BACKGROUND:Pain, fatigue, and impaired health-related quality of life are common manifestations of rheumatoid arthritis. The aim of this study was to compare the effects of active conventional treatment with three different biological disease-modifying antirheumatic drugs (DMARDs) on patient-reported outcomes after 48 weeks, in patients with early rheumatoid arthritis using data from the NORD-STAR trial. METHODS:NORD-STAR was an investigator-initiated open-label randomised controlled trial done at 29 rheumatology centres across Denmark, Finland, Iceland, Norway, Sweden, and the Netherlands. Newly diagnosed patients aged 18 years or older, with rheumatoid arthritis (according to the 2010 American College of Rheumatology-European Allience of Associations for Rheumatology classification criteria for rheumatoid arthritis), symptom duration less than 24 months and who were naïve to DMARDs were randomly assigned (1:1:1:1) to receive active conventional treatment, certolizumab pegol, abatacept, or tocilizumab. The patient-reported outcomes assessed at baseline and weeks 4, 8, 12, 16, 24, 32, 40, and 48 included pain, patient's global assessment of disease activity, Health Assessment Questionnaire Disability Index, Fatigue, Short Form-36 (reflecting health-related quality of life, morning stiffness, and patient's acceptable symptom state). Linear mixed regression and logistic regression analyses were adjusted for sex, country, baseline patient-reported outcomes values, anti-citrullinated protein antibody status, and treatment group. Proportions of patients reporting improvements greater than or equal to the minimal clinically important difference (MCID) were assessed. There was lived experience involvement in the design and implementation of the study. This trial was registered with ClinicalTrials.gov, NCT01491815, and EudraCT, 2011-004720-35. FINDINGS:Between Dec 14, 2012, and Dec 11, 2018, 812 patients were enrolled and randomly assigned; after exclusion of 17 patients not receiving tocilizumab due to administrative issues, the intention-to-treat population consisted of 795 patients (200 [25%] received active conventional treatment, 203 [26%] received certolizumab pegol plus methotrexate, 204 [26%] received abatacept plus methotrexate, and 188 [24%] received tocilizumab plus methotrexate). 547 (69%) of 795 patients were female, 248 (31%) were male, the mean age was 54 years (SD 15). Between baseline and week 48 large and clinically relevant improvements in patient-reported outcomes were observed in all treatment groups. At 48 weeks the biological DMARD groups had larger improvements in pain, fatigue, physical component score, and bodily pain of SF-36 compared with the active conventional treatment group. For pain, improvement exceeding MCID was reported by 155 (76%) of 203 patients with certolizumab pegol plus methotrexate and 162 (79%) of 204 patients with abatacept plus methotrexate compared with 136 (68%) of 200 patients in the active conventional treatment group. In the group of patients with tocilizumab and methotrexate 132 (70%) of 188 patients reported pain improvement exceeding MCID. The absolute differences between the biological DMARD groups and the active conventional treatment group were otherwise generally marginal. INTERPRETATION:All treatment groups showed substantial improvements in patient-reported outcomes over time. Biological DMARDs produced somewhat greater gains in pain, fatigue, and physical quality of life measures than conventional treatments, though overall differences between groups were small. The results highlight that early treatment and effective disease control in rheumatoid arthritis lead to strong patient-reported benefits regardless of therapy type. FUNDING:Stockholm County Council, Swedish Medical Research Council, Swedish Rheumatism Association, Academy of Finland, Finska Läkaresällskapet, South-Eastern Health Region Norway, HUS Institutional grant, Icelandic Society for Rheumatology, Interregional grant from all health regions in Norway, NordForsk, Regionernes Medicinpulje, The Research Fund of University Hospital Reykjavik, UCB, Bristol Myers Squibb.

According to the modified New York criteria (mNYc), moderate-severe sacroiliac joint (SIJ) structural damage on radiography is necessary for classifying radiographic axial spondyloarthritis (r-axSpA). In contrast to radiography, MRI provides no ionizing radiation, higher sensitivity for structural damage, better inter-reader reliability, and is gradually replacing radiography. Therefore, we aimed to develop and validate a high specificity MRI cut-off to the radiographic component of the mNYc (rad-mNYc), defined as MRI findings that correspond to an mNY-positive radiograph. Patients diagnosed with axSpA with available SIJ MRI and radiograph from five European clinical registries in the EuroSpA Collaboration were included. MRIs were read according to the SPARCC structural score (based on 5 predefined or all slices) and radiographs the rad-mNYc. Cut-offs with 95

OBJECTIVES:In the NOrdic Rheumatic Diseases Strategy Trials And Registries (NORD-STAR) trial, the active conventional arm had 2 nonrandomised regimens: arm 1A (oral group; Sweden, Norway, Netherlands, and Iceland) and arm 1B (injection group; Denmark and Finland). We report clinical, patient-reported, safety, and radiographic outcomes after 48 weeks. METHODS:Oral group received methotrexate plus oral prednisolone (20.0 mg/d, tapered rapidly, discontinued week 36); Injection group received triple therapy (methotrexate, sulphasalazine, hydroxychloroquine) and mandatory intra-articular glucocorticoid injections. The primary end point was analysed by logistic regression with several approaches for handling missing outcomes. RESULTS:In total, 137 and 80 patients were included in the oral group and injection group; 78% vs. 89% completed, respectively. At 48 weeks, adjusted clinical disease activity index remission ≤2.8 rates (95% CI) were 36% (28-44) and 55% (42-68), respectively; the risk difference (primary outcome) was 19% (2-35). Similarly, key secondary clinical, patient-reported and safety outcomes showed numerically better results in the injection group vs oral group, for example, infections occurred in 53% vs 30%, respectively. Radiographic progression (Δtotal van der Heijde-modified Sharp Score) was low: oral group: adjusted mean, 0.26 (95% CI, 0.08-0.43); injection group: adjustedd mean, 0.80 (95% CI, 0.55-1.05). Cumulative dose of oral/intra-articular glucocorticoids (median) was 1905 mg prednisolone for the oral group and 165 mg for the injection group. CONCLUSIONS:In treatment-naïve patients with early rheumatoid arthritis, triple therapy and mandatory glucocorticoid joint injections had numerically better clinical outcomes, fewer withdrawals, fewer adverse events, and lower cumulative dose of glucocorticoids, but slightly worse radiographic outcomes than treatment with methotrexate and oral prednisolone. These findings, although nonrandomised, suggest a potential for optimising treatment strategy with conventional therapies in early rheumatoid arthritis.

Axial involvement in psoriatic arthritis (axPsA) is associated with more severe disease and increased pain, yet no consensus definition of axPsA exists. This study aims to describe the occurrence and characteristics of MRI and radiographic sacroiliac joint (SIJ) involvement in a European PsA cohort. Patients with a clinical diagnosis of PsA or of axial spondyloarthritis with psoriasis and available routine care SIJ MRIs were included from five European registries in the EuroSpA collaboration. SIJ MRIs and radiographs were centrally assessed for inflammatory and structural lesions, differential diagnoses, and globally evaluated for SpA-indicative findings. Among 581 PsA patients (mean age 45 years, 47

Background Sacroiliac joint (SIJ) MRI is commonly used in diagnosing spondyloarthritis (SpA). Current Assessment of SpondyloArthritis International Society (ASAS) recommendations on reporting SIJ MRIs in patients with known or suspected axial SpA recommend always stating whether bone marrow oedema (BME), erosions and fat lesions are present/absent and whether the MRI is compatible with axial SpA.Purpose To investigate if routine care radiologists already report what has now been recommended and to assess the agreement between local radiologists and central SpA experts.Materials and methods This study includes retrospective interpretation of images acquired in routine care. Patients diagnosed with SpA enrolled in a clinical registry in one of five European countries involved in the EuroSpA Collaboration, with an available SIJ MRI and an associated local MRI report, were included. MRIs were read centrally by two readers, who registered global features (eg, MRI indicative of SpA), and various inflammatory and structural lesions as present/absent. Similar information was extracted from local reports. Findings were analysed with descriptive statistics.Results Overall, 913 patients (40 years±13, 492 men) were included. In 24%, the local MRI reports stated whether the MRI was overall indicative of SpA or not. Presence/absence of BME, erosions and fat lesions was mentioned in 88%, 48% and 29% of local reports, respectively. Inflammatory lesions were more often reported as present by local than central readers (46% vs 36%), and structural lesions less often (33% vs 50%).Conclusion This study demonstrated a large gap between the clinical practice of reporting SIJ MRIs and recent reporting recommendations.

OBJECTIVE:Radiographic assessment of sacroiliac joints (SIJs) according to the modified New York (mNY) criteria is key in the classification of axial spondyloarthritis but has moderate interreader agreement. We aimed to investigate the improvements of the reliability in scoring SIJ radiographs after applying an online real-time iterative calibration (RETIC) module, in addition to a slideshow and video alone. METHODS:Nineteen readers, randomized to 2 groups (A or B), completed 3 calibration steps: (1) review of manuscripts, (2) review of slideshow and video with group A completing RETIC, and (3) re-review of slideshow and video with group B completing RETIC. The RETIC module gave instant feedback on readers' gradings and continued until predefined reliability ([Formula: see text]) targets for mNY positivity/negativity were met. Each step was followed by scoring different batches of 25 radiographs (exercises I to III). Agreement ([Formula: see text]) with an expert radiologist was assessed for mNY positivity/negativity and individual lesions. Improvements by training strategies were tested by linear mixed models. RESULTS:In exercises I, II, and III, mNY [Formula: see text] were 0.61, 0.76, and 0.84, respectively, in group A; and 0.70, 0.68, and 0.86, respectively, in group B (ie, increasing, mainly after RETIC completion). Improvements were observed for grading both mNY positivity/negativity and individual pathologies, both in experienced and, particularly, inexperienced readers. Completion of the RETIC module in addition to the slideshow and video caused a significant [Formula: see text] increase of 0.17 (95% CI 0.07-0.27; P = 0.002) for mNY-positive and mNY-negative grading, whereas completion of the slideshow and video alone did not ([Formula: see text] = 0.00, 95% CI -0.10 to 0.10; P = 0.99). CONCLUSION:Agreement on scoring radiographs according to the mNY criteria significantly improved when adding an online RETIC module, but not by slideshow and video alone.

Objectives To investigate the detection of erosion, sclerosis and ankylosis using 1 mm 3D T1-weighted spoiled gradient echo (T1w-GRE) MRI and 1 mm MRI-based synthetic CT (sCT), compared with conventional 4 mm T1w-TSE.Materials and methods Prospective, cross-sectional study. Semi-coronal 4 mm T1w-TSE and axial T1w-GRE with 1.6 mm slice thickness and 0.8 mm spacing between overlapping slices were performed. The T1w-GRE images were processed into sCT images using a commercial deep learning algorithm, BoneMRI. Both were reconstructed into 1 mm semi-coronal images. T1w-TSE, T1w-GRE and sCT images were assessed independently by 3 expert and 4 non-expert readers for erosion, sclerosis and ankylosis. Cohen's kappa for inter-reader agreement, exact McNemar test for lesion frequencies and Wilcoxon signed-rank test for confidence in lesion detection were used.Results Nineteen patients with axial spondyloarthritis were evaluated. T1w-GRE increased inter-reader agreement for detecting erosion (kappa 0.42 vs 0.21 in non-experts), increased detection of erosion (57 vs 43 of 152 joint quadrants) and sclerosis (26 vs 17 of 152 joint quadrants) among experts, and increased reader confidence for scoring erosion and sclerosis. sCT increased inter-reader agreement for detecting sclerosis (kappa 0.69 vs 0.37 in experts) and ankylosis (0.71 vs 0.52 in non-experts), increased detection of sclerosis (34 vs 17 of 152 joint quadrants) and ankylosis (20 vs 13 of 76 joint halves) among experts, and increased reader confidence for scoring erosion, sclerosis and ankylosis.Conclusion T1w-GRE and sCT increase sensitivity and reader confidence for the detection of erosion, sclerosis and ankylosis, compared with T1w-TSE.Clinical relevance statement These methods improve the detection of sacroiliac joint structural lesions and might be a useful addition to SIJ MRI protocols both in routine clinical care and as structural outcome measures in clinical trials.

Background Radiographic assessment of the sacroiliac joints (SIJ) according to the modified New York (mNY) criteria is essential in the classification of ankylosing spondylitis, but low to moderate inter-reader agreement and limited improvement by calibration have been reported [1].A web-based real-time iterative calibration (RETIC) module for scoring SIJ radiographs according to the mNY criteria has been developed by experienced readers to allow remote standardized calibration. Objectives To test the performance of this online RETIC calibration module in enhancing scoring proficiency with an expert reader as gold standard reference. Methods This RETIC module consisted of 50 cases with radiographs of the SIJ at one timepoint with an integrated scoring interface with real time feedback to the reader's grading compared to the expert readers' grading. The mNY grade (0-4) was assessed for each joint. Reliability for fulfilling versus not fulfilling the mNY criteria was assessed in real-time by kappa data being provided every 10 cases, until proficiency targets (kappa > 0.5) were achieved.In this study, 19 readers from the EuroSpA Imaging project were randomized to one of two reader calibration strategies (groups A and B) that comprised of 3 calibration steps, each followed by a reading exercise (Exercises 1-3; 25 patients per exercise). Calibration steps were as follows: Group A; 1. Review of original manuscripts describing the mNY method. 2. Review of PowerPoint summary of mNY method and video with grading examples PLUS completion of mNYRETIC module. 3. Re-review of PowerPoint summary and video. Group B; same 3-step strategy as group A except that the mNYRETIC module was completed at step 3, i.e. immediately before Exercise 3. The reliability of scoring was compared to an expert radiologist (RL) using kappa statistics for positivity of mNY criteria and intraclass correlation coefficients (ICCs) for the grades of the mNY criteria. Results The mean agreement for all readers on fulfillment of the mNY criteria with kappa was 0.69 in exercise 1, 0.72 in exercise 2 and 0.83 in exercise 3. Corresponding ICCs for mNY scoring 0-4 were 0.77, 0.77 and 0.82 in exercises 1, 2 and 3, respectively, see Table 1 and Figure 1.For Reader Group A, kappas for exercises 1-3 were 0.65, 0.76 and 0.83, respectively and ICCs 0.71, 0.82 and 0.81 (exercise 3). Interestingly, the main increase in agreement occurred between Exercises 1 and 2, i.e. after the RETIC module was performed. For Reader group B, corresponding kappas were 0.71, 0.77 and 0.83 and ICCs 0.80, 0.72 and 0.80, for exercises 1-3, respectively. Similarly, agreements predominantly improved directly after the RETIC module was performed. Conclusion Agreement on scoring radiographs of the SIJ according to the mNY criteria was noticeably improved when using a systematic online calibration module and in general readers achieved very good agreement with experts implying that systematic calibration of readers before scoring of images can enhance scoring proficiency. Reference [1]van Tubergen A, Heuft-Dorenbosch L, Schulpen G, Landewé R, Wijers R, van der Heijde D, et al. Radiographic assessment of sacroiliitis by radiologists and rheumatologists: does calibration improve quality? Ann Rheum Dis. 62(6):519–25. Acknowledgements: NIL. Disclosure of Interests Anna E F Hadsbjerg Grant/research support from: Novartis., Mikkel Østergaard Speakers bureau: AbbVie/Abbott, Eli Lilly, Gilead, Novartis, Janssen, Pfizer, UCB, Grant/research support from: AbbVie/Abbott, Eli Lilly, Novartis, Janssen, UCB, Amgen, BMS, Celgene, Joel Paschke: None declared, Raphael Micheroli: None declared, Susanne Juhl Pedersen Speakers bureau: AbbVie/Abbott, Merck/MSD, Novartis, Pfizer, UCB, Grant/research support from: Merck/MSD, Novartis, Adrian Ciurea Speakers bureau: AbbVie, Merck/MSD, Novartis, Michael J Nissen Speakers bureau: Janssen, Amgen, Novartis, Consultant of: AbbVie/Abbott, Pfizer, Kristyna Bubova: None declared, Stephanie Wichuk: None declared, Manouk de Hooge: None declared, Simon Krabbe Grant/research support from: Novartis, Ashish Jacob Mathew: None declared, Monika Gregová: None declared, Marie Wetterslev: None declared, Karel Gorican: None declared, Karlo Pintaric: None declared, Ziga Snoj: None declared, Burkhard Moeller: None declared, Alexander Bernatschek: None declared, Maurice Donzallaz: None declared, Robert G Lambert Consultant of: Calyx, CARE Arthritis, Image Analysis Group, Walter P Maksymowych Speakers bureau: Novartis, Consultant of: AbbVie, Boehringer-Ingelheim, Celgene, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer, UCB, Grant/research support from: AbbVie, Janssen, Pfizer, Employee of: CARE Arthritis LimitedFigure 1Reader agreement for all readers combinedTable 1Reader agreement versus expert radiologist, after different training steps.All Readers (n=19)Reader Group A(RETIC before exercise 2)(n=8)Reader Group B(RETIC before exercise 3)(n=11)Agreement mNY+ vs mNY- (Kappa)Exercise 10.690.650.71Exercise 20.720.76#0.67Exercise 30.830.830.77#Agreement mNY score 0-4* (ICC)Exercise 10.770.710.80Exercise 20.770.82#0.72Exercise 30.820.810.80##: Reading performed right after doing the RETIC module.*Grading per sacroiliac jointICC: Intra-class correlation coefficient (two-way, single measurement, absolute agreement), mNY+: Fulfilling radiographic part of Modified NY criteria; mNY-: Not fulfilling radiographic part of Modified NY criteria.

Background The optimal first-line treatment in early rheumatoid arthritis (RA) is debated. We compared clinical and radiographic outcomes of active conventional therapy with each of three biological treatments with different modes of action. Methods Investigator-initiated, randomised, blinded-assessor study. Patients with treatment-naïve early RA with moderate–severe disease activity were randomised 1:1:1:1 to methotrexate combined with (1) active conventional therapy: oral prednisolone (tapered quickly, discontinued at week 36) or sulfasalazine, hydroxychloroquine and intra-articular glucocorticoid injections in swollen joints; (2) certolizumab pegol; (3) abatacept or (4) tocilizumab. Coprimary endpoints were week 48 Clinical Disease Activity Index (CDAI) remission (CDAI ≤2.8) and change in radiographic van der Heijde-modified Sharp Score, estimated using logistic regression and analysis of covariance, adjusted for sex, anticitrullinated protein antibody status and country. Bonferroni's and Dunnet's procedures adjusted for multiple testing (significance level: 0.025). Results Eight hundred and twelve patients were randomised. Adjusted CDAI remission rates at week 48 were: 59.3% (abatacept), 52.3% (certolizumab), 51.9% (tocilizumab) and 39.2% (active conventional therapy). Compared with active conventional therapy, CDAI remission rates were significantly higher for abatacept (adjusted difference +20.1%, p<0.001) and certolizumab (+13.1%, p=0.021), but not for tocilizumab (+12.7%, p=0.030). Key secondary clinical outcomes were consistently better in biological groups. Radiographic progression was low, without group differences.The proportions of patients with serious adverse events were abatacept, 8.3%; certolizumab, 12.4%; tocilizumab, 9.2%; and active conventional therapy, 10.7%. Conclusions Compared with active conventional therapy, clinical remission rates were superior for abatacept and certolizumab pegol, but not for tocilizumab. Radiographic progression was low and similar between treatments. Trial registration number NCT01491815.

Objective To 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). Methods Sustained 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. Results Of 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). Conclusion The 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.

Background The optimal first-line treatment of patients with early rheumatoid arthritis (eRA) is not established. Objectives To compare clinical and radiographic outcomes of active conventional therapy (ACT) with each of three biological therapies with different modes of action. Methods In this investigator-initiated, randomized, open-label, blinded-assessor study ( NCT01491815 ), patients with treatment-naïve eRA with DAS28>3.2 and RF+/ACPA+/CRP>10mg/L, were randomized 1:1:1:1 to methotrexate combined with: 1) oral prednisolone (tapered quickly; discontinued at w36); or: sulphasalazine, hydroxychloroquine and mandatory intra-articular (IA) glucocorticoid injections in swollen joints (ACT); 2) certolizumab-pegol (CZP); 3) abatacept (ABA) or 4) tocilizumab (TCZ). IA glucocorticoid was allowed in all arms except w20-24 and w44-48. Co-primary outcomes at w48 were CDAI remission (CDAI≤2.8) and change in total van der Heijde-modified Sharp Score from baseline (ΔvdHSS w0-w48 ). A combination of Bonferroni and Dunnet’s procedure adjusted for multiple testing. The primary endpoints were estimated using logistic regression and analysis of covariance, adjusted for sex, anti-CCP status and country. Results 812 patients were randomized. Adjusted CDAI remission rates at w48 were: 59.3% (ABA), 52.3% (CZP), 51.9% (TCZ) and 39.2% (ACT). Compared to ACT, CDAI remission rates were superior for ABA (adjusted difference +20.1%; adjusted p<0.001) and CZP (+13.1%; p=0.021), but not TCZ (+12.7%; p=0.030) (Table 1). Key secondary clinical outcomes were consistently better in biological groups compared to ACT. Adjusted mean ΔvdHSS w0-w48 was low (Table 1), with no significant differences between drugs. Table 1. Baseline characteristics ACT (n=200) CZP+MTX (n=203) ABA+MTX (n=204) TCZ+MTX (n=188) § Age (y) 55 (15) 55 (15) 55 (14) 52 (15) Women, % 139 (70%) 139 (69%) 140 (69%) 129 (69%) Time from diagnosis to baseline, days 13 (21) 12 (17) 16 (34) 16 (33) Anti-CCP/RF positive, % 82% / 76% 82% / 73% 83% / 78% 82% / 72% CDAI 28.7 (12.1) 27.9 (12.4) 28.6 (11.3) 26.6 (11.7) Total vdHSS (0-448) [median; IQR) 6.3 (8.2) [4; 1 - 8.5] 5.9 (7.6) [3; 1 - 8] 5.8 (9.8) [3; 1 - 6] 4.2 (6.7) [2; 0.5 - 5] Estimated adjusted outcome (ITT) 1 , Primary CDAI remission, w48 39.2% (32.5 - 45.9) 52.3% (45.5 - 59.1) 59.3% (52.6 - 66) 51.9% (44.9 - 59.0) Δ1.9% (44.9 - 0.45 (0.31 to 0.59) 0.47 (0.33 to 0.61) 0.62 (0.48 to 0.76) 0.5 (0.36 to 0.64) Estimated adjusted treatment difference (ITT) 2 , Primary CDAI remission, w48 Ref 13.1% (3.5 to 22.6 )* 20.1% (10.6 to 29.5 )* 12.7% (3 to 22.5) Δ2.7% (3 to 2 Ref 0.02 (-0.17 to 0.22) 0.17 (-0.02 to 0.37) 0.05 (-0.15 to 0.25) Key secondary ACR/EULAR Boolean remission, w48 Ref 14.7% (5.4 to 23.9) 19.4% (10.1 to 28.7) 13% (3.5 to 22.4) DAS28 remission,w48 Ref 12.9% (3.5 to 22.2) 17.4% (8.2 to 26.6) 14.4% (5 to 23.9) EULAR good response, w48 Ref 8.2% (-0.6 to 17.1) 11.3% (2.7 to 20) 2.9% (-6.3 to 12.2) vdHSS progression ≤0.5, w0-w48 Ref -3.3% (-11.1 to 4.6) 3.5% (-4.7 to 11.8) -2.2% (-10.3 to 5.9) Values are mean (SD), if not otherwise indicated. §Finnish patients randomised to TCZ+MTX, but not receiving it due to unavailability, are not included. 1 Values are estimated adjusted marginal means and estimated marginal differences against ACT with 95% CI. ITT: intention to treat population. *Superiority compared with ACT was demonstrated. No new safety signals were reported. Total numbers of serious adverse events (% patients with ≥1 event) were for ABA 21 (8.3%), CZP 28 (12.4%), TCZ 20 (9.2%) and ACT 23 (10.7%). Conclusion Compared with active conventional therapy (csDMARD + glucocorticoids), superiority regarding CDAI remission rates was demonstrated for abatacept and certolizumab-pegol, and not for tocilizumab. Radiographic progression was low and similar between treatments. Figure 1. Acknowledgements We thank the patients, investigators, nurses, joint assessors and study teams who were involved in the NORD-STAR trial; Eleonore Nilsson, chief study nurse, Lise Hejl Hyldstrup, coordinating study nurse, Niels Steen Krogh, data manager, Monica Rydén Aulin study coordinator and Eva Larsson, patient research partner. We also thank members of the NORD-STAR study group: Anders Bengtsson, Anders Gülfe, Annelies Blanken, Annette Schlemmer, Åsa Reckner Olsson, Aulikki Kononoff, Carl Turesson, Christina Dackhammar, Cidem Gentline, Elisabet Lindqvist, Ellen-Margrethe Hauge, Emma Grenholm, Erik af Klint, Erik Rødevand, Eva Baecklund, Fredrik Markros, Hamed Rezaei, Hanne Merete Lindegaard, Heikki Relas, Heikki Valleala, Ilia Qirjazo, Inger Marie Jensen Hansen, Jarno Rutanen, Jens Kristian Pedersen, Jens Rathmann, Johan Wallman, Johanna Carlestam, Jon Einarsson, Jörgen Lysholm, Kajsa Öberg, Katarina Almehed, Kathrine Lederballe Grøn, Kati Mykkänen, Lena Karlberg, Malin Hemberg, Maria K. Stilling-Vinther, Marjatta Leirisalo-Repo, Mohaned Hameed, Nancy Vivar, Oili Kaipiainen-Seppänen, Peter Olsson, Petrus Linge, Pia Lindell, Pia Neuer Jensen, René Østgård, Riitta Tuompo, Sabine Dieperink, Sara Nysom Christiansen, Sofia Exarchou, Thiab Saleh, Tomas Husmark, Tor Olofsson, Torkell Ellingsen, Trude Bruun, Vappu Rantalaiho and Ylva Borgas. Disclosure of Interests Mikkel Østergaard Speakers bureau: AbbVie, BMS, Boehringer-Ingelheim, Eli Lilly, Janssen, Merck, Pfizer, Roche, UCB, Celgene, Sanofi, Regeneron, Novartis, Orion, Hospira, Consultant of: AbbVie, BMS, Boehringer-Ingelheim, Eli Lilly, Janssen, Merck, Pfizer, Roche, UCB, Celgene, Sanofi, Regeneron, Novartis, Orion, Hospira, Grant/research support from: AbbVie, BMS, Merck, UCB, Celgene, Novartis, Ronald van Vollenhoven Speakers bureau: AbbVie, AstraZeneca, Biogen, Celgene, Galapagos, Gilead, Janssen, Pfizer, Servier, UCB, Consultant of: AbbVie, AstraZeneca, Biogen, Celgene, Galapagos, Gilead, Janssen, Pfizer, Servier, UCB, Grant/research support from: BMS, GSK, Eli Lilly, UCB, Pfizer, Roche, Anna Rudin Grant/research support from: AstraZeneca, Merete L. Hetland Speakers bureau: Merck, Biogen, Pfizer, Eli Lilly, Orion Pharma, CellTrion, Samsun Bioepsi, Janssen Biologics BV, MSD, Consultant of: Merck, Biogen, Pfizer, Eli Lilly, Orion Pharma, CellTrion, Samsun Bioepsi, Janssen Biologics BV, MSD, Grant/research support from: BMS, AbbVie, Roche, Novartis, Merck, Biogen, Pfizer, Marte Heiberg Speakers bureau: Eli Lilly, Consultant of: Eli Lilly, Dan Nordström Grant/research support from: UCB, BMS, AbbVie, Celgene, MSD, Novartis, Pfizer, Michael Nurmohamed Speakers bureau: Celltrion, Eli Lilly, Consultant of: Celltrion, Eli Lilly, Grant/research support from: BMS, AbbVie, MSD, Pfizer, Amgen, Björn Gudbjornsson Speakers bureau: Novartis, Consultant of: Novartis, Lykke Midtbøll Ørnbjerg Grant/research support from: Novartis, Pernille Bøyesen: None declared, Inge Olsen: None declared, Kristina Lend: None declared, Kim Hørslev-Petersen: None declared, Till Uhlig Speakers bureau: Grünenthal, Eli Lilly, Novartis, Pfizer, Consultant of: Grünenthal, Eli Lilly, Novartis, Pfizer, Grant/research support from: NORDFORSK, Tuulikki Sokka-Isler Speakers bureau: AbbVie, BMS, Celgene, Medac, Merck, Novartis Orion Pharma, Pfizer, Roche, Sandoz, UCB, Boehringer Ingelheim, Consultant of: AbbVie, BMS, Celgene, Medac, Merck, Novartis Orion Pharma, Pfizer, Roche, Sandoz, UCB, Boehringer Ingelheim, Gerdur Gröndal: None declared, Simon Krabbe Grant/research support from: AbbVie, MSD, Novartis, Joakim Lindqvist: None declared, Inger Gjertsson: None declared, Daniel Glinatsi Speakers bureau: AbbVie, Eli Lilly, Consultant of: AbbVie, Eli Lilly, Meliha C Kapetanovic: None declared, Anna-Birgitte Aga Speakers bureau: AbbVie, Eli Lilly, Novartis, Pfizer, Consultant of: AbbVie, Eli Lilly, Novartis, Pfizer, Francesca Faustini: None declared, Pinja Parmanne Speakers bureau: Novartis, Consultant of: Novartis, Tove Lorenzen Speakers bureau: UCB, Consultant of: UCB, Giovanni Cagnotto: None declared, Johan Back: None declared, Oliver Hendricks Speakers bureau: AbbVie, Novartis, Consultant of: AbbVie, Novartis, Daisy Vedder: None declared, Tuomas Rannio: None declared, Emma Grenholm: None declared, Hanne Merete Lindegaard: None declared, Maud-Kristine A Ljosa: None declared, Eli Brodin: None declared, Annika Soderbergh: None declared, Milad Rizk: None declared, Elsa Hermansson: None declared, Line Uhrenholt Speakers bureau: AbbVie, Eli Lilly, Novartis, Consultant of: AbbVie, Eli Lilly, Novartis, Per Larsson: None declared, Søren Andreas Just: None declared, Gunnstein Bakland Speakers bureau: BMS, Consultant of: BMS, David Stevens Grant/research support from: KLINBEFORSK, Trine Bay Laurberg Speakers bureau: UCB, Consultant of: UCB, Espen A Haavardsholm Speakers bureau: Pfizer, AbbVie, Celgene, Novartis, Janssen, Gilead, Eli Lilly, UCB, Consultant of: Pfizer, AbbVie, Celgene, Novartis, Janssen, Gilead, Eli Lilly, UCB, Grant/research support from: NORDFORSK, Jon Lampa: None declared.

Objectives: The aim of this study was to investigate the reliability, validity, and sensitivity to change of a novel MRI scoring system in early peripheral SpA (pSpA). Methods: MRI of the pelvis and lower extremities was performed before initiation of the TNF inhibitor golimumab in 56 patients and repeated in 46 patients who achieved sustained clinical remission after 24, 36 or 48 weeks. Three readers applied a semi-quantitative MRI scoring system for lower-extremity joint and entheseal inflammation. Four lesion types were assessed: entheseal osteitis, entheseal soft-tissue inflammation, joint osteitis, and joint synovitis/effusion. MRI response was defined as a decrease in MRI lower-extremity inflammation index (sum of scores from 75 sites, each scored 0-3) above the smallest detectable change (SDC). Results: At follow-up, the MRI index decreased in 34 of 46 patients (74%), and 15 (33%) patients achieved MRI response, i.e. a decrease above SDC of 2.8. When restricting the analysis to patients with clinical involvement of lower-extremity sites that were assessed by MRI, 13 of 28 (46%) achieved MRI response. Interreader reliability was very good, with an average-measure intraclass correlation coefficient of 0.92 (95% CI: 0.85-0.95) for status scores and 0.89 (0.80-0.94) for change in scores. The MRI index correlated with other measures of disease activity, including CRP [Spearman's rho 0.41 (0.23-0.56)], swollen joint count of 6 joints [0.47 (0.27-0.63)], tender enthesis count of 14 entheses [0.32 (0.12-0.50)] and pain score [0.28 (0.08-0.46)], all P< 0.05. Conclusion: The proposed MRI lower-extremity inflammation index demonstrated reliability, validity, and sensitivity to change in patients with early pSpA.

Aim To 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. Methods All 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. Results Of 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%; p<0.001). In patients with score ≥2 in any gland, significantly more had positive autoantibodies, sialometry, Schirmer’s test and positive labial biopsy compared with those with scores ≤1. The best ultrasound cut-off value for diagnosing pSS was ≥1 gland with a score ≥2 (sensitivity=0.72, specificity=0.91). Conclusion The 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 <0.001). Inflammatory load on MRI decreased significantly upon TNFi treatment (P < 0.001). Whereas 80% of the joints that were clinically involved at baseline showed no effusion on remission MRI, 2 of 3 entheses involved at baseline showed residual inflammation. In addition, patients who experienced a relapse after treatment discontinuation displayed more entheseal soft tissue inflammation on remission MRI compared to those who maintained drug-free remission (P = 0.028).CONCLUSION:Our findings delineate a differential response of synovitis and enthesitis, with enthesitis on MRI being less responsive to TNFi treatment. Furthermore, residual entheseal inflammation might be indicative of the need for continuous therapy.