Professor David Hunter

Intra-articular injection of a liposomal formulation of dexamethasone sodium phosphate (DSP) is showing efficacy in reducing knee OA pain, Australian research suggests.

Professor David Hunter, Florance and Cope Chair of Rheumatology at the University of Sydney, told ACR Convergence 2023 that TLC599 uses multi-layer lipid membranes to encapsulate the dexamethasone which allows for a controlled release.

“It also provides free DSP for some immediate effect and a depot compartment of DSP for sustained release,” he said.

Professor Hunter said a phase 2 study published last year [link here] found a single dose of TLC599 12 mg improved pain on a visual analogue scale (VAS) and pain, stiffness and function on the Western Ontario and McMaster Universities Arthritis Index (WOMAC) scales through to 24 weeks.

Now, a phase 3 RCT conducted in the US and Australia has compared TLC599 with placebo and DSP 4mg in 500 patients with Kellgren-Lawrence grade 2-3 OA of the knee, average daily pain (ADP) scores of 5-9 on a scale of 0-10 in the index knee, and a WOMAC pain score of ≥6 on a scale of 0-20.

Patients had a mean age of 61 years, BMI of 31, and had been diagnosed with OA for about eight years.

The study found ADP, WOMAC pain and WOMAC function at 12 weeks all favoured TLC599 compared to placebo with a significantly greater proportion of TLC599 patients having a 50% improvement in pain compared to placebo (48% v 36%; p<0.05).

For the most part, the findings extended out to 24 weeks. For example with WOMAC pain, TLC599 remained numerically superior to placebo at all time points through to week 24.

In addition, the change in both WOMAC pain and ADP between pre- and post-treatment met the threshold for minimal important change, indicating a clinically important benefit for the patient.

The study also evaluated the additional benefit of repeat injections of TLC599 in the TLC599 and DSP arms at week 24 and found a marked improvement in symptoms compared to placebo that persisted out to week 52.

“As far as adverse events are concerned the most frequent adverse event related to a local, self-limited arthralgia around the site of injection which was more frequent, at least numerically in the TLC599 arm compared to dexamethasone, and placebo. There was no other substantial numerical difference between any of the other adverse events between the treatment groups.”

Professor Hunter said non-surgical treatment options for OA currently offered modest benefits and particularly for pharmacological therapies, were often associated with a range of side effects.

“Intra-articular corticosteroid injections are frequently used, but again, have modest effects that are of short term benefit, and at least according to the Cochrane Review, on average lasts about two to four weeks. So ideally a longer term resolution of symptoms would be advantageous.”

He said TLC599 may provide those prolonged benefits and offer an alternative treatment to corticosteroids for the management of knee OA pain.

The study has not identified any between group differences in time to arthroplasty.

“The numbers are incredibly small, but it would be important post-registration and post-marketing to continue to follow that.”