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

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.