Are repeated injections of Zilretta (triamcinolone acetonide) beneficial?

From the Guidelines

Repeated injections of Zilretta are not recommended due to limited evidence and potential long-term negative effects on bone health, joint structure, and meniscal thickness associated with repeat intra-articular corticosteroid administration. The evidence for repeated injections of Zilretta (triamcinolone acetonide extended-release) is limited, and most studies focus on single-dose administration 1. While some small studies and real-world experience indicate that patients who respond well to an initial injection may benefit from subsequent treatments when pain returns, the potential risks associated with repeated injections, such as negative effects on bone health and joint structure, must be considered 1.

Key Points to Consider

• The FDA has approved Zilretta for single-dose administration, and the manufacturer's clinical trials primarily focused on single injections.
• Some small studies and real-world experience indicate that patients who respond well to an initial injection may benefit from subsequent treatments when pain returns, typically after 3-6 months.
• The mechanism behind potential benefits from repeated injections relates to Zilretta's microsphere formulation, which provides extended release of triamcinolone in the joint, potentially reducing inflammation and pain for longer periods than standard corticosteroid injections.
• Patients considering repeated Zilretta injections should discuss with their healthcare provider the appropriate timing between injections (generally waiting at least 3 months) and monitor for any cumulative effects on cartilage health, as long-term safety data remains limited 1.

Important Considerations

• The potential long-term negative effects on bone health, joint structure, and meniscal thickness associated with repeat intra-articular corticosteroid administration must be taken into account 1.
• Providers must weigh the potential benefits of repeated injections against the potential risks and consider alternative treatment options for patients with persistent knee and/or hip OA pain.

From the Research

Repeated Injections of Zilretta

• The efficacy and safety of repeated injections of Zilretta (triamcinolone acetonide extended-release) have been evaluated in several studies 2, 3.
• A phase IIIb study found that repeat administration of triamcinolone acetonide extended-release may be similarly efficacious to an initial injection without having deleterious effects on cartilage or other aspects of joint structure 2.
• Another study, a phase 3b, open-label study, assessed the safety and efficacy of repeat administration of triamcinolone acetonide extended-release in patients with symptomatic knee osteoarthritis, and found that both injections were well tolerated, with no unexpected adverse events or significant radiographic changes at week 52 3.
• The study also found that the magnitude and duration of clinical benefit after the first and second injections were similar, and most patients reported a substantial (≥ 50%) analgesic response after both doses 3.

Efficacy of Zilretta

• The efficacy of Zilretta has been compared to other formulations of triamcinolone acetonide in several studies 4, 5.
• A non-inferiority, randomized, controlled, double-blind, multicenter study found that 10 mg of triamcinolone acetonide was non-inferior to 40 mg of triamcinolone acetonide in improving pain in patients with symptomatic knee osteoarthritis 4.
• A phase 2, double-blind, multicenter study found that an extended-release formulation of triamcinolone acetonide (FX006) provided a clinically relevant improvement in pain relief in patients with knee osteoarthritis relative to immediate-release triamcinolone acetonide 5.

Safety of Zilretta

• The safety of Zilretta has been evaluated in several studies, and has been found to be generally well tolerated 2, 3, 5, 6.
• A randomized double-blind placebo-controlled trial found that intra-articular injection of triamcinolone acetonide was effective in symptoms control and improving functional outcome in clinically diagnosed osteoarthritis of knees in community set up during health camps, with no major complications noted 6.