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

ABSTRACT

Introduction

Knee 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 covered

This 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 opinion

Currently 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.

KEYWORDS:

• Cartilage repair
• clinical trial
• intra-articular injection
• knee osteoarthritis
• pain control

Article highlights

• The treatment of osteoarthritis (OA) is currently limited to symptomatic control since the development of disease modifying OA drugs is largely arrested by the heterogeneity of the disease.

• Intra-articular (IA) injection has been widely used to clinical treatment of OA and the development of new drugs.

• New drugs targeting cartilage repair, cellular senescence and homeostasis are under massive investigation and some results are promising.

• Drugs for OA pain control are still on their way to achieve an efficient, long-lasting, and safe goal.

• IA-based genetic therapies are under development based on new insights of molecular mechanisms of OA.

• Early intervention, precise phenotyping and novel delivery systems may help to develop efficient OA IA drugs.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This work is funded by the Clinical Research Center of Zhujiang Hospital and the Special Program of Chinese Postdoctoral Science Foundation (2022T150301), National Natural Science Foundation of China (82003542 & 82002331), Guangdong Basic and Applied Basic Research Foundation General Program (2023A1515011518) and Major Program of Guangzhou Science and Technology (202206010075).