SPARCC) SIJ structural score for erosion, backfill, and ankylosis into 3 versions of a novel preliminary axSpA magnetic resonance imaging (MRI) SIJ Composite Structural Damage Score (CSDS) and to test these.Methods.Thirty-three patients with axSpA, followed for 5 years after initiation of tumor necrosis factor inhibitor, had MRIs of the SIJs at baseline, and yearly thereafter. Three versions of CSDS were calculated based on different weightings of erosion, backfill, and ankylosis: (1) equal weighting: CSDSequal = (erosion × 0.5) + backfill + ankylosis; (2) advanced stages weighting more: CSDSstepwise = (erosion × 1) + (backfill × 4) + (ankylosis × 6); and (3) advanced stages overruling earlier stages (“hierarchical”) with “hierarchical = (erosion × 1) < (backfill × 4) < (ankylosis × 6).Results.At baseline, all CSDS correlated positively with SPARCC fat and ankylosis scores and modified New York radiography grading, and negatively with the Bath Ankylosing Spondylitis Disease Index and SPARCC SIJ inflammation scores. CSDSstepwise and CSDShierarchical (not CSDSequal) correlated positively with symptom duration and the Bath Ankylosing Spondylitis Metrology Index, and closer with SPARCC ankylosis score and modified New York radiography grading than CSDSequal. The adjusted annual progression rate for CSDSstepwise and CSDShierarchical (not CSDSequal) was higher the first year compared with fourth year (P = 0.04 and P = 0.01). Standardized response mean (baseline to Week 46) was moderate for CSDShierarchical (0.64) and CSDSstepwise (0.59) and small for CSDSequal (0.25).Conclusion.Particularly CSDSstepwise and CSDShierarchical showed construct validity and responsiveness, encouraging further validation in larger clinical trials. The potential clinical implication is assessment of SIJ damage progression by 1 composite score.

Background Sagittal magnetic resonance (MR) images are typically obtained with the same spatial resolution along the entire spine, but cervical vertebrae are smaller and may be harder to assess. Purpose To investigate if high-resolution (high-res) short tau inversion recovery (STIR) and T1-weighted turbo spin echo (T1W) MR imaging (MRI) sequences are superior to standard resolution for detecting inflammatory and structural lesions in the cervical spine of patients with axial spondyloarthritis. Material and Methods Images were obtained in 36 patients. Voxel sizes at high/standard resolution were 1.99/4.33 mm3 (STIR) and 0.89/3.71 mm3 (T1W). High-resolution and standard-resolution images were scored by two readers according to the Canada-Denmark (CANDEN) MRI spine scoring system. Results Higher bone marrow edema scores were obtained at high resolution versus standard resolution (mean 2.1 vs. 1.2, P = 0.040), whereas fat lesion scores (1.8 vs. 1.5, P = 0.27) and new bone formation scores (3.5 vs. 2.8, P = 0.21) were similar. High-resolution MRI did not classify more patients as positive for bone marrow edema, fat, or new bone formation in the cervical spine compared to standard resolution. Using lateral radiographs as reference standard, sensitivity for detecting anterior corner syndesmophytes with both high-resolution and standard-resolution MRI was low (range 7–22%) and sensitivity for detecting ankylosis was low to moderate (20–55%), while specificity was high (≥96%). Conclusion High-resolution MRI allowed identification of more inflammatory lesions in the cervical spine in patients with axial spondyloarthritis when compared to standard resolution, but it did not classify more patients as positive for bone marrow edema. The slightly increased sensitivity at high-resolution MRI seemed to be too modest to have any real clinical importance.

ObjectivesThe Assessment of SpondyloArthritis international Society (ASAS) MRI working group (WG) was convened to generate a consensus update on standardised definitions for MRI lesions in the sacroiliac joint (SIJ) of patients with spondyloarthritis (SpA), and to conduct preliminary validation.MethodsThe literature pertaining to these MRI lesion definitions was discussed at three meetings of the group. 25 investigators (20 rheumatologists, 5 radiologists) determined which definitions should be retained or required revision, and which required a new definition. Lesion definitions were assessed in a multi-reader validation exercise using 278 MRI scans from the ASAS classification cohort by global assessment (lesion present/absent) and detailed scoring (inflammation and structural). Reliability of detection of lesions was analysed using kappa statistics and the intraclass correlation coefficient (ICC).ResultsNo revisions were made to the current ASAS definition of a positive SIJ MRI or definitions for subchondral inflammation and sclerosis. The following definitions were revised: capsulitis, enthesitis, fat lesion and erosion. New definitions were developed for joint space enhancement, joint space fluid, fat metaplasia in an erosion cavity, ankylosis and bone bud. The most frequently detected structural lesion, erosion, was detected almost as reliably as subchondral inflammation (κappa/ICC:0.61/0.54 and 0.60/0.83) . Fat metaplasia in an erosion cavity and ankylosis were also reliably detected despite their low frequency (κappa/ICC:0.50/0.37 and 0.58/0.97).ConclusionThe ASAS-MRI WG concluded that several definitions required revision and some new definitions were necessary. Multi-reader validation demonstrated substantial reliability for the most frequently detected lesions and comparable reliability between active and structural lesions.

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.

Objectives To investigate the diagnostic utility of different combinations of SI joint MRI lesions for differentiating patients with axial SpA (axSpA) from other conditions with and without buttock/pelvic pain. Methods A prospective cross-sectional study included patients with axSpA (n = 41), patients with lumbar disc herniation (n = 25), women with (n = 46) and without (n = 14) post-partum (birth within 4–16 months) buttock/pelvic pain and cleaning assistants (n = 26), long-distance runners (n = 23) and healthy men (n = 29) without pain. Two independent readers assessed SI joint MRI lesions according to the Spondyloarthritis Research Consortium of Canada MRI definitions and pre-defined MRI lesion combinations with bone marrow oedema (BME) and fat lesions (FAT), respectively. Statistical analyses included the proportion of participants with scores above certain thresholds, sensitivity, specificity, positive and negative predictive values and likelihood ratios. Results BME adjacent to the joint space (BME@joint space) was most frequent in axSpA (63.4%), followed by women with post-partum pain (43.5%), but was present in nearly all groups. BME adjacent to fat lesions (BME@FAT) and BME adjacent to erosions (BME@erosion) were only present in axSpA patients and in women with post-partum pain, but scores ≥3 and ≥4, respectively, were only seen in axSpA patients. FAT@erosion was exclusively recorded in axSpA patients. FAT@joint space and FAT@sclerosis were present in most groups, but with higher scores in the axSpA group. Conclusion BME@joint space and FAT@joint space were frequent in axSpA but also in other conditions, reducing the diagnostic utility. FAT@erosion, and BME@FAT, BME@erosion and FAT@sclerosis above certain thresholds, were exclusively seen in axSpA patients and may thus have diagnostic utility in the differentiation of axSpA from other conditions.

Purpose: To compare three region-of-interest (ROI) settings in the assessment of ADC in a clinical trial, and to evaluate the effectiveness of ADC in assessing therapy-induced changes and predicting clinical outcomes. Methods: In a 52-week clinical trial involving patients with axial spondyloarthritis, mean sacroiliac joint (SIJ) ADC measurements using structured, lesion-based, and index-lesion ROI-settings were assessed at baseline and weeks 4, 16, and 52. Variation among the three ROI-settings, correlations with Spondyloarthritis Research Consortium of Canada (SPARCC)-bone marrow edema (BME) SIJ inflammation indices, standardized response means (SRMs), and effectiveness in predicting clinical outcomes were analyzed. Results: Forty of the 53 patients had at least one assessable SIJ lesion on ADC at baseline. The mean of the structured ROI ADC (ADCstruc) was 230 μmm2/s (standard deviation [SD] = 120). This was significantly lower (p < 0.01) than the means of the lesion-based ROI ADC (ADClesion = 420 μmm2/s, SD = 210) and index-lesion ROI ADC (ADCindex = 471 μmm2/s, SD = 278), which did not differ. ADC correlated with SPARCC-BME scores at baseline (p < 0.01) as did changes over time in ADC- and SPARCC-BME (plesion (SRM > 0.92) and ADCindex (SRM > 0.87) while moderate for ADCstruc (SRM:0.54-0.67). Baseline ADC and changes in ADC did not predict clinical outcomes. Conclusions: Lesion-based and index-lesion ROI ADC could both be used to evaluate the effectiveness of tumor necrosis factor inhibitor therapy. None of the methods could predict clinical outcomes.

Background The apparent diffusion coefficient (ADC), as determined by whole-body diffusion-weighted MRI, may be useful as an outcome measure for monitoring response to treatment in chronic non-bacterial osteitis. Purpose To test and demonstrate the feasibility of ADC-measurement methods for use as outcome measure in chronic non-bacterial osteitis. Materials and Methods Using data from a randomized pilot study, feasibility of change-score ADC between baseline and second MRI (ΔADC12) and third MRI (ΔADC13) as outcome measure was assessed in three settings: “whole-lesion,” “single-slice per lesion,” and “index-lesion per patient”. Bone marrow edema lesions were depicted on short tau inversion recovery sequence at baseline and copied to ADC maps at the three time-points. Correlations between the three settings were measured as were analysis of variances. Discriminant validity was assessed as inter- and intra-observer reproducibility and smallest detectable change. Results 12 subjects were enrolled, and MRI was performed at baseline and weeks 12 and 36. Pearson correlation was high ( r > 0.86; p ≤ 0.01) for ΔADC between single-slice—whole-lesion and whole-lesion—index-lesion and tended to be significant for single-slice—index-lesion settings ( p = 0.06). For ΔADC12 and ΔADC13, Bland–Altman plots showed small differences (0.02, 0.03) and narrow 95% limits-of-agreement (−0.13–0.09, −0.07–0.05 μm2/s) between whole-lesion and single-slice ROI settings. Inter-observer reproducibility measured by intra-class correlation coefficient was poor-to-fair (range: 0.09–0.31), whereas intra-observer reproducibility was good-to-excellent (range: 0.67–0.90). Smallest detectable changes were between 0.21–0.28 μm2/s. Conclusion ADC change-score as outcome measure was feasible, and the single-slice per lesion ROI setting performed almost equally to whole-lesion setting resulting in reduced assessment time.

Objectives: To investigate the anatomical distribution, morphological abnormalities and response to adalimumab therapy of ultrasound(US)-detected peripheral enthesitis in patients with axial spondyloarthritis (SpA). Methods: In a randomized, placebo-controlled, double-blinded, investigator-initiated trial (NCT01029847), patients with axial SpA according to the Assessment of Spondyloarthritis International Society criteria were randomized to subcutaneous adalimumab 40 mg every other week or placebo from baseline to week 6. From week 6 to 24, all patients received adalimumab 40 mg every other week. Of 49 patients enrolled, 21 patients participated in our observational US sub-study. US assessment applying the OMERACT US definitions for enthesitis of 10 peripheral entheseal regions of the upper and lower extremities and clinical examination were performed at baseline, weeks 6 and 24. US was performed by one experienced investigator. Hypo-echogenicity, increased thickness and Doppler activity of the enthesis were considered signs of active inflammation, whereas insertional bone erosions, intratendinous calcifications, and enthesophytes were regarded as signs of structural lesions. Results: Enthesitis on US was mostly present in the lower limbs, especially in the Achilles tendon (81%), the quadriceps tendon (62%), and the greater femoral trochanter (52%). Structural lesions were predominant (38 vs. 12% of examined entheses with inflammatory changes), particularly in the entheses of the lower limbs, and exhibited no change during treatment. Conclusion: US-detected structural lesions were common while inflammatory lesions were relatively rare in patients initiating adalimumab due to axial SpA. Structural lesions did not appear to change during 24 weeks follow-up, suggesting that these lesions may not be helpful outcome measures in short-term clinical trials.

Objectives To investigate criteria for treatment response and remission in patients with axial SpA as assessed by whole-body magnetic resonance imaging (WB-MRI) of axial and peripheral joints and entheses during treatment with golimumab. Methods We performed an investigator-initiated cohort study of 53 patients who underwent WB-MRI at weeks 0, 4, 16 and 52 after initiation of golimumab. Images were assessed according to the Spondyloarthritis Research Consortium of Canada MRI SI joint inflammation index, Canada–Denmark MRI spine inflammation score and the MRI peripheral joints and entheses inflammation index. Results At weeks 4, 16 and 52, WB-MRI demonstrated an at least 50% reduction of MRI inflammation of the sacroiliac joints in 16, 29 and 32 (30%, 55% and 60%) patients, of the spine in 20, 30 and 31 (38%, 57% and 58%) patients and of peripheral joints and entheses in 8, 17 and 15 (15%, 32% and 28%) patients, respectively. The BASDAI50 response was achieved by 29, 31 and 31 (55%, 58% and 58%) patients, while ASDAS clinically important improvement (ASDAS-CII) was achieved by 37, 40 and 34 (70%, 75% and 64%) patients. WB-MRI remission criteria for spine, sacroiliac joints and peripheral joints and entheses were explored; total WB-MRI remission was attained by 2, 6 and 3 (4%, 11% and 6%) patients. At week 16, among 35 patients with an at least 50% reduction in the MRI Axial Inflammation Index (sacroiliac joint and spine inflammation), 29 (83%) achieved BASDAI50 and 35 (100%) achieved ASDAS-CII; among 16 patients with MRI axial inflammation non-response, 14 (88%) were BASDAI50 non-responders and 11 (69%) did not achieve ASDAS-CII. Conclusion WB-MRI demonstrated a significant reduction of inflammation in both the spine, sacroiliac joints and peripheral joints and entheses during golimumab treatment. Few patients achieved total WB-MRI remission. Combining spinal and sacroiliac joint inflammation in an MRI Axial Inflammation Index increased the ability to capture response. Trial registration ClinicalTrials.gov, http://clinicaltrials.gov, NCT02011386.

OBJECTIVE: Sacroiliac (SI) joint bone marrow edema (BME) is considered to be pivotal in the detection of early spondyloarthritis. However, the link between BME and development of spondyloarthritis-related bone remodeling remains unclear. This study was undertaken to investigate the evolution of BME and structural lesions in the SI joints over time.METHODS: Baseline and 4-year follow-up magnetic resonance imaging scans were conducted in 604 patients ages 18-40 years who were referred with low back pain to an outpatient spine clinic. Eight SI joint regions were scored for BME and categorized as absent, limited (50%). Structural lesions including erosions and fat lesions were scored as absent or present.RESULTS: SI joint BME was seen at either time point (baseline or at 4 years) in 41% of participants but was persistent at both time points in only 16% of participants. Structural SI joint lesions developed according to the extent of BME at baseline: limited, intermediate, and extensive BME (as compared to absent BME) were independently associated with erosion at follow-up with odds ratios (ORs) of 3, 5, and 46, respectively, and with fat lesions (ORs 3, 7, and 33, respectively). In regions with limited and intermediate BME at baseline, 60% and 50% had resolved by follow-up, respectively, while only 2% and 7% had evolved into extensive BME by follow-up.CONCLUSION: While extensive SI joint BME was a strong independent predictor of development of structural lesions, limited and intermediate BME were mostly transient and only rarely evolved into extensive BME or structural lesions. These findings enhance our understanding of the natural development of SI joint lesions and indicate different progression patterns for limited/intermediate versus extensive BME, possibly due to different etiologies.

OBJECTIVE: To evaluate whether different types of sacroiliac (SI) joint lesions identified by magnetic resonance imaging (MRI) could differentiate axial spondyloarthritis (SpA) from conditions with buttock or pelvic pain attributable to other reasons, including postpartum women and healthy subjects.METHODS: The study was designed as a prospective, cross-sectional study involving 204 participants, comprising patients with axial SpA (n = 41) and control groups of subjects with or without SI joint pain, including patients with lumbar disc herniation (n = 25), women with (n = 46) or without (n = 14) postpartum buttock/pelvic pain (having given birth within the preceding 4-16 months), hospital cleaning staff (n = 26), long-distance runners (n = 23), and healthy men (n = 29). Participants underwent clinical examination and MRI, and MRIs were evaluated in a blinded manner by 2 readers according to the Spondyloarthritis Research Consortium of Canada (SPARCC) SI joint inflammation and structural lesion scores. SPARCC score cutoff levels were defined as scores above a certain threshold. Primary analyses were based on reader agreement with regard to the presence of SI joint pathologic features on MRI ("concordant reads"). Sensitivity, specificity, and positive and negative predictive values were calculated.RESULTS: SI joint ankylosis and backfill were detected by MRI only in patients with axial SpA (32% and 37%, respectively), while bone marrow edema (BME) and fat lesions were seen in all non-axial SpA control groups (3-39% with BME and 4-14% with fat lesions). SI joint erosion was present only in patients with axial SpA and in women with postpartum buttock/pelvic pain (at erosion score cutoffs of >1 and >4, 61% and 34%, respectively, in patients with axial SpA, and 9% and 2%, respectively, in women with postpartum buttock/pelvic pain). A SPARCC BME score of ≥5 was present only in patients with axial SpA (56%) and in women with postpartum buttock/pelvic pain (24%), while fat lesions were present, albeit rarely, at high SPARCC cutoff scores in nearly all groups. Of the 38 women from the non-postpartum control groups who had given birth (mean time since birth 9.7 years), 2 (5%) had BME, whereas none had SI joint erosion or fat lesions, and none had a BME score of ≥4.CONCLUSION: BME and fat lesions were most pronounced in patients with axial SpA, but also occurred in other groups, particularly women with postpartum buttock/pelvic pain. Erosion above a certain SPARCC score threshold as well as backfill and ankylosis were highly specific for axial SpA.

Ankylosing spondyloarthritis (AS) is a chronic inflammatory disease that involves the axial joints and entheses. Extra-spinal manifestations such as anterior uveitis, psoriasis, and colitis also occur frequently. This review on the pathogenesis of AS includes an update on the recent discoveries within the field. HLA-B*27 is still considered of major importance in the pathogenesis, and it has recently been shown to profoundly affect the gut microbiome and its metabolites and the handling of bacteria during infection. Biochemical and biophysical properties of HLA-B*27 influence its ability to misfold, to induce an endoplasmic reticulum stress response, and to promote autophagy/unfolded protein responses (UPR). HLA-B*27 free heavy chains may induce inflammation through T cells, NK cells, and myeloid cells. Induction of UPR genes results in release of tumor necrosis factor-α (TNF-α), interleukin-17 (IL-17), IL-23, and interferon-γ and increase in T helper (Th) 17 cells. Several other HLA-B and non-B molecules have been associated with AS, although their role in the pathogenesis is unknown. Genotypes of endoplasmic reticulum aminopeptidases (ERAP) 1 and 2 have been associated with alterations in the antigenic pool expressed by HLA-B*27 molecules. In the gut, innate immune cells type 3 (ILC3) influence T cell expression of IL-17 and IL-22. Gamma-delta (γ/δ) T cells are induced by IL-23 to produce IL-17. IL-7 induces mucosa-associated invariant T (MAIT) cells to produce IL-17. Besides the microbiome, zonulin may be important through its effects on the permeability of tight junctions in the intestinal epithelial barrier.

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 The use of ultrasound (US) as a tool for assessing disease activity in patients with rheumatoid arthritis (RA) has increased in recent years and its value is supported by studies showing that US provides more accurate assessment of joint inflammation than clinical examination at time of diagnosis and in clinical state of remission. Various scoring systems have been proposed for monitoring of synovitis. Among these are the novel consensus-based Global OMERACT-EULAR Synovitis Score (GLOESS) was developed applying the highest score of grey-scale (GS) or Doppler as the final score for the joint. Different joint sets have been proposed for optimal and feasible evaluation of patients with inflammatory arthritis but currently there is no agreement on a specific reduced set of joints that should be evaluated by US to acquire the best information about clinical and subclinical activity when monitoring patients with RA. Objectives To evaluate if synovitis assessment of hands only is enough (testing GS, Doppler and GLOESS sum scores) for assessing changes during treatment in order to increase clinical feasibility of US in daily clinical practice. Methods US and clinical assessment for tender/swollen joint count (TJC/SJC) were performed in 19 patients fulfilling ACR 1987 criteria for RA initiating treatment with TNF inhibitor (TNFi) (week 0), and after 6 and 16 weeks of follow up. Forty-six joints were evaluated by US (sternoclavicular, acromioclavicular, glenohumeral, elbow, wrist, MCP1-5, PIP1-5, hip, knee, ankle and MTP 1-5 bilaterally) using a GE Logiq E9 machine with a linear array transducer. Joint inflammation was graded 0-3 on GS and Colour Doppler (CD) and synovitis was defined as a GS score >1 with or without Doppler score >1. Doppler settings for slow flow was applied according to guidelines. GS, CD and GLOESS sum scores were obtained for the total joint set and different joint subsets: hands as joint set (wrist, 1-5 MCP, 1-5 PIP bilaterally), 28 conventional joints evaluated for DAS and the 9-joint set suggested for the GLOESS (shoulder, elbow, wrist, MCP1 and 4, PIP2, MTP 3 and 5, knee). Data from the different joint sets were analyzed applying Spearman’s correlation coefficient. Results Mean change in GS sum score between week 0 and 16 was of 2.58, 1.35, 1.47 and 1.11 for 46-joint set, hands, 28-joint set and 9-joint set, respectively. Compared to the 46 joint set the GS and CD sums core had a high correlation coefficient (>0.78) for 28 joint set and the hand as joint set for all time points - table 1. The 9 joint set GS sum score had low correlation when compared to the 46 joint set at baseline and during follow up – table 1. GLOESS for the hands performed equally well with a correlation coefficient (>0.70) for all joint sets at all time points – table 1. DAS28-CRP did not correlate with the total joint set or the different joint subsets. Conclusion The present study of patients with RA shows that the US examination of both hands only for assessing disease activity is highly correlated for with the 46-joint evaluation at all time points, both regarding GS and Doppler sum scores. Using hands as a reduced joint set US assessment of inflammation could be an option to increase the feasibility of US in routine clinical practice. Disclosure of Interests Dolores Ramos-Bello: None declared, Hilde Berner Hammer Grant/research support from: AbbVie, Pfizer and Roche, Paid instructor for: AbbVie, Pfizer, UCB, Novartis, Roche, Speakers bureau: AbbVie, Pfizer, UCB, Novartis, Roche, Mette BjOrndal Axelsen: 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, Sin Ngai Ng: None declared, Merete L. Hetland Grant/research support from: BMS, MSD, AbbVie, Roche, Novartis, Biogen, Pfizer, Consultant for: Eli Lilly, Speakers bureau: Orion Pharma, Biogen, Pfizer, CellTrion, Merck, Samsung Bioepis, Susanne Juhl Pedersen: None declared, Lene Terslev Speakers bureau: Speakers fee from : Roche, Novartis, Pfizer, MSD, BMS, Celgene

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 MRI detected bone marrow edema (BME) plays a central role in the ASAS (Assessment of Spondyloarthritis International Society) classification criteria for axial spondyloarthritis (axSpA)[1, 2]. However, BME in the sacroiliac joints (SIJs) is also present in other conditions[3-7]. Objectives The aim was to investigate the diagnostic utility of MRI BME and its relation to different types of MRI SIJ lesions to separate patients with axSpA from persons with other conditions. Methods The MASH study is a prospective cross-sectional study of 204 participants, aged ≤45 yrs. The study included patients with axSpA (n=41), women with (n=46) and without (n=14) postpartum pain, patients with lumbar disc herniation (n=25), persons with hard physical labor (cleaning assistants) (n=25), long-distance runners (≥30 km/week) (n=23) and healthy men (n=29). Participants with pain should all have VAS pain >2 (on a scale 0-10) for ≥2 months. Participants in the non-axSpA groups were not allowed to have any clinical SpA features or rheumatological conditions. Participants underwent clinical, laboratory and MRI examination (semi-coronal STIR and T1W sequences) of the SIJs. MRIs were evaluated for BME, erosion, fat, ankylosis, and sclerosis according to the SPARCC MRI definitions of lesions[8, 9] by two independent readers. In nine slices of the cartilaginous compartment each SIJ was separately assessed for the presence of BME in relation to joint space and each of the above-mentioned structural lesions (range of total score per patient: 0-18). Results The table shows the clinical characteristics of each group, the mean MRI scores and MRI cut-off levels for the concordant reads. BME located adjacent to joint space, adjacent to erosions and adjacent to fat were more frequent in patients with axSpA, but these lesions were also seen in the other study groups, mainly women with postpartum pain. When increasing amounts of lesions were required (higher cut-offs), almost only AxSpA patients fulfilled the requirements. BME adjacent to sclerosis was most frequent in women with postpartum pain, whereas BME adjacent to ankylosis was only seen in patients with axSpA. Conclusion BME located adjacent to joint space, adjacent to erosion and adjacent to fat was most frequently, but not exclusively, occurring in patients with axSpA, whilst BME adjacent to sclerosis was most frequent in women with postpartum pain. Detailed analysis of lesions and their anatomical location may help differentiate axSpA from other conditions. References [1] Rudwaleit, et al. Ann Rheum 2009. [2] Lambert, et al. Ann Rheum 2016. [3] Weber, et al. Arthritis Rheum 2010. [4] Varkas, et al. Rheumatology (Oxford) 2018. [5] de Winter, et al. Arthritis Rheumatol 2018. [6] Arnbak, et al. Eur Radiol 2016. [7] Seven, et al. Ann Rheum 2018. [8] Maksymowych, et al. Arthritis Rheum 2005. [9] Maksymowych, et al. J Rheumatol 2015. Disclosure of Interests Sengul Seven: None declared, Pernille Hededal: 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, Lone Morsel-Carlsen: None declared, Inge Juul Sorensen: None declared, Birthe Bonde: None declared, Gorm Thamsborg: None declared, Jens Jorgen Lykkegaard: None declared, Oliver Hendricks Grant/research support from: AbbVie, Novartis, Niklas Rye Jorgensen: None declared, Susanne Juhl Pedersen: None declared

Background Whole body MRI (WBMRI) is a new promising tool for assessing synovitis in the whole body in one session, but is less validated. Ultrasound (US) is another sensitive and well-validated imaging technique that can assess the whole body in one session. Objectives To evaluate the agreement between US, WBMRI and clinical assessment of joint inflammation in rheumatoid arthritis (RA) patients on joint and patient level. Methods US, WBMRI and clinical assessment for tender joints (TJ) and swollen joints (SwJ) were performed in 19 RA patients (90% Women, median age 55 (26-73), diseases duration 5.5 years (1-42), SwJ(28) 5 (1-13), TJ(28) 7 (2-24) and DAS28-CRP 4.66 (3.48 -6.66))) fulfilling ACR 1987 criteria for RA. The 28 conventional joints, bilateral ankles and MTP 1-5 were assessed by WBMRI and US. Joint inflammation by US was graded 0-3 on both B-mode and colour Doppler (CD), and subsequently converted to +/- by defining US synovitis as B mode >2 or CD >1, and scored for individual joint. For WBMRI, joint inflammation was defined in two ways; 1) as presence of synovitis and/or osteitis, 2) as the presence of synovitis only. The total inflammatory burden was established as sum scores for the 28 conventional joints for US (US28) and for 26 joints (WBMRI26) for WMBRI - same 28 joints except elbows (due to poor image quality). The max score of a joint in US and WBMRI including osteitis was 2, while WMBRI excluding osteitis was 1. The agreement between the clinical joint assessment, US and WBMRI for joint inflammation was calculated with Cohen’s kappa (κ). The correlations between US28, WBMRI26 and DAS28-CRP were calculated by Spearman correlation coefficient (rho). Results When considering joint inflammation by WBMRI as synovitis and/or osteitis, US28 for synovitis and WBMRI26 sum scores showed good correlation rho= 0.72 (p=0.003) (Fig. 1), whereas US28 and WBMRI26 did not correlate with DAS28 CRP (rho=-0.26, p=0.28; rho=0.20, p=0.47 respectively). Moderate-good agreement was found between US and WBMRI in wrists and MCP 1, 2 and 5(κ= 0.42–0.62) but poor in other joints (κ By comparing WBMRI synovitis (excluding osteitis) with US synovitis, US28 and WBMRI26 sum scores showed weakened correlation rho= 0.46 (p=0.049) (Fig. 2), and without correlation between WBMRI26 and DAS28 CRP (rho=-0.07, p=0.78). At joint level, moderate-good agreement was found between US and WBMRI in wrists, MCP 2 and 5, and PIP 5(κ= 0.41–0.62) but poor in other joints (κ Agreement between US and clinical joint tenderness was poor (all κ Conclusion WBMRI and US sum scores of joint inflammation showed good correlation in RA patients for the overall inflammatory burden. The agreement at joint level was variable. Disclosure of Interests: Sin Ngai Ng: None declared, Mette Bjorndal Axelsen: 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, Iris Eshed: None declared, Merete L. Hetland Grant/research support from: BMS, MSD, AbbVie, Roche, Novartis, Biogen, Pfizer, Consultant for: Eli Lilly, Speakers bureau: Orion Pharma, Biogen, Pfizer, CellTrion, Merck, Samsung Bioepis, Jakob Mollenbach Moller: None declared, Susanne Juhl Pedersen: None declared, Lene Terslev Speakers bureau: Speakers fee from : Roche, Novartis, Pfizer, MSD, BMS, Celgene

Objective.To investigate the distribution of whole-body magnetic resonance imaging (WB-MRI) inflammatory lesions of peripheral joints and entheses, and their response to adalimumab (ADA) treatment and agreement with clinical measures of disease activity in patients with axial spondyloarthritis (axSpA).Methods.Explorative analysis of an investigator-initiated randomized controlled trial of ADA. WB-MRI was performed at weeks 0, 6, 24, and 48. Detailed analyses of WB-MRI lesions in peripheral joints and entheses were performed, including agreement with clinical measures of disease activity.Results.WB-MRI inflammatory lesions were most frequently observed in the acromioclavicular, metatarsophalangeal, and wrist joints (> 10% of joints), and at the greater trochanter, calcaneal insertion of the Achilles tendon, and ischial tuberosity (> 15% of entheses). Inflammation resolved in ≥ 2/3 of involved sternoclavicular, metacarpophalangeal, first carpometacarpal, hip, and tarsometatarsal joints, and pubic symphyses and medial femoral condyles. In contrast, inflammation resolved in ≤ 1/6 of involved acromioclavicular joints, knee joints, and supraspinatus tendon insertions at humerus. Tenderness of joints and entheses agreed poorly with WB-MRI inflammation (κ < 0.40). Joint tenderness resolved more frequently in MRI-positive than MRI-negative joints (8/13, 62% vs 9/34, 26%) after 6 weeks of active treatment.Conclusion.Inflammatory lesions of peripheral joints and entheses in patients with predominantly axSpA, and changes therein, can be mapped using WB-MRI, and it may contribute to differentiate between inflammatory and noninflammatory joint tenderness. (Trial registration: ClinicalTrials NCT01029847).

Objective The Assessment of SpondyloArthritis international Society (ASAS) has previously published criteria for spondyloarthritis (SpA). In the Spines of Southern Denmark cohort, which included patients with persistent low back pain and an unknown proportion of patients with SpA, our objectives were 1) to estimate the prevalence of magnetic resonance imaging (MRI) findings and clinical features included in the ASAS criteria for SpA and 2) to explore the associations between MRI findings and clinical features. Methods We included patients ages 18–40 years with persistent low back pain who had been referred to the Spine Centre of Southern Denmark. We collected information on clinical features (including HLA–B27 and high-sensitivity C-reactive protein) and MRI findings in the spine and sacroiliac (SI) joints. Results Of 1,020 included patients, 537 (53%) had at least 1 of the clinical features included in the ASAS criteria for SpA. Three clinical features were common—inflammatory back pain according to the ASAS criteria, a good response to nonsteroidal antiinflammatory drugs (NSAIDs), and family history of SpA. The prevalence of these features ranged from 15% to 17%. Sacroiliitis on MRI according to the ASAS definition was present in 217 patients (21%). Of those 217 patients, 91 (42%) had the minimum amount of bone marrow edema required according to the ASAS definition (a low bone marrow edema score). The presence of HLA–B27, peripheral arthritis, a good response to NSAIDs, and preceding infection were independently positively associated with MRI findings in the SI joints (odds ratios [ORs] of 1.9–9.0). The remaining 8 clinical features were not positively associated with MRI findings. Importantly, only age was independently associated with low bone marrow edema score at the SI joints (OR of 1.1 per year). Conclusion In this population, 53% had at least 1 clinical feature included in the ASAS criteria for SpA, and 21% had sacroiliitis according to the ASAS definition; furthermore, the associations between the clinical and imaging domains were inconsistent. The results indicate a need for further investigation of the importance of these findings in SpA, including investigation of the minimum requirements for defining sacroiliitis on MRI.

Objectives: The apparent diffusion coefficient (ADC) may be used as a biomarker for diagnosis and/or monitoring treatment response in patients with axial spondyloarthritis (axSpA), but this requires reliable ADC measurements. This study assessed test–retest repeatability and reproducibility of ADC measurements using four different region of interest (ROI) settings. Methods: In this prospective study, the sacroiliac joints (SIJs) of 25 patients with axSpA and 24 age- and sex-matched healthy volunteers were imaged twice at a mean interval of 6.8 days in a 1.5 T scanner using, multishot echoplanar diffusion-weighted sequences. ADCs at four ROI settings were assessed: 5 mm and 10 mm anatomic band-shaped, 15 mm linear, and 40 mm2 circular. Results: Intraclass correlation coefficient (ICC) assessments showed that the interstudy repeatability was good for median ADC (ADCmed) and 95th-percentile ADC (ADC95) measurements in patients with axSpA (0.77–0.83 and 0.75–0.83, respectively), but poor-to-moderate in healthy subjects (0.27–0.55 and 0.13–0.37, respectively). For all ROI settings, intrareader reproducibility was excellent for ADCmed-measurements (ICC:0.85–0.99) and moderate-to-excellent for ADC95 measurements (ICC:0.68–0.96). The 5 mm ROI had the least estimated bias and highest level of agreement on Bland–Altman plots. The interreader reproducibility was moderate (ICC:0.71). The 15 mm linear ROI produced significantly greater ADCmed and ADC95 measurements than all other ROI settings (p < 0.01–0.02), except for the circular ROI ADC95 measurements. Conclusion: ROI settings influence ADC measurements. Interstudy repeatability of SIJ ADC measurements is independent of ROI settings. However, the 5 mm ROI showed the least bias and random error and seems preferable. Advances in knowledge: ADC measurements are affected by ROI settings, and this should be taken into account when assessing ADC maps.

In Table 3, in the first row, 'Number of participants', all numbers had accidentally been moved one column to the left. This has now been corrected. The Publisher apologises for the error.

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: The apparent diffusion coefficient (ADC) may be used as a biomarker to diagnose axial spondyloarthritis (axSpA) and monitor therapeutic response.Purpose: To measure the repeatability of the ADC in healthy individuals and in patients with axSpA with and without active sacroiliitis in a test-retest set-up, and to correlate ADC to conventional magnetic resonance imaging (MRI) bone marrow edema (BME) scores and clinical findings.Material and Methods: A total of 25 patients with axSpA and 24 sex- and age-matched healthy individuals were prospectively examined with MRI twice within 10 days. Short tau inversion recovery (STIR), T1-weighted and diffusion-weighted imaging sequences were performed. Mono-exponential ADC maps were based on four b-values: 0; 50; 500; and 800. Inter-study repeatability and intra-reader reproducibility were investigated in subgroups, as were associations with conventional MRI and clinical findings.Results: The inter-study repeatability for the median ADC was moderate for all individuals (intraclass correlation coefficient [ICC] 0.66); it was good in patients with axSpA (ICC 0.79) and poor in healthy individuals (ICC 0.27). Significant differences in ADC were found between women and men (P = 0.03), and between patients with versus without BME on STIR (P = 0.01). ADC was associated with an MRI BME score and with age in women.Conclusion: ADC seems to be a repeatable parameter in patients with axSpA but not in healthy individuals. ADC is correlated with MRI sacroiliac joint BME score and with age in women.

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 …

Objective.To assess reliability, feasibility, and responsiveness of Hip Inflammation Magnetic resonance imaging Scoring System (HIMRISS) for bone marrow lesions (BML) in hip osteoarthritis (OA).Methods.HIMRISS was scored by 8 readers in 360 hips of 90 patients imaged pre/post-hip steroid injection. Pre-scoring, new readers trained online to achieve intraclass correlation coefficient (ICC) > 0.80 versus experts.Results.HIMRISS reliability was excellent for BML status (ICC 0.83–0.92). Despite small changes post-injection, reliability of BML change scores was high in femur (0.76–0.81) and moderate in acetabulum (0.42–0.56).Conclusion.HIMRISS should be a priority for further assessment of hip BML in OA, and evaluated for use in other arthropathies.

AIM Magnetic resonance imaging (MRI) can be used to identify sacroiliac joint (SIJ) inflammation and provide an earlier diagnosis of nonradiographic axial spondyloarthritis (nrAxSpA). However, MRI is frequently a resource-limited examination. Our aim was to assess if a set of physical clinical tests can identify SIJ inflammation in patients with nrAxSpA. METHODS Twenty participants with nrAxSpA underwent two functional tests (active straight leg raise, and stork test on the support side) and four pain provocation tests (Gaenslen's, posterior pelvic pain provocation, Patrick's Faber and palpation of the long dorsal SIJ ligament) for the SIJ, and then proceeded to a contemporaneous reference standard MRI. The Spondyloarthritis Research Consortium of Canada scoring system (SPARCC) was used to score MRI. Specificity, sensitivity, and likelihood ratios (LR) were calculated for individual clinical tests, and for the composite of tests. RESULTS Pain provocation tests were superior to functional tests, which showed poor accuracy. The Patrick's Faber test was the best performing procedure (sensitivity 71%, specificity 75%, positive LR 2.9, negative LR 0.4). When combining the provocation tests, a positive test in one out of two tests demonstrated the strongest predictive value (sensitivity 86%, specificity 62%, positive LR 2.2, negative LR 0.2). CONCLUSIONS Sacroiliac joint pain provocation tests correlate modestly with inflammation. The Patrick's Faber test showed the greater LR to identify SIJ inflammation in patients with nrAxSpA. SIJ pain provocation tests may offer a simple and cost-effective way of identifying patients with nrAxSpA who are most likely to have MRI evidence of inflammation.

OBJECTIVE: To investigate temporal changes in structural progression assessed by serial conventional radiography and magnetic resonance imaging (MRI) of the sacroiliac joints (SIJs) and spine in patients with ankylosing spondylitis (AS) treated with tumour necrosis factor (TNF) inhibitor for 5 years.METHOD: Forty-two patients were included and 33 patients were followed for 5 years in a prospective investigator-initiated study. Conventional radiographs were required four times and MRI seven times. The modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS); Spondyloarthritis Research Consortium of Canada (SPARCC) MRI SIJ and Spine Inflammation, and SPARCC MRI SIJ Structural Score (SSS) for Fat, Erosion, Backfill, and Ankylosis; and the Canada-Denmark MRI scores for Spine Inflammation, Fat, Erosion, and New Bone Formation (NBF) were applied.RESULTS: Compared with baseline, MRI Inflammation had decreased significantly at week 22 (spine)/week 46 (SIJ) and thereafter. MRI SIJ Fat (from week 22), SIJ Ankylosis, Spine NBF, and mSASSS had increased significantly at week 46 and thereafter. SIJ Erosion had decreased from year 2. The annual progression rate in mSASSS was significantly higher during weeks 0-46 compared to week 46 to year 3. In multivariate regression analyses, baseline SIJ Inflammation and Backfill were independent predictors of 5 year progression in SIJ Ankylosis. Spine Erosion predicted progression in Spine NBF. Longitudinally, Ankylosing Spondylitis Disease Activity Score, Bath Ankylosing Spondylitis Disease Activity Index, MRI Spine Inflammation, Fat, and Erosion scores were significantly associated with mSASSS. SIJ Inflammation, Fat, Erosion, and Backfill scores were longitudinally associated with SIJ Ankylosis. Structural progression was not associated with body mass index, smoking, or Assessment of SpondyloArthritis international Society Non-Steroidal Anti-Inflammatory Drug Index.CONCLUSION: In a 5 year follow-up study of patients with AS treated with TNF inhibitor, structural progression decreased over time.

Axial spondyloarthritis (axSpA) is a complex disease that affects the joints and entheses of axial and peripheral joints, and is associated with inflammation in extra-articular sites such as the gut. Improved knowledge on genetics and immunology has improved treatment options with the availability of treatments targeting tumor necrosis factor-α (TNF-α) and interleukin (IL)-17. However, these agents do not provide clinical benefit for about 40% of patients, and additional therapeutic options are necessary. Theories on pathogenesis includes misfolding of HLA-B*27 during its assembly leading to endoplasmic reticulum stress and autophagy/unfolded protein response (UPR). HLA-B*27 may express free heavy chain on the cell surface, which activates innate immune receptors on T, natural killer, and myeloid cells with pro-inflammatory effects. Activation of UPR genes is associated with increased TNF-α, interleukin-23 (IL-23), IL-17, interferon-γ expression, and expansion of T helper (Th)-17 cells. Certain genotypes of endoplasmic reticulum aminopeptidase (ERAP) 1 and 2 are associated with ankylosing spondylitis (AS) and functionally interact with the HLA-B27 peptidome. Innate immune cells type 3, which express RORγt, regulate expression of IL-17 and IL-22 in T cells. Stimulation of gamma-delta T cells with IL-23 also induces IL-17. Mucosa-associated invariant T cells residing in the gut mucosa express IL-17 in AS patients after stimulation with IL-7. Prostaglandin E2 induces IL-17A independent of IL-23 via IL-1β and IL-6. The pathogenic role of gut inflammation, zonulin and microbiota, which has a different composition in AS patients, remains to be elucidated. This article also includes a comprehensive review on the mechanism of action and efficacy of the biological treatments currently approved for axSpA (TNF-α inhibitors and IL-17 inhibitors) and future targets for treatment (other IL-17 family member (s), Janus kinase, IL-23, and phosphodiesterase 4).

Background Multiple correspondence analysis (MCA) is a statistical method that allows for the translation of data from multiple categorical variables into single coordinates per individual. When combined with cluster analysis, individuals that share phenotypic characteristics can be grouped together. The Assessment of Axial Spondyloarthritis international Society (ASAS) published classification criteria for axial spondyloarthritis (axSpA) in 20091 that included active sacroiliitis on magnet resonance imaging (MRI) of the sacroiliac joints (SIJ) defined as bone marrow oedema (BME) present in either as 2 lesions on one slice, or 1 lesion on 2 consecutive slices.2 It has been shown that extent of BME is associated with risk of radiographic progression.3 Objectives To identify phenotypes in low back pain (LBP) patients recruited from primary care with findings suggestive of early axSpA and to assess differences in size and frequency of BME lesions on SIJ MRI. Methods Age, gender and the ASAS SpA features (SIJ BME on MRI, HLA-B27, inflammatory back pain, arthritis, heel enthesitis, uveitis, psoriasis, inflammatory bowel disease, good response to NSAIDs, family history of SpA, but not dactylitis (not observed) or radiographic sacroiliitis) of 134 LBP patients who either met of were one feature short of meeting the ASAS classification criteria for axSpA were analysed by MCA and subsequent k-means cluster analysis in order to identify various clinical phenotypes. The above listed SpA features, and if present, the size and frequency of SIJ BME as defined by the Aarhus scoring module,4 were compared across clusters. Results MCA and cluster analysis revealed 3 clusters. Cluster 1 was predominantly HLA-B27 positive (96.7%) with SIJ BME in half of the cases. Cluster 2 and 3 had SIJ BME in all cases. Cluster 3 had fewer features suggestive of axSpA than clusters 1 and 2. There were significant differences in frequency (3.0 vs 2.0 vs 1.0) and extent of BME (4.0 vs 2.0 vs 1.0) across clusters 1, 2 and 3. Conclusions Three clusters were identified among LBP patients with findings suggestive of axSpA: 1 predominantly HLA-B27 positive cluster with SIJ BME in half of the subjects, and 2 clusters having less features suggestive of SpA and with SIJ BME in all subjects. The predominantly HLA-B27 positive cluster had more and larger BME lesions than the other 2, which may indicate individuals at risk for progression. References [1] Ann Rheum Dis2009;68(6):777–83; [2] Ann Rheum Dis2009;68(10):1520–7. [3] Arthritis Rheum2008;58(11):3413–3418. [4] ACR62(1):11–8. Disclosure of Interest None declared