Musculoskeletal

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.

Osteoarthritis Phenotypes and Novel Therapeutic Targets.

Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.
Biochemical Pharmacology. 2019 Jul;37 doi: 10.1016/j.bcp.2019.02.037. Epub 2019 Mar 1.

Abstract

The success of disease-modifying osteoarthritis drug (DMOAD) development is still elusive. While there have been successes in preclinical and early clinical studies, phase 3 clinical trials have failed so far and there is still no approved, widely available DMOAD on the market. The latest research suggests that, among other causes, poor trial outcomes might be explained by the fact that osteoarthritis (OA) is a heterogeneous disease with distinct phenotypes. OA trials might be more successful if they would address and target a specific phenotype. The increasing availability of advanced techniques to detect particular OA characteristics expands the possibilities to distinguish between such potential OA phenotypes. Magnetic resonance imaging is among the key imaging techniques to stratify and monitor patients with changes in bone, cartilage and inflammation. Biochemical markers have mainly used as secondary parameters and could further delineate phenotypes. Moreover, post-hoc analyses of trial data have suggested the existence of distinct pain phenotypes and their relevance in the design of clinical trials. Although ongoing work in the field supports the concept of OA heterogeneity, this has not yet resulted in more effective treatment options. This paper reviews the current knowledge about potential OA phenotypes and suggests that combining patient clinical data, quantitative imaging, biochemical markers and utilizing data-driven approaches in patient selection and efficacy assessment will allow for more successful development of effective DMOADs.

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.

The Role of Dual-Energy Computed Tomography in Musculoskeletal Imaging

Abstract

Dual-energy computed tomography (DECT) enables material decomposition and virtual monochromatic images by acquiring 2 different energy X-ray data sets. DECT can detect musculoskeletal pathologic conditions that CT alone cannot, and that would otherwise require MR imaging. In this review, the authors discuss several useful techniques and applications of DECT in musculoskeletal research: virtual monochromatic images, virtual noncalcium images, gout, iodine map, and tendons.

KEY POINTS
 Dual-energy computed tomography (DECT) can reduce beam hardening artifacts by synthesizing a
virtual monochromatic image and enables detailed evaluation of prosthetic complications.
 DECT can display monosodium urate crystal deposition, which helps to make a correct diagnosis in
atypical gout and precise therapeutic assessment.
 DECT iodine maps can delineate soft tissue inflammation of arthritis and may be beneficial for
evaluating peripheral joints because of its high spatial resolution.

Role of tissue perfusion, muscle strength recovery and pain in rehabilitation after acute muscle strain injury: A randomized controlled trial comparing early and delayed rehabilitation

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Abstract
Muscle strain injuries disrupt the muscle-tendon unit, early rehabilitation is associated with
a faster return to sports (RTS), but the time course of tissue healing remains sparsely
described. The purpose was to examine tissue regeneration and the effectiveness of early
versus delayed rehabilitation onset on functional and structural recovery after strain
injuries. 50 recreational athletes with a severe acute strain injury in their thigh or calf
muscles were randomized to early or delayed rehabilitation onset. Magnetic resonance
imaging (MRI) was obtained initially, 3 and 6 months post injury and dynamic contrastenhanced
MRI (DCE-MRI) estimated tissue inflammation initially and after 6 months. Muscle
strength was determined 5 weeks, 3 and 6 months post injury and a questionnaire
determined soreness, pain and confidence. DCE-MRI microvascular perfusion was higher in
the injured compared to an uninjured muscle acutely (p< 0.01) and after 6 months (p< 0.01),
for both groups (p> 0.05) and unrelated to RTS (p> 0.05). Total volume of the injured muscle
decreased from the acute to the 3 months scan, and to the 6 months scan (p< 0.01) in both
groups. Muscle strength was similar in both groups at any time. There was a non-significant
trend (p≤ 0.1) towards less pain and higher confidence with early rehabilitation. One reinjury
was recorded. In conclusion, our data showed prolonged tissue repair with the initial
response linked to muscle atrophy but did not explain why early rehabilitation onset
accelerated recovery considering that structural and functional recovery was similar with
early and delayed rehabilitation.

Role of tissue perfusion, muscle strength recovery and pain in rehabilitation after acute muscle strain injury: A randomized controlled trial comparing early and delayed rehabilitation

Muscle strain injuries disrupt the muscle‐tendon unit, early rehabilitation is associated with a faster return to sports (RTS), but the time course of tissue healing remains sparsely described. The purpose was to examine tissue regeneration and the effectiveness of early versus delayed rehabilitation onset on functional and structural recovery after strain injuries. 50 recreational athletes with a severe acute strain injury in their thigh or calf muscles were randomized to early or delayed rehabilitation onset. Magnetic resonance imaging (MRI) was obtained initially, 3 and 6 months post injury and dynamic contrast‐enhanced MRI (DCE‐MRI) estimated tissue inflammation initially and after 6 months. Muscle strength was determined 5 weeks, 3 and 6 months post injury and a questionnaire determined soreness, pain and confidence. DCE‐MRI microvascular perfusion was higher in the injured compared to an uninjured muscle acutely (p< 0.01) and after 6 months (p< 0.01), for both groups (p> 0.05) and unrelated to RTS (p> 0.05). Total volume of the injured muscle decreased from the acute to the 3 months scan, and to the 6 months scan (p< 0.01) in both groups. Muscle strength was similar in both groups at any time. There was a non‐significant trend (p≤ 0.1) towards less pain and higher confidence with early rehabilitation. One re‐injury was recorded. In conclusion, our data showed prolonged tissue repair with the initial response linked to muscle atrophy but did not explain why early rehabilitation onset accelerated recovery considering that structural and functional recovery was similar with early and delayed rehabilitation.