Publications by authors named "Mikkel Østergaard"

361 Publications

The value of magnetic resonance imaging for assessing disease extent and prediction of relapse in early peripheral spondyloarthritis.

Arthritis Rheumatol 2021 May 13. Epub 2021 May 13.

Department of Internal Medicine and Pediatrics, Ghent University Hospital, Corneel Heymanslaan 10, 9000, Ghent, Belgium.

Objective: We aimed to assess the inflammatory burden in pSpA by lower-extremity MRI in an early remission-induction strategy study with TNF blockade. Furthermore, we sought to determine the value of MRI to predict disease relapse versus sustained remission after treatment discontinuation.

Methods: Thirty-two early pSpA patients with lower limb involvement on clinical examination and confirmed by ultrasonography, participated in a remission-induction trial with a TNF-inhibitor (TNFi). Patients underwent MRI of joints and entheses of the lower extremities at baseline and at clinical remission, after which TNFi treatment was withdrawn. Images were evaluated for joint effusion, joint osteitis, entheseal soft tissue inflammation (STI), and entheseal osteitis.

Results: Joint effusion and enthesitis on clinical examination and ultrasonography correlated well with MRI abnormalities. In addition, a substantial amount of subclinical involvement was seen on MRI, mainly in ankle joints and heel entheses. Inflammation scores were markedly lower in the subclinical joints and entheses versus those clinically involved. Inflammatory load on MRI decreased significantly upon TNFi treatment. Whereas 80% of the clinically involved joints at baseline showed no effusion on remission MRI, two out of three involved entheses at baseline showed residual inflammation. In addition, patients relapsing after treatment discontinuation displayed more entheseal STI on remission MRI compared to those maintaining drug-free remission.

Conclusion: Our findings delineate a differential response of synovitis and enthesitis, with enthesitis on MRI responding less upon TNFi treatment. Furthermore, residual entheseal inflammation might be indicative for the need for continuous therapy.
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http://dx.doi.org/10.1002/art.41783DOI Listing
May 2021

Do tender joints in active psoriatic arthritis reflect inflammation assessed by ultrasound and magnetic resonance imaging?

Rheumatology (Oxford) 2021 Apr 24. Epub 2021 Apr 24.

Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Rigshospitalet, Glostrup, Denmark.

Objective: To investigate the association between clinical joint tenderness and intra- and periarticular inflammation as assessed by ultrasound and magnetic resonance imaging (MRI) in patients with active psoriatic arthritis (PsA) and to explore if the associations differ according to patient-reported outcomes (PROs) and structural damage.

Methods: Forty-one patients with active PsA and hand involvement had 76/78 joints examined for swelling/tenderness and ultrasound and MRI of 24 and 12 finger joints, respectively. Synovitis, tenosynovitis, periarticular inflammation and erosions were assessed using OMERACT definitions and scoring systems. Correlation between imaging inflammation sum-scores (intra-and periarticular) and tender/swollen joint counts were calculated using Spearman's rho, agreement at joint level was examined using prevalence and bias adjusted kappa (PABAK). Subgroup analyses explored the influence of PROs and radiographic erosive disease on these associations.

Results: No significant correlations were found between tender or swollen joint counts and imaging inflammation sum-scores (rho=-0.31-0.38). In patients with higher level of overall pain, disability and lower self-reported mental health, a tendency towards negative correlations were found. At joint level, intra- and periarticular imaging inflammatory lesions had slight agreement with joint tenderness (PABAK=0.02-0.19) and slight to moderate with swelling (PABAK=0.16-0.54). For tender joints, agreement with imaging inflammation was even weaker in patients with either high overall pain scores, high disability scores, and/or non-erosive disease.

Conclusion: Joint tenderness had low association with imaging signs of inflammation in PsA patients, particularly in patients with high self-reported pain, disability and low mental health, indicating that tenderness is influenced by other parameters than local inflammation.
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http://dx.doi.org/10.1093/rheumatology/keab384DOI Listing
April 2021

A Novel Fluorescence Optical Imaging Scoring System for Hand Synovitis in Rheumatoid Arthritis - validity and agreement with ultrasound.

Rheumatology (Oxford) 2021 Apr 23. Epub 2021 Apr 23.

Center for Rheumatology and Spine Diseases, Rigshospitalet, Denmark.

Objectives: To develop and validate a new semiquantitative Fluorescence Optical Imaging (FOI) scoring system - the FOI Enhancement-Generated rheumatoid arthritis (RA) Score (FOIE-GRAS) for synovitis assessment in the hand.

Methods: The development of FOIE-GRAS was based on consensus of 4 experts in musculoskeletal imaging. Forty-six RA patients, eligible for treatment intensification and with ≥1 clinically swollen joint in the hands and 11 healthy controls were included. FOI, ultrasound and clinical assessment of both hands were obtained at baseline and for RA patients after 3- and 6-months' follow-up. Twenty RA patients had an FOI rescan after 4 hours. Synovitis was scored using FOIE-GRAS and the OMERACT ultrasound synovitis scoring system. All FOI images were scored by 2 readers. Inter-scan, inter-and intra-reader reliability were determined. Furthermore, FOIE-GRAS agreement with ultrasound and responsiveness was assessed.

Results: FOIE-GRAS synovitis was defined as early enhancement and scores based on the degree of coverage of the specific joint region after 3 seconds (0-3). Inter-scan, intra- and inter-reader intraclass correlations coefficients (ICC) were good-excellent for all baseline scores (0.76-0.98) and moderate-to-good for change (0.65-76).The FOIE-GRAS had moderate agreement with ultrasound (ICC 0.30-0.54) for total score, a good standardized response mean (>0.80), and moderate correlation with clinical joint assessment and DAS28-CRP. The median (IQR) reading time per FOI examination was 133 (109;161) seconds. Scores were significantly lower in controls 1(0;4) than RA patients 11(6;19).

Conclusion: The FOIE-GRAS offers a feasible and reliable assessment of synovitis in RA, with a moderate correlation with ultrasound and DAS28CRP, and good responsiveness.
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http://dx.doi.org/10.1093/rheumatology/keab377DOI Listing
April 2021

Quantifying the bone marrow composition of the healthy adult wrist with dual-energy CT.

Eur J Radiol 2021 Apr 16;139:109725. Epub 2021 Apr 16.

Department of Radiology, Bispebjerg and Frederiksberg Hospital, Bispebjerg Bakke 23, 2400, København, Denmark.

Purpose: Purpose of this study was to investigate Dual-energy CT (DECT) derived virtual non-calcium (VNCa) values for absolute quantification of the bone marrow composition in the wrist.

Materials And Methods: We prospectively included consecutive adult participants and examined their wrists with DECT. Ranges of VNCa and calcium values were measured in the carpal bones, radius and ulna using a semi-automatic method. Bones with bone marrow edema, assessed by two blinded radiologists, were excluded. After determining optimum parameters for the three-material decomposition, the influence of calcium values, age and sex on VNCa values was assessed using multiple linear regression.

Results: 41 participants (Median age 53 years, range 20 years - 88 years, 51 % men) were enrolled and 399 bones assessed. At participant level mean VNCa values were -143 HU (SD 14 HU) using the current parameters for three-material decomposition and -104HU (SD 11 HU) with optimized parameters. There was a strong and significant influence of calcium values on VNCa values with the current parameters (p < 0.001, -0.137 HU / HU). With optimized parameters the calcium values and sex were not statistically significant predictors of VNCa values. Age was a significant, but clinically negligible, predictor (p = 0.03, -0.225 HU / year).

Conclusions: After optimizing three-material decomposition parameters, calcium values, age and sex do not substantially influence virtual non-calcium values, and DECT may therefore be used for absolute quantification of the bone marrow composition - alleviating the need for reference bones or groups.
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http://dx.doi.org/10.1016/j.ejrad.2021.109725DOI Listing
April 2021

Development and Validation of Three Preliminary MRI Sacroiliac Joint Composite Structural Damage Scores in a 5-year Longitudinal Axial Spondyloarthritis Study.

J Rheumatol 2021 Apr 15. Epub 2021 Apr 15.

Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Rigshospitalet, Copenhagen, Denmark; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark; Danish Hospital for Rheumatic Diseases, University Hospital of Southern Denmark, Soenderborg, Denmark; Department of Regional Health Research, University of Southern Denmark, Odense, Denmark; Department of Rheumatology, Lillebælt Hospital, Vejle, Denmark; Department of Rheumatology, Aarhus University Hospital, Aarhus, Denmark; Department of Radiology, Herlev and Gentofte Hospital, Copenhagen, Denmark. The source(s) of support in the form of grants or industrial support: The BIOSPA study was conducted without any financial support. The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors. The Danish Rheumatism Association supported MW with a PhD fellowship grant (R131- A5381). Address correspondence to Marie Wetterslev Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases Rigshospitalet, Glostrup Valdemar Hansen Vej 17 Email:

Objective: In axial spondyloarthritis (axSpA), sacroiliac joint (SIJ) erosion is often followed by fat metaplasia in an erosion cavity (backfill), and subsequently ankylosis. We aimed to combine Spondyloarthritis Research Consortium of Canada (SPARCC) SIJ Structural score for Erosion, Backfill and Ankylosis into 3 versions of a novel preliminary Composite axSpA MRI SIJ Structural Damage Score (CSDS) and test these.

Methods: Thirty-three axSpA patients followed for 5 years after initiation of tumor necrosis factor inhibitor had MRI of SIJs at baseline, and yearly thereafter. Three versions of CSDSs were calculated based on different weightings of erosion, backfill and ankylosis: Equal weighting: CSDS=(erosion x0.5)+backfill+ankylosis; Advanced stages weighting more: CSDS=(erosion x1)+(backfill x4)+(ankylosis x6); Advanced stages overruling earlier stages ("hierarchical") with "<" meaning "overruled by": CSDS=(erosion x1)<(backfill x4)<(ankylosis x6).

Results: At baseline all CSDSs correlated positively with SPARCC Fat and Ankylosis, modified New Yorkradiography grading and negatively with BASDAI and SPARCC SIJ Inflammation. CSDS and CSDS (not CSDS) correlated positively with symptom duration and BASMI, and closer with SPARCC ankylosis and Modified New York-radiography grading than CSDS. The adjusted annual progression rate for CSDS and CSDS (not CSDS) was higher the first year compared with fourth year (p=0.04 and p=0.01). Standardized response mean (baselineweek 46) was moderate for CSDS (0.64) and CSDS (0.59) and small for CSDS (0.25).

Conclusion: Particularly CSDS and CSDS showed construct validity and responsiveness, encouraging further validation in larger clinical trials. The potential clinical implication is assessment of sacroiliac joint damage progression by one composite score.
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http://dx.doi.org/10.3899/jrheum.201075DOI Listing
April 2021

Volumetric quantitative measurement of hip effusions by manual versus automated artificial intelligence techniques: An OMERACT preliminary validation study.

Semin Arthritis Rheum 2021 Mar 17. Epub 2021 Mar 17.

Department of Medicine, University of Alberta, Canada.

Objective: Preliminary assessment, via OMERACT filter, of manual and automated MRI hip effusion Volumetric Quantitative Measurement (VQM).

Methods: For 358 hips (93 osteoarthritis subjects, bilateral, 2 time points), 2 radiologists performed manual VQM using custom Matlab software. A Mask R-CNN artificial-intelligence (AI) tool was trained to automatically compute joint fluid volumes.

Results: Manual VQM had excellent inter-observer reliability (ICC 0.96). AI predicted hip fluid volumes with ICC 0.86 (status), 0.58 (change) vs. 2 human readers.

Conclusion: Hip joint fluid volumes are reliably assessed by VQM. It is feasible to automate this approach using AI, with promising initial reliability.
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http://dx.doi.org/10.1016/j.semarthrit.2021.03.009DOI Listing
March 2021

Doppler ultrasound predicts successful discontinuation of biological DMARDs in rheumatoid arthritis patients in clinical remission.

Rheumatology (Oxford) 2021 Mar 20. Epub 2021 Mar 20.

Center for Rheumatology and Spine Diseases, Center of Head and Orthopedics, Glostrup, Rigshospitalet, Capital Region, Denmark.

Objective: To assess the ability of ultrasound to predict successful tapering and successful discontinuation of biological disease-modifying anti-rheumatic drugs (bDMARDs) at 2-year follow-up in rheumatoid arthritis (RA) patients in sustained remission.

Methods: Patients in sustained remission (DAS28-CRP≤2.6) and no radiographic progression the previous year tapered bDMARD according to a standardized regime. One-hundred-and-nineteen of these patients were included in this ultrasound sub-study. 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 Outcome in Rheumatology (OMERACT) scoring system at joint level for both greyscale and Doppler activity. Sum scores for each ultrasound modality were calculated for 24 joints at patient level. Final state of treatment was assessed after 2 years. The predictive value of ultrasound measures for successful tapering and discontinuation at 2-year follow-up was assessed via logistic regression analyses.

Results: Negative IgM-RF (OR = 0.29; 95% Confidence Interval (CI)=0.10-0.85; p = 0.024) and lower Doppler sum score of 24 joints (OR(95%CI)=0.44;(0.15-0.87); p = 0.014) were independent predictors for successful discontinuation of bDMARD at 2-year follow-up. The predictive value of Doppler sum score was independent of MRI findings. Previous numbers of bDMARDs were predictive of successful tapering (OR(95% CI)=0.58(0.35-0.91); p = 0.018), whereas ultrasound was not. Clinical parameters were not predictive for successful tapering/discontinuation.

Conclusions: Doppler sum score was an independent predictor for successful discontinuation of bDMARDs at 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.
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http://dx.doi.org/10.1093/rheumatology/keab276DOI Listing
March 2021

Secukinumab Efficacy on Enthesitis in Patients with Ankylosing Spondylitis: Pooled Analysis of Four Pivotal Phase 3 Studies.

J Rheumatol 2021 Mar 15. Epub 2021 Mar 15.

Department of Internal Medicine, Friedrich Alexander University Erlangen-Nuremberg, Erlangen, Germany; Rheumazentrum Ruhrgebiet Herne, Ruhr University Bochum, Germany; Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium; VIB Center for Inflammation Research, Ghent, Belgium; Oregon Health & Science University, Portland, Oregon, United States; Copenhagen Center for Arthritis Research, University of Copenhagen, Copenhagen, Denmark; Novartis Healthcare Pvt Ltd, Hyderabad, India; Novartis Pharma AG, Basel, Switzerland; Novartis Pharmaceuticals Corporation, East Hanover, United States; University of California, San Francisco, University of California CA, United States. This study was funded by Novartis Pharma AG, Basel, Switzerland. Conflict of interest. G. Schett, Grant/research support from: BMS, Celgene, GSK, Lilly, Novartis, Consultant for: AbbVie, BMS, Celgene, Janssen, Lilly, Novartis, UCB, Speakers bureau: AbbVie, BMS, Celgene, Janssen, Lilly, Novartis, Pfizer X. Baraliakos: Consultant for: AbbVie, BMS, Chugai, MSD, Novartis, Pfizer, UCB, Speakers bureau: AbbVie, BMS, Chugai, MSD, Novartis, Pfizer, UCB; F. Van Den Bosch: Consultant/speaker fees from: AbbVie, Bristol-Myers Squibb, Celgene, Galapagos, Janssen, Lilly, MSD, Novartis, Pfizer, Sanofi and UCB; A. Deodhar: Grant/research support from: AbbVie, Eli Lilly, GSK, Novartis, Pfizer and UCB, Consultant for: AbbVie, Amgen, Boheringer Ingelheim, Celgene, Eli Lilly, Gilead, Glaxo Smith Kline, Janssen, Novartis, Pfizer and UCB; L. Gensler: Grant/research support from: Novartis Pfizer and UCB, Consultant for: AbbVie, Gilead, GSK, Eli Lilly, Novartis, Pfizer and UCB; M Østergaard: Speaker/consultant fees from Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli-Lilly, Gilead, Hospira, Janssen, Merck, Novartis, Novo, Orion, Pfizer, Regeneron, Roche, and UCB, and research grants from Abbvie, Celgene, Centocor, Merck, and Novartis; A. Das Gupta: Employee of: Novartis; S. Mpofu, T. Fox, A. Winseck, B. Porter and A. Shete: Employee of: Novartis: Shareholder: Novartis. Address correspondence to Dr. Georg Schett Department of Internal Medicine 3 and Institute for Clinical Immunology Krankenhausstr. 12 D-91054 Erlangen. E-Mail:

Objective: To assess the efficacy of secukinumab on axial and peripheral enthesitis in patients with ankylosing spondylitis (AS) using pooled data from randomized controlled phase 3 studies.

Methods: In this post-hoc analysis, data were pooled from patients originally randomized to secukinumab 150 mg, 300 mg, or placebo from phase 3 MEASURE 1-4 studies (ClinicalTrials.gov identifiers: NCT01358175, NCT01649375, NCT02008916 and NCT02159053). Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) was used for assessments of enthesitis through Week 52. Efficacy outcomes were mean change in MASES score and complete resolution (MASES=0) of enthesitis in patients with baseline MASES>0.

Results: A total of 693 (71.5%) patients had enthesitis at baseline in secukinumab 300 mg, 150 mg and placebo groups (58 [76.3%], 355 [70.4%] and 280 [72%]), respectively, out of 969 patients pooled in this analysis. At Week 16, mean change from baseline for overall MASES and enthesitis at axial MASES-sites was: secukinumab 300 mg (-2.9 [P<0.01] and -2.9 [P<0.01]); 150 mg (-2.4 [P<0.015] and -2.3 [P<0.05]), and placebo (-1.9 and -1.8), with improvements seen through Week 52. More than a third of secukinumab-treated patients (300 mg, 36.2% and 150 mg, 40.8%) achieved complete resolution of enthesitis at Week 16.

Conclusion: Secukinumab improved enthesitis at overall MASES and axial sites in patients with ankylosing spondylitis.
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http://dx.doi.org/10.3899/jrheum.201111DOI Listing
March 2021

Magnetic Resonance Imaging of Axial and Peripheral Disease in Psoriatic Arthritis: A Report From the 2020 GRAPPA Annual Meeting.

J Rheumatol 2021 Feb 15. Epub 2021 Feb 15.

As part of the supplement series GRAPPA 2020, this report was reviewed internally and approved by the Guest Editors for integrity, accuracy, and consistency with scientific and ethical standards. W.P. Maksymowych, FRCP, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada; M. Østergaard, MD, PhD, DMSc, Copenhagen Center for Arthritis Research (COPECARE), Center for Rheumatology and Spine Diseases, Centre of Head and Orthopaedics, Rigshospitalet, Glostrup, and Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark. The authors declare no relevant conflicts of interest for this work. This paper does not require institutional review board approval. Patients gave written informed consent was received. Address correspondence to Dr. W.P. Maksymowych, 568 Heritage Medical Research Building, University of Alberta, Edmonton, AB T6R 2G8, Canada. Email:

Psoriatic arthritis (PsA) presents with diverse features of musculoskeletal inflammation that affect both axial and peripheral joints as well as entheses, tenosynovium, and bursae. Magnetic resonance imaging (MRI) is the imaging modality that is uniquely capable of identifying pathology in all these structures. The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) Magnetic Resonance Imaging Working Group has increasingly explored diverse MRI methodologies for the purposes of quantifying inflammatory and structural abnormalities in clinical trials and research. The 2020 GRAPPA virtual workshop presented an opportunity to review progress in the field, summarize the status of MRI scoring systems developed for PsA, and review representative patient cases.
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http://dx.doi.org/10.3899/jrheum.201676DOI Listing
February 2021

Data-Driven Definitions for Active and Structural MRI Lesions in the Sacroiliac Joint in Spondyloarthritis and their Predictive Utility.

Rheumatology (Oxford) 2021 Feb 1. Epub 2021 Feb 1.

Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Rigshospitalet, Copenhagen, Denmark.

Objectives: To determine quantitative sacroiliac joint (SIJ) MRI lesion cut-offs that optimally define a positive MRI for inflammatory and structural lesions typical of axial spondyloarthritis (axSpA) and that predict clinical diagnosis.

Methods: The ASAS MRI group assessed MRIs from the ASAS Classification Cohort in two reading exercises: A. 169 cases and 7 central readers; B. 107 cases and 8 central readers. We calculated sensitivity/specificity for the number of SIJ quadrants or slices with bone marrow edema (BME), erosion, fat lesion, where a majority of central readers had high confidence there was a definite active or structural lesion. Cut-offs with ≥95% specificity were analyzed for their predictive utility for follow-up rheumatologist diagnosis of axSpA by calculating positive/negative predictive values (PPV/NPV) and selecting cut-offs with PPV≥95%.

Results: Active or structural lesions typical of axSpA on MRI had PPV≥95% for clinical diagnosis of axSpA. Cut-offs that best reflect definite active lesion typical of axSpA were either ≥4 SIJ quadrants with BME at any location or at the same location in ≥ 3 consecutive slices. For definite structural lesion, the optimal cut-offs were any one of ≥ 3 SIJ quadrants with erosion or ≥ 5 with fat lesion, erosion at the same location for ≥2 consecutive slices, fat lesion at the same location for ≥3 consecutive slices, or presence of a 'deep' (>1cm) fat lesion.

Conclusion: We propose cut-offs for definite active and structural lesions typical of axSpA that have high PPV for a long-term clinical diagnosis of axSpA for application in disease classification and clinical research.
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http://dx.doi.org/10.1093/rheumatology/keab099DOI Listing
February 2021

Using a DAS28-CRP-steered treat-to-target strategy does not eliminate subclinical inflammation as assessed by ultrasonography in rheumatoid arthritis patients in longstanding clinical remission.

Arthritis Res Ther 2021 02 1;23(1):48. Epub 2021 Feb 1.

Copenhagen Center for Arthritis Research (COPECARE), Center for Rheumatology and Spine Diseases, Copenhagen University Hospital, Rigshospitalet, Glostrup, Copenhagen, Denmark.

Background: Subclinical synovitis by ultrasound is a frequent finding in rheumatoid arthritis (RA) patients in remission and has been shown to be related to erosive progression, risk of flare and unsuccessful drug tapering, but it has not been investigated how a DAS28 T2T-steered strategy in routine care affects the presence of subclinical synovitis in RA patients in remission. The aim of the current study was to investigate the presence of ultrasound-detected subclinical inflammation in RA patients in long-term remission receiving either biological or conventional disease-modifying anti-rheumatic drugs (bDMARD/csDMARD) and, finally, to investigate the presence of ultrasound remission using different ultrasound remission criteria.

Methods: Eighty-seven RA patients (42 patients receiving bDMARD and 45 csDMARD) received DAS28-CRP-steered treatment in routine care and had achieved DAS28-CRP-remission for > 1 year without radiographic progression. Twenty-four joints were scored 0-3 by ultrasound (elbows, wrists, knees, ankles, metacarpophalangeal and metatarsophalangeal joints 2-5) for grey-scale synovial hypertrophy (GS) and colour Doppler activity (CD) using the OMERACT scoring system. Ultrasound remission was defined as strict (GS score = 0 and CD score = 0), semi-strict (GS score < 1 and Doppler score = 0) and Doppler remission (Doppler score = 0).

Results: No differences between treatment groups were found for GS sum score and Doppler sum score (median (range) 6 (0-19) and 0 (0-12), respectively). A Doppler score > 0 in at least 1 joint was seen in 44%, a GS score > 1 in at least 1 joint in 93% and a GS score > 2 in at least 1 joint in 54% of patients. Strict ultrasound remission was only observed in bDMARD patients (7%; p = 0.01). Thirty-seven per cent were in semi-strict ultrasound remission and 56% in Doppler remission (no significant difference between groups) with similar results across the subgroups of patients who also fulfilled the ACR-EULAR Boolean-, CDAI- and SDAI-remission criteria.

Conclusions: Ultrasound frequently detected subclinical synovitis in RA patients in longstanding DAS28-remission obtained through a DAS28-CRP-steered strategy. This was independent of treatment and applied ultrasound remission criteria. Strict ultrasound remission was rare.
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http://dx.doi.org/10.1186/s13075-021-02426-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7849184PMC
February 2021

Risk of serious infections in arthritis patients treated with biological drugs: a matched cohort study and development of prediction model.

Rheumatology (Oxford) 2021 Jan 25. Epub 2021 Jan 25.

Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Rigshospitalet, Glostrup, Denmark.

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.
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http://dx.doi.org/10.1093/rheumatology/keaa876DOI Listing
January 2021

Real-world 6 and 12-month Drug Retention, Remission and Response Rates of Secukinumab in 2,017 Psoriatic Arthritis patients in 13 European Countries.

Arthritis Care Res (Hoboken) 2021 Jan 18. Epub 2021 Jan 18.

Amsterdam University Medical Centres, location VU University medical centre, Department Rheumatology & Immunology Center (ARC), Amsterdam, the Netherlands.

Objective: There is a lack of real-life studies on IL-17 inhibition in psoriatic arthritis (PsA). We assessed real-life 6-/12-month effectiveness (i.e. retention, remission, low-disease-activity [LDA] and response rates) of the IL-17 inhibitor secukinumab in PsA patients overall, and across 1) number of prior biologic/targeted synthetic Disease-Modifying Anti-Rheumatic Drugs (b/tsDMARDs), 2) years since diagnosis, and 3) European registries.

Methods: Thirteen quality registries in rheumatology participating in the European Spondyloarthritis Research Collaboration Network provided longitudinal, observational data collected as part of routine care, for secondary use. Data were pooled and analysed with Kaplan-Meier plots, log-rank tests, Cox regression, and multiple linear and logistic regression analyses.

Results: A total of 2,017 PsA patients started treatment with secukinumab between 2015 and 2018. Overall secukinumab retention rates were 86%/76% after 6/12 months. Crude (LUNDEX adjusted) 6-month remission/LDA (LDA including remission) rates for DAPSA28, DAS28-CRP and SDAI were 13%/46% (11%/39%), 36%/55% (30%/46%) and 13%/56% (11%/47%), and 12-month rates 11%/46% (7%/31%), 39%/56% (26%/38%) and 16%/62% (10%/41%), respectively. CDAI remission/LDA rates were similar to the SDAI rates. Six-month ACR20/50/70 responses were 34%/19%/11% (29%/16%/9%); 12-month: 37%/21%/11% (24%/14%/7%). Secukinumab effectiveness was significantly better for b/tsDMARD naïve patients, similar across time since diagnosis (<2/2-4/>4 years) and varied significantly across the European registries.

Conclusion: In this large real-world study on secukinumab treatment in PsA, 6- and 12-month effectiveness was comparable to previous observational studies of TNFi. Retention, remission, LDA and response rates were significantly better for b/tsDMARD naïve patients, independent of time since diagnosis and varied significantly across the European countries.
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http://dx.doi.org/10.1002/acr.24560DOI Listing
January 2021

Repeatability and reproducibility of MRI apparent diffusion coefficient applied on four different regions of interest for patients with axial spondyloarthritis and healthy volunteers scanned twice within a week.

BJR Open 2020 21;2(1):20200004. Epub 2020 Dec 21.

Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Rigshospitalet, Glostrup, Denmark.

Objectives: The apparent diffusion coefficient (ADC) may be used as a biomarker for diagnosis and/or monitoring treatment response in patients with axial spondyloarthritis (axSpA), but this requires reliable ADC measurements. This study assessed test-retest repeatability and reproducibility of ADC measurements using four different region of interest (ROI) settings.

Methods: In this prospective study, the sacroiliac joints (SIJs) of 25 patients with axSpA and 24 age- and sex-matched healthy volunteers were imaged twice at a mean interval of 6.8 days in a 1.5 T scanner using, multishot echoplanar diffusion-weighted sequences. ADCs at four ROI settings were assessed: 5 mm and 10 mm anatomic band-shaped, 15 mm linear, and 40 mm circular.

Results: Intraclass correlation coefficient (ICC) assessments showed that the interstudy repeatability was good for median ADC (ADC) and 95th-percentile ADC (ADC) measurements in patients with axSpA (0.77-0.83 and 0.75-0.83, respectively), but poor-to-moderate in healthy subjects (0.27-0.55 and 0.13-0.37, respectively). For all ROI settings, intrareader reproducibility was excellent for ADC-measurements (ICC:0.85-0.99) and moderate-to-excellent for ADC measurements (ICC:0.68-0.96). The 5 mm ROI had the least estimated bias and highest level of agreement on Bland-Altman plots. The interreader reproducibility was moderate (ICC:0.71). The 15 mm linear ROI produced significantly greater ADC and ADC measurements than all other ROI settings ( < 0.01-0.02), except for the circular ROI ADC measurements.

Conclusion: ROI settings influence ADC measurements. Interstudy repeatability of SIJ ADC measurements is independent of ROI settings. However, the 5 mm ROI showed the least bias and random error and seems preferable.

Advances In Knowledge: ADC measurements are affected by ROI settings, and this should be taken into account when assessing ADC maps.
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http://dx.doi.org/10.1259/bjro.20200004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7768406PMC
December 2020

Self-protection strategies and health behaviour in patients with inflammatory rheumatic diseases during the COVID-19 pandemic: results and predictors in more than 12 000 patients with inflammatory rheumatic diseases followed in the Danish DANBIO registry.

RMD Open 2021 01;7(1)

DANBIO and Copenhagen Center for Arthritis Research (COPECARE), Center for Rheumatology and Spine Diseases, Centre of Head and Orthopedics, Rigshospitalet Glostrup, Glostrup, Denmark.

Aims: In Danish patients with inflammatory rheumatic diseases to explore self-protection strategies and health behaviour including adherence to disease-modifying antirheumatic treatment (DMARD) during the initial phase of the COVID-19 pandemic and again after the reopening of the society started. Furthermore, to identify characteristics of patients with high levels of anxiety and self-isolation.

Methods: Patients in routine care followed prospectively in the nationwide DANBIO registry were invited to answer an online questionnaire regarding disease activity and COVID-19 infection, behaviour in March and June 2020. Responses were linked to patient data in DANBIO. Characteristics potentially associated with anxiety, self-isolation and medication adherence (gender/age/diagnosis/education/work status/comorbidity/DMARD/smoking/EQ-5D/disease activity) were explored with multivariable logistic regression analyses.

Results: We included 12 789 patients (8168 rheumatoid arthritis/2068 psoriatic arthritis/1758 axial spondyloarthritis/795 other) of whom 65% were women and 36% treated with biological DMARD. Self-reported COVID-19 prevalence was 0.3%. Patients reported that they were worried to get COVID-19 infection (March/June: 70%/45%) and self-isolated more than others of the same age (48%/38%). The fraction of patients who changed medication due to fear of COVID-19 were 4.1%/0.6%. Female gender, comorbidities, not working, lower education, biological treatment and poor European Quality of life, 5 dimensions were associated with both anxiety and self-isolation.

Conclusion: In >12 000 patients with inflammatory arthritis, we found widespread anxiety and self-isolation, but high medication adherence, in the initial phase of the COVID-19 pandemic. This persisted during the gradual opening of society during the following months. Attention to patients' anxiety and self-isolation is important during this and potential future epidemics.
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http://dx.doi.org/10.1136/rmdopen-2020-001505DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7786545PMC
January 2021

Validation of the adjusted multi-biomarker disease activity score as a prognostic test for radiographic progression in rheumatoid arthritis: a combined analysis of multiple studies.

Arthritis Res Ther 2021 01 4;23(1). Epub 2021 Jan 4.

Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, Netherlands.

Background: The multi-biomarker disease activity (MBDA) test measures 12 serum protein biomarkers to quantify disease activity in RA patients. A newer version of the MBDA score, adjusted for age, sex, and adiposity, has been validated in two cohorts (OPERA and BRASS) for predicting risk for radiographic progression. We now extend these findings with additional cohorts to further validate the adjusted MBDA score as a predictor of radiographic progression risk and compare its performance with that of other risk factors.

Methods: Four cohorts were analyzed: the BRASS and Leiden registries and the OPERA and SWEFOT studies (total N = 953). Treatments included conventional DMARDs and anti-TNFs. Associations of radiographic progression (ΔTSS) per year with the adjusted MBDA score, seropositivity, and clinical measures were evaluated using linear and logistic regression. The adjusted MBDA score was (1) validated in Leiden and SWEFOT, (2) compared with other measures in all four cohorts, and (3) used to generate curves for predicting risk of radiographic progression.

Results: Univariable and bivariable analyses validated the adjusted MBDA score and found it to be the strongest, independent predicator of radiographic progression (ΔTSS > 5) compared with seropositivity (rheumatoid factor and/or anti-CCP), baseline TSS, DAS28-CRP, CRP SJC, or CDAI. Neither DAS28-CRP, CDAI, SJC, nor CRP added significant information to the adjusted MBDA score as a predictor, and the frequency of radiographic progression agreed with the adjusted MBDA score when it was discordant with these measures. The rate of progression (ΔTSS > 5) increased from < 2% in the low (1-29) adjusted MBDA category to 16% in the high (45-100) category. A modeled risk curve indicated that risk increased continuously, exceeding 40% for the highest adjusted MBDA scores.

Conclusion: The adjusted MBDA score was validated as an RA disease activity measure that is prognostic for radiographic progression. The adjusted MBDA score was a stronger predictor of radiographic progression than conventional risk factors, including seropositivity, and its prognostic ability was not significantly improved by the addition of DAS28-CRP, CRP, SJC, or CDAI.
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http://dx.doi.org/10.1186/s13075-020-02389-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7784276PMC
January 2021

Similar lipid level changes in early rheumatoid arthritis patients following 1-year treat-to-target strategy with adalimumab plus methotrexate versus placebo plus methotrexate: secondary analyses from the randomised controlled OPERA trial.

Rheumatol Int 2021 Mar 2;41(3):543-549. Epub 2021 Jan 2.

Faculty of Health Sciences, Research Unit of Rheumatology, Department of Clinical Research, University of Southern Denmark, Odense University Hospital, J.B. Winsløws Vej 4, Indgang 96, 1. Sal, 5000, Odense, Denmark.

To compare changes in low-density lipoprotein cholesterol and other lipids in patients with rheumatoid arthritis (RA) randomised to a 1-year treat-to-target strategy with either adalimumab plus methotrexate or placebo plus methotrexate. Prespecified secondary analyses from the OPERA trial, where 180 early and treatment-naïve RA patients received methotrexate 20 mg once weekly in combination with either placebo or subcutaneous adalimumab 40 mg every other week. Serum lipid levels were measured at baseline and after 1 year. Changes in lipid levels were analysed using mixed linear models based on the intention-to-treat (ITT) population. Overall, 174 patients were included in the ITT population (adalimumab plus methotrexate n = 86; placebo plus methotrexate n = 88). Differences between changes in lipid levels were low-density lipoprotein cholesterol 0.18 mmol/l [95% CI - 0.05 to 0.42], total cholesterol 0.27 mmol/l [- 0.002 to 0.54], high-density lipoprotein cholesterol 0.05 mmol/l [- 0.06 to 0.15], triglycerides 0.11 mmol/l [- 0.08 to 0.29], very-low-density lipoprotein cholesterol 0.03 mmol/l [- 0.05 to 0.12], and non-high-density lipoprotein cholesterol 0.22 mmol/l [- 0.02 to 0.46]. In early RA patients treated to tight control of inflammation over a period of 1 year with either adalimumab plus methotrexate or placebo plus methotrexate, changes in lipid levels were similar. Trial registration number: NCT00660647.
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http://dx.doi.org/10.1007/s00296-020-04756-5DOI Listing
March 2021

Active conventional treatment and three different biological treatments in early rheumatoid arthritis: phase IV investigator initiated, randomised, observer blinded clinical trial.

BMJ 2020 12 2;371:m4328. Epub 2020 Dec 2.

Department of Rheumatology, Ålesund Hospital, Ålesund, Norway.

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.
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http://dx.doi.org/10.1136/bmj.m4328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7708829PMC
December 2020

Evolving the comprehensive management of rheumatoid arthritis: identification of unmet needs and development of practical and educational tools.

Clin Exp Rheumatol 2020 Nov-Dec;38(6):1056-1067. Epub 2020 Nov 17.

University of Twente, Faculty of Behavioural, Management and Social Sciences, Enschede, The Netherlands.

Objectives: Despite availability of efficacious treatments, unmet needs still exist, preventing optimal and comprehensive management of rheumatoid arthritis (RA). Evolving the management of RA (eRA) is a European-wide educational initiative aiming to support improved patient care through practical and educational tools addressing specific unmet needs.

Methods: A multidisciplinary Steering Committee (17 members, 12 countries) identified unmet needs within the management of RA and prioritised those with the greatest impact on patient outcomes. Practical educational tools addressing priority needs were then developed for dissemination and implementation by the rheumatology community across Europe.

Results: Five areas of priority need were identified: increasing early recognition of RA and treatment initiation; treating RA to target; optimal, holistic approach to selection of treatment strategy, including shared decision-making; improving identification and management of comorbidities; and non-pharmacological patient management. A suite of 14 eRA tools included educational slides, best-practice guidance, self‑assessment questionnaires, clinical checklists, a multidisciplinary team training exercise, an interactive patient infographic, and case scenarios. By April 2020, rheumatology professionals in 17 countries had been actively engaged in the eRA programme; in 11 countries, eRA tools were selected by national leaders in rheumatology and translated for local dissemination. A web platform, with country-specific pages, was developed to support access to the translated tools (https://www.evolvingthemanagementofra.com/).

Conclusions: The eRA programme supports comprehensive management of RA across Europe through development and dissemination of practical educational tools. The eRA tools address priority needs and are available free of charge to the rheumatology community.
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December 2020

Secukinumab Provides Sustained Reduction in Fatigue in Patients with Ankylosing Spondylitis: Long-term Results of Two Phase III Randomized Controlled Trials.

Arthritis Care Res (Hoboken) 2020 Nov 23. Epub 2020 Nov 23.

Oregon Health & Science University, Portland, OR, United States.

Objective: To investigate the longer-term effects of secukinumab 150 mg on fatigue in patients with ankylosing spondylitis (AS) in MEASURE 1 (up to 3 years) and MEASURE 2 (up to 2 years).

Methods: Patients with active AS were randomized to secukinumab or placebo in MEASURE 1 (10 mg/kg intravenous [IV] followed by 150 mg subcutaneous [SC]) and MEASURE 2 (150 mg SC). Patients were naive to or had an inadequate response/intolerance to tumor necrosis factor inhibitors (anti-TNF-naive/ anti-TNF-IR). Fatigue was measured using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) scale. Relationships between fatigue response and baseline characteristics and clinical/laboratory variables were explored.

Results: Significant improvements in FACIT-F scores from baseline were observed with secukinumab across both studies versus placebo at week 16 (P < 0.05). Improvements were sustained through week 156 (MEASURE 1)/week 104 (MEASURE 2). Significantly more patients reported fatigue responses (FACIT-F increase ≥4; observed data) with secukinumab 150 mg than placebo at week 16 in both MEASURE 1 (P < 0.05) and MEASURE 2 (P < 0.01). Fatigue responses were achieved by 75.6% of patients receiving secukinumab at week 156 (MEASURE 1) and 81.4% at week 104 (MEASURE 2); these results were consistent in both anti-TNF-naive (74.3% and 84.6%) and anti-TNF-IR (81.3% and 75.0%) patients. Baseline characteristics did not predict improvement in fatigue consistently. Fatigue responses were moderately to strongly correlated with responses in several clinical measures, including Assessment of SpondyloArthritis international Society (ASAS)20/40, ASAS5/6 responses, Ankylosing Spondylitis Disease Activity Score-C reactive protein (ASDAS-CRP), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), and Short-form (SF)-36 scores.

Conclusion: Secukinumab provided rapid and sustained improvements in fatigue for up to 3 years, regardless of prior anti-TNF exposure.
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http://dx.doi.org/10.1002/acr.24517DOI Listing
November 2020

Validation of assessment methods for the apparent diffusion coefficient in a clinical trial of axial spondyloarthritis patients treated with golimumab.

Eur J Radiol Open 2020 5;7:100285. Epub 2020 Nov 5.

Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

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 (ADC) was 230 μmm/s (standard deviation [SD] = 120). This was significantly lower ( < 0.01) than the means of the lesion-based ROI ADC (ADC = 420 μmm/s, SD = 210) and index-lesion ROI ADC (ADC = 471 μmm/s, SD = 278), which did not differ. ADC correlated with SPARCC-BME scores at baseline ( < 0.01) as did changes over time in ADC- and SPARCC-BME (<0.05). At all follow-up time points, responsiveness was high for ADC (SRM > 0.92) and ADC (SRM > 0.87) while moderate for ADC (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.
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http://dx.doi.org/10.1016/j.ejro.2020.100285DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7649611PMC
November 2020

Which ultrasound lesions contribute to dactylitis in psoriatic arthritis and their reliability in a clinical setting.

Clin Rheumatol 2021 Mar 5;40(3):1061-1067. Epub 2020 Nov 5.

Copenhagen Center for Arthritis Research and Center for Rheumatology and Spine Diseases, Centre of Head and Orthopaedics, Rigshospitalet, Glostrup, Denmark.

Objectives: To explore the frequency of ultrasound elementary lesions in dactylitis in psoriatic arthritis (PsA), and the reliability of scoring these lesions in a clinical setting.

Methods: In 31 patients with PsA and clinical dactylitis, ultrasound assessment of the affected finger or toe was performed using greyscale and color Doppler mode. One examiner scanned all patients and a second examiner scanned 10 patients for inter-reader reliability. For each digit, the following lesions were evaluated: subcutaneous edema; soft tissue thickening; synovitis of the digital joints; tenosynovitis of the flexor tendon; enthesitis at the deep flexor tendon and the extensor tendon entheses; and paratenonitis of the extensor tendon. A dactylitis sum-score was calculated. Findings in clinically tender and non-tender digits were compared.

Results: The most frequent lesions were soft tissue thickening (81%) and subcutaneous edema (74%) followed by synovitis (56-68%) and flexor tenosynovitis (52%). Color Doppler was most frequently found subcutaneously (55%) and around the flexor tendons (45%). All lesions were typically found in combinations, most commonly subcutaneous edema and synovitis (71%), subcutaneous edema and flexor tenosynovitis (52%), and all three in combination (52%). Tender digits had a higher dactylitis sum-score and numerically higher prevalence of most lesions than non-tender digits. Intra- and inter-reader agreements were moderate to excellent, though lower for few components of digital enthesitis, especially hypoechogenicity.

Conclusion: Dactylitis in PsA appears to encompass several lesions, most often subcutaneous changes combined with synovitis and/or flexor tenosynovitis. Reliability of scoring established ultrasound lesions of dactylitis in a clinical setting is moderate-excellent. Key Points • Dactylitis in psoriatic arthritis consists of multiple ultrasound lesions • A dactylitis ultrasound sum-score gives an impression of severity by including all lesions • Reliability of ultrasound scoring of dactylitis components is good.
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http://dx.doi.org/10.1007/s10067-020-05483-9DOI Listing
March 2021

Axial involvement in patients with early peripheral spondyloarthritis: a prospective MRI study of sacroiliac joints and spine.

Ann Rheum Dis 2021 01 28;80(1):103-108. Epub 2020 Oct 28.

Internal Medicine and Pediatrics, Ghent University Faculty of Medicine and Health Sciences, Ghent, Belgium.

Objectives: To assess axial involvement on MRI in early peripheral spondyloarthritis (pSpA) and to evaluate whether axial inflammation predicts relapse on treatment withdrawal.

Methods: Fifty-six patients with early, active, newly diagnosed pSpA underwent MRI of the sacroiliac joints (SIJs) and spine prior to golimumab initiation. At sustained clinical remission of pSpA, treatment was withdrawn and a second MRI was performed. Bone marrow oedema (BME) was scored by three readers according to the Spondyloarthritis Research Consortium of Canada (SPARCC) method. Scores were compared with an axial spondyloarthritis cohort (Belgian Arthritis and Spondylitis cohort). Structural lesions were assessed using a similar method. Furthermore, fulfilment of the Assessment of Spondyloarthritis International Society (ASAS) definition of a positive MRI for sacroiliitis was assessed. Spinal images were evaluated for BME and structural lesions using the Canada-Denmark MRI spine scoring system by two readers.

Results: Thirty-six per cent showed SIJ BME at baseline, all fulfilling the ASAS definition of sacroiliitis. No association with back pain was found. Twenty-one per cent displayed SIJ structural lesions. Spinal BME was limited: the median inflammation scores were low and no patients had ≥5 inflammatory corner lesions. On clinical remission, a significant decrease in SIJ SPARCC scores was detected. On clinical remission, no significant differences in SIJ SPARCC scores were noted between patients relapsing and those maintaining remission after treatment discontinuation.

Conclusion: In patients with early pSpA, a surprisingly high prevalence of sacroiliitis on MRI was observed; SPARCC scores decreased significantly on tumour necrosis factor inhibition. Residual inflammation on MRI was not predictive of relapse of peripheral manifestations. No relevant inflammatory spinal involvement was detected. Collectively, our findings suggest a higher inflammatory burden in patients with early pSpA than anticipated.
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http://dx.doi.org/10.1136/annrheumdis-2020-218480DOI Listing
January 2021

Imaging in the diagnosis and management of peripheral psoriatic arthritis.

Best Pract Res Clin Rheumatol 2020 12 6;34(6):101594. Epub 2020 Oct 6.

Copenhagen Center for Arthritis Research (COPECARE), Center for Rheumatology and Spine Diseases, Rigshospitalet, Glostrup, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. Electronic address:

Psoriatic arthritis is a heterogenous disease affecting peripheral and axial joints, tendons, ligaments, and their insertions, in addition to the skin and the nails. The complexity of the involved structures has puzzled clinicians trying to understand the underlying pathology that leads to symptoms in order to choose the appropriate medications with different modes of actions. Imaging, mainly ultrasound and magnetic resonance imaging, allows of accurate detection of inflammatory changes in the musculoskeletal structures, which helps to avoid false positive and negative assessments. The linking of different anatomical structures' involvement using imaging also provides insights into the pathogenesis of psoriatic arthritis. In this review, ultrasound and magnetic resonance imaging will be discussed in depth with regard to their use in the field of peripheral psoriatic arthritis, with a focus on the literature from the last 4 years and recent advances.
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http://dx.doi.org/10.1016/j.berh.2020.101594DOI Listing
December 2020

Anatomic Distribution of Sacroiliac Joint Lesions on Magnetic Resonance Imaging in Patients With Axial Spondyloarthritis and Control Subjects: A Prospective Cross-Sectional Study, Including Postpartum Women, Patients With Disc Herniation, Cleaning Staff, Runners, and Healthy Individuals.

Arthritis Care Res (Hoboken) 2021 May;73(5):742-754

Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Center of Head and Orthopedics, Rigshospitalet, Glostrup, and University of Copenhagen, Copenhagen, Denmark.

Objective: To investigate the anatomic location and distribution of lesions on magnetic resonance imaging (MRI) in the sacroiliac (SI) joints in patients with axial spondyloarthritis (SpA), women with and without postpartum pain (childbirth within 4-16 months), patients with disc herniation, cleaning staff, runners, and healthy persons.

Methods: In a prospective cross-sectional study of 204 participants, MRI of the entire cartilaginous compartment of the SI joint was scored blindly by 2 independent, experienced readers, according to Spondyloarthritis Research Consortium of Canada definitions of SI joint inflammation and structural lesions in each SI joint quadrant or half and in each of 9 slices. The locations of the lesions (unilateral/bilateral, upper/lower, sacral/iliac, and anterior/central/posterior slices) were analyzed based on concordant reads.

Results: Bone marrow edema (BME) occurred in all quadrants in nearly all participant groups, but rarely bilaterally, except in patients with axial SpA and women with postpartum pain. Fat lesions were mainly found in axial SpA and occurred in all quadrants, but mostly bilaterally in sacral quadrants. Erosion was rare, except in axial SpA, where it was mainly iliac and often bilateral. Sclerosis was exclusively iliac and most frequent in women with postpartum pain.

Conclusion: The location and distribution of common SI joint lesions in axial SpA and non-axial SpA were reported, and group-specific patterns were revealed. BME distributed bilaterally or unilaterally, both locally and more widespread in the SI joint, is common in both postpartum women with pain and axial SpA patients, which limits the use of BME to differentiate these groups. This study indicates that the presence of fat lesions, especially when widespread, and/or erosion, particularly when located centrally or posteriorly, are diagnostically important and should be investigated further.
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http://dx.doi.org/10.1002/acr.24473DOI Listing
May 2021

Drug retention, inactive disease and response rates in 1860 patients with axial spondyloarthritis initiating secukinumab treatment: routine care data from 13 registries in the EuroSpA collaboration.

RMD Open 2020 09;6(3)

Copenhagen Center for Arthritis Research (COPECARE), Center for Rheumatology and Spine Diseases, Centre for Head and Orthopedics, Rigshospitalet Glostrup, Copenhagen, Denmark.

Objectives: To explore 6-month and 12-month secukinumab effectiveness in patients with axial spondyloarthritis (axSpA) overall, as well as across (1) number of previous biologic/targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs), (2) time since diagnosis and (3) different European registries.

Methods: Real-life data from 13 European registries participating in the European Spondyloarthritis Research Collaboration Network were pooled. Kaplan-Meier with log-rank test, Cox regression, χ² and logistic regression analyses were performed to assess 6-month and 12-month secukinumab retention, inactive disease/low-disease-activity states (Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) <2/<4, Ankylosing Spondylitis Disease Activity Score (ASDAS) <1.3/<2.1) and response rates (BASDAI50, Assessment of Spondyloarthritis International Society (ASAS) 20/40, ASDAS clinically important improvement (ASDAS-CII) and ASDAS major improvement (ASDAS-MI)).

Results: We included 1860 patients initiating secukinumab as part of routine care. Overall 6-month/12-month secukinumab retention rates were 82%/72%, with significant (p<0.001) differences between the registries (6-month: 70-93%, 12-month: 53-86%) and across number of previous b/tsDMARDs (b/tsDMARD-naïve: 90%/73%, 1 prior b/tsDMARD: 83%/73%, ≥2 prior b/tsDMARDs: 78%/66%). Overall 6-month/12-month BASDAI<4 were observed in 51%/51%, ASDAS<1.3 in 9%/11%, BASDAI50 in 53%/47%, ASAS40 in 28%/22%, ASDAS-CII in 49%/46% and ASDAS-MI in 25%/26% of the patients. All rates differed significantly across number of previous b/tsDMARDs, were numerically higher for b/tsDMARD-naïve patients and varied significantly across registries. Overall, time since diagnosis was not associated with secukinumab effectiveness.

Conclusions: In this study of 1860 patients from 13 European countries, we present the first comprehensive real-life data on effectiveness of secukinumab in patients with axSpA. Overall, secukinumab retention rates after 6 and 12 months of treatment were high. Secukinumab effectiveness was consistently better for bionaïve patients, independent of time since diagnosis and differed across the European countries.
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http://dx.doi.org/10.1136/rmdopen-2020-001280DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7539854PMC
September 2020

Predictors of joint damage progression and stringent remission in patients with established rheumatoid arthritis in clinical remission.

Rheumatology (Oxford) 2021 01;60(1):380-391

Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Centre for Head and Orthopaedics, Rigshospitalet, Glostrup, Denmark.

Objectives: To study if clinical, radiographic and MRI markers can predict MRI and radiographic damage progression and achievement of stringent remission in patients with established RA in clinical remission followed by a targeted treatment strategy.

Methods: RA patients (DAS28-CRP <3.2, no swollen joints) receiving conventional synthetic DMARDs were randomized to conventional or MRI-targeted treat-to-target strategies with predefined algorithmic treatment escalations. Potentially predictive baseline variables were tested in multivariate logistic regression analyses.

Results: In the 171 patients included, baseline MRI osteitis independently predicted progression in MRI erosion [odds ratio (OR) 1.13 (95% CI 1.06, 1.22)], joint space narrowing [OR 1.15 (95% CI 1.07, 1.24)] and combined damage [OR 1.23 (95% CI 1.13, 1.37)], while tenosynovitis independently predicted MRI erosion progression [OR 1.13 (95% CI 1.03, 1.25)]. A predictor of radiographic erosion progression was age, while gender predicted progression in joint space narrowing. Following an MRI treat-to-target strategy predicted stringent remission across all remission definitions: Clinical Disease Activity Index remission OR 2.94 (95% CI 1.25, 7.52), Simplified Disease Activity Index remission OR 2.50 (95% CI 1.01, 6.66), ACR/EULAR Boolean remission OR 5.47 (95% CI 2.33, 14.13). Similarly, low tender joint count and low patient visual analogue scale pain and global independently predicted achievement of more stringent remission.

Conclusion: Baseline MRI osteitis and tenosynovitis were independent predictors of 2 year MRI damage progression in RA patients in clinical remission, while independent predictors of radiographic damage progression were age and gender. Following an MRI treat-to-target strategy, low scores of patient-reported outcomes and low tender joint count predicted achievement of stringent remission.

Trial Registration: ClinicalTrials.gov (https://clinicaltrials.gov), NCT01656278.
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http://dx.doi.org/10.1093/rheumatology/keaa496DOI Listing
January 2021

Dual-energy CT in gout patients: Do all colour-coded lesions actually represent monosodium urate crystals?

Arthritis Res Ther 2020 09 11;22(1):212. Epub 2020 Sep 11.

Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Rigshospitalet, Glostrup, Valdemar Hansens Vej 17, 2600, Glostrup, Denmark.

Background: Dual-energy CT (DECT) can acknowledge differences in tissue compositions and can colour-code tissues with specific features including monosodium urate (MSU) crystals. However, when evaluating gout patients, DECT frequently colour-codes material not truly representing MSU crystals and this might lead to misinterpretations. The characteristics of and variations in properties of colour-coded DECT lesions in gout patients have not yet been systematically investigated. The objective of this study was to evaluate the properties and locations of colour-coded DECT lesions in gout patients.

Methods: DECT of the hands, knees and feet were performed in patients with suspected gout using factory default gout settings, and colour-coded DECT lesions were registered. For each lesion, properties [mean density (mean of Hounsfield Units (HU) at 80 kV and Sn150kV), mean DECT ratio and size] and location were determined. Subgroup analysis was performed post hoc evaluating differences in locations of lesions when divided into definite MSU depositions and possibly other lesions.

Results: In total, 4033 lesions were registered in 27 patients (23 gout patients, 3918 lesions; 4 non-gout patients, 115 lesions). In gout patients, lesions had a median density of 160.6 HU and median size of 6 voxels, and DECT ratios showed an approximated normal distribution (mean 1.06, SD 0.10), but with a right heavy tail consistent with the presence of smaller amounts of high effective atomic number lesions (e.g. calcium-containing lesions). The most common locations of lesions were 1st metatarsophalangeal (MTP1), knee and midtarsal joints along with quadriceps and patella tendons. Subgroup analyses showed that definite MSU depositions (large volume, low DECT ratio, high density) had a similar distribution pattern, whereas possible calcium-containing material (high DECT ratio) and non-gout MSU-imitating lesions (properties as definite MSU depositions in non-gout patients) were primarily found in some larger joints (knee, midtarsal and talocrural) and tendons (Achilles and quadriceps). MTP1 joints and patella tendons showed only definite MSU depositions.

Conclusion: Colour-coded DECT lesions in gout patients showed heterogeneity in properties and distribution. MTP1 joints and patella tendons exclusively showed definite MSU depositions. Hence, a sole focus on these regions in the evaluation of gout patients may improve the specificity of DECT scans.
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http://dx.doi.org/10.1186/s13075-020-02283-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7488422PMC
September 2020