An update on the up and coming therapies to treat osteoarthritis, a multifaceted disease

ABSTRACT

Introduction: The lack of a complete understanding of the complex processes involved in the etiopathogenesis and subsequent appropriate phenotyping makes it difficult to find therapies that may be efficacious in most patients with osteoarthritis (OA). Consensus recommendations involve mainly non-pharmacological approaches. Analgesics and NSAIDs are considered second choice options due to their poor efficacy/safety ratios. To some extent, OA may be considered an orphan disease. Therefore, there is an urgent need to identify effective and safe new pharmacologic modalities for treating OA.

Areas covered: This review is based on a Medline comprehensive literature search for published articles evaluating new formulations of current drugs and promising emerging therapies in OA. We discuss the current status of novel systemic agents in development including potent analgesic options, inhibitors of innate immunity, inducible nitric oxide synthase (iNOS), pro-inflammatory cytokines and cartilage proteases as well as bone agents. Furthermore, we also revise the potential benefit of intraarticular (IA) therapy with hyaluronic acid (HA), pro-inflammatory mediator blockers, cartilage anabolic agents, mesenchymal stem cell and gene transfer.

Expert opinion: Despite the renewed interest in the search of new compounds for treatment of OA, results have been limited. Novel systemic and IA administered agents are in active development. IA drug administration is particularly an attractive approach because can diminish some of the severe side effects associated with systemic drugs. Indeed, one of the most promising fields for pharmacology innovation in OA is joint injected therapy, as suggested by preliminary data from recent studies using IA sprifermin (rhFGF-18), mesenchymal stem cells or TGF-B1 transduced allogenic chondrocytes. Last, the effort to develop new drugs must be accompanied by the interest for establishing well-defined phenotypes, and only then, a more tailored therapy should be practiced in OA.

KEYWORDS:

• Osteoarthritis
• therapy
• SYSADOAs
• DMOADs
• intraarticular therapy

Article highlights

• The complexity of the etiopathogenesis and subsequent clinical course of the OA process impede the development of efficacious therapies for most patients with OA.

• The poor efficacy/safety ratio of analgesics and NSAIDs and the contradictory results of SYSADOAs and current intraarticular therapies have triggered the search for drugs able to provide symptomatic relief but at the same time to modify the natural course of OA, slowing or halting the loss of joint function.

• Novel promising agents focused on three main structural targets: cartilage, synovial membrane and subchondral bone are at now under evaluation for their applicability as DMOADs in OA patients. Systemic agents in development include potent analgesic options, inhibitors of innate immunity, inducible nitric oxide synthase (iNOS), pro-inflammatory cytokines and cartilage proteases as well as bone agents

• IA drug administration is particularly an attractive approach for OA treatment because it can diminish some of the severe side effects associated with systemic delivery, mainly in the elderly. . Encouraging preliminar results have been reported with cartilage anabolic agents, mesenchymal stem cell and gene transfer.

• The effort to develop new drugs must be accompanied by the interest for establishing well-defined phenotypes, and only then, a more tailored therapy should be practiced in OA.

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Declaration of interest

R Largo’s work was funded by the Instituo de Salud Carlos III through a research staff stabilization program. The authors have no other 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 apart from those disclosed.

Additional information

Funding

This work was partially supported by research grants from the Instituto de Salud Carlos III (PI12/00144; PI13/00570; PI15/00340 and RETICEF-FEDER RD12/0043/0008).