MULTI‐TISSUE ASSESSMENT AND 24‐MONTH PROGRESSION OF SEMI‐QUANTITATIVE MRI BIOMARKERS OF KNEE OSTEOARTHRITIS IN THE IMI‐APPROACH COHORT

Abstract

The IMI-APPROACH (Applied Public-Private Research enabling OsteoArthritis Clinical Headway) study is an exploratory, European, 5-centre, 2-year prospective follow-up cohort project. IMI-APPROACH was designed to prospectively describe pre-identified progressor phenotypes of patients with symptomatic and/or structural knee OA by use of conventional and novel clinical, imaging, and biochemical biomarkers, and to validate and refine a predictive model for progressor phenotypes based on these markers. The recruitment for IMI-APPROACH was based on rankings produced by machine-learning models that were trained using data from existing cohorts to estimate the likelihood of joint space width loss and/or increased or sustained knee pain over the course of the study from demographic data, pain scores, and radiographic features. 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. MRIs were acquired using 1.5T or 3T 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 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. 289 participants had a readable baseline scan. Participants were on average 66.6±7.1 years old and had a BMI of 28.1±5.3 kg/m². The majority (55.3%) of the knees had definite signs of radiographic OA. Any change in total cartilage MOAKS score was seen in 53.1% considering only full-grade changes and in 73.9% including full-grade and within-grade changes. Any medial cartilage progression was seen in 23.9% and any lateral progression in 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 the ROA- compared to the non-ROA subgroup (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). A wide range of MRI-detected structural pathologies was present in the IMI-APPROACH cohort. Baseline prevalence and change of features was significantly more common in the ROA subgroup compared to the knees without ROA. This work was supported by the Innovative Medicines Initiative Joint Undertaking under grant agreement no 115770, resources of which are composed of financial contribution from the European Union's Seventh Framework Programme (FP7/2007-2013) and EFPIA companies’ in kind contribution. See www.imi.europa.eu and www.approachproject.eu . FWR is shareholder of Boston Imaging Core Lab. (BICL),LLC. And is consultant to Calibr and Grünenthal (in thals t 36 months) CL reports other from Merck KGaA, during the conduct of the study; 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, outside the submitted work; 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; IKH reports personal fees from AbbVie, grants from Pfizer, outside the submitted work; 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 CORRESPONDENCE ADDRESS: frank.roemer@uk-erlangen.de .