Abstract

Imaging plays an important role in defining structural disease severity and potential suitability of patients recruited to disease-modifying osteoarthritis drug (DMOAD) trials. Three main structural phenotypes in knee OA have been proposed based on MRI, i.e., inflammation, cartilage-meniscus and subchondral bone. The cartilage-meniscus phenotype has received particular attention as such knees are likely to benefit most from pharmacological intervention. However, cartilage damage that is too severe may be of negative impact. To describe frequencies for different thresholds regarding an MRI-defined cartilage-meniscus phenotype and to report phenotypic progression in Kellgren-Lawrence (KL) 2 and 3 knees over 48 months. The study sample was selected as a nested case-control study with knees showing either 1) radiographic and pain progression (“composite” case), 2) radiographic progression only, 3) pain progression only, and 4) no progression. MRI was performed on 3T systems. MRIs were read according to the MOAKS scoring system. Three different phenotypes were defined according to the maximum severity of medial cartilage damage: ‘D1’: ≤ 2.2, ‘D2’ ≤ 2.1 and ‘D3’ ≤ 2.0. The odds of being a composite case for those with vs. without each phenotype definition was determined using logistic regression. 485 knees were included. For KL2 knees 191(64%) knees fulfilled D1 criteria, 183 (62%) D2 and 167 (56%) D3. For KL3 these numbers were 164 (87%), 103 (55%) and 77 (41%). Odds for being a composite case were 2.52 (95% CI 1.40,4.54) for D1, 1.93 (95% CI 1.11,3.35) for D2 and 1.92 (95% CI 1.13,3.28) for KL2 knees. For KL3 knees odds were 0.32 (95% CI 0.13,0.78) for D1, 0.56 (95% CI 0.31,1.01) for D2 and 0.49 (95% CI 0.26,0.91) for D3. Details for the medial compartment are presented in Table 1 . Increased odds for progression are seen for KL2 knees and all definitions, while a seemingly protective effect is seen for KL3 knees. The latter is explained by the fact that KL3 knees stratified as suggested will have comparably mild cartilage damage at screening. Scientific and financial support for the Foundation for the National Institutes of Health (FNIH) Osteoarthritis (OA) Biomarkers Consortium and for this study has been made possible through grants as well as direct and indirect in-kind contributions from AbbVie, Amgen Inc., the Arthritis Foundation, Bioiberica SA, DePuy Mitek, Inc., Flexion Therapeutics, Inc., GlaxoSmithKline, Merck Serono, Rottapharm | Madaus, Sanofi, Stryker, and the Pivotal Osteoarthritis Initiative Magnetic Resonance Imaging Analyses (POMA) Study (NIH/National Heart, Lung, and Blood Institute grant HHSN- 2682010000). The Osteoarthritis Initiative (OAI) is a public–private partnership between the NIH (contracts N01-AR-2-2258, N01-AR-2- 2259, N01-AR-2-2260, N01-AR-2-2261, and N01-AR-2-2262) and private funding partners (Merck Research Laboratories, Novartis Pharmaceuticals, GlaxoSmithKline, and Pfizer, Inc.) and is conducted by the OAI Study Investigators. Private sector funding for the Biomarkers Consortium and the OAI is managed by the FNIH. AG has received consultancies, speaking fees, and/or honoraria from Pfizer, Novartis, AstraZeneca, Merck Serono, and TissuGene and is President and shareholder of Boston Imaging Core Lab (BICL), LLC a company providing image assessment services. FWR is Chief Medical Officer and shareholder of BICL, LLC. and has received consultancies, speaking fees, and/or honoraria from Calibr –California Institute of Biomedical Research and Grünenthal, GmbH. DJH is funded by an NHMRC Practitioner Fellowship and received a grant from the FNIH OA Biomarkers Consortium. He reports consulting fees from Merck Serono, TLCBio, Pfizer and Lilly CORRESPONDENCE ADDRESS: frank.roemer@uk-erlangen.de .

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