Shedding light on experimental intra-articular drugs for treating knee osteoarthritis

IntroductionKnee osteoarthritis (KOA) is a leading cause of disability among older adults without a curative therapy available. The development of disease-modifying OA drugs based on intra-articular injection (IA) is drawing extensive attention for its advantages in bioavailability and reduced systemic exposure. Based on the newly revealed pathogenesis of OA, several experimental IA drugs are successful in preclinical studies; moreover, some of them are in different phases of randomized clinical trials, bringing new opportunities for disease modification of OA.Areas coveredThis is a targeted literature review to summarize experimental IA drugs targeting cartilage repair, cellular homeostasis, cellular senescence, and pain control. We also introduced targeted gene/oligonucleotide products.Expert opinionCurrently available therapeutics for KOA remain symptomatic relief and surgical replacement of damaged joints. Recently emerging experimental IA drugs are in different stages of development and are likely to enter practice in the near future and address many of the unmet needs. The major challenges for development of the new drugs are limited knowledge about the responsive subjects, heterogenicity of subjects and the complexity of the disease. Despite this, IA-based experimental drugs still hold great potential to be future disease-modifying treatments for their intrinsic advantages.