The current state of the osteoarthritis drug development pipeline: a comprehensive narrative review of the present challenges and future opportunities

Abstract

In this narrative review article, we critically assess the current state of the osteoarthritis (OA) drug development pipeline. We discuss the current state-of-the-art in relation to the development and evaluation of candidate disease-modifying OA drugs (DMOADs) and the limitations associated with the tools and methodologies that are used to assess outcomes in OA clinical trials. We focus on the definition of DMOADs, highlight the need for an updated definition in the form of a consensus statement from all the major stakeholders, including academia, industry, regulatory agencies, and patient organizations, and provide a summary of the results of recent clinical trials of novel DMOAD candidates. We propose that DMOADs should be more appropriately targeted and investigated according to the emerging clinical phenotypes and molecular endotypes of OA. Based on the findings from recent clinical trials, we propose key topics and directions for the development of future DMOADs.

Senolytic therapy combining Dasatinib and Quercetin restores the chondrogenic phenotype of human osteoarthritic chondrocytes by promoting the release of pro-anabolic mediators

“…The relevance of research into new therapies for the treatment of OA becomes particularly clear, given that 654.1 million people worldwide are affected by osteoarthritis of the knee joint, as estimated in 2020 [48]. Currently, no disease modifying OA drugs (DMOADs) are approved and therefore OA is still an uncurable disease [49, 50]. Due to the detrimental effects of cellular senescence on tissue homeostasis, selective elimination of senescent cells received increasing attention in OA as well as other degenerative diseases during the last decades [32, 51].…”

Current status of catabolic, anabolic and inflammatory biomarkers associated with structural and symptomatic changes in the chronic phase of post-traumatic knee osteoarthritis– a systematic review

“…IL-6) allows the understanding of responses to targeted mechanism-specific interventions. This is relevant for DMOAD development and would allow heterogenous study populations to be classified based on predominant pathophysiological pathways or likelihood of rapid progression, as well as overcoming some of the challenges associated with outcome measures [ 4 , 25 , 62 , 63 ].…”

Osteoarthritis in the UK Armed Forces: a review of its impact, treatment and future research

“…Specific pathological changes in cartilage, bone and synovium, and concurrent inflammatory and metabolic responses, can be indirectly measured, allowing the identification of homogeneous subgroups/phenotypes based on shared clinical, epidemiological, and biochemical characteristics. [20,23] All of these measures are components of a continuum extending from genome proximity to a clinical phenotype of a painful joint limiting function.…”

“…The use of genotyping, phenotyping and endotyping has been suggested to categorise OA subgroups and target appropriate investigations and interventions (Table 2). [23] Currently, this remains crude, with categories such as Primary (or idiopathic) and Secondary, such as PTOA.…”

“…OPTIKNEE clinical and research recommendations to knee health promotion and post-traumatic OA prevention. Adapted from 'OPTIKNEE 2022: consensus recommendations to optimise knee health after traumatic knee injury to prevent osteoarthritis'[11] Beyond analgesia, there are no effective pharmacological interventions for OA, however there is a renewed focus on the development of disease-modifying anti-osteoarthritis drugs (DMAODs) [23]. These have proven difficult and costly to develop, in part due to study population selection, given that OA has a heterogenous population who respond differently depending on…”