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Objective: This study aimed to test a novel treatment combination (TC) (equivalent to sildenafil, mepivacaine, and glucose) with disease-modifying properties compared to Celestone® bifas® (CB) in a randomized triple-blinded phase III clinical study in horses with mild osteoarthritis (OA). Joint biomarkers (reflecting the articular cartilage and subchondral bone remodelling) and clinical lameness were used as readouts to evaluate the treatment efficacy. Methods: Twenty horses with OA-associated lameness in the carpal joint were included in the study and received either TC (n = 10) or CB (n = 10) drug intra-articularly-twice in the middle carpal joint with an interval of 2 weeks (visit 1 & 2). Clinical lameness was assessed both objectively (Lameness locator) and subjectively (visually). Synovial fluid and serum were sampled for quantification of the extracellular matrix (ECM) neo-epitope joint biomarkers represented by biglycan (BGN262) and cartilage oligomeric matrix protein (COMP156). Another two weeks later clinical lameness was recorded, and serum was collected for biomarkers analysis. The overall health status was compared pre and post-intervention by interviewing the trainer. Results: Post-intervention, SF BGN262 levels significantly declined in TC (P = 0.002) and COMP156 levels significantly increased in CB (P = 0.002). The flexion test scores improved in the TC compared to CB (P =0.033) and also had an improved trotting gait quality (P =0.044). No adverse events were reported. Conclusion: This is the first clinical study presenting companion diagnostics assisting in identifying OA phenotype and evaluating the efficacy and safety of a novel disease-modifying osteoarthritic drug.

Osteoarthritis (OA) is a degenerative joint disease in which structural changes of hyaline articular cartilage, subchondral bone, ligaments, capsule, synovium, muscles, and periarticular changes are involved. The knee is the most commonly affected joint, followed by the hand, hip, spine, and feet. Different pathological mechanisms are at play in each of these various involvement sites. Although systemic inflammation is more prominent in hand OA, knee and hip OA have been associated with excessive joint load and injury. As OA has varied phenotypes and the primarily affected tissues differ, treatment options must be tailored accordingly. In recent years, ongoing efforts have been made to develop disease-modifying options that halt or slow disease progression. Many are still in clinical trials, and as insights into the pathogenesis of OA evolve, novel therapeutic strategies will be developed. In this chapter, we provide an overview of the novel and emerging strategies in the management of OA., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Multiple disease-modifying osteoarthritis drug (DMOAD) trials were done in the last two decades, but no pharmacological agent has yet been approved by regulatory agencies as an effective therapy to date. Given the fact that we have seen the recent discontinuation of several late-stage drug development trials, a careful strategy is needed in formulating a plan for a successful DMOAD trial - including the various roles of imaging. This narrative review article will summarize how imaging is utilized in osteoarthritis from the perspective of disease modification to clinical utility. We will describe how semi-quantitative and quantitative magnetic resonance imaging approaches have been deployed in DMOAD trials. We will then review the utility of musculoskeletal ultrasound in research and clinical settings. Finally, novel hybrid positron emission tomography/MRI techniques and current research using artificial intelligence will be discussed, focusing on original research. Older publications are included for the discussion of the previous DMOAD trials and other relevant topics where deemed appropriate., Competing Interests: Declaration of competing interest Felix Eckstein is the CEO of Chondrometrics GmbH and has received consulting fees from Merck KGaA, Samumed LLC, Abbvie, BioClinica, Kolon TissueGene, Servier, Galapagos, Novartis, and Roche. Ali Guermazi is the President of Boston Imaging Core Lab (BICL), LLC, and a Consultant to MerckSerono, AstraZeneca, Pfizer, GE Healthcare, OrthoTrophix, Sanofi, and TissueGene. Frank Roemer is a shareholder of BICL, LLC, and is a consultant to Calibr – California Institute of Biomedical Research. Other authors have nothing to disclose., (Copyright © 2020 Elsevier Ltd. All rights reserved.)