Endotype discovery and their longitudinal stability in osteoarthritis

More than 500 million people worldwide are affected by osteoarthritis for which we have no effective treatment. This unfortunate situation is partially attributed to the non-optimal design of past clinical trials. Despite significantly different underlying causes of the disease, the osteoarthritis patients had been treated as a homogenous group. However, in recent years, the research into subpopulations of OA, specifically endotypes, has received increasing attention. In Angelini2022 three molecular endotypes have been suggested by machine learning applied to an observational cohort of 295 knee OA patients, and described as driven by: (1) structural damage, (2) inflammation, and (3) low tissue turnover. However, the longitudinal stability of such endotypes has yet to be assessed.

In this talk, I will describe the problems with clinical trials design and the need for endotype discovery. Then, I will discuss the longitudinal stability of the previously suggested molecular endotypes. And finally, I will show the results of an external validation of these endotypes in a significantly different population from an knee OA clinical trial.