Intra-articular sustained-release colchicine is efficacious in an inflammatory arthritis rat model

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Journal
RMD Open

Abstract
Objectives Gout is a common disease causing excruciatingly painful and disabling flares. Although currently approved treatments for gout flares are generally effective, their use is restricted in many patients who present contraindications. There is a clear unmet need for treatments, with a rapid onset of action and a good safety profile. This study evaluates the efficacy of intra-articular (IA) colchicine (COL)-loaded microspheres enabling sustained-release colchicine (SR-COL), and of a combination of SR-COL with an anaesthetic (Ropivacaine HCl, ROPI) (PKM-01) in a rat model of acute inflammatory arthritis.Methods PKM-01 combines ROPI with SR-COL, prepared using a polylactic-co-glycolic acid matrix polymer. A model of IA carrageenan (CAR)-induced arthritis in knees or ankles was adapted for this study. Treatments (phosphate buffer saline, dexamethasone, SR-COL, ROPI or PKM-01) were administered intra-articularly immediately following the CAR injection. Pain was assessed using Von Frey filaments or weight-bearing tests. Histological scores assessed joint inflammation and destruction.Results All animals experienced acute painful and destructive arthritis following CAR injection. ROPI effectively alleviated pain but had no significant impact on inflammation or joint destruction. SR-COL demonstrated efficacy in reducing pain, inflammation and joint destruction across all parameters. PKM-01 provided a strong and rapid analgesic effect and exhibited anti-inflammatory properties, as evidenced by histological analysis of joint inflammation and destruction. Blood levels of COL after ankle injections were significantly below toxicity thresholds.Conclusions These data indicate that PKM-01 may serve as an effective and safe treatment option for acute inflammatory arthritis. A clinical trial is planned in gout flare patients.

Keywords/Topics
arthritis;pain

BIOSEB Instruments Used:
Von Frey Filaments (BIO-VF-M)

Source :

https://rmdopen.bmj.com/content/11/3/e005988

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