Structural tissue damage and 24-month progression of semi-quantitative MRI biomarkers of knee osteoarthritis in the IMI-APPROACH cohort

Abstract

Background: The IMI-APPROACH cohort is an exploratory, 5-centre, 2-year prospective follow-up study of knee osteoarthritis (OA). Aim was to describe baseline multi-tissue semiquantitative MRI evaluation of index knees and to describe change for different MRI features based on number of subregion-approaches and change in maximum grades over a 24-month period.

Methods: MRIs were acquired using 1.5 T or 3 T MRI systems and assessed using the semi-quantitative MRI OA Knee Scoring (MOAKS) system. MRIs were read at baseline and 24-months for cartilage damage, bone marrow lesions (BML), osteophytes, meniscal damage and extrusion, and Hoffa- and effusion-synovitis. In descriptive fashion, the frequencies of MRI features at baseline and change in these imaging biomarkers over time are presented for the entire sample in a subregional and maximum score approach for most features. Differences between knees without and with structural radiographic (R) OA are analyzed in addition.

Results: Two hundred eighty-nine participants had readable baseline MRI examinations. Mean age was 66.6 ± 7.1 years and participants had a mean BMI of 28.1 ± 5.3 kg/m2. The majority (55.3%) of included knees had radiographic OA. Any change in total cartilage MOAKS score was observed in 53.1% considering full-grade changes only, and in 73.9% including full-grade and within-grade changes. Any medial cartilage progression was seen in 23.9% and any lateral progression on 22.1%. While for the medial and lateral compartments numbers of subregions with improvement and worsening of BMLs were very similar, for the PFJ more improvement was observed compared to worsening (15.5% vs. 9.0%). Including within grade changes, the number of knees showing BML worsening increased from 42.2% to 55.6%. While for some features 24-months change was rare, frequency of change was much more common in knees with vs. without ROA (e.g. worsening of total MOAKS score cartilage in 68.4% of ROA knees vs. 36.7% of no-ROA knees, and 60.7% vs. 21.8% for an increase in maximum BML score per knee).

Conclusions: A wide range of MRI-detected structural pathologies was present in the IMI-APPROACH cohort. Baseline prevalence and change of features was substantially more common in the ROA subgroup compared to the knees without ROA.

Trial registration: Clinicaltrials.gov identification: NCT03883568.

Keywords: Knee; MRI; Osteoarthritis; Progression; reliability.

Conflict of interest statement

The IMI-APPROACH project received a grant from Innovative Medicines Institute, grant agreement 11577.

Competing interests outside the submitted work:

FWR is Chief Medical Officer and shareholder of BICL, LLC. He has received consulting honoraria from Calibr and Grünenthal; MJ did not declare any conflict of interest; ACAM did not declare any conflict of interest, AG has received consultancies, speaking fees, and/or honoraria from Sanofi-Aventis, Merck Serono, and TissuGene and is President and shareholder of Boston Imaging Core Lab (BICL), LLC a company providing image assessment services; RH did not declare any conflict of interest; SM is employee and shareholder of Chondrometrics GmbH; AL is employee of Institut de Recherches Internationales Servier; FJB reports grants from Gebro Pharma, grants from BIOIBERICA, grants from AB Science, grants from Abbvie, grants from Ablynx N.V., grants from Amgen, grants from Archigen Biotech Limited, grants from Boehringer, grants from Bristol-Myers, grants from Celgene Int., grants from Eli Lilly and Company, grants from F. Hoffmann- La Roche, grants from Galapagos, grants from Gedeon, grants from Genentech, grants from Gideal Sciences, NC, grants from Glaxosmithkline, grants from Hospira, grants from INC Research UK, grants from Inventiv Health Clinical, grants from Janssen, grants from Lilly, grants from Nichi-IKO Pharmaceutical, grants from Novartis, grants from ONO Pharma, grants from Pfizer, grants from Pharmaceutical Research, grants from Regeneron, grants from Roche, grants from SA UCB Pharma, grants from Sanofi, grants from TRB Chemedica, grants from UCB Biosciences GMBH, outside the submitted work; In addition, FJB has a patent Molecular block-matching method for gel image analysis issued, a patent Targeting A Specific Receptor On Cells With A Specific Compound For Use In The Treatment And/Or The Prevention Of Osteoarthritis And Rheumatoid Arthritis pending, a patent Genetic markers for osteoarthritis issued, a patent Method for the diagnosis of osteoarthritis issued, a patent Genetic markers for osteoarthritis pending, a patent Method for the diagnosing Arthrosis pending, a patent Method for diagnosing Arthrosis pending, a patent Method for the diagnosis of osteoarthritis pending, and a patent Anti-connexin compounds for use in the prevention and/or treatment of degenerative joint diseases. pending; FB reports personal fees from Boehringer, Bone Therapeutics, Expanscience, Galapagos, Gilead, GSK, Merck Sereno, MSD, Nordic, Novartis, Pfizer, Regulaxis, Roche, Sandoz, Sanofi, Servier, UCB, Peptinov, TRB Chemedica, 4P Pharma; LAvdS did not declare any conflict of interest; MK reports grants from IMI-APPROACH, grants from Dutch Arthritis Association, during the conduct of the study; other from GlaxoSmithKline, Pfizer, Merck-Serono, Kiniksa, Abbvie; IKH reports personal fees from AbbVie, grants from Pfizer; CL was employee of Merck KGaA, at start of the study; JB did not declare any conflict of interest; AW is employee of Chondrometrics GmbH; FE is CEO and shareholder of Chondrometrics GmbH and received personal fees from AbbVie, Galapagos NV, HealthLink, ICM, IRIS, Kolon TissueGene, Merck KGaA, Novartis, Roche and Samumed and grants from Foundation for the NIH, University of California, San Francisco, NIH/National Heart, Lung, and Blood Institute, Bioclinica, Galapagos NV, Novartis, TissueGene, Erlangen University Hospital, University of Sydney, CALIBR, University of Basel, University of Western Ontario, Stanford University, ICM Co., Ltd., UMC Utrecht, Federal Ministry of Education and Research, Germany; FPJGL did not declare any conflict of interest; HHW did not declare any conflict of interest; WW is employee and shareholder of Chondrometrics GmbH and received consulting fees from Galapagos NV.

© 2022. The Author(s).

Figures

Fig. 1

Subregional division for cartilage and bone marrow lesion assessment using the MOAKS instrument. Both features are assessed in 14 articular subregions. A. Axial intermediate-weighted fat suppressed image shows subregional division of the patella into the medial (mP) and lateral patella (lP). Note that the patella apex is part of the medial patella. B. Sagittal intermediate-weighted fat suppressed image of the medial compartment shows the three femoral and three tibial subregions. The femur is subdivided into the anterior (amF), central (cmF) and posterior (pmF) subregions. The tibia is subdivided into the anterior (amT), central (cmT) and posterior (pmT) subregions. The lateral compartment is subdivided in corresponding fashion in the sagittal plane (not shown). C. Coronal intermediate-weighted fat suppressed image shows the central femoral and tibial subregions. The tibial S region (subspinous – adjacent to the tibial spines) is not considered for BML and cartilage evaluation