Can Repeat Injections Improve Knee OA Pain?

Promising Results from a Phase 3 Study

SAN DIEGO—An investigational liposomal formulation of dexamethasone sodium phosphate (TLC599) for intra-articular injection is being studied to treat patients with knee osteoarthritis (OA). George Spencer-Green, MD, MS, chief medical officer of Taiwan Liposome Company (TLC), Cambridge, Mass., presented recent data on this agent in a late-breaking abstract session at ACR Convergence 2023.¹

Background: According to the U.S. Centers for Disease Control and Prevention, OA is a degenerative joint disease and the most common form of arthritis, affecting more than 32.5 million adults in the U.S.² OA is a disease of the entire joint that can degrade cartilage, change bone shape and cause inflammation, leading to pain, stiffness and mobility loss. No cure currently exists.

OA is a manageable condition, with patients able to minimize pain, continue physical activities and maintain a good quality of life. Intra-articular corticosteroid injections are used to relieve pain, reduce inflammation and improve mobility. But the effects of these agents are not predictable, and the pain relief duration can be short. To date, the benefit of repeat corticosteroid injections has not been confirmed.

The study by Spencer-Green et al. sought to confirm prior study results that showed OA pain relief in patients treated with TLC599 over 24 weeks. This study also sought to evaluate the benefit of a repeat injection at week 24 over a year (NCT03005873).³

Methods

This three-arm, placebo- and active-controlled study evaluated the efficacy and safety of TLC599 as a single and repeated dose. A screening diary was used to enroll patients with K-L (Kellgren and Lawrence) grade 2–3 OA of the knee. The K-L system is used in research to classify OA severity. Grade 2 is minimal—definite osteophytes and possible joint space narrowing. Grade 3 is moderate—moderate, multiple osteophytes, definite joint space narrowing, some sclerosis and possible deformity of bone ends. Enrolled patients also had an average daily pain score from screening diary completion in the index knee of 5–9 (i.e., on a scale of 0–10, in which 0 is no pain and 10 is the worst pain).

The study’s efficacy parameters included average daily pain using mixed models for repeated measures (MMRM), Western Ontario and McMaster Universities OA (WOMAC) index and analysis of covariance (ANCOVA). The WOMAC pain score at week 12 was the study’s primary end point.

In the double-blinded study, 509 patients were randomized in a 2:1:1 ratio to receive a 12 mg injection of TLC599, a 4 mg injection of dexamethasone sodium phosphate or an injection of saline (placebo). At week 24, eligible patients in the TLC599 group and the placebo group received a second injection of the same treatment. Also at week 24, patients in the dexamethasone sodium phosphate group received a blinded injection of TLC599.

The effectiveness and safety were assessed through to week 52.

Results

Through week 24, TLC599 was numerically superior to placebo with regard to WOMAC pain at all measured study time points and statistically superior at week 12 (P<0.05). For average daily pain, TLC599 was numerically and statistically better than placebo at all time points after the first injection (P<0.05).

When compared with dexamethasone sodium phosphate at week 12, TLC599 was superior in reducing the average daily pain after the first injection (P<0.05). After the second injection, when 203 patients received TLC599 and 94 received placebo, TLC599 proved numerically superior to placebo for reducing the average daily pain of patients at all time points from baseline to week 52.

TLC599 was also statistically superior to placebo through week 34.

The safety data showed the adverse effects among the three treatment groups were comparable, and TLC599 was generally well tolerated. After the first and second injections in patients who received TLC599, the morning serum cortisol level had a transient decrease. This result normalized by weeks 2 and 26. No patients showed signs or symptoms of adrenal insufficiency.

Conclusion

This phase 3 study demonstrated that patients with knee OA who received TLC599 experienced a greater reduction in average daily pain and WOMAC pain scores than those who received placebo at week 24 and week 52 following a second injection. Minimal side effects were seen after the two injections. 

These results provide additional information about benefits of repeated corticosteroid injections for patients with knee OA. Additionally, they suggest that managing knee OA pain with TLC599 may provide a prolonged benefit and offer an alternative to corticosteroids in a nonsurgical treatment.

Michele B. Kaufman, PharmD, BCGP, is a freelance medical writer based in New York City and a pharmacist at New York Presbyterian Lower Manhattan Hospital.

References

1. Spencer-Green G, Hunter D, Schnitzer T, et al. A phase 3 study of repeat injection of TLC599 in osteoarthritis of the knee: Benefits to 52 weeks [abstract L19]. Arthritis Rheumatol. 2023 Oct;75 (suppl 9).
2. About osteoarthritis. Arthritis Foundation. 2024.
3. Phase 2a, randomized, double blinded, placebo controlled, dose finding study for TLC599 in OA patients (NCT03005873). ClincalTrials.org. 19 Sep 2018.