Osteoarthritis – a case for personalized health care?

Abstract

For both economic and ethical reasons, identification of the optimal treatment for each individual patient is a pressing concern, not only for the patients and their physician, but also health care payers and the pharmaceutical industry. In the field of osteoarthritis (OA) this is of particular relevance, due to the heterogeneity of the disease and the very large number of affected individuals. There is a need to pair the right patients with the right therapeutic modes of action. At present, the clinical trial failures in OA may be a consequence of both bona fide treatment failures and trial failures due to clinical design deficiencies. Tools are needed for characterization and segregation of patients with OA. Key lessons may be learned from advances with another form of arthritis, namely rheumatoid arthritis (RA). Personalized health care (PHC) may be more advantageous for a number of specific indications which are characterized by costly therapy, low response rates and significant problems associated with trial and error prescription, including the risk of serious side effects. We discuss the use of diagnostic practices guiding RA treatment, which may serve as a source of key insights for diagnostic practices in OA. We discuss the emerging concept of PHC, and outline the opportunities and current successes and failures across the RA field, as the OA field collects further data to support the hypothesis. We attempt to outline a possible path forward to assist patients, physicians, payers and the pharmaceutical industry in assuring the 'right' patients are treated with the 'right drug' in OA. Finally we highlight methods for possible segregation of OA patients that would allow identification of patient subtypes, such as OA driven by inflammation that may be ideally suited for PHC and for targeted therapies.

The Influence of Joint Loading on Bone Marrow Lesions in the Knee

“…In this context, it should be noted that recently, different hypothetical phenotypes of OA were suggested, each with their respective key drivers of the disease. 42 Two of these drivers (ie, mechanotransduction and metabolic drivers) can both be linked to body weight. Mechanotransduction has been interpreted as a ''mechanical load that may drive a wear and tear effect,'' and the metabolic driver was interpreted as ''unhealthy phenotypes, such as obesity, that may drive OA through adipokines.''…”

What steps are needed to achieve perfect diagnostic and monitoring tests for osteoarthritis?

“…For this aim, improvements in imaging technologies and analytical validation of multiplex analyses by targeted proteomics will be highly useful to facilitate the identification and qualification of sensitive and specific imaging or biochemical markers [19]. Furthermore, knowledge being currently acquired on the diverse OA phenotypes must be employed in clinical development plans in order to adopt a personalized medicine mindset, trying to pair patient subpopulations with the right therapeutic modes of action [20]. It is anticipated that this will undoubtedly aid the development of novel therapeutic strategies for OA management.…”

Investigational drugs for the treatment of osteoarthritis

“…The failure of some clinical trials may be partly due to the failure to identify right OA phenotypes in clinical design [114]. Further, OA disease progression can be varied at different stages but it may only be preventable or retarded at early to mid-stages, so selection of patients with mild-to-moderate disease severity would be essential for establishing the disease-modifying effect of a drug in future clinical trials.…”