Osteoarthrits

MIMEDX and IAG Partner to Support Knee Osteoarthritis Ph 3 Clinical Trial Program

MIMEDX and IAG Partner to Support Knee Osteoarthritis Ph 3 Clinical Trial Program

Image Analysis Group to Partner with MIMEDX in Support of MIMEDX’s Knee Osteoarthritis Clinical Trial Program

Image Analysis Group to Provide Imaging Strategy and Advanced Imaging Analytics in Support of MIMEDX’s Knee Osteoarthritis Clinical Trial Program

MIMEDX is a transformational placental biologics company, developing and distributing placental tissue allografts and IAG, Image Analysis Group, a strategic bio-pharma imaging expert announce a partnership in the development of MIMEDX’s mdHACM.

The IAG team has significant experience in using medical imaging to support drug development.

‘We have significant evidence that mdHACM injected into the knees of people with OA provides lasting pain relief and improves function, and we believe it has potential as a DMOAD. MIMEDX has discovered how to preserve the remarkable healing properties of placental membranes when we produce mdHACM, and we have demonstrated that it contains many proteins that influence the biology of cartilage-forming cells and reduce inflammation. We believe these active proteins contribute to the striking, long-lasting benefits we have seen in patients receiving a single injection of mdHACM into their osteoarthritic knee. Following an extensive review and selection process, we are very excited to have world-class partners who are at the forefront of advancing meaningful medicines; working in collaboration accelerates our ability to gather quality data for our future Biologics License Application (BLA), and our potential to bring tremendous benefit for people living with OA.’ said Dr Robert B. Stein, M.D., Ph.D., MIMEDX President, Regenerative Medicine & Biologics Innovation.

About Image Analysis Group (IAG):

IAG, Image Analysis Group is a unique clinical development partner to life sciences companies. We broadly leverage our proprietary image analysis methodologies, power of our cloud platform DYNAMIKA, years of experience in AI and Machine Learning as well as bespoke co-development business models to ensure higher probability for promising therapeutics to reach the patients. Our independent Bio-Partnering division fuses risk-sharing business models and agile culture to accelerate novel drug development. wp1.ia-grp.com

About MIMEDX: 

MIMEDX is a transformational placental biologics company, developing and distributing placental tissue allografts with patent-protected, proprietary processes for multiple sectors of healthcare. As a pioneer in placental tissue engineering, we have both a commercial business, focused on addressing the needs of patients with acute and chronic non-healing wounds, and a promising late-stage pipeline targeted at decreasing pain and improving function for patients with degenerative musculoskeletal conditions. We derive our products from human placental tissues and process these tissues using our proprietary methods, including the PURION® process. We employ Current Good Tissue Practices, Current Good Manufacturing Practices, and terminal sterilization to produce our allografts. MIMEDX has supplied over two million allografts, through both direct and consignment shipments.

For more information, please reach out to: imaging.experts@ia-grp.com

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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.

Less Severe Synovitis in Patients with Knee Osteoarthritis is Associated with Higher Self-Reported Pain Intensity 12 Months After Total Knee Arthroplasty- An Exploratory Cohort Study.

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.5695

Abstract

BACKGROUND:
Synovitis is a pain generator in patients with osteoarthritis and associated with upregulation of pro-inflammatory cytokines, which have been found to lead to pain sensitivity and worse self-reported pain(1).

OBJECTIVES:
This study aimed to investigate the association between pre- and perioperative synovitis from imaging and histology and self-reported pain 12 months after total knee arthroplasty (TKA).

METHODS:
Preoperative synovitis was assessed from MRI data of the knee by 11 point synovitis score a.m Guermazi (2) using contrast enhanced MRI (CE-synovitis) and heuristic time intensity curve analysis of the dynamic contrast enhanced MRI (DCE-MRI) data using the DYNAMIKA® software (Image Analysis group, London) providing Dynamic Enhanced MR Quantification (DEMRIQ) Indices (3). Perioperative synovitis was also assessed from biopsies of the synovium in 6 predefined places graded histologically a.m Krenn (4). Worst pain within the last 24-hours (visual analog scale, VAS, 0-100) was assessed before and 12 months after TKA. Patients were divided into a low-pain (VAS≤30) and a high-pain (VAS>30) group based on 12-months postoperative VAS.

RESULTS:
Twenty-six patients had full pre- and postoperative data and were analysed. The high-pain group had significantly lower CE-synovitis (P=0.03), DCE-MRI inflammation indices (DEMRIQ-inflammation) (P<0.03) and a trend towards lower histologically assessed synovitis grades (P=0.077) compared to the low-pain group at baseline. Preoperative synovitis scores were also inversely correlated with pain 12-months after TKA, CE-synovitis (R = – 0.455, P = 0.022) and DCE-MRI inflammation (R = -0.528, P = 0.007), indicating that more severe preoperative synovitis is associated with less severe pain at 12-months.

CONCLUSION:
Higher preoperative synovitis scores are associated with less postoperative pain 12-months after TKA. Further, correlation analysis revealed that less severe preoperative synovitis was associated with worse pain 12-months after TKA, suggesting that CE and DCE-MRI synovitis quantification could be used as imaging markers for prediction of good surgical outcomes.

Effect of Liraglutide on Body Weight and Pain in Patients with Overweight and Knee Osteoarthritis: Protocol for a Randomised, Double-Blind, Placebo-Controlled, Parallel-Group, Single-Centre Trial

Copyright © Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ
BMJ Open. 2019 May;9(5) doi: 10.1136/bmjopen-2018-024065

Abstract

INTRODUCTION:
With an increasing prevalence of citizens of older age and with overweight, the health issues related to knee osteoarthritis (OA) will intensify. Weight loss is considered a primary management strategy in patients with concomitant overweight and knee OA. However, there are no widely available and feasible methods to sustain weight loss in patients with overweight and knee OA. The present protocol describes a randomised controlled trial evaluating the efficacy and safety of the glucagon-like peptide-1 receptor agonist liraglutide in a 3 mg/day dosing in patients with overweight and knee OA.

METHODS AND ANALYSIS:
150 volunteer adult patients with overweight or obesity and knee OA will participate in a randomised, double-blind, placebo-controlled, parallel-group and single-centre trial. The participants will partake in a run-in diet intervention phase (week −8 to 0) including a low calorie diet and dietetic counselling. At week 0, patients will be randomised to either liraglutide 3 mg/day or liraglutide placebo 3 mg/day for 52 weeks as an add-on to dietetic guidance on re-introducing regular foods and a focus on continued motivation to engage in a healthy lifestyle. The co-primary outcomes are changes in body weight and the Knee Injury and Osteoarthritis Outcome Score pain subscale from week 0 to week 52.

ETHICS AND DISSEMINATION:
The trial has been approved by the regional ethics committee in the Capital Region of Denmark, the Danish Medicines Agency and the Danish Data Protection Agency. An external monitoring committee (The Good Clinical Practice Unit at Copenhagen University Hospitals) will oversee the trial. The results will be presented at international scientific meetings and through publications in peer-reviewed journals.

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.

Intra-Operative Synovitis Predicts Worse Pain and Function 2 Years after Total Knee Arthroplasty for Osteoarthritis

Background/Purpose:

Total knee arthroplasty (TKA) is one of the most common elective
orthopedic procedures in the US.  However, up to 20% of patients have chronic
post-operative pain.  There is therefore an urgent need to identify modifiable
risk factors to improve patients’ outcomes. Inflammation is reversible, and has
been associated with pain in knee osteoarthritis (KOA). However, whether
inflammation is associated with chronic pain or other suboptimal outcomes after
TKR is unknown. Therefore, this study investigated the association between pre-operative
synovial inflammation and 2-year outcomes following TKA for KOA.

 

Methods:

We identified 33 KOA patients who underwent primary unilateral
TKA and had chronic pain (WOMAC ≤60; 100 =best) at 2 years. Patients were
matched 2:1 on surgeon and surgery date with TKA cases with little pain at 2
years, (WOMAC ≥70).   All patients provided demographic and pre-and
post-operative self-report data. Preoperative radiographs were graded by two blinded
evaluators for alignment and Kellgren and Lawrence score.  H+E slides of
intra-operative synovial tissue were reviewed and graded for inflammation
according to the validated Krenn Criteria. Prosthesis information, history of previous
surgery to the index knee, post-operative steroid injection and manipulations
were recorded from surgeons’ and inpatient charts.  Regression analyses were performed
to evaluate whether pre-operative inflammation was an independent predictor of
pain, function or stiffness 2 years after TKA.

Results:

Average age was 67 years, (±7.9), 65% were women and 91%
were Caucasian.  In a multivariate linear regression controlling for Krenn
Score, post-operative steroid injection, age, MCS, PCS, pre-operative WOMAC
pain and Euroqol, patients with greater inflammation (Krenn  ≥3) had more
pain at 2-years (WOMAC 65.01 vs. 76.14; p-value 0.03). Patients who had a
steroid injection soon after TKA (based on surgeon’s suspicion  of
tenosynovitis) were more likely to have worse 2 year WOMAC pain scores (60.3
vs. 80.9;  p-value = 0.0495).  Every 10 year increase in age was associated
with a 6.6 unit increase in 2-year WOMAC pain score,( i.e. less pain.). Separate
models showed a similar association between high Krenn score and worse 2-year
function, (WOMAC Function 70.2 vs. 81.1; p-value 0.01), but no association
between Krenn score and 2 year WOMAC stiffness. Neither radiographic findings nor
implant type were associated with 2-year outcomes.

Conclusion:

Increased synovial inflammation at the time of surgery
predicts worse WOMAC pain and function 2 years after TKA.  This is a
potentially modifiable risk factor which could be a target for future
interventional trials.