FULL‐GRADE AND WITHIN-GRADE CARTILAGE CHANGE OVER TWO YEARS AS ASSESSED USING THE MOAKS SCORING INSTRUMENT AND CONCURRENT QUANTITATIVE CARTILAGE THICKNESS LOSS: DATA FROM THE OAI FNIH BIOMARKERS CONSORTIUM STUDY

Both semi-quantitative (SQ) MOAKS cartilage scores and quantitative (Q) cartilage thickness measurements are used as outcome measures in observational studies and interventional knee osteoarthritis (OA) trials. In order to increase sensitivity to change of SQ instruments in longitudinal observational studies or clinical DMOAD trials, so-called within-grade changes not fulfilling criteria of a full-grade change have been introduced in SQ assessment. While the validity of these changes has been shown, the association between longitudinal change of SQ-defined within-grade and full-grade changes and longitudinal Q cartilage loss has not been established. To study the association between full-grade only changes, within-grade only changes and full-grade plus within-grade change in MOAKS cartilage scores and concurrent change in quantitative cartilage thickness measurements over 24 months within the FNIH Biomarker Consortium study. Of the 600 participants from FNIH Biomarker Consortium study, 599 had MOAKS cartilage assessments and quantitative cartilage thickness measurements (age: 62y, BMI: 31kg/m², 59% female). The maximum MOAKS area extent score (MOAKSext), and the maximum MOAKS cartilage damage full thickness score (MOAKSft) in each 3 tibial and 1 central femoral MOAKS subregion were determined at baseline and two-year follow-up for the medial and lateral compartment. Within-grade changes were assessed in knees without full-grade change in comparison to knees without any change. Knees with full grade changes only, with within-grade changes only and with any (either full-grade change, within-grade change or both) change in MOAKSext and MOAKS ft were considered separately and compared. Between-group comparisons were performed using ANCOVA with adjustment for age, sex, and BMI. Results were presented as mean adjusted difference (MAD) and 95% confidence intervals. 331 knees had no change in cartilage SQ scores, 41 knees had only within-grade changes, 170 knees had only full-grade changes, and 57 knees had both within-grade and full-grade changes. Knees with any increase in MOAKS cartilage scores in the MFTC (n=268) showed more MFTC cartilage loss than knees that remained stable (mean adjusted difference (MAD) -0.16 mm, 95% CI: [-0.19, -0.13] mm). Cartilage thickness loss increased with higher-grade MOAKSext cartilage change (change by 1 grade: MAD 0.13 mm, 95% CI: [-0.18, -0.08] mm; change by 2 grades: MAD -0.22 mm, 95% CI: [-0.27, -0.17] mm). Similar findings were observed for increase in MOAKSft dimension. While knees with within-grade-only changes showed markedly less cartilage thickness loss compared to knees with full grade-only changes, the amount of loss was still three times higher than for those without any change. The number of knees with any change in MOAKS cartilage (full-grade, within-grade or both) was markedly higher, including within grade changes(n=268) compared to knees with full grade changes only (n= 170). Both full-grade and within-grade changes in MOAKS cartilage scores corresponded with ipsicompartmental Q cartilage thickness loss. In the medial compartment, concurrent change in cartilage thickness was comparable for change in the MOAKSext and MOAKSft change dimensions. The effect was less pronounced for MOAKS within-grade changes. Including within-grade change-only knees, number of knees showing any change increased by 24% compared to using full grade change-only. SQ assessment seems a potential alternative as an outcome measure when Q evaluation is not feasible or available. 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, Regeneron, AstraZeneca, Novartis, 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. AW is employee of Chondrometrics GmbH. SM and WW are employees and shareholders of Chondrometrics GmbH. DJH reports personal fees from Pfizer, Lilly, Merck Serono, TLCBio, Kolon Tissuegene. CORRESPONDENCE ADDRESS: [email protected].