Rheumatoid Arthritis

The Effects of Weight Loss on Imaging Outcomes in Osteoarthritis of the Hip or Knee in People who are Overweight or Obese: A Systematic Review

Copyright © 2019 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
Osteoarthritis Cartilage. 2020 Jan;28(1):10-21. doi: 10.1016/j.joca.2019.10.013. Epub 2019 Nov 26.

Abstract

OBJECTIVE:
To evaluate the structural effects of weight loss on hip or knee osteoarthritis (OA) and to summarize which structural joint pathologies have been examined and the evidence for the outcome measurement instruments applied.
DESIGN:
Based on a pre-specified protocol (available: PROSPERO CRD42017065263), we conducted a systematic search of the bibliographic databases, Medline, Embase and Web of Science identifying longitudinal articles reporting the effects of weight loss on structural imaging outcomes in OA of the hip or knee in people who are overweight or obese.
RESULTS:
From 1625 potentially eligible records, 14 articles (from 6 cohorts) were included. 2 cohorts were derived from RCTs. Evaluated pathologies were: articular cartilage (n = 7), joint space width (n = 3), bone marrow lesions (n = 5), synovitis (n = 2), effusion (n = 1), meniscus (n = 3), bone marrow density (n = 1) and infrapatellar fat pad (IPFP; n = 2). Cartilage showed conflicting results when evaluating cartilage thickness by direct thickness measurements. Compositional dGEMRIC and T2 mapping measures in early knee OA showed trends towards reduced cartilage degeneration. Joint space width on conventional radiographs showed no change. Weight loss reduced the size of the IPFP. Synovitis and effusion were not affected. Following weight loss DXA showed bone loss at the hip.
CONCLUSION:
We did not find consistent evidence of the effects of weight loss on OA structural pathology in people who are overweight or obese. There is a need to achieve consensus on which structural pathologies and measurements to apply in weight loss and OA research.

The Role of Advanced MRI in the Development of Treat-to-Target Therapeutic Strategies, Patient Stratification and Phenotyping in Rheumatoid Arthritis

In this commentary we discuss the potential of advanced imaging, particularly Dynamic Contrast Enhanced (DCE) magnetic resonance imaging (MRI) for the objective assessment of disease progression in rheumatoid arthritis (RA). We emphasise the potential DCE-MRI in advancing the field and exploring new areas of research and development in RA. We believe that different grades of bone marrow edema (BME) and synovitis in RA can be examined and monitored in a more sensitive manner with DCE-MRI. Future treatments for RA will be significantly improved by enhanced imaging of BMEs and synovitis. DCE-MRI will also facilitate enhanced stratification and phenotyping of patients enrolled in clinical trials.

Magnetic Resonance Imaging Tenosynovitis and Osteitis are Independent Predictors of Radiographic and MRI Damage Progression in Rheumatoid Arthritis Patients In Clincial Remission

Copyright © Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ
Annals of the Rheumatic Diseases. 2019 June;78(2)_suppl. doi: 10.1136/annrheumdis-2019-eular.2006

Abstract

BACKGROUND:
Progression of structural joint damage occurs in 20-30 % of patients with rheumatoid arthritis (RA) in clinical remission1. Magnetic resonance imaging (MRI)-detected synovitis and in particular osteitis/bone marrow edema (BME) are known predictors of structural progression in both active RA and in remission, but the predictive value of adding MRI tenosynovitis assessment as potential predictor in patients in clinical remission has not been investigated.

OBJECTIVES:
To investigate the predictive value of baseline MRI inflammatory and damage parameters on 2 year MRI and X-ray damage progression in an RA cohort in clinical remission, following MRI and conventional treat-to-target (T2T) strategies.

METHODS:
200 RA patients in clinical remission (DAS28-CRP<3.2 and no swollen joints) on conventional DMARDs, included in the randomized IMAGINE-RA trial2 (conventional DAS28 + MRI-guided T2T strategy targeting absence of BME vs conventional DAS28 guided T2T strategy) had baseline and 2 years contrast-enhanced MRIs of the dominant wrist and 2nd-5th MCP joints and X-rays of hands and feet performed, which were evaluated with known chronology by two experienced readers according to the OMERACT RAMRIS scoring system and Sharp/van der Heijde method, respectively.

The following potentially predictive baseline variables: MRI BME, synovitis, tenosynovitis, MRI and X-ray erosion and joint space narrowing (JSN) score, CRP, DAS28, smoking status, gender, age and patient group were tested in univariate logistic regression analyses with 2-year progression in MRI combined damage score, Total Sharp Score (TSS), and MRI and X-ray JSN and erosion scores as dependent variables. Variables with p<0.1, age, gender and patient group were included in multivariable logistic regression analyses with backward selection.

RESULTS:
Based on univariate analyses MRI BME, synovitis, tenosynovitis, x-ray erosion and JSN, gender and age were included in subsequent multivariable analyses. Independent MRI predictors of structural progression were BME (MRI progression) and tenosynovitis (MRI and X-ray progression), MRI combined damage score: sum score of MRI erosion and JSN scores.

CONCLUSION:
This trial is the first to report that MRI tenosynovitis independently predicts both X-ray and MRI damage progression in RA patients in clinical remission. Further studies are needed to confirm MRI-determined tenosynovitis as predictor of progressive joint destruction in RA clinical remission.

Impact of a Magnetic Resonance Imaging-Guided Treat-to-Target Strategy on Disease Activity and Progression in Patients with Rheumatoid Arthritis (The IMAGINE-RA Trial): Study Protocol for a Randomized Controlled Trial.

Copyright © Author(s) (or their employer(s)) 2015.
Trials. 2015 Apr;7(178)_suppl doi: 10.1186/s13063-015-0693-2
Trial registration: http://www.ClinicalTrials.gov identifier: NCT01656278 (5 July 2012)

Abstract

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.

Synovial Cellular and Molecular Signatures Stratify Clinical Response to csDMARD Therapy and Predict Radiographic Progression in Early Rheumatoid Arthritis Patients

Copyright © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.
Annals of the Rheumatic Diseases. 2019 Jun;78(6) doi: 10.1136/annrheumdis-2018-214539. Epub 2019 Mar 16.

Abstract

OBJECTIVES:
To unravel the hierarchy of cellular/molecular pathways in the disease tissue of early, treatment-naïve rheumatoid arthritis (RA) patients and determine their relationship with clinical phenotypes and treatment response/outcomes longitudinally.
METHODS:
144 consecutive treatment-naïve early RA patients (<12 months symptoms duration) underwent ultrasound-guided synovial biopsy before and 6 months after disease-modifying antirheumatic drug (DMARD) initiation. Synovial biopsies were analysed for cellular (immunohistology) and molecular (NanoString) characteristics and results compared with clinical and imaging outcomes. Differential gene expression analysis and logistic regression were applied to define variables correlating with treatment response and predicting radiographic progression.
RESULTS:
Cellular and molecular analyses of synovial tissue demonstrated for the first time in early RA the presence of three pathology groups: (1) lympho-myeloid dominated by the presence of B cells in addition to myeloid cells; (2) d iffuse-myeloid with myeloid lineage predominance but poor in B cells nd (3) pauci-immune characterised by scanty immune cells and prevalent stromal cells. Longitudinal correlation of molecular signatures demonstrated that elevation of myeloid- and lymphoid-associated gene expression strongly correlated with disease activity, acute phase reactants and DMARD response at 6 months. Furthermore, elevation of synovial lymphoid-associated genes correlated with autoantibody positivity and elevation of osteoclast-targeting genes predicting radiographic joint damage progression at 12 months. Patients with predominant pauci-immune pathology showed less severe disease activity and radiographic progression.
CONCLUSIONS:
We demonstrate at disease presentation, prior to pathology modulation by therapy, the presence of specific cellular/molecular synovial signatures that delineate disease severity/progression and therapeutic response and may pave the way to more precise definition of RA taxonomy, therapeutic targeting and improved outcomes.

Imaging in Rheumatoid Arthritis: The Role of Magnetic Resonance Imaging and Computed Tomography.

Abstract

In suspected and diagnosed rheumatoid arthritis (RA), magnetic resonance imaging (MRI) allows detection of all relevant pathologies, such as synovitis, tenosynovitis, bone marrow edema (osteitis), bone erosion and cartilage damage. MRI is more sensitive than clinical examination for monitoring disease activity (i.e., inflammation) and more sensitive than conventional radiography and ultrasonography for monitoring joint destruction. In suspected RA, MRI bone marrow edema predicts development of RA, and in early RA patients, it predicts subsequent structural damage progression. CT is the standard reference imaging modality for visualizing bone damage, including bone erosions in RA, but lacks sensitivity for soft-tissue changes, including synovitis and tenosynovitis. CT has a minimal role in RA clinical trials and practice, except in selected patients where MRI is contraindicated or not available or if crystal arthritis such as gout or pseudo-gout is suspected. MRI has documented utility in diagnosis, monitoring and prognostication of patients with RA and is increasingly used for these purposes in clinical practice and particularly clinical trials.

Added value of combining methotrexate with a biological agent compared to biological monotherapy in rheumatoid arthritis patients: A systematic review and meta-analysis of randomised trials

Abstract

Background Methotrexate (MTX) is considered the anchor drug in rheumatoid arthritis (RA) treatment, based on efficacy, safety, and its ability to increase the efficacy of biologic agents when used in combination. Both the “American College of Rheumatology” (ACR) and the “European League Against Rheumatism” (EULAR) recommend the use of biologic agents with concomitant MTX in RA. However, analyses from health care claims suggest that the MTX prescribed in conjunction with a biologic disease-modifying antirheumatic drug (bDMARD), is not collected at the pharmacy by more than half of the patients. Despite claims from pivotal trial data, the empirical evidence supporting combination MTX plus bDMARD in terms of the actual benefit-harm has not been evaluated extensively.

Objectives To review the evidence for benefit and harm associated with combining MTX with a biologic agent in RA patients.

Methods A systematic review and meta-analysis of randomised controlled trials (RCTs) was performed to identify all trials relating treatment of RA with MTX in combination with bDMARD compared to a bDMARD in monotherapy. Random-effects models were applied for meta-analyses with risk ratio and 95% confidence intervals (RR, 95%CI) and inconsistency (I2, %) estimated using Review Manager. According to the protocol the major outcomes were ACR50 for benefit and withdrawals due to adverse events (AEs) for harm (PROSPERO: CRD42014014633).

Results From the 4,405 identified references, 14 trials were eligible for inclusion in the meta-analysis. The overall likelihood of responding to therapy (ie, RR according to ACR50) was 1.36 [1.24 to 1.49] – with a low degree of inconsistency (28%) – in favour of concomitant use of MTX when treating with a biologic (P<0.001). There was no reason to suspect that added value of MTX varied with the choice of bDMARD (Test for subgroup differences P=0.38): abatacept 1.27 [0.97 to 1.67], adalimumab 1.42 [1.24 to 1.61], etanercept 1.44 [1.22 to 1.69], golimumab 1.60 [1.13 to 2.27], infliximab 3.54 [1.38 to 9.08], rituximab 1.31 [0.74 to 2.32], and tocilizumab 1.24 [1.03 to 1.51]. The overall estimate of discontinuing therapy due to AEs from concomitant use of MTX was 1.17 [0.94 to 1.44] (P=0.16) compared to bDMARD in monotherapy – corresponding to a possible 17% increased risk.

Conclusions This systematic review and meta-analysis of RCTs provides empirical evidence about the clinical value of combining the prescribed bDMARD with the recommended concomitant use of MTX. Combination therapy increases the probability of achieving treatment success at the level of ACR50 by approximately 40% compared to patients using biologics in monotherapy. Although the precision around the estimate of concomitant MTX use does not rule out an increased risk of clinically important harms, these findings justify the recommendation that all patients prescribed biologics should be encouraged to continue MTX therapy.

Vertebral Compression Fractures and Antibodies to Citrullinated Vimentin in Established Rheumatoid Arthritis

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Background/Purpose:

Patients with RA have high rates of osteoporosis and fractures and RA induces articular and extra-articular bone loss. Seropositivity for any CCP antibody is associated with risk of erosions and osteoporosis. In vitro, human antibodies against citrullinated vimentin bind osteoclast cell surfaces, activate their bone resorptive activity and in an animal model, induce bone loss. In humans, it is not known whether these antibodies are a specific risk factor for osteoporosis. The aim of this study was to assess the prevalence of radiographic vertebral compression fractures (VCF), as a marker of skeletal fragility, in an established RA cohort and whether the presence of antibodies to citrullinated vimentin were associated with this.

Methods:

Data was obtained from a prospective established RA cohort (ACR/EULAR 2010 or ACR 1987 criteria) undergoing elective arthroplasty. VCF were identified on the lateral pre-operative chest radiograph by two independent readers utilizing the Genant semi-quantitative method. Antibodies to citrullinated vimentin epitopes were measured by mean fluorescence intensity utilizing a custom, bead-based, antigen array comprising CCP and RA-associated citrullinated antigens. To identify risk factors predictive of vertebral compression, univariate logistic regression analysis was performed including known potential risk factors for bone loss in RA.

Results:

181 participants had an available chest radiograph. Median age was 65 years [IQR 56, 71] and median disease duration 11 years [IQR 3, 20]. 80% were female, 37% were on current glucocorticoid therapy and 21% had prior exposure. Only 3% self-reported a diagnosis of osteoporosis or use of osteoporosis medications. Despite these numbers, almost half, 76/181 (42%) [58 female] had radiographic VCF (Table 1). Participants with VCF were older [median age 68 years vs. 64 years, p=0.03]. In univariate analysis of potential risk factors, only age was associated with VCF (Table 2). No significant differences were seen in antibody levels, including antibody isotypes to citrullinated vimentin.

Conclusion:

Vertebral compression fractures were prevalent in patients in this established RA cohort. The strongest risk factor for VCF was age. Antibodies to citrullinated vimentin, implicated in early RA models, were not associated with VCF. Our results highlight the profound detrimental skeletal effects of RA. Further studies are needed to investigate the mechanisms of focal versus generalized bone loss, as well as skeletal changes that occur with RA progression.