Search

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 assess the ability of ultrasound to predict successful tapering and successful discontinuation of biological DMARDs (bDMARDs) at the 2-year follow-up in RA patients in sustained remission. Methods Patients in sustained remission (DAS28-CRP ≤ 2.6) and with no radiographic progression the previous year tapered bDMARDs according to a standardized regime. A total of 119 of these patients were included in this ultrasound substudy. At baseline, clinical assessment, MRI, X-ray and ultrasound of 24 joints were performed. Ultrasound-detected synovitis was defined and scored 0–3 using the OMERACT scoring system at the joint level for both grey-scale and Doppler activity. Sum scores for each ultrasound modality were calculated for 24 joints at the patient level. The final state of treatment was assessed after 2 years. The predictive value of ultrasound measures for successful tapering and discontinuation at the 2-year follow-up was assessed via logistic regression analyses. Results Negative IgM-RF [odds ratio (OR) = 0.29, 95% CI: 0.10–0.85; P = 0.024] and lower Doppler sum score of 24 joints (OR = 0.44, 95% CI: 0.15, 0.87; P = 0.014) were independent predictors for successful discontinuation of bDMARDs at the 2-year follow-up. The predictive value of the Doppler sum score was independent of MRI findings. Previous numbers of bDMARDs were predictive of successful tapering (OR = 0.58, 95% CI: 0.35, 0.91; P = 0.018), whereas ultrasound was not. Clinical parameters were not predictive of successful tapering/discontinuation. Conclusion Doppler sum score was an independent predictor for successful discontinuation of bDMARDs at the 2-year follow-up—the odds for achieving successful discontinuation decreased by 56% per one-unit increase in Doppler sum score. Ultrasound could not predict successful tapering.

ObjectiveTo identify predictors of flare in a 2-year follow-up study of patients with rheumatoid arthritis (RA) in sustained clinical remission tapering towards withdrawal of biological disease-modifying anti-rheumatic drugs (bDMARDs).MethodsSustained clinical remission was defined as Disease Activity Score for 28 joints (DAS28)-C reactive protein (CRP) ≤2.6 without radiographic progression for >1 year. bDMARDs were tapered according to a mandatory clinical guideline to two-thirds of standard dose at baseline, half of dose at week 16 and discontinuation at week 32. Prospective assessments for 2 years included clinical evaluation, conventional radiography, ultrasound and MRI for signs of inflammation and bone changes. Flare was defined as DAS28-CRP ≥2.6 with ∆DAS28-CRP ≥1.2 from baseline. Baseline predictors of flare were assessed by logistic regression analyses.ResultsOf 142 included patients, 121 (85%) flared during follow-up of which 86% regained remission within 24 weeks after flare. Patients that flared were more often rheumatoid factor positive, had tried more bDMARDs and had higher baseline ultrasound synovitis sum scores than those not flaring. For patients on standard dose, predictors of flare within 16 weeks after reduction to two-thirds of standard dose were baseline MRI-osteitis (OR 1.16; 95% CI 1.03 to 1.33; p=0.014), gender (female) (OR 6.71; 95% CI 1.68 to 46.12; p=0.005) and disease duration (OR 1.06; 95% CI 1.01 to 1.11; p=0.020). Baseline predictors for flare within 2 years were ultrasound grey scale synovitis sum score (OR 1.19; 95% CI 1.02 to 1.44; p=0.020) and number of previous bDMARDs (OR 4.07; 95% CI 1.35 to 24.72; p=0.007).ConclusionThe majority of real-world patients with RA tapering bDMARDs flared during tapering, with the majority regaining remission after stepwise dose increase. Demographic and imaging parameters (MR-osteitis/ultrasound greyscale synovitis) were independent predictors of immediate flare and flare overall and may be of importance for clinical decision-making in patients eligible for tapering.

AimTo describe salivary gland involvement in patients suspected of Sjögren’s syndrome (SS) using the OMERACT Ultrasound Scoring System for SS. Next, using different ultrasound cut-offs, to assess the performance of the scoring system for diagnosis and fulfilment of 2016 ACR/EULAR SS classification criteria.MethodsAll patients referred to our department with a suspicion of SS in a 12-month period were included. All underwent grey-scale ultrasound of the parotid and submandibular glands prior to clinical examination, Schirmer’s test, unstimulated salivary flow, blood samples including autoantibody analysis. Labial biopsy was performed according to clinicians’ judgement. Images of the four glands were scored 0–3 according to the scoring system and a consensus score was obtained using a developed ultrasound atlas.ResultsOf the 134 patients included in the analysis, 43 were diagnosed with primary SS (pSS) and all fulfilled the 2016 American College of Rheumatology (ACR)/EULAR classification criteria. More patients with pSS compared with non-pSS had score ≥2 in at least one gland (72% vs 13%; pConclusionThe OMERACT Ultrasound Scoring System showed good sensitivity (0.72) and excellent specificity (0.91) for fulfilling 2016 ACR/EULAR criteria using cut-off score >2 in at least one gland. Our data supports the use of ultrasound for diagnosing pSS and supports incorporation of ultrasound in the classification criteria.

Objective This study was undertaken to assess the inflammatory burden in peripheral spondyloarthritis (SpA) by magnetic resonance imaging (MRI) of the legs in an early remission-induction strategy study of tumor necrosis factor (TNF) blockade. Furthermore, we sought to determine the value of MRI to predict disease relapse versus sustained remission after treatment discontinuation. Methods Thirty-two patients with early peripheral SpA with involvement of the legs determined on clinical examination and confirmed by ultrasonography (US) participated in a remission-induction trial of a TNF inhibitor (TNFi). Patients underwent MRI of the joints and entheses of the legs at baseline and at clinical remission, after which TNFi treatment was withdrawn. Images were evaluated for joint effusion, joint osteitis, entheseal soft tissue inflammation, and entheseal osteitis. Results Joint effusion and enthesitis on clinical examination and US correlated well with MRI abnormalities. In addition, a substantial amount of subclinical involvement was seen on MRI, mainly in the ankle joints and heel entheses. Inflammation scores were markedly lower in the subclinically involved joints and entheses versus those that were clinically involved (P values ranged from 0.01 to

Objective To evaluate and compare benefits and harms of three biological treatments with different modes of action versus active conventional treatment in patients with early rheumatoid arthritis. Design Investigator initiated, randomised, open label, blinded assessor, multiarm, phase IV study. Setting Twenty nine rheumatology departments in Sweden, Denmark, Norway, Finland, the Netherlands, and Iceland between 2012 and 2018. Participants Patients aged 18 years and older with treatment naive rheumatoid arthritis, symptom duration less than 24 months, moderate to severe disease activity, and rheumatoid factor or anti-citrullinated protein antibody positivity, or increased C reactive protein. Interventions Randomised 1:1:1:1, stratified by country, sex, and anti-citrullinated protein antibody status. All participants started methotrexate combined with (a) active conventional treatment (either prednisolone tapered to 5 mg/day, or sulfasalazine combined with hydroxychloroquine and intra-articular corticosteroids), (b) certolizumab pegol, (c) abatacept, or (d) tocilizumab. Main outcome measures The primary outcome was adjusted clinical disease activity index remission (CDAI≤2.8) at 24 weeks with active conventional treatment as the reference. Key secondary outcomes and analyses included CDAI remission at 12 weeks and over time, other remission criteria, a non-inferiority analysis, and harms. Results 812 patients underwent randomisation. The mean age was 54.3 years (standard deviation 14.7) and 68.8% were women. Baseline disease activity score of 28 joints was 5.0 (standard deviation 1.1). Adjusted 24 week CDAI remission rates were 42.7% (95% confidence interval 36.1% to 49.3%) for active conventional treatment, 46.5% (39.9% to 53.1%) for certolizumab pegol, 52.0% (45.5% to 58.6%) for abatacept, and 42.1% (35.3% to 48.8%) for tocilizumab. Corresponding absolute differences were 3.9% (95% confidence interval −5.5% to 13.2%) for certolizumab pegol, 9.4% (0.1% to 18.7%) for abatacept, and −0.6% (−10.1% to 8.9%) for tocilizumab. Key secondary outcomes showed no major differences among the four treatments. Differences in CDAI remission rates for active conventional treatment versus certolizumab pegol and tocilizumab, but not abatacept, remained within the prespecified non-inferiority margin of 15% (per protocol population). The total number of serious adverse events was 13 (percentage of patients who experienced at least one event 5.6%) for active conventional treatment, 20 (8.4%) for certolizumab pegol, 10 (4.9%) for abatacept, and 10 (4.9%) for tocilizumab. Eleven patients treated with abatacept stopped treatment early compared with 20-23 patients in the other arms. Conclusions All four treatments achieved high remission rates. Higher CDAI remission rate was observed for abatacept versus active conventional treatment, but not for certolizumab pegol or tocilizumab versus active conventional treatment. Other remission rates were similar across treatments. Non-inferiority analysis indicated that active conventional treatment was non-inferior to certolizumab pegol and tocilizumab, but not to abatacept. The results highlight the efficacy and safety of active conventional treatment based on methotrexate combined with corticosteroids, with nominally better results for abatacept, in treatment naive early rheumatoid arthritis. Trial registration EudraCT2011-004720-35, NCT01491815 .

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.

Objectives Serious infection is a concern for patients with inflammatory joint diseases treated with biological drugs (bDMARDs). The objectives were to compare risk of serious infection, defined as infection leading to hospitalization, in patients initiating bDMARD treatment with the general population and, second, to develop a simple clinical prediction model and to obtain risk estimates for individual patients. Methods Matched-cohort study based on nationwide registries in Denmark. Patients with rheumatoid arthritis, axial spondyloarthritis and psoriatic arthritis initiating first bDMARD monitored in the DANBIO registry were matched 1:10 by age, gender and postal code with controls from the general population. The risk of serious infection during 12 months’ follow-up was assessed with Cox regression. Prediction models were developed using logistic regression and compared using area under the ROC curve (AUC). Results We included 11 372 patients and 113 715 controls. During follow-up, 522 patients (4.6%) and 1,434 controls (1.3%) developed a serious infection (hazard ratio 3.7, 95% confidence interval: 3.4–4.1). Age-stratified risk was largely similar across diagnoses. A simple prediction model, the “DANBIO infection risk score” based on age and a count of six clinical risk factors had moderate discriminative power (internal validation: AUC 0.69), which was comparable to that of the existing RABBIT risk score (external validation: AUC 0.68). Conclusion Patients with inflammatory joint diseases initiating bDMARD treatment had four times increased risk of serious infection compared with the general population. A simple prediction model, feasible for shared decision-making, was developed to obtain risk estimates for individual patients.

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.

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

Background:The optimal first-line treatment of patients (pts) with early rheumatoid arthritis (RA) is yet to be established.Objectives:The primary aim was to assess and compare the proportion of pts who achieved remission with active conventional therapy (ACT) and with three different biologic therapies after 24 wks. Secondary aims were to assess and compare other efficacy measures.Methods:The investigator-initiated NORD-STAR trial (NCT01491815) was conducted in the Nordic countries and Netherlands. In this multicenter, randomized, open-label, blinded-assessor study pts with treatment-naïve, early RA with DAS28>3.2, and positive RF or ACPA, or CRP >10mg/L were randomized 1:1:1:1. Methotrexate (25 mg/week after one month) was combined with: 1) (ACT): oral prednisolone (tapered quickly);or: sulphasalazine, hydroxychloroquine and mandatory intra-articular (IA) glucocorticoid (GC) injections in swollen joints Results:812 pts were randomized. Age was 54.3±14.7 yrs (mean±SD), 31.2% were male, DAS28 5.0±1.1, 74.9% were RF and 81.9% ACPA positive. Fig 1 shows the adjusted CDAI remission rates over time with 95% CI. Table shows crude remission and response rates and absolute differences in adjusted remission and response rates (superiority analysis). Differences in remission and response rates with CZP and TCZ, but not with ABA, remained within the pre-defined non-inferiority margin versus ACT, Fig 2.Figure 1.CDAI remission over time (adj. estimates with 95% CI)Figure 2.Non-inferiority analysis of protocol population. Estimated differences in CDAI remission rates between Arm 1 (active conventional therapy) and Arms 2, 3, and 4 (biologic arms) as reference with 95% confidence intervals, adjusted for gender, ACPA status, country, age, body-mass index and baseline DAS28-CRP. ABA, abatacept; CZP, certolizumab-pegol; MTX, methotrexate; TCZ, tocilizumab.Conclusion:High remission rates were found across all four treatment arms at 24 wks. Higher CDAI remission rate was observed for ABA versus ACT (+9%) and for CZP (+4%), but not for TCZ (-1%). With the predefined 15% margin, ACT was non-inferior to CZP and TCZ, but not to ABA. This underscores the efficacy of active conventional therapy based on MTX combined with glucocorticoids and may guide future treatment strategies for early RA.Table.Primary and key secondary outcomes at 24 weeks (ITT)Active conventional therapy (ACT)Certolizumab+MTXAbatacept+MTXTocilizumab+MTXNo of pts (ITT)200203204188§Crude remission and response ratesCDAI remission42.0%47.8%52.5%41.0%ACR/EULAR Boolean remission34.0%38.4%37.3%31.4%DAS28 remission63.5%68.5%69.6%63.3%SDAI remission41.5%49.8%51.5%42.6%EULAR good response71.5%76.9%79.9%71.3%Difference (95% CI) in rates with Arm 1 as reference (adjusted)CDAI remissionRef4% (-5 to 13%)9% (0.1 to 19%)-1% (-10 to 9%)ACR/EULAR Boolean remissionRef4% (-6 to 13%)5% (-5 to 14%)-4% (-13 to 6%)DAS28 remissionRef3% (-6 to 11%)5% (-4 to 13%)-1% (-10 to 8%)SDAI remissionRef6% (-3 to 18%)9% (-0.3 to 18%)1% (-8 to 11%)EULAR good responseRef4% (-4 to 14%)8% (-2 to 18%)0.4% (-10 to 11%)§17 patients allocated to Tocilizumab did not receive it due to its unavailability and were excluded from ITT.Acknowledgments:Manufacturers provided CZP and ABA.Disclosure of Interests:Merete L. Hetland Grant/research support from: BMS, MSD, AbbVie, Roche, Novartis, Biogen and Pfizer, Consultant of: Eli Lilly, Speakers bureau: Orion Pharma, Biogen, Pfizer, CellTrion, Merck and Samsung Bioepis, Espen A Haavardsholm Grant/research support from: AbbVie, UCB Pharma, Pfizer Inc, MSD Norway, Roche Norway, Consultant of: Pfizer, AbbVie, Janssen-Cilag, Gilead, UCB Pharma, Celgene, Lilly, Paid instructor for: UCB Pharma, Speakers bureau: Pfizer, AbbVie, UCB Pharma, Celgene, Lilly, Roche, MSD, Anna Rudin Consultant of: Astra/Zeneca, Dan Nordström Consultant of: Abbvie, Celgene, Lilly, Novartis, Pfizer, Roche and UCB., Speakers bureau: Abbvie, Celgene, Lilly, Novartis, Pfizer, Roche and UCB., Michael Nurmohamed Grant/research support from: Not related to this research, Consultant of: Not related to this research, Speakers bureau: Not related to this research, Björn Gudbjornsson Speakers bureau: Novartis and Amgen, Jon Lampa Speakers bureau: Pfizer, Janssen, Novartis, Kim Hørslev-Petersen: None declared, Till Uhlig Consultant of: Lilly, Pfizer, Speakers bureau: Grünenthal, Novartis, Gerdur Gröndal: 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, Marte Heiberg: None declared, Jos Twisk: None declared, Simon Krabbe: None declared, Kristina Lend: None declared, Inge Olsen: None declared, Joakim Lindqvist: None declared, Anna-Karin H Ekwall Consultant of: AbbVie, Pfizer, Kathrine L. Grøn Grant/research support from: BMS, Meliha C Kapetanovic: None declared, Francesca Faustini: None declared, Riitta Tuompo: None declared, Tove Lorenzen: None declared, Giovanni Cagnotto: None declared, Eva Baecklund: None declared, Oliver Hendricks Grant/research support from: Pfizer, MSD, Daisy Vedder: None declared, Tuulikki Sokka-Isler: None declared, Tomas Husmark: None declared, Maud-Kristine A Ljosa: None declared, Eli Brodin: None declared, Torkell Ellingsen: None declared, Annika Soderbergh: None declared, Milad Rizk Speakers bureau: AbbVie, Åsa Reckner: None declared, Per Larsson: None declared, Line Uhrenholt Speakers bureau: Abbvie, Eli Lilly and Novartis (not related to the submitted work), Søren Andreas Just: None declared, David Stevens: None declared, Trine Bay Laurberg Consultant of: UCB Pharma (Advisory Board), Gunnstein Bakland Consultant of: Novartis, UCB, Ronald van Vollenhoven Grant/research support from: BMS, GSK, Lilly, UCB, Pfizer, Roche, Consultant of: AbbVie, AstraZeneca, Biogen, Biotest, Celgene, Gilead, Janssen, Pfizer, Servier, UCB, Speakers bureau: AbbVie, Pfizer, UCB

Background Whole-body MRI (WBMRI) is a promising tool for monitoring disease activity in inflammatory joint diseases. Earlier studies have shown good correlation with conventional MRI and scoring systems for WBMRI have been developed [1,2]. However, the validation of WBMRI is limited; no studies have evaluated the agreement between repeated scans (interscan agreement) and only few studies have evaluated the intra- and interreader agreement. Objectives To validate WBMRI by evaluating the interscan agreement in patients with psoriatic arthritis (PsA), rheumatoid arthritis (RA) and healthy controls (HC) and to evaluate the intra- and interreader agreement and determine the distribution of pathologies in the subjects. Methods WBMRI was performed twice with a one-week interval in 14 patients with PsA, 10 with RA and 16 HC. Coronal images of shoulders, hips, hands and ankles/feet, and sagittal images of knees, ankles, feet and spine were obtained (STIR and pre- and post-contrast T1 weighted spin echo images). Images were anonymized and read in pairs with unknown chronological order by experienced readers (peripheral: IE; spine: SK). WBMRI was scored for 83 peripheral joints and for 33 peripheral entheses according to the OMERACT WBMRI scoring system [1], and according to the CanDen MRI spine scoring system [2]. Ten image sets were re-anonymized for assessment of intra- and interreader agreement (peripheral and spine: MO). Agreement was calculated on lesion level by percentage exact agreement (PEA) and Cohen’s kappa with squared weights, and for sum scores by absolute agreement single-measure intraclass correlation coefficient (ICC). Results The age in the PsA/RA/HC was median (range) 48(31-68)/49(26-58)/35(23-54) years and the symptom duration 10(0-24)/7(3-24)/NA years. WBMRI of the spine and peripheral joints and entheses generally showed moderate to almost perfect interscan agreement with a PEA ranging from 95-100%, kappa ranging from 0.71-1.00 and ICC ranging from 0.95-1.00 (Table 1). Intra- and interreader agreement showed moderate to almost perfect agreement with few exceptions (Table 2). More lesions were found in patients than HC. PsA patients had more lesions in acromioclavicular and sternoclavicular joints, whereas RA patients had more hand lesions (Figure 1). PsA patients had more lesions in the spine (Figure 2). Conclusion WBMRI of the spine and peripheral joints and entheses showed very good interscan agreement, implying that repositioning between examinations does not markedly affect scoring of lesions. Intra- and interreader agreement showed moderate to almost perfect agreement. The distribution of findings in PsA, RA and HC was determined. References [1] Krabbe, et al., J Rheumatol, 2019 (in press) [2] Krabbe, et al., RMD Open, 2018;4;e000624. Disclosure of Interests Anna Enevold Floeistrup Poulsen: None declared, Mette Bjoerndal Axelsen: None declared, Rene Panduro Poggenborg: None declared, Iris Eshed: None declared, Simon Krabbe: None declared, Daniel Glinatsi: None declared, Jakob Mollenbach Moller: 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

Background: Patients with rheumatoid arthritis (RA), axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) treated with biological drugs (bDMARDs) have increased risk of hospitalized infection (i.e. infection causing admission to hospital) compared to the general population. Since patients with RA, axSpA and PsA have different age distributions, and age is an important predictor for infection, we found it of interest to quantify the excess burden of hospitalized infection in patients with inflammatory arthritis treated with bDMARDs compared to the general population and to investigate whether risk depended on age and diagnosis. Objectives: To compare the risk of hospitalized infection in bio-naive patients with inflammatory arthritis, who started treatment with a bDMARD with that of the general population, and to explore how this risk was influenced by age and diagnosis. Methods: Matched cohort study based on data from The Danish Rheumatology Register (DANBIO) linked with The Danish National Patient Register and The Danish National Prescription Register. Patients with a diagnosis of RA, PsA or axSpA in DANBIO initiating first bDMARD January 2006-December 2016 were included. For each patient, 10 controls from the general population, matched by age, sex, postal code and date were obtained. Infection risk in patients and matched controls were compared in analyses stratified by age and diagnosis, with Cox proportional hazards models accounting for matching. Follow-up time was 12 months irrespective of whether treatment was continued or changed during follow-up. Clinicaltrials.gov: NCT03496831. Results: In total, 11,372 patients and 113,715 controls were included. Overall, hospitalized infection was observed during follow-up in 4.6% of patients and 1.3% of controls; hazard ratio 3.7 (95% confidence interval (CI): 3.4-4.1). The absolute risk was highest in RA patients, followed by PsA, axSpA and controls (unadjusted comparison). When stratified by age, the absolute risk increased with age, but was largely similar across diagnoses (Figure). In the stratum ≥60 years, RA patients appeared to have higher risk than axSpA patients, but the subgroup of axSpA patients ≥60 years was small. Conclusion: The risk of hospitalized infection during 12 months of follow-up was approximately four times higher in bio-naive patients with inflammatory arthritis who started treatment with a biological drug (bDMARD) compared to matched controls from the general population. When stratified by age, the absolute risk was largely similar across the diagnoses RA, axSpA and PsA. Thus, attention to preventive strategies such as vaccination seems prudent in these patients, especially those ≥60 years of age. Disclosure of Interests: Simon Krabbe: None declared, Kathrine L. Gron: None declared, Bente Glintborg Grant/research support from: Biogen, Pfizer, AbbVie, Frank Mehnert: None declared, Dorte E. Jarbol: 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, 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

Objective.A systematic literature review was performed to document published magnetic resonance imaging (MRI) lesion definitions and scoring systems for enthesitis in spondyloarthritis (SpA).Methods.PubMed, Embase, and Cochrane Library databases were searched for original publications involving adult patients with SpA undergoing MRI of axial/peripheral joints. Selected articles were assessed for quality using a standardized assessment tool and metric indices.Results.Considering the heterogeneous design, quality, and outcome measures of studies, statistical data pooling was considered inappropriate. A qualitative narrative of results was undertaken based on study designs.Conclusion.Lack of a comprehensive, validated score warrants additional research to develop an MRI enthesitis scoring system. PROSPERO registration number: CRD42018090537.

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: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

The effect of formation and modification methods on the physical properties of polymersomes is critical for their use in applications relying on their ability to mimic functional properties of biological membranes. In this study, we compared two formation methods for polymersomes made from polybutadiene-polyethylene oxide diblock copolymers: detergent-mediated film rehydration (DFR) and solvent evaporation (SE). DFR-prepared polymersomes showed a three times higher permeability compared to SE-prepared polymersomes as revealed by stopped-flow light scattering. SE-prepared polymersomes broke down faster to structures

Background:MRI allows an objective assessment of signs of inflammation in peripheral joints and entheses and is therefore of potential interest as outcome measure in trials. No knowledge exists on the reliability and validity of semi-quantitative MRI scores in the setting of peripheral spondyloarthritis (pSpA).Objectives:To describe the reliability of a semi-quantitative lower-extremity MRI scoring system, to investigate correlation with known measures of disease activity and ability to capture patients with improvement during treatment.Methods:In a post-hoc analysis, scores from 3 readers (LJ, MØ, SK) who independently assessed MRI images of pelvis (except sacroiliac joints), knees and ankles in the CRESPA trial blinded to chronology and all clinical data, were further analyzed. Entheses were scored 0-3 (none/mild/moderate/severe) for soft tissue inflammation (19 sites) and 0-3 for bone marrow edema (24 sites), joints were scored 0-3 for effusion/synovitis (10 sites) and 0-3 for bone marrow edema (22 sites). MRI score was defined as the sum of scores from all joints and entheses (i.e. all 75 sites). The CRESPA trial (NCT01426815) included 60 patients with early pSpA, defined as a symptom duration of Results:MRI scores at baseline were mean 7.2 (median 5, inter-quartile range 3 to 9, range 0 to 32). MRI change scores were mean −3.1 and (median −1, IQR −4 to 0, range −18 to 2). MRI status scores at baseline (n=56) had single measure ICC 0.78 (95% CI: 0.66-0.87) and average measure ICC 0.92 (0.85-0.95). MRI change scores (n=46) had single measure ICC 0.73 (0.57-0.84) average measure ICC 0.89 (0.80-0.94).MRI status scores correlated significantly with CRP, ESR, swollen joint count and pain score.Patients with PSpARC40 response (n=34) (≥40% improvement in disease activity according to the Peripheral SpA Response Criteria) had larger decreases in MRI scores compared to patients without PSpARC40 response (n=11), mean −3.4 vs. −1.0, p=0.03.When using all MRI data from pelvis, knees and ankles combined, more patients could be identified to have improvement, as compared to only taking one of three parts into account.MRI scores of pelvis, knees and feet combinedMRI scores of pelvis onlyMRI scores of knees onlyMRI scores of ankles onlyNumber of patients with improvement in MRI score > SDC15 (33%)9 (20%)12 (26%)14 (30%)Number of patients with improvement in MRI score ≥ 50%21 (46%)10 (22%)20 (43%)17 (37%)Net number of patients with improvement in MRI score*24 (52%)6 (13%)21 (46%)15 (33%)Number of patients with improvement in MRI score as assessed by 3 readers17 (37%)3 (7%)11 (24%)13 (28%)*Patients with improvement minus patients with worsening.Conclusion:The semi-quantitative lower-extremity MRI score showed acceptable reliability and validity. The ability to capture response was best when combining information from all available areas that were imaged, i.e. both pelvis, knees and ankles.*First authorship is shared between SK and TR.Disclosure of Interests:Simon Krabbe Grant/research support from: AbbVie, MSD, Novartis, Thomas Renson: None declared, Lennart Jans: None declared, Dirk Elewaut: None declared, Filip van den Bosch Consultant of: AbbVie, Celgene Corporation, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer, and UCB, Speakers bureau: AbbVie, Celgene Corporation, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer, and UCB, Philippe Carron: 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

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 …

Obesity is a major threat to global health and metabolically associated with glycerol homeostasis. Here we demonstrate that in human adipocytes, the decreased pH observed during lipolysis (fat burning) correlates with increased glycerol release and stimulation of aquaglyceroporin AQP10. The crystal structure of human AQP10 determined at 2.3 Å resolution unveils the molecular basis for pH modulation—an exceptionally wide selectivity (ar/R) filter and a unique cytoplasmic gate. Structural and functional (in vitro and in vivo) analyses disclose a glycerol-specific pH-dependence and pinpoint pore-lining His80 as the pH-sensor. Molecular dynamics simulations indicate how gate opening is achieved. These findings unravel a unique type of aquaporin regulation important for controlling body fat mass. Thus, targeting the cytoplasmic gate to induce constitutive glycerol secretion may offer an attractive option for treating obesity and related complications., Uptake and release of glycerol from the small intestine and adipocytes is facilitated by a subclass of aquaporins (AQP), but how glycerol flow is regulated remains poorly understood. Here authors solve the crystal structure of AQP10 and show how lipolysis is coupled to AQP10 regulation in

Background Enthesitis is a hallmark of spondyloarthritis (SpA), which occurs in 30% to 50% of psoriatic arthritis patients (pts).1 Evaluation of tenderness at the site of an enthesis with a standard palpation approach remains the gold standard for detection of enthesitis. However, inter- and intra-observer variability is rather high. All existing clinical enthesitis scoring systems lack validity. Imaging could avoid these drawbacks. Objectives To compare the performance of ultrasound (US) and magnetic resonance imaging (MRI) with clinical examination (CE) of joints and entheses in peripheral (p)SpA. Methods Clinical REmission in peripheral SPondyloArthritis (CRESPA) is a placebo-controlled trial of golimumab treatment in 60 early (symptom duration Results Synovitis detected by US and MRI was most prevalent at knee joints (table 1). A discrepancy was noted between TC synovitis detected by CE, US and MRI. Enthesitis was most prevalent at Achilles tendon and plantar fascia. Regarding enthesitis, agreement between CE and US ranged from no (kappa −0.082) to moderate agreement (kappa 0.562). The highest agreement was observed at the entheseal sites of Achilles tendon (left 0.511, right 0.350) and plantar fascia (left 0.321, right 0.507). MRI did not correlate better with CE than US (kappa from −0.077 to 0.446). The correlation between MRI and US was overall poor and only in the Achilles tendon moderate (range −0.106 to 0.656). Conclusions There was a weak agreement between CE and imaging in detecting enthesitis. In general, US detects less enthesitis compared to CE, while MRI detects more. Reference [1] Gladmann DD, Chadran V. Observational cohort studies: Lessons learnt from the university of Toronto Psoriatic Arthritis Program. Rheumatology2011;50(1):25–31. Disclosure of Interest None declared

Background Patients with predominantly axial spondyloarthritis (axSpA) may also have inflammation of peripheral joints and entheses. Using a whole-body MRI (WBMRI) approach, peripheral joints and entheses can be assessed objectively and followed during treatment. Objectives To describe the localization and extent of inflammation of peripheral joints and entheses by WBMRI in patients with axSpA initiating TNF-inhibitor therapy, and to assess treatment-induced changes. Methods Fifty-three patients that fulfilled the ASAS criteria for axSpA were included. MRI of SIJs and spine and WBMRI of peripheral joints and entheses were performed at baseline and 4/16/52 weeks after starting TNF inhibitor treatment. 75 peripheral joints and 30 peripheral entheses were scored in chronological order by an experienced musculoskeletal radiologist (IE). Osteitis, synovitis and entheseal soft tissue inflammation were scored separately [0(none)/1(mild)/2(moderate/severe)]. A WBMRI peripheral joint and enthesis index (WBMRI index) was derived by summing scores of all peripheral lesions. Results Median age (IQR/range) was 35 years. (28–44/22–73); median symptom duration was 5 years. (3–13/0–31); 53% were male. Baseline median WBMRI index (n=53) was 7,4–14; 0–40 after 52 weeks (n=46) 4 (2–9; 0–26). WBMRI index decreased mean 0.6 at week 4 (p=0.17, paired t-test), 2.3 at week 16 (p In univariate analysis, WBMRI index at week 52 was associated with age (2.5 higher per 10 years increase in age, p In univariate analysis, higher age was not significantly associated with change in WBMRI index, but when adjusted for baseline WBMRI index, higher age was associated with a less prominent reduction in WBMRI index (+0.9 per 10 years increase in age). Conclusions Inflammation of peripheral joints and entheses decreased over time in a cohort of patients with predominantly axSpA. Most patients had WBMRI index above zero during follow-up, and this was related to age and involved sites prone to osteoarthritis. Thus, the WBMRI Index may capture both disease activity related to axSpA and age-related degenerative changes. Disclosure of Interest None declared

Background Magnetic resonance imaging (MRI) allows objective assessment of inflammation in peripheral joints and entheses. MRI scoring systems have until now focused on assessing specific parts of the musculoskeletal system in detail, e.g. the Rheumatoid Arthritis MRI Scoring System (RAMRIS), which is applied to wrist and metacarpophalangeal joints and adjacent tendon sheaths. The interest in a whole-body MRI approach is growing as modern MRI scanners now permit whole-body scanning within an acceptable time frame, and future improvements in MRI hardware and pulse sequences are expected to improve scan time and image resolution further. Objectives To develop a whole-body MRI scoring system for inflammation of peripheral joints and entheses and to investigate its feasibility and reliability. Methods Definitions of the key pathologies and locations for assessment have been agreed upon in the OMERACT MRI Working Group1. In a first round in June 2017, 9 readers (AJM/DG/FG/IE/MO/PB/SJP/SK/WPM) scored MR images of 2 patients with spondyloarthritis using a draft web-based scoring system. Results were discussed and the scoring system was slightly modified. Hereafter, in a second round in October 2017, 14 MRI readers (3 musculoskeletal radiologist (IE/JLJ/RGL) and 11 rheumatologists with varying exposure to MRI (AJM/DG/FG/MS/MO/PB/RP/SJP/SK/VF/WPM), scored 5 similar patients by the modified scoring system. Using a semiquantitative scale 0–3 (none/mild/moderate/severe), synovitis and osteitis were scored separately for 83 joints, and soft tissue inflammation and osteitis were scored separately for 33 entheses. Discrepancies between readers were discussed during an online meeting to obtain consensus, to train inexperienced readers, and to identify potential pitfalls when applying the scoring system. Results Inter-reader reliability was overall moderate for joint scores and poor for enthesis scores; however, among the 3 musculoskeletal radiologists, enthesis scores were as reliable as joint scores (Table). Reliability did not improve between the first and second round, possibly because patients with several very conspicuous inflammatory lesions were selected as cases in the first round. Conclusions It is feasible to perform online multi-reader scoring exercises of whole-body MRI using a web-based scoring interface. MRI readers need to be further trained and calibrated in the semiquantitative scoring approach used to increase inter-reader reliability. Reference [1] Ostergaard M, et al. J Rheumatol2017;44:1699–1705. Disclosure of Interest None declared

Background A cohort of routine care rheumatoid arthritis (RA) patients in sustained remission had biological disease-modifying anti-rheumatic drugs (bDMARDs) tapered according to a treatment guideline. Little is known about predictors of successful tapering and discontinuation of bDMARDs. Objectives We studied: 1) the proportion of patients whose bDMARD could be successfully tapered or discontinued; 2) unwanted consequences of tapering/discontinuation; 3) potential baseline predictors of successful tapering and discontinuation. Methods One-hundred-and-forty-three patients with sustained disease activity score (DAS28-CRP)≤2.6 and no radiographic progression the previous year were included. bDMARD was reduced to 2/3 of standard dose at baseline, ½ after 16 weeks, and discontinued after 32 weeks. Patients who flared (defined as either DAS28-CRP≥2.6 and DAS28-CRP≥1.2 from baseline, or erosive progression on X-ray and/or MRI) stopped tapering and were escalated to the previous dose level. Results One-hundred-and-forty-one patients completed 2 year follow-up. At 2 years, 87 patients (62%) had successfully tapered bDMARDs, with 26 (18%) receiving 2/3 of standard dose, 39 (28%) ½ dose and 22 (16%) having discontinued; 54 patients (38%) were receiving full dose. DAS28-CRP0–2yrs was 0.1((−0.2)–0.4) (median(interquartile range)) and mean Total-Sharp-Score0–2yrs was 0.01 (1.15) (mean(SD)). Radiographic progression was observed in 9 patients (7%). Successful tapering was independently predicted by: ≤1 previous bDMARD, male gender, low baseline MRI combined inflammation score and low MRI combined damage score. Negative IgM-rheumatoid factor predicted successful discontinuation. The association between potential predictors and the proportion of patients with successful tapering of bDMARDs is shown in figure 1. Conclusions By implementing a clinical guideline, 62% of RA patients in sustained remission in routine care were successfully tapered, including 16% successfully discontinued at 2 years. Radiographic progression was rare. IgM-RF was an independent predictor for successful discontinuation of bDMARDs. Maximum one bDMARDs, male gender, and low baseline MRI combined inflammation and MRI combined damage scores were independent predictors for successful tapering. Disclosure of Interest None declared

Background Evaluation of disease activity and treatment response in peripheral spondyloarthritis (pSpA) is currently based upon clinical findings, laboratory tests and ultrasound examination. Whole-body magnetic resonance imaging (WB MRI) is a relatively new imaging technique that could offer additional information regarding the inflammatory status of joints, entheses and soft tissues. Objectives To determine A) the value of WB MRI, performed at baseline, in relation to clinical remission in pSpA and B) the value of subclinical inflammation, detected by WB MRI, at time of clinical remission in predicting flare after treatment withdrawal in pSpA. Methods Clinical REmission in peripheral SPondyloArthritis (CRESPA) is a placebo-controlled trial of golimumab treatment in 60 early (symptom duration Results Pts reaching clinical remission had significant lower baseline BME sum scores then the non-remission group (mean 1.86 vs. 2.89, p=0.024). At the time of clinical remission 10/45 (22%) and 11/45 (24%) pts had residual talocrural and subtalar synovitis respectively. However, there was no statistically significant difference between patients who relapsed after treatment withdrawal and those who remained in remission concerning synovitis sum scores (p=0.497) as well as BME sum scores (p=0.741) and STI sum scores (p=0.131) at time of clinical remission (table 1). Conclusions Early pSpA pts who reach clinical remission have less BME on baseline WB MRI compared to those with ongoing disease activity. At time of clinical remission, a substantial part of the participants showed residual ankle synovitis on MRI. However, residual inflammatory lesions detected by WB MRI did not differ significantly between pts who relapsed after treatment withdrawal and those in ongoing clinical remission. Disclosure of Interest None declared

Background The SPARCC sacroiliac joint (SIJ) scoring system assesses 6 semicoronal MRI slices for inflammation and 5 slices for structural lesions in patients with axial spondyloarthritis (axSpA). 1,2 However, the cartilaginous SIJ compartment may show 1–2 additional slices anteriorly or posteriorly, depending on body size and scan orientation/tilt. Objectives To investigate inter-reader reliability of an “all slices” approach versus the standard SPARCC scoring of 6/5 slices. Methods Fifty-three patients with axSpA were treated with TNF inhibitor and had MRIs obtained at weeks 0/4/16/52. An experienced (UW) and two newly trained (GK, SK) blinded readers independently scored 199 SIJ MRI scans in chronological order. The cartilaginous SIJ compartment was scored slice by slice by the SPARCC 6/5 slices approach and by all available cartilaginous slices. Initially, the most anterior and posterior slices covering the cartilaginous compartment and the transitional slice were identified. The transitional slice was defined as the most anterior cartilaginous slice with the first portion of the ligamentous compartment, clearly visible on the left and/or right side. We scored SIJ inflammation, fat metaplasia, erosion and backfill, and a combined erosion and backfill score was created. Inter-reader reliability for reader pairs SK-UW/GK-UW/SK-GK was assessed using percent agreement (for individual scores) and intra-class correlation coefficients for sum scores. Results Pairwise percent agreement was 67%/63%/79% for identification of anterior slice, 47%/56%/44% for posterior slice and 69%/68%/72% for transitional slice. Using the “all slices” approach, readers UW/SK/GK scored mean 7.2/7.7/7.0 slices per MRI scan. “6/5 slices” and “all slices” correlated closely with each other for status scores at baseline/status scores at week 52, and change scores at week 52; BME 0.983/0.985/0.983; fat metaplasia 0.994/0.982/0.953; erosion 0.981/0.974/0.957; backfill 0.993/0.983/0.978; combined erosion and backfill 0.983/0.971/0.919. Conclusions The standardised 6/5 slices SPARCC methods had equal reliability as compared to evaluation of all cartilaginous slices. There was limited reliability to identify the posterior slice in the ”all slices” approach, as opposed to good reproducibility to determine the transitional slice in the ”6/5 slices” approach. Combining erosion and backfill scores tended to result in superior reliability compared to the 2 lesions separately, indicating a challenge to identify the transition from erosion to backfill. References [1] Arthritis Care Res2005;53:703–9. [2] J Rheumatol2015;42:79–86. Disclosure of Interest None declared

Background Enthesitis is regarded the primary lesion in spondyloarthritis (SpA) and MRI allows sensitive visualisation of entheseal inflammation/damage, but no validated, internationally accepted scoring system exists. Objectives To develop and perform preliminary validation of a novel OMERACT MRI scoring system for assessing ankle enthesitis in SpA patients, and to improve this through iterative multi-reader scoring exercises and calibration sessions. Methods A systematic literature review of MRI studies on enthesitis in SpA identified key inflammatory and structural pathologies. Definitions were agreed by consensus within the OMERACT MRI in arthritis working group. Then, in a first internet-based multireader exercise the Achilles tendon and plantar fascia entheses in 10 ankle MRIs (sagittal T1W, sagittal and Axial T2W fat suppressed) were scored by 15 readers (3 radiologists and 12 rheumatologists), with varying expertise in ankle MRI, for tendon/fascia thickness/signal change, tendon/peritendon signal alteration, retrocalcaneal bursitis, bone spur, erosion and bone marrow oedema, using semi-quantitative scores (0–3: no/mild/moderate/severe pathology). After a subsequent calibration session leading to minor modifications of assessed parameters, 16 ankle MRIs (specifications as above), were scored by 15 readers in exercise 2 with a modified score sheet. Rules were agreed for scoring pathologies. In both exercises, scores for each reader for individual variables were compared and discussed, and mean scores for each variable were determined using descriptive statistics, as were sum scores. Inter-reader agreement was calculated using two-way consistency single measures intra-class correlation coefficient (ICC 3,1) for inflammatory and structural lesions. Results Exercise 1: Mean pairwise inter-reader ICC for combined score of inflammatory and structural variables was 0.65 (range 0.10–0.94), with 75% of values being good/very good (≥0.50). Discussion of results led to minor modifications of parameters to be assessed. Exercise 2: Inter-reader agreement (ICC) for all inflammatory variables combined ranged from 0.26–0.93 among reader pairs (mean 0.64; median 0.66; IQR 0.46–0.79). For structural variables combined ICC ranged from 0.05–0.91 among reader pairs (mean 0.45; median 0.45; IQR 0.2–0.6). Conclusions Initial steps in developing an OMERACT MRI heel enthesitis scoring system have demonstrated overall moderate reliability of the proposed variables. Further modification, refinement, calibration and validation (ongoing) are needed before this system is ready for use in SpA clinical trials. 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

Objectives A cohort of routine care RA patients in sustained remission had biological DMARD (bDMARDs) tapered according to a treatment guideline. We studied: the proportion of patients whose bDMARD could be successfully tapered or discontinued; unwanted consequences of tapering/discontinuation; and potential baseline predictors of successful tapering and discontinuation. Methods One-hundred-and-forty-three patients (91% receiving TNF inhibitor and 9% a non-TNF inhibitor) with sustained disease activity score (DAS28-CRP)⩽2.6 and no radiographic progression the previous year were included. bDMARD was reduced to two-thirds of standard dose at baseline, half after 16 weeks, and discontinued after 32 weeks. Patients who flared (defined as either DAS28-CRP ⩾ 2.6 and ΔDAS28-CRP ⩾ 1.2 from baseline, or erosive progression on X-ray and/or MRI) stopped tapering and were escalated to the previous dose level. Results One-hundred-and-forty-one patients completed 2-year follow-up. At 2 years, 87 patients (62%) had successfully tapered bDMARDs, with 26 (18%) receiving two-thirds of standard dose, 39 (28%) half dose and 22 (16%) having discontinued; and 54 patients (38%) were receiving full dose. ΔDAS28-CRP0-2yrs was 0.1((-0.2)-0.4) (median (interquartile range)) and mean ΔTotal-Sharp-Score0-2yrs was 0.01(1.15)(mean(s.d.)). Radiographic progression was observed in nine patients (7%). Successful tapering was independently predicted by: ⩽1 previous bDMARD, male gender, low baseline MRI combined inflammation score or combined damage score. Negative IgM-RF predicted successful discontinuation. Conclusion By implementing a clinical guideline, 62% of RA patients in sustained remission in routine care were successfully tapered, including 16% successfully discontinued at 2 years. Radiographic progression was rare. Maximum one bDMARDs, male gender, and low baseline MRI combined inflammation and combined damage scores were independent predictors for successful tapering.

Background The Canada-Denmark (CANDEN) definitions of spinal MRI lesions allow a detailed anatomy-based evaluation of inflammatory and structural lesions in vertebral bodies and posterior elements of the spine in patients with axial spondyloarthritis (axSpA). The objective was to examine the reliability, responsiveness and discrimination of scores for spinal inflammation, fat, bone erosion and new bone formation based on the CANDEN system and to describe patterns of inflammatory and structural lesions and their temporal development. Methods 49 patients with axSpA from an investigator-initiated, randomised, placebo-controlled trial of adalimumab underwent spinal MRI at weeks 0/6/24/48. MR images were scored according to the CANDEN system and the Spondyloarthritis Research Consortium of Canada (SPARCC) method. Total scores, and various subscores, were created by summing individual lesion scores. Results The CANDEN spine inflammation score had high responsiveness, similar to the SPARCC MRI spine index (Guyatt’s responsiveness index 1.88 and 1.67, respectively), and discriminated between adalimumab and placebo treatment already at 6 weeks’ follow-up (P=0.03). Anterior/posterior corner inflammation subscores showed similar responsiveness. Inter-reader reliability for the CANDEN spine inflammation and fat scores was good to very good for status and change scores (intraclass correlation coefficient (ICC)=0.71–0.92). Reliability for CANDEN new bone formation and erosion scores was good to very good for status scores (ICC=0.61–0.75) but, due to minimal progression, poor for change scores (ICC≤0.40). Conclusions The CANDEN spine inflammation score showed good responsiveness, discrimination between active treatment and placebo and reliability. The CANDEN spine structural scores had good cross-sectional reliability, but longer studies are needed to investigate their sensitivity to change. Trial registration number NCT01029847; Results.

To investigate whether axial spondyloarthritis (axSpA) patients with extremely poor patient-reported outcomes (PROs) at start of first tumour necrosis factor inhibitor (TNFi) treatment have poorer treatment response and shorter treatment retention than other patients.This observational cohort study was based on the nationwide DANBIO registry. Patients with axSpA who started first TNFi during 2011-2016 were stratified according to baseline Bath Ankylosing Spondylitis Disease Activity Index (BASDAI ≥ 0.0 to ≤ 4.0, 4.0 to ≤ 5.0, 5.0 to ≤ 6.0, 6.0 to ≤ 7.0, 7.0 to ≤ 8.0, 8.0 to ≤ 9.0, and 9.0 to ≤ 10.0). An extremely poor BASDAI was defined as BASDAI 9.0 to ≤ 10.0. Treatment responses after 6 months [≥ 50% improvement from baseline BASDAI (BASDAI50), ≥ 40% improvement in Assessment of SpondyloArthritis international Society (ASAS40) response, and ASAS partial remission] in patients with extremely poor PROs were compared with other patients by chi-squared tests, and retention rates by log-rank tests. Similar analyses were done for Bath Ankylosing Spondylitis Functional Index (BASFI), pain score, and patient global score.The study included 1396 patients (median age 39 years, 60% men). Patients with extremely poor baseline BASDAI [63 patients (5%)] were more often women, ever smokers, and human leucocyte antigen-B27 negative, and had higher body mass index. Response rates were poorer in patients with extremely poor BASDAI vs remaining patients (BASDAI50 19% and 41%, respectively, p0.001; ASAS40 16% and 35%, p = 0.002; ASAS partial remission 6% and 22%, p 0.001). Patients with extremely poor BASDAI had lower 1 year treatment retention (51% and 68%, p 0.001). Largely similar results were found for patients with extremely poor BASFI, pain score, and patient global score.Patients who reported an unusually large symptom burden at baseline had poor response rates and low retention rate. In such cases, competing causes of pain should carefully be taken into account when considering treatment with TNFi.

Background Peripheral enthesitis (PE) is a characteristic feature of spondyloarthritis (SpA) that may be asymptomatic and only detectable by imaging. Ultrasonography (US) has greater sensitivity than clinical examination for the detection of PE.[1] Objectives The aim of the study was to investigate the anatomical distribution, morphological abnormalities and response to anti-tumor necrosis factor (anti-TNF) therapy of US-detected PE in patients with axial SpA (axSpA) initiating adalimumab (ADA). Methods In a randomized, placebo-controlled, double-blinded investigator-initiated trial (NCT01029847), patients with axSpA according to the Assessment of SpA International Society (ASAS) criteria were randomized to subcutaneous ADA 40 mg every other week (eow) or placebo from baseline to week 6. From week 6 to 24, all patients received ADA 40 mg eow. Of 49 patients enrolled, 21 participated in the US sub-study. US assessment applying the OMERACT US definitions for enthesitis[2] of 10 peripheral entheseal regions (Tables 1 & 2) and clinical examination were performed at baseline, weeks 6 and 24. US was performed by an 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 chronic lesions.[2] Results See tables. Conclusions In this axSpA cohort, US assessment primarily identified PE in the lower extremities, and predominantly chronic lesions. No change in chronic PE lesions were found during treatment indicating a low sensitivity to change of these lesions. The number of entheses with inflammatory activity was too low to detect any changes on US during ADA therapy. References D9Agostino MA, et al. Ann Rheum Dis 2011, 70(8):1433–1440. Terslev L, et al. Arthritis Care Res (Hoboken) 2014, 66(5):741–748. Disclosure of Interest None declared

Background None of the currently accepted remission criteria in rheumatoid arthritis (RA) incorporate inflammation on imaging. Signs of inflammation on ultrasound (US) and magnetic resonance imaging are frequently seen in RA patients in clinical remission.(1–3) It is not known whether patients in longstanding clinical and radiographic remission obtained through a DAS28 driven treat to target (T2T) strategy by conventional synthetic disease modifying anti-rheumatic drugs (csDMARD) or by biologic (bDMARD) therapy differ with respect to US detected synovitis. Objectives In RA patients in longstanding clinical and radiographic remission, achieved by a DAS28-driven T2T strategy, to investigate if US signs of inflammation differs between RA patients, treated with csDMARD or bDMARD (+/- csDMARD). Methods Eighty-seven patients with RA in longstanding clinical (continuous DAS28 Results Clinical characteristics and US findings are shown in the table. All 87 patients fulfilled DAS28 remission criteria at entry and CDAI remission was fulfilled in 76% and 79% in the csDMARD and bDMARD group, respectively. Complete absence of any signs of US inflammation (GSS=0 and CDA=0) was seen in 0% and 14% in the csDMARD and bDMARD groups, respectively (p=0.01), while minimal US inflammation (GSS≤1 and CDA=0) was seen in 33% and 40% (NS). CDA in at least one joint was seen in the majority of patients in both groups, 58% and 57% respectively. Conclusions The majority of RA patients, in this cohort of patients in longstanding clinical and radiographic remission obtained through a DAS28 driven T2T strategy, had signs of inflammation as assessed by US, irrespective of receiving biologic treatment or not. For patients in clinical remission, the consequences of sustained US inflammation still have to be investigated. References Brown AK et al.: Arthritis Rheum 2006;54(12):3761–73. Saleem B et al.: Arthritis Rheum 2009;60(7):1915–22. Gandjbakhch F et al.: J Rheumatol 2011;38(9):2039–44. Disclosure of Interest None declared

Background The vertebrae of the cervical spine are rather small and it may be difficult to assess if small areas with signal intensity changes represent the bones, joints or entheses, or derive from the surrounding blood vessels. Objectives To investigate if image resolution affects the assessment of inflammatory and structural lesions of the cervical spine. Methods Forty-nine patients with axial spondyloarthritis according to the ASAS criteria started anti-TNF treatment and had “standard” resolution (std-res) and “high” resolution (high-res) MRI sequences of the cervical spine performed at baseline and after 48 weeks. 3 patients had follow-up scan already after 6–24 weeks due to study exclusion. Std-res: STIR sequence: Voxel size 5.0 mm3 (slice thickness 4.0, spatial resolution 1x1.25); T1W sequence: voxel size 4.5 mm3 (slice thickness 4.0, spatial resolution 0.9x1.25). High-res: STIR sequence: Voxel size 3.1 mm3 (slice thickness 3.5, spatial resolution 0.8x1.11); T1W sequence: voxel size 1.4 mm3 (slice thickness 3.0, spatial resolution 0.6x0.76). Images were assessed in known chronology by an experienced axSpA MRI reader (SJP) blinded to clinical data. High-res and std-res were read in random order. MRI lesions of inflammation, fat and new bone formation were defined according to the Canada-Denmark working group [1,2]. Erosions were not assessed. Results Inflammatory lesions: In 9 of 43 patients (21%), inflammatory lesions were detected in the cervical spine at baseline at std-res, while this was detected in 14 of 43 patients (33%) at high-res. Using high-res, as compared to std-res, 6 patients were reclassified from negative to positive for inflammation, 1 patient was reclassified from positive to negative, and 8/28 patients remained classified as positive/negative, p=0.13 by Exact McNemar test. The mean inflammation score was significantly higher at high-res compared to std-res (1.7 (SD 4.5) vs. 0.8 (SD 2.7), p=0.04 by paired t-test). Fat lesions: 11 of 43 patients (26%) had fat lesions in the cervical spine at baseline using std-res, while 10 of 43 patients (23%) had this using high-res. The mean fat score was significantly higher at high-res compared with std-res (1.6 (SD 3.5) vs. 0.8 (SD 1.8), p=0.02 by paired t-test). Bone spurs/ankylosis: 11 of 43 patients (26%) had bone spurs/ankylosis of the cervical spine at baseline at std-res, while 10 of 43 patients (23%) using high-res. The mean new bone formation score was significantly higher at high-res compared with std-res (2.7 (SD 6.1) vs. 1.4 (SD 3.5), p=0.01 by paired t-test). Responsiveness: Standardized response mean for inflammation score at std-res was 0.15, and at high-res 0.14. Structural lesions remained largely unchanged in all patients. Conclusions More patients were classified as having inflammatory lesions in the cervical spine when using high-res MRI, compared to std-res. Likewise, mean scores of inflammatory lesions, fatty lesions and new bone formation were significantly higher compared with std-res. Further studies are needed to investigate the clinical significance of these findings as well as the frequency of these minor lesions in healthy controls. ClinicalTrials.gov: NCT01029847. References Lambert RGW, et al. J Rheumatol 2009;S84:3–17. Ostergaard M, et al. J Rheumatol 2009;S84:18–34. Disclosure of Interest None declared

This case report describes a patient with scleroderma who developed Mycobacterium intracellulare infection, which for more than a year mimicked worsening of her connective tissue disorder. The patient was diagnosed with scleroderma based on puffy fingers that developed into sclerodactyly, abnormal nail fold capillaries, interstitial lung disease, Raynaud’s phenomenon, esophageal dysmotility, and positivity for rheumatoid factor and anti-SSA antibodies. She developed massive inflammatory changes of the cutis, the subcutis, and the muscle fasciae of the right leg, that after several failed attempts of immunosuppressive treatments were found to be caused by Mycobacterium intracellulare. While she was receiving high-dose prednisolone, as worsening of her connective tissue disease was suspected to be the cause of the inflammatory changes, she had Listeria monocytogenes meningitis and was hospitalized for several weeks, but she recovered from this without sequelae. After Mycobacterium intracellulare infection was diagnosed, she was treated with clarithromycin and rifampicin. Her skin manifestations, arthralgias, and fatigue improved considerably, and the wounds of the right leg healed, unfortunately with significant scarring. Immunodeficiency testing was unremarkable. In summary, an infection with Mycobacterium intracellulare was mistaken for an unusually severe progression of scleroderma.

The sparse number of high-resolution human membrane protein structures severely restricts our comprehension of molecular physiology and ability to exploit rational drug design. In the search for a standardized, cheap and easily handled human membrane protein production platform, we thoroughly investigated the capacity of S. cerevisiae to deliver high yields of prime quality human AQPs, focusing on poorly characterized members including some previously shown to be difficult to isolate. Exploiting GFP labeled forms we comprehensively optimized production and purification procedures resulting in satisfactory yields of all nine AQP targets. We applied the obtained knowledge to successfully upscale purification of histidine tagged human AQP10 produced in large bioreactors. Glycosylation analysis revealed that AQP7 and 12 were O-glycosylated, AQP10 was N-glycosylated while the other AQPs were not glycosylated. We furthermore performed functional characterization and found that AQP 2, 6 and 8 allowed flux of water whereas AQP3, 7, 9, 10, 11 and 12 also facilitated a glycerol flux. In conclusion, our S. cerevisiae platform emerges as a powerful tool for isolation of functional, difficult-to-express human membrane proteins suitable for biophysical characterization.

ObjectiveTo validate the Canada-Denmark (CANDEN) MRI scoring system for the spine in axial spondyloarthritis with updated lesion definitions.MethodsLesion definitions in the CANDEN system were updated and illustrated by a consensus set of reference images. Sagittal spine MRIs of 40 patients with axial spondyloarthritis obtained at baseline and at week 52 after initiation of treatment with the tumour necrosis factor inhibitor golimumab were evaluated in unknown chronology by seven readers blinded to all other data.ResultsCANDEN MRI spine inflammation score had very good reliability for status scores (single-measure intraclass correlation coefficient (ICC) of 21 reader pairs median of 0.91 (IQR 0.88–0.92)) and change scores (ICC 0.88 (0.86–0.92)). CANDEN MRI spine fat score had good to very good reliability for status scores (ICC 0.79 (0.75–0.86)) and moderate to good reliability for detecting change (ICC 0.59 (0.46–0.73)). CANDEN MRI spine bone erosion score and CANDEN MRI spine new bone formation score had slight to moderate reliability for status scores (ICC 0.38 (0.32–0.52) and 0.39 (0.27–0.49), respectively).ConclusionThe CANDEN MRI spine scoring system allows a comprehensive evaluation of inflammation, fat, bone erosion and new bone formation of the spine in patients with axial spondyloarthritis. It demonstrated very good reliability for detecting change in inflammation, moderate to good reliability for detecting change in fat, and slight to moderate reliability for detecting bone erosions and new bone formation. Studies with longer follow-up or patients with more advanced spinal involvement may be needed to reliably detect change in bone erosion and new bone formation scores.Trial registration numberNCT02011386.

This case report describes a patient with arthritis of the large joints, bilateral sacroiliitis, and positive anti-SSA and anti-dsDNA antibody, who received sulfasalazine and shortly thereafter became critically ill. He developed toxic epidermal necrolysis, hemolytic anemia, lymphopenia, markedly elevated ferritin, and muscle wasting. A diagnosis of systemic lupus erythematosus was made, and mycophenolate mofetil and systemic glucocorticoids brought this severe disease under control. Toxic epidermal necrolysis-like lesions and hemophagocytic syndrome have been reported as manifestations of systemic lupus erythematosus. This patient possibly had spondyloarthritis or an undifferentiated connective tissue disease at presentation, and we suggest, based on the timing of events, that sulfasalazine may have acted as a trigger of the severe disease manifestations.

Most purinergic receptors activate intracellular Ca2+ signalling, and in epithelia they stimulate transport of major ions. Aim of the present study on pancreatic ducts was to find whether P2 receptors also regulate cellular Ca2+ transport, such as that via the Na+/Ca2+ exchanger (NCX). Since NCX can also be connected with epithelial Ca2+ transport, we also investigated expression of some Ca2+-handling/transporting proteins. Expression analysis revealed that pancreatic ducts of rat and human duct cell line CFPAC-1 (also PANC-1 and Capan-1) express the Na+/Ca2+ exchanger (splice variants NCX1.3 and 1.7), as well as the Ca2+-sensing receptor and the Ca2+-binding protein calbindin-D 9k. These proteins localize to the luminal and lateral membranes of pancreatic duct epithelia. Ca2+ imaging experiments showed that activation of purinergic P2Y and P2X receptors stimulated NCX in human and rat duct cells. Application of ATP to CFPAC-1 monolayers also stimulated Ca2+ transport from the luminal to the basolateral side. Taken together, these results show that pancreatic ducts express a number of Ca2+-handling/transporting proteins and we propose that these together with purinergic receptors play a role in regulation of duct lumen Ca2+ content.

Selecting the appropriate analytical methods for characterizing the assembly and morphology of polymer-based vesicles, or polymersomes are required to reach their full potential in biotechnology. This work presents and compares 17 different techniques for their ability to adequately report size, lamellarity, elastic properties, bilayer surface charge, thickness and polarity of polybutadiene-polyethylene oxide (PB-PEO) based polymersomes. The techniques used in this study are broadly divided into scattering techniques, visualization methods, physical and electromagnetical manipulation and sorting/purification. Of the analytical methods tested, Cryo-transmission electron microscopy and atomic force microscopy (AFM) turned out to be advantageous for polymersomes with smaller diameter than 200 nm, whereas confocal microscopy is ideal for diameters >400 nm. Polymersomes in the intermediate diameter range can be characterized using freeze fracture Cryo-scanning electron microscopy (FF-Cryo-SEM) and nanoparticle tracking analysis (NTA). Small angle X-ray scattering (SAXS) provides reliable data on bilayer thickness and internal structure, Cryo-TEM on multilamellarity. Taken together, these tools are valuable for characterizing polymersomes per se but the comparative overview is also intended to serve as a starting point for selecting methods for characterizing polymersomes with encapsulated compounds or polymersomes with incorporated biomolecules (e.g. membrane proteins).

Pancreas secretes fluid rich in digestive enzymes and bicarbonate. The alkaline secretion is important in buffering of acid chyme entering duodenum and for activation of enzymes. This secretion is formed in pancreatic ducts, and studies to date show that plasma membranes of duct epithelium express H(+)/HCO(3)(-) transporters, which depend on gradients created by the Na(+)/K(+)-ATPase. However, the model cannot fully account for high-bicarbonate concentrations, and other active transporters, i.e. pumps, have not been explored. Here we show that pancreatic ducts express functional gastric and non-gastric H(+)-K(+)-ATPases. We measured intracellular pH and secretion in small ducts isolated from rat pancreas and showed their sensitivity to H(+)-K(+) pump inhibitors and ion substitutions. Gastric and non-gastric H(+)-K(+) pumps were demonstrated on RNA and protein levels, and pumps were localized to the plasma membranes of pancreatic ducts. Quantitative analysis of H(+)/HCO(3)(-) and fluid transport shows that the H(+)-K(+) pumps can contribute to pancreatic secretion in several species. Our results call for revision of the bicarbonate transport physiology in pancreas, and most likely other epithelia. Furthermore, because pancreatic ducts play a central role in several pancreatic diseases, it is of high relevance to understand the role of H(+)-K(+) pumps in pathophysiology.