, Volume 79, Issue 4, pp 455–462 | Cite as

Triamcinolone Acetonide Extended-Release: A Review in Osteoarthritis Pain of the Knee

  • Julia PaikEmail author
  • Sean T. Duggan
  • Susan J. Keam
Adis Drug Evaluation


Triamcinolone acetonide extended-release (ER) 32 mg (Zilretta®) is approved in the USA for the management of osteoarthritis (OA) pain of the knee and is administered as a single, 5 mL intra-articular (IA) injection. Although the therapeutic effects from IA corticosteroids are typically short-lived, triamcinolone acetonide ER is formulated in poly (lactic-co-glycolic acid) (PLGA) microspheres that slowly release triamcinolone acetonide in the synovium, enabling their prolonged presence in the joint. This reduces systemic exposure and lessens corticosteroid-related systemic adverse reactions, such as blood glucose elevations. In a 24-week, randomized, phase III clinical trial, triamcinolone acetonide ER 32 mg significantly improved mean average daily pain intensity in patients with knee OA relative to placebo, and pain, stiffness and physical function (according to WOMAC criteria) relative to placebo and triamcinolone acetonide crystalline suspension (CS). Triamcinolone acetonide ER was generally well tolerated, with a tolerability profile similar to that of triamcinolone acetonide CS and placebo. Findings from a single-arm phase IIIb study indicated that a repeat administration of triamcinolone acetonide ER may be similarly efficacious to an initial injection without having deleterious effects on cartilage or other aspects of joint structure. Thus, triamcinolone acetonide ER expands the treatment options available for the management of OA pain of the knee.



During the peer review process, the manufacturer of triamcinolone acetonide ER was also offered an opportunity to review this article. Changes resulting from comments received were made on the basis of scientific and editorial merit.

Compliance with Ethical Standards


The preparation of this review was not supported by any external funding.

Conflicts of interest

Julia Paik, Sean Duggan and Susan Keam are salaried employees of Adis/Springer and declare no relevant conflicts of interest.


  1. 1.
    Vos T, Flaxman AD, Naghavi M, et al. Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012;380(9859):2163–96.CrossRefGoogle Scholar
  2. 2.
    Osteoarthritis Research Society International. Osteoarthritis: a serious disease, a white paper submitted to the U.S. Food and Drug Administration. 2016. Accessed 22 Feb 2019.
  3. 3.
    Hawker GA, Stewart L, French MR, et al. Understanding the pain experience in hip and knee osteoarthritis: an OARSI/OMERACT initiative. Osteoarthr Cartil. 2008;16(4):415–22.CrossRefGoogle Scholar
  4. 4.
    Nuesch E, Dieppe P, Reichenbach S, et al. All cause and disease specific mortality in patients with knee or hip osteoarthritis: population based cohort study. BMJ. 2011;342:d1165.CrossRefGoogle Scholar
  5. 5.
    Sellam J, Berenbaum F. The role of synovitis in pathophysiology and clinical symptoms of osteoarthritis. Nat Rev Rheumatol. 2010;6(11):625–35.CrossRefGoogle Scholar
  6. 6.
    Hochberg MC, Altman RD, Brandt KD, et al. Guidelines for the medical management of osteoarthritis. Part II. Osteoarthritis of the knee. American College of Rheumatology. Arthritis Rheum. 1995;38(11):1541–6.Google Scholar
  7. 7.
    Juni P, Hari R, Rutjes AW, et al. Intra-articular corticosteroid for knee osteoarthritis. Cochrane Database Syst Rev. 2015(10):CD005328.Google Scholar
  8. 8.
    Koenig KM, Ong KL, Lau EC, et al. The use of hyaluronic acid and corticosteroid injections among Medicare patients with knee osteoarthritis. J Arthroplast. 2016;31(2):351–5.CrossRefGoogle Scholar
  9. 9.
    da Costa BR, Hari R, Juni P. Intra-articular corticosteroids for osteoarthritis of the knee. JAMA. 2016;316(24):2671–2.CrossRefGoogle Scholar
  10. 10.
    Habib GS. Systemic effects of intra-articular corticosteroids. Clin Rheumatol. 2009;28(7):749–56.CrossRefGoogle Scholar
  11. 11.
    Flexion Therapeutics Inc. ZILRETTA (triamcinolone acetonide extended-release injectable suspension): US prescribing information. 2017. Accessed 22 Feb 2019.
  12. 12.
    US Center for Drug Evaluation and Research. Non-clinical review(s) (Zilretta). 2017. Accessed 22 Feb 2019.
  13. 13.
    Anderson JM, Shive MS. Biodegradation and biocompatibility of PLA and PLGA microspheres. Adv Drug Deliv Rev. 1997;28(1):5–24.CrossRefGoogle Scholar
  14. 14.
    Flexion Therapeutics Inc. ZILRETTA® (triamcinolone acetonide extended-release injectable suspension). 2019. Accessed 22 Feb 2019.
  15. 15.
    Spenlehauer G, Vert M, Benoit JP, et al. In vitro and in vivo degradation of poly(d, l lactide/glycolide) type microspheres made by solvent evaporation method. Biomaterials. 1989;10(8):557–63.CrossRefGoogle Scholar
  16. 16.
    Jackson D, Cotton L, Turkington M, et al. Physical and chemical compatibility of extended-release triamcinolone acetonide (TA-ER) with common local anesthetics. Adv Ther. 2019.
  17. 17.
    Scherer J, Rainsford KD, Kean CA, et al. Pharmacology of intra-articular triamcinolone. Inflammopharmacology. 2014;22(4):201–17.CrossRefGoogle Scholar
  18. 18.
    US Center for Drug Evaluation and Research. Clinical pharmacology and biopharmaceutics review (Zilretta). 2017. Accessed 22 Feb 2019.
  19. 19.
    Wernecke C, Braun HJ, Dragoo JL. The effect of intra-articular corticosteroids on articular cartilage: a systematic review. Orthop J Sports Med. 2015;3(5):2325967115581163.Google Scholar
  20. 20.
    Kumar A, Bendele AM, Blanks RC, et al. Sustained efficacy of a single intra-articular dose of FX006 in a rat model of repeated localized knee arthritis. Osteoarthr Cartil. 2015;23(1):151–60.CrossRefGoogle Scholar
  21. 21.
    Williamson TL, Walz A, Garlick D, et al. Systemic and local effects following intra-articular injection of FX006, an extended release, PLGA microsphere formulation of triamcinolone acetonide: results from two nonclinical toxicity studies in dogs (abstract no. 713). Osteoarthr Cartil. 2017;25(Suppl. 1):S431–S2.Google Scholar
  22. 22.
    Bodick N, Williamson T, Strand V, et al. Local effects following single and repeat intra-articular injections of triamcinolone acetonide extended-release: results from 3 nonclinical toxicity studies in dogs. Rheumatol Ther. 2018;5(2):475–98.CrossRefGoogle Scholar
  23. 23.
    Russell SJ, Sala R, Conaghan PG, et al. Triamcinolone acetonide extended-release in patients with osteoarthritis and type 2 diabetes: a randomized, phase 2 study. Rheumatology (Oxford). 2018;57(12):2235–41.CrossRefGoogle Scholar
  24. 24.
    Kraus VB, Conaghan PG, Aazami HA, et al. Synovial and systemic pharmacokinetics (PK) of triamcinolone acetonide (TA) following intra-articular (IA) injection of an extended-release microsphere-based formulation (FX006) or standard crystalline suspension in patients with knee osteoarthritis (OA). Osteoarthr Cartil. 2018;26(1):34–42.CrossRefGoogle Scholar
  25. 25.
    Collegium Pharmaceutical Inc. AllerNaze (triamcinolone acetonide nasal spray): US prescribing information. 2009. Accessed 22 Feb 2019.
  26. 26.
    Bodick N, Lufkin J, Willwerth C, et al. An intra-articular, extended-release formulation of triamcinolone acetonide prolongs and amplifies analgesic effect in patients with osteoarthritis of the knee: a randomized clinical trial. J Bone Jt Surg Am. 2015;97(11):877–88.CrossRefGoogle Scholar
  27. 27.
    Conaghan PG, Cohen SB, Berenbaum F, et al. Brief report: a phase IIb trial of a novel extended-release microsphere formulation of triamcinolone acetonide for intraarticular injection in knee osteoarthritis. Arthritis Rheumatol. 2018;70(2):204–11.CrossRefGoogle Scholar
  28. 28.
    Conaghan PG, Hunter DJ, Cohen SB, et al. Effects of a single intra-articular injection of a microsphere formulation of triamcinolone acetonide on knee osteoarthritis pain: a double-blinded, randomized, placebo-controlled, multinational study. J Bone Jt Surg Am. 2018;100(8):666–77.CrossRefGoogle Scholar
  29. 29.
    Spitzer AI, Richmond JC, Kraus VB, et al. Safety and efficacy of repeat administration of triamcinolone acetonide extended-release in osteoarthritis of the knee: a phase 3b, open-label study. Rheumatol Ther. 2019.
  30. 30.
    US Center for Drug Evaluation and Research. Summary review (Zilretta). 2018. Accessed 22 Feb 2019.
  31. 31.
    Henriksen M, Klokker L, Graven-Nielsen T, et al. Association of exercise therapy and reduction of pain sensitivity in patients with knee osteoarthritis: a randomized controlled trial. Arthritis Care Res (Hoboken). 2014;66(12):1836–43.CrossRefGoogle Scholar
  32. 32.
    American Academy of Orthopaedic Surgeons. Treatment of osteoarthritis of the knee: evidence-based guideline, 2nd edn. 2013. Accessed 22 Feb 2019.
  33. 33.
    Hochberg MC, Altman RD, April KT, et al. American College of Rheumatology 2012 recommendations for the use of nonpharmacologic and pharmacologic therapies in osteoarthritis of the hand, hip, and knee. Arthritis Care Res (Hoboken). 2012;64(4):465–74.CrossRefGoogle Scholar
  34. 34.
    Radnovich R, Scott D, Patel AT, et al. Cryoneurolysis to treat the pain and symptoms of knee osteoarthritis: a multicenter, randomized, double-blind, sham-controlled trial. Osteoarthr Cartil. 2017;25(8):1247–56.CrossRefGoogle Scholar
  35. 35.
    Dhillon MS, Patel S, John R. PRP in OA knee—update, current confusions and future options. SICOT-J. 2017;3:27.CrossRefGoogle Scholar
  36. 36.
    Glynn LG, Mustafa A, Casey M, et al. Platelet-rich plasma (PRP) therapy for knee arthritis: a feasibility study in primary care. Pilot Feasibility Study. 2018;4:93.CrossRefGoogle Scholar
  37. 37.
    Dworkin RH, Peirce-Sandner S, Turk DC, et al. Outcome measures in placebo-controlled trials of osteoarthritis: responsiveness to treatment effects in the REPORT database. Osteoarthr Cartil. 2011;19(5):483–92.CrossRefGoogle Scholar
  38. 38.
    Bristol-Myers Squibb. KENALOG-40 injection (triamcinolone acetonide injectable suspension): US prescribing information. 2018. Accessed 22 Feb 2019.

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.SpringerAucklandNew Zealand

Personalised recommendations