MedicalResearch.com Interview with:
Dr. Andrew Spitzer MD
Co-director Joint Replacement Program
Cedars-Sinai Orthopedic Center
Los Angeles, CA
MedicalResearch.com: What is the background for this study? How does this product differ from other steroid injections for inflammatory arthritis?
Dr. Spitzer: Many patients receive repeat injections of intra-articular corticosteroids to manage recurrent osteoarthritis pain and other symptoms. However, in most clinical trials to date, patients only received a single corticosteroid injection, and patients were only followed for 12 to 24 weeks after treatment. For trials that have evaluated repeated injections of corticosteroids over a longer period of time—2 years, for example—injections were administered every 3 months, regardless of the timing of the return of OA symptoms. This is not reflective of what is done in clinical practice, where corticosteroids are administered again in response to the return of pain or a flare of inflammation in the knee. In this study, we used a flexible dosing schedule based on the patients’ symptoms, meaning that patients received the second injection of a recently approved extended-release corticosteroid only when their pain and/or symptoms returned, not before. Safety was monitored for 52 weeks—this length of time should be sufficient to identify any associated side effects, including any potential impact on the knee tissue.
Triamcinolone acetonide extended-release (TA-ER; Zilretta®) was approved in late 2017 as an intra-articular injection for the management of osteoarthritis pain of the knee. The formulation utilizes microspheres which enable a slow release of the active agent (triamcinolone acetonide) into the synovial fluid for 12 weeks following injection. Previously, a Phase 3 study demonstrated safety and efficacy of a single injection of TA-ER (Conaghan PG, et al. J Bone Joint Surg Am. 2018;100:666-77). This is the first study evaluating the safety and patient response to repeat administration of TA-ER. This study also included patients that were more typical of who we see in the clinic—those who have higher body mass index, more severe disease, and received prior treatments for their osteoarthritis pain.
MedicalResearch.com: What are the main findings?
Dr. Spitzer: There were 208 patients in the study and the majority—86.1%—received 2 TA‑ER injections. The median time to the second injection was 16.6 weeks following initial treatment. This means that for most of the patients in this study, pain and other osteoarthritis symptoms did not return for 4-6 months after their first TA-ER injection. Both injections were well tolerated, with safety profiles that were similar between injections and consistent with previous single-dose clinical trials. There were no reports of post-injection flare and no radiographic evidence of cartilage impact over the 52 weeks of follow-up.
Following each injection, more than two thirds of patients experienced a ≥50% reduction in pain. Stiffness, function, and quality of life similarly improved after each TA-ER injection.
These safety and exploratory efficacy results are consistent with and expand upon what was observed in the pivotal Phase 3 study, because here we were not precluded from treating patients with a higher BMI, who had prior injections or procedures for osteoarthritis, and/or had more advanced radiological disease.
MedicalResearch.com: What should readers take away from your report?
Dr. Spitzer: The main take-away is that repeat administration of TA-ER in response to return of patients’ symptoms was well tolerated: there were no unexpected adverse events or significant radiographic changes 1 year after having 2 injections of TA-ER. In addition, the magnitude and duration of pain relief were similar following the first and second TA-ER injections—so the effect of TA-ER on osteoarthritis symptoms did not diminish with repeated injections.
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Dr. Spitzer: We are always trying to identify which patients will respond best to injection treatments for osteoarthritis. We are continuing to analyze the results of this trial across various patient subgroups including baseline Kellgren-Lawrence grade, prior intra-articular corticosteroid use, and unilateral versus bilateral osteoarthritis to help identify characteristics that influence patient response.
Dr. Spitzer: I have received research support from DePuy and Flexion Therapeutics, Inc., and consulting fees from DePuy, Flexion Therapeutics, Inc., Sanofi Biosurgical, and Zimmer Biomet.
Rheumatol Ther. 2019 Feb 11. doi: 10.1007/s40744-019-0140-z. [Epub ahead of print]
Spitzer AI1, Richmond JC2, Kraus VB3, Gomoll A4, Jones DG5, Huffman KM3, Peterfy C6, Cinar A7, Lufkin J8, Kelley SD7.
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