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To compare the effect of treat-to-target-based escalations in conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and biologics on clinical disease activity and magnetic resonance imaging (MRI) inflammation in a rheumatoid arthritis (RA) cohort in clinical remission. One-hundred patients with established RA, Disease Activity Score based on 28-joint count–C-reactive protein (DAS28-CRP) < 3.2, and no swollen joints (hereafter referred to as 'in clinical remission') who received csDMARDs underwent clinical evaluation and MRI of the wrist and second to fifth metacarpophalangeal joints every 4 months. They followed a 2 year MRI treatment strategy targeting DAS28-CRP ≤ 3.2, no swollen joints, and absence of MRI osteitis, with predefined algorithmic treatment escalation: first: increase in csDMARDs; second: adding a biologic; third: switch biologic. MRI osteitis and Health Assessment Questionnaire (HAQ) (co-primary outcomes) and MRI combined inflammation and Simplified Disease Activity Index (SDAI) (key secondary outcomes) were assessed 4 months after treatment change and expressed as estimates of group differences. Statistical analyses were based on the intention-to-treat population analysed using repeated-measures mixed models. Escalation to first biologic compared to csDMARD escalation more effectively reduced MRI osteitis (difference between least squares means 1.8, 95% confidence interval 1.0–2.6), HAQ score (0.08, 0.03–0.1), MRI combined inflammation (2.5, 0.9–4.1), and SDAI scores (2.7, 1.9–3.5). Treat-to-target-based treatment escalations to biologics compared to escalation in csDMARDs more effectively improved MRI inflammation, physical function, and clinical disease activity in patients with established RA in clinical remission. Treatment escalation in RA patients in clinical remission reduces clinical and MRI-assessed disease activity. Clinicaltrials.gov identifier: NCT01656278 [ABSTRACT FROM AUTHOR]

Objectives: To investigate whether a treat-to-target strategy based on methotrexate (MTX) and intra-articular (IA) betamethasone suppresses magnetic resonance imaging (MRI)-determined measures of disease activity and reduces joint destruction in early rheumatoid arthritis (eRA) patients, and to investigate whether concomitant cyclosporin A (CyA) provides an additional effect.Method: In the 2-year randomized, double-blind, treat-to-target trial CIMESTRA, 160 patients with eRA (< 6 months) were randomized to MTX, intra-articular betamethasone and CyA, or placebo CyA. A total of 129 patients participated in the MRI substudy, and had contrast-enhanced MR images of the non-dominant hand at months 0, 6, 12, and 24. MR images were evaluated for osteitis, synovitis, tenosynovitis, bone erosion, and joint space narrowing (JSN), using validated scoring methods.Results: Significant reductions were seen at 6 months in all inflammatory parameters [synovitis, mean change -1.6 (p < 0.001, Wilcoxon), tenosynovitis, -3.5 (p < 0.001), and osteitis, -1.3 (p < 0.05)] and at 12/24 months in synovitis and tenosynovitis [-1.6/-2.2 and -3.6/-3.8, respectively; all p < 0.001]. MRI signs of inflammation were not fully eliminated, and increases in erosion and JSN scores were observed at 6 months [0.4 (p < 0.01)/0.1 (p < 0.05)], 12 months [0.8 (p < 0.001)/0.3 (p < 0.01)], and 24 months [1.0 (p < 0.001)/0.4 (p < 0.001)]. Clinical measures decreased significantly (p < 0.001) at all time points. There were no consistent statistically significant differences between treatment groups.Conclusions: In this eRA treat-to-target trial, MTX and intra-articular glucocorticoids markedly reduced, but did not eliminate, MRI osteitis, synovitis, and tenosynovitis. Accordingly, minimal but statistically significant increases in bone erosion and JSN were observed. No additional effect of CyA was demonstrated. [ABSTRACT FROM AUTHOR]

Proper assessment of patients with psoriatic arthritis (PsA) requires assessment of all disease domains, including axial disease. Magnetic resonance imaging (MRI) is the method of choice for evaluating axial involvement in PsA. When assessing patients with PsA for spinal involvement, it is important to assess both vertebral body lesions and posterolateral lesions, such as inflammation in facet joints and costovertebral joints, and enthesitis at spinous and transverse processes. The Canada-Denmark (CanDen) assessment system for spine MRIs is the preferred method for detailed evaluation of inflammation and structural damage at various anatomical locations in the spine, and it is reproducible and sensitive to change. The Assessment of Spondyloarthritis international Society (ASAS) has recently published MRI definitions of inflammatory and structural lesions in the spine, incorporating the CanDen definitions of spinal lesions on MRI. Applying the ASAS definitions and the CanDen assessment system in clinical practice and trials is recommended. Ongoing research/studies, not least the Axial Involvement in Psoriatic Arthritis (AXIS) study, may provide a data-driven definition of axial involvement in PsA. Ongoing research is expected to further improve and validate assessment tools for axial PsA and to provide a much-needed data-driven consensus-based definition of axial involvement in PsA., (Copyright © 2024 by The Journal of Rheumatology.)

Objective: To develop a reference image atlas for the Outcome Measures in Rheumatology whole-body MRI scoring system for inflammation in peripheral joints and entheses (OMERACT MRI-WIPE) of the knee region., Methods: Image examples of each pathology, location and grade, were collected and discussed at web-based, interactive meetings within the OMERACT MRI in Arthritis Working Group. Subsequently, reference images were selected by consensus., Results: Reference images for each grade, pathology and location are depicted, along with definitions, reader rules and recommended MRI-sequences., Conclusion: The atlas guides scoring whole-body MRIs for inflammation in joints and entheses of the knee region according to MRI-WIPE methodology in clinical trials and cohorts., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Mikkel Østergaard has received research grants from Abbvie, BMS, Merck, Novartis and UCB, consultancy fees from Abbvie, BMS, Celgene, Eli-Lilly, Galapagos, Gilead, Janssen, MEDAC, Merck, Novartis, Pfizer, Sandoz, and UCB Abbvie, BMS, Celgene, Eli-Lilly, Galapagos, Gilead, Janssen, MEDAC, Merck, Novartis, Pfizer, Sandoz, and UCB and speaker fees from Abbvie, BMS, Celgene, Eli-Lilly, Galapagos, Gilead, Janssen, MEDAC, Merck, Novartis, Pfizer, Sandoz, and UCB. Walter P Maksymowych is Chief Medical Officer at CARE Arthritis Limited. Helena Marzo-Ortega has received research grants from Janssen, Novartis, Pfizer and UCB, and speaker fees from AbbVie, Amgen, Biogen, Eli Lilly, Janssen, Novartis, Pfizer, Takeda, UCB. Philip G Conaghan has received consultancy fees from AbbVie, BMS, Eli Lilly, Galapagos, GSK, Janssen, Novartis and Takeda and speaker fees from AbbVie, Eli Lilly and Novartis. Robert GW Lambert has received research grants from Calyx and Care Arthritis, and consultancy fees from Image Analysis Group, Calyx and Care Arthritis. The remaining authors declare no financial interests/personal relationships., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: To develop a reference image atlas for scoring the hip/pelvis region according to the OMERACT whole-body MRI scoring system for inflammation in peripheral joints and entheses (MRI-WIPE)., Methods: We collected image examples of each pathology, location and grade, discussed them at web-based, interactive meetings and, finally, selected reference images by consensus., Results: Reference images for each grade and location of osteitis, synovitis and soft tissue inflammation are provided, as are definitions, reader rules and recommended MRI-sequences., Conclusion: A reference image atlas was created to guide scoring whole-body MRIs for arthritis and enthesitis in the hip/pelvis region in spondyloarthritis/psoriatic arthritis clinical trials and cohorts., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests Mikkel Østergaard has received research grants from Abbvie, BMS, Merck, Novartis and UCB, consultancy fees from Abbvie, BMS, Celgene, Eli-Lilly, Galapagos, Gilead, Janssen, MEDAC, Merck, Novartis, Pfizer, Sandoz, and UCB Abbvie, BMS, Celgene, Eli-Lilly, Galapagos, Gilead, Janssen, MEDAC, Merck, Novartis, Pfizer, Sandoz, and UCB and speaker fees from Abbvie, BMS, Celgene, Eli-Lilly, Galapagos, Gilead, Janssen, MEDAC, Merck, Novartis, Pfizer, Sandoz, and UCB. Robert GW Lambert has received research grants from Calyx and Care Arthritis, and consultancy fees from Image Analysis Group, Calyx and Care Arthritis. Walter P Maksymowych is Chief Medical Officer at CARE Arthritis Limited. Helena Marzo-Ortega has received research grants from Janssen, Novartis, Pfizer and UCB, and speaker fees from AbbVie, Amgen, Biogen, Eli Lilly, Janssen, Novartis, Pfizer, Takeda, UCB. Philip G Conaghan has received consultancy fees from AbbVie, BMS, Eli Lilly, Galapagos, GSK, Janssen, Novartis and Takeda and speaker fees from AbbVie, Eli Lilly and Novartis. The remaining authors declare no financial interests/personal relationships., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate whether a 2-year MRI treat-to-target strategy targeting the absence of osteitis combined with clinical remission, compared with a conventional treat-to-target strategy targeting clinical remission only (IMAGINE-rheumatoid arthritis (RA) trial) improves clinical and radiographic outcomes over 5 years in patients with RA in clinical remission., Methods: IMAGINE-more was an observational extension study of the original 2-year IMAGINE-RA randomised trial (NCT01656278). Clinical examinations and radiographs (hands and feet) were obtained yearly. Prespecified coprimary outcomes at year 5 were Disease Activity Score in 28 joints C reactive protein (DAS28-CRP) remission rate (DAS28-CRP<2.6) and no radiographic progression (van der Heijde-modified Sharp score (vdHSS) ≤0) from baseline. Secondary outcomes included 5-year changes in radiographic, MRI and clinical measures of disease activity and physical function., Results: In total 131 patients, 86 women (67%), mean age 61.2, disease duration 9.5 years, median baseline DAS28-CRP 1.9 (IQR 1.6-2.2) and vdHSS 16.0 (IQR 7.0-36.0) were included in the study; 59 (59%) patients from the original MRI treat-to-target group and 72 (72%) from the conventional group. At year 5, 47 patients (80%) in the MRI treat-to-target group vs 54 patients (75%) in the conventional treat-to-target group were in DAS28-CRP remission (OR 2.00 (95% CI 0.76 to 5.28); p=0.16) while 14 patients (24%) vs 19 patients (26%) had no radiographic progression (OR 0.70, (95% CI 0.28 to 1.71); p=0.43)., Conclusion: A 2-year combined MRI and clinical treat-to-target strategy, compared with a conventional clinical treat-to-target strategy alone, had no effect on the long-term probability of achieving DAS28-CRP remission and of avoiding radiographic progression., Competing Interests: Competing interests: SMB has received research support from AbbVie and support for attending meetings and/or travl from Medac and Novartis. KHP has received research support from AbbVie. LMØ has received research grant from Novartis. MLH has received research grant from AbbVie, Biogen, BMS, Celltrion, Eli Lilly, Janssen Biologics B.V, Lundbeck Foundation, MSD, Pfizer, Roche, Samsung Biopies, Sandoz, Novartis, Nordforsk and speaking fees and/or honoraria from Pfizer, Medac, Sandoz paid to institution and has chaired the steering committee of the Danish Rheumatology Quality Registry (DANBIO, DRQ), which receives public funding from the hospital owners and funding from pharmaceutical companies. MLH co-chairs EuroSpA, which generates real-world evidence of treatment of psoriatic arthritis and axial spondylorthritis based on secondary data and is partly funded by Novartis. DG has received consulting fees from Janssen and speaking fees from Eli Lilly and Advisory board activity for AbbVie and Eli Lilly. MB has received research support from AbbVie and speaking fees from AbbVie, UCB, Eli Lilly, Image Analysis Group, Esaote. EMH has received research grants from Independent Research Fund Denmark, Novo Nordic Foundation, Danish Rheumatism Association, Aarhus University, Danish Regions Medicine Grants, Galapagos, AbbVie, Roche, Novartis, consulting fees from Novo Nordic, Novartis, AbbVie, Sanofi, Sobi, MSD, UCB, spekin fees from Novo Nordic, Novartis, AbbVie, Sanofi, Sobi, MSD, UCB, support for attending meetings and/or travl from Pfizer Sobi, AbbVie, Celgene, MSD, Roche, advisory board SynACT Pharma and principal trial investigator/site investigator for trials supported by AbbVie, Novartis, Novo Nordic, Sanofi, SynACT Pharma. OH has received speaking fees from Abbvie, Pfizer, Novartis, Eli-Lilly and support for attending meetings and/or travl from Pfizer, Abbvie. NSK has received grants from ScandRA and EuroStar. MØ has received research support 15 from AbbVie and grants from Amgen, BMS, Merck, Celgene and Novartis, Galapagos, Gilead, Hospira, Janssen, Merck, Novartis, Pfizer, UCB and consulting fees from Abbvie, BMS, Eli-Lilly, Galapagos, Gilead, Janssen, Merck, Novartis, Pfizer, UCB, speaking fees from Abbvie, BMS, EliLilly, Galapagos, Gilead, Janssen, Merck, Novartis, Pfizer, UCB. BE, JM, SMN, KSP, ORM, BJ, JAV, HL, AGJ, HST, RC, have nothing to disclose., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Importance: Whether using magnetic resonance imaging (MRI) to guide treatment in patients with rheumatoid arthritis (RA) improves disease activity and slows joint damage progression is unknown., Objective: To determine whether an MRI-guided treat-to-target strategy vs a conventional clinical treat-to-target strategy improves outcomes in patients with RA in clinical remission., Design, Setting, and Participants: Two-year, randomized, multicenter trial conducted at 9 hospitals in Denmark. Two hundred patients with RA in clinical remission (disease activity score in 28 joints-C-reactive protein [DAS28-CRP] <3.2 and no swollen joints) were enrolled between April 2012 and June 2015. The final follow-up visit was April 2017., Interventions: Patients were randomly allocated (1:1) to an MRI-guided vs a conventional treat-to-target strategy. In the MRI-guided group, the treatment goal was absence of MRI bone marrow edema combined with clinical remission, defined as DAS28-CRP of 3.2 or less and no swollen joints. In the conventional group, the treatment goal was clinical remission., Main Outcomes and Measures: Co-primary outcomes were proportions of patients achieving DAS28-CRP remission (DAS28-CRP <2.6) and with no radiographic progression (no increase in total van der Heijde-modified Sharp score) at 24 months. Significance testing for the primary outcome was based on 1-sided testing. Secondary outcomes were clinical and MRI measures of disease activity, physical function, and quality of life., Results: Of 200 patients randomized (133 women [67%]; mean [SD] age, 61.6 [10.5] years; median baseline DAS28-CRP, 1.9 [interquartile range, 1.7-2.2]; van der Heijde-modified Sharp score, 18.0 [interquartile range, 7.0-42.5]), 76 patients (76%) in the MRI-guided group and 95 (95%) in the conventional group completed the study. Of these, 64 (85%) vs 83 (88%), respectively, reached the primary clinical end point (risk difference, -4.8% [1-sided 95% CI, -13.6% to + ∞; 1-sided P = .19]) and 49 (66%) vs 58 (62%), respectively, reached the primary radiographic end point (risk difference, 4.7% [1-sided 95% CI, -7.0% to + ∞; 1-sided P = .25). Of 10 key secondary end points, 8 were null and 2 showed statistically significant benefit for the MRI treat-to-target group. Seventeen patients (17%) in the MRI-guided treat-to-target group and 6 patients (6%) in the conventional treat-to-target group experienced serious adverse events., Conclusions and Relevance: Among patients with RA in clinical remission, an MRI-guided treat-to-target strategy compared with a conventional treat-to-target strategy did not result in improved disease activity remission rates or reduce radiographic progression. These findings do not support the use of an MRI-guided strategy for treating patients with RA., Trial Registration: ClinicalTrials.gov Identifier: NCT01656278.

Objectives: To examine whether MRI assessed inflammation and damage in the wrist of patients with early rheumatoid arthritis (RA) are associated with patient-reported outcomes (PROs)., Methods: Wrist and hand MRIs of 210 patients with early RA from two investigator-initiated, randomised controlled studies (CIMESTRA/OPERA) were assessed according to the Outcome Measures in Rheumatology RA MRI score (RAMRIS) for synovitis, tenosynovitis, osteitis, bone erosions and joint space narrowing (JSN) at baseline, 1 and 5 years follow-up. These features, and changes therein, were assessed for associations with health assessment questionnaires (HAQ), patient global visual analogue scales (VAS-PtGlobal) and VAS-pain using Spearman's correlations, generalised estimating equations and univariate/multivariable linear regression analyses. MRI features were further tested for trends against specific hand-related HAQ items using Jonckheere trend tests., Results: MRI inflammation, but not damage, showed statistically significant associations with HAQ, VAS-PtGlobal and VAS-pain for status and change scores, independently of C reactive protein and swollen joint count. MRI-assessed synovitis was most consistently associated with PROs, particularly VAS-PtGlobal and VAS-pain. MRI-assessed synovitis and tenosynovitis mean scores were positively associated with patient-reported difficulty to cut meat and open a milk carton (p<0.01), and similar patterns were seen for other hand-related HAQ items. Incorporating metacarpophalangeal joints in the analyses did not strengthen the associations between MRI pathology and PROs., Conclusions: MRI-assessed inflammation, but not damage, in early RA wrists is associated with patient-reported physical impairment, global assessment of disease activity and pain and influences the physical function in the hand., Trial Registration Number: NCT00660647., Competing Interests: Competing interests: MLH: research support and grants from: BMS, AbbVie, Pfizer, UCB-Nordic, MSD and Biogen; consultation fees from: Orion, KH-P: consultation fees from: AbbVie and UCB, MBA: research support and grants from: AbbVie, MØ: consultation fees from: AbbVie, BMS, Boehringer-Ingelheim, Celgene, Eli-Lilly, Centocor, GSK, Hospira, Janssen, Merck, Mundipharma, Novartis, Novo, Orion, Pfizer, Regeneron, Schering-Plough, Roche, Takeda, UCB, Wyeth; research support and grants from: AbbVie, BMS, Janssen and Merck., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Rheumatoid arthritis (RA) is a chronic, progressive joint disease, which frequently leads to irreversible joint deformity and severe functional impairment. Although patients are treated according to existing guidelines and reach clinical remission, erosive progression still occurs. This demonstrates that additional methods for prognostication and monitoring of the disease activity are needed. Bone marrow edema (BME) detected by magnetic resonance imaging (MRI) has proved to be an independent predictor of subsequent radiographic progression. Guiding the treatment based on the presence/absence of BME may therefore be clinically beneficial. We present the design of a randomized controlled trial (RCT) aiming to evaluate whether an MRI-guided treatment strategy compared to a conventional treatment strategy in anti-CCP-positive erosive RA is better to prevent progression of erosive joint damage and increase the remission rate in patients with low disease activity or clinical remission., Methods/design: The study is a non-blinded, multicenter, 2-year RCT with a parallel group design. Two hundred anti-CCP-positive, erosive RA patients characterized by low disease activity or remission, no clinically swollen joints and treatment with synthetic disease-modifying antirheumatic drugs (DMARDs) will be included. Patients will be randomized to either a treatment strategy based on conventional laboratory and clinical examinations (control group) or a treatment strategy based on conventional laboratory and clinical examinations as well as MRI (intervention group). Treatment is intensified according to a predefined treatment algorithm in case of inflammation defined as a disease activity score (DAS28) >3.2 and at least one clinically swollen joint (control and intervention groups) and/or MRI-detected BME (intervention group only). The primary outcome measures are DAS28 remission (DAS28 < 2.6) and radiographic progression (Sharp/vdHeijde score)., Discussion: The perspectives, strengths and weaknesses of this study are discussed. This study has been approved by The Regional Scientific Ethical Committees for Southern Denmark, S-20110109. Dissemination will occur through presentations and publication in international peer-reviewed journals., Trial Registration: The study is registered in http://www.ClinicalTrials.gov identifier: NCT01656278 (5 July 2012).

Magnetic resonance imaging (MRI) clearly is more sensitive than clinical examination and conventional radiography (x-ray) for detection of inflammation (synovitis, bone marrow oedema (osteitis) and tenosynovitis) and damage (bone erosion and cartilage loss/joint space narrowing) in patients with rheumatoid arthritis (RA). The question is when and how MRI should be used. The present article reviews our knowledge about, and provides suggestions for, the use of MRI in clinical trials, clinical care and clinical registries. In clinical trials, the OMERACT RA MRI scoring system (RAMRIS) is a thoroughly validated method which in less time and with fewer patients than x-ray can discriminate between different therapies regarding structural damage progression, and which on top of this offers detailed assessment of upstream inflammatory drivers of damage. In routine clinical care, MRI can contribute to an earlier diagnosis of RA, can reveal subclinical disease activity, e.g. in the synovium (synovitis) and bone (osteitis), and can provide information of strong prognostic significance for the subsequent disease course, which may be useful when deciding the treatment strategy. Future studies will clarify the benefits of including MRI in treat-to-target strategies. The benefits of incorporating MRI into clinical registries are not yet known, but may include improved knowledge about the real-life advantages of MRI, as well as opportunities to develop better clinical and laboratory composite measures to monitor and predict the disease course in RA. In conclusion, MRI has well-documented relevance in several settings in clinical trials and care, but not yet in clinical registries.