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

Julia Paik, Sean T Duggan, Susan J Keam, Julia Paik, Sean T Duggan, Susan J Keam

Abstract

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.

Conflict of interest statement

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

References

    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):2163–2196. doi: 10.1016/S0140-6736(12)61729-2.
    1. 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.
    1. 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):415–422. doi: 10.1016/j.joca.2007.12.017.
    1. 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. doi: 10.1136/bmj.d1165.
    1. Sellam J, Berenbaum F. The role of synovitis in pathophysiology and clinical symptoms of osteoarthritis. Nat Rev Rheumatol. 2010;6(11):625–635. doi: 10.1038/nrrheum.2010.159.
    1. 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.
    1. Juni P, Hari R, Rutjes AW, et al. Intra-articular corticosteroid for knee osteoarthritis. Cochrane Database Syst Rev. 2015(10):CD005328.
    1. 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):351–355. doi: 10.1016/j.arth.2015.08.024.
    1. da Costa BR, Hari R, Juni P. Intra-articular corticosteroids for osteoarthritis of the knee. JAMA. 2016;316(24):2671–2672. doi: 10.1001/jama.2016.17565.
    1. Habib GS. Systemic effects of intra-articular corticosteroids. Clin Rheumatol. 2009;28(7):749–756. doi: 10.1007/s10067-009-1135-x.
    1. Flexion Therapeutics Inc. ZILRETTA (triamcinolone acetonide extended-release injectable suspension): US prescribing information. 2017. . Accessed 22 Feb 2019.
    1. US Center for Drug Evaluation and Research. Non-clinical review(s) (Zilretta). 2017. . Accessed 22 Feb 2019.
    1. Anderson JM, Shive MS. Biodegradation and biocompatibility of PLA and PLGA microspheres. Adv Drug Deliv Rev. 1997;28(1):5–24. doi: 10.1016/S0169-409X(97)00048-3.
    1. Flexion Therapeutics Inc. ZILRETTA® (triamcinolone acetonide extended-release injectable suspension). 2019. . Accessed 22 Feb 2019.
    1. 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):557–563. doi: 10.1016/0142-9612(89)90063-X.
    1. 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. 10.1007/s12325-019-0878-2.
    1. Scherer J, Rainsford KD, Kean CA, et al. Pharmacology of intra-articular triamcinolone. Inflammopharmacology. 2014;22(4):201–217. doi: 10.1007/s10787-014-0205-0.
    1. US Center for Drug Evaluation and Research. Clinical pharmacology and biopharmaceutics review (Zilretta). 2017. . Accessed 22 Feb 2019.
    1. 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. doi: 10.1177/2325967115581163.
    1. 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):151–160. doi: 10.1016/j.joca.2014.09.019.
    1. 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.
    1. 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):475–498. doi: 10.1007/s40744-018-0125-3.
    1. 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):2235–2241. doi: 10.1093/rheumatology/key265.
    1. 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. doi: 10.1016/j.joca.2017.10.003.
    1. Collegium Pharmaceutical Inc. AllerNaze (triamcinolone acetonide nasal spray): US prescribing information. 2009. . Accessed 22 Feb 2019.
    1. 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):877–888. doi: 10.2106/JBJS.N.00918.
    1. 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):204–211. doi: 10.1002/art.40364.
    1. 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):666–677. doi: 10.2106/JBJS.17.00154.
    1. 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. 10.1007/s40744-019-0140-z.
    1. US Center for Drug Evaluation and Research. Summary review (Zilretta). 2018. . Accessed 22 Feb 2019.
    1. 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):1836–1843. doi: 10.1002/acr.22375.
    1. American Academy of Orthopaedic Surgeons. Treatment of osteoarthritis of the knee: evidence-based guideline, 2nd edn. 2013. . Accessed 22 Feb 2019.
    1. 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):465–474. doi: 10.1002/acr.21596.
    1. 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):1247–1256. doi: 10.1016/j.joca.2017.03.006.
    1. Dhillon MS, Patel S, John R. PRP in OA knee—update, current confusions and future options. SICOT-J. 2017;3:27. doi: 10.1051/sicotj/2017004.
    1. 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. doi: 10.1186/s40814-018-0288-2.
    1. 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):483–492. doi: 10.1016/j.joca.2011.02.020.
    1. Bristol-Myers Squibb. KENALOG-40 injection (triamcinolone acetonide injectable suspension): US prescribing information. 2018. . Accessed 22 Feb 2019.

Source: PubMed

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