Focus of the Report: The use of Zilretta (triamcinolone acetonide extended-release injectable suspension) for the treatment of pain associated with knee osteoarthritis (KOA).

Technology Description: Zilretta (Flexion Therapeutics Inc.) is an extended-release intra-articular therapy for patients with pain associated with KOA. The injectable suspension is comprised of proprietary microsphere technology that combines triamcinolone acetonide (TA)—a commonly administered, short-acting corticosteroid—with biodegradable polylactic-co-glycolic acid (PLGA) matrix that prolongs drug release. Small TA crystals are embedded within the PLGA matrix, creating microspheres that are 35 to 55 micrometers (µm) in size. When the suspension comes into contact with synovial fluid in the knee, TA is released from the microspheres via nanochannels that are roughly 500 nanometers (nm) in diameter. The small channels limit both TA egress from the microsphere’s interior and polymer hydration, which slows PLGA erosion and extends drug release. After TA is released over time, the microspheres degrade and are metabolized to carbon dioxide and water.

Controversy: Intra-articular corticosteroid injections typically contain standard formulations of TA that is immediately released into the joint. Zilretta is an extended-release TA (TA-ER) suspension that prolongs the residence time in the joint. The efficacy and safety of repeat administration of TA-ER have not been demonstrated. In addition, the comparative benefit of the extended-release over the immediate-release (TA-IR) formulations is in question. Proponents suggest that TA-ER may be an alternative for patients with KOA and type 2 diabetes mellitus (Russell et al., 2018). Among individuals with type 2 diabetes blood glucose elevation has been observed and associated with the intra-articular deliver of TA-IR, posing a potential clinical challenge in this distinct patient population.

Key Questions:

  • Is TA-ER effective in treating chronic pain associated with KOA?

  • How does TA-ER compare with clinical standards for treating chronic pain associated with KOA?

  • Is treatment with TA-ER in patients with chronic pain associated with KOA safe?

  • Have definitive patient selection criteria been identified for TA-ER as a treatment for chronic pain associated with KOA?

If you have a Hayes login, click here to view the full report on the Knowledge Center.