FNIH 2 PROJECT (PROGRESS OA) NOW PUBLISHED IN ACR OPEN RHEUMATOLOGY

ACR Open Rheumatol. 2025 Sep;7(9):e70085 https://pubmed.ncbi.nlm.nih.gov/40977252/

With Jamie Collins from Harvard University and Chondrometrics SAB member as a first author, the 2^nd large osteoarthritis biomarker consortium qualification project that was supported by the Foundation of the National Institutes of Health (FNIH), has now been published:

The goal was to validate MRI-based prognostic biomarkers using data from the placebo arms of available and previously completed randomized placebo-controlled clinical trials (RCTs)

A key finding was that the following structural features, each qualified by the FNIH1 study, were consistently associated with disease progression: Quantitative cartilage thickness, semiquantitative cartilage damage, meniscal extrusion, and synovitis (Hoffa- and effusion-synovitis). These biomarkers each predicted radiographic (JSW loss ≥0.7 mm) and symptomatic progression (WOMAC pain increase ≥9). Cross-validated models achieved AUCs of around 0.7 for structural and around 0.77 for symptomatic progression, confirming robust prognostic performance.

The study represents a collaborative effort across multiple international partners, highlighting the power of shared data to advance osteoarthritis research. Validating imaging biomarkers can help enrich disease modifying osteoarthritis drug (DMOAD) trials by selectively including putative progressors”, rendering  the studies more efficient. The current work supports ongoing efforts toward formal biomarker qualification with regulatory agencies, a key step in accelerating DMOAD development.

Thanks to Jamie E Collins, Peter Mesenbrink, Rui Jin, Erik B Dam, Leticia A Deveza, Felix Eckstein, Ali Guermazi, Christoph Ladel, Thomas A Perry, Douglas Robinson, Frank W Roemer, Christopher J Swearingen, Wolfgang Wirth, Virginia B Kraus, and David J Hunter for this huge collaborative effort.

In the Foundation for the National Institutes of Health (FNIH) Osteoarthritis Biomarkers Consortium (Phase 1), quantitative MRI biomarkers of cartilage morphology, derived using Chondrometrics software and expertise, were shown to predict structural progression in knee osteoarthritis, and to contribute to the multivariate models of predicting progression:

Cartilage Thickness Change as an Imaging Biomarker of Knee Osteoarthritis Progression: Data From the Foundation for the National Institutes of Health Osteoarthritis Biomarkers Consortium.
F Eckstein, JE Collins , MC Nevitt, JA Lynch, VB Kraus, JN Katz, E Losina, W Wirth, A Guermazi, FW Roemer, DJ Hunter; FNIH OA Biomarkers Consortium.
Arthritis Rheumatol. 2015 Dec;67(12):3184-9. https://pubmed.ncbi.nlm.nih.gov/26316262/

Multivariable Modeling of Biomarker Data From the Phase I Foundation for the National Institutes of Health Osteoarthritis Biomarkers Consortium.
Hunter DJ, Deveza LA, Collins JE, Losina E, Katz JN, Nevitt MC, Lynch JA, Roemer FW, Guermazi A, Bowes MA, Dam EB, Eckstein F, Kwoh CK, Hoffmann S, Kraus VB.
Arthritis Care Res 2022 Jul;74(7):1142-1153 https://pubmed.ncbi.nlm.nih.gov/33421361/

The current findings in FNIH2 (Progress OA) confirm similar associations between baseline quantitative cartilage MRI biomarkers and radiographic disease progression as in Phase 1, both in direction and magnitude. Cartilage thickness measures demonstrated consistent prognostic associations across Phases 1 and 2, underscoring their robustness and reproducibility as biomarkers. In multivariable models, cartilage thickness over the central medial femoral condyle (cMF) and the medial femorotibial compartment (MFTC) were consistently identified as predictors of progression.

Chondrometrics is proud to contribute to this effort in the FNIH OA Biomarker Consortium through two decades of innovation and rigorous validation of quantitative MRI analysis, enabling precise, standardized measurement of tissue morphology using its regulatory compliant platform, to help advance scientific and clinical development.