Sustained efficacy of a single intra-articular dose of FX006 in a rat model of repeated localized knee arthritis

Osteoarthritis and Cartilage

Volumn 23, Issue 1, 2015, Pages 151-160

  Kumar, A ^a   Bendele, A M ^b   Blanks, R C ^c   Bodick, N ^a  

^a Flexion Therapeutics   (United States)

^b BolderPATH   (United States)

^c Ardelyx Inc   (United States)

Author keywords

Animal model; Corticosteroids; Intra articular; Joint protection; Sustained release; Synovitis

Indexed keywords

CORTICOSTERONE; MICROSPHERE; POLYGLACTIN; TRIAMCINOLONE ACETONIDE; GLUCOCORTICOID; LACTIC ACID; POLYGLYCOLIC ACID; POLYLACTIC ACID-POLYGLYCOLIC ACID COPOLYMER;

ANALGESIC ACTIVITY; ANIMAL EXPERIMENT; ANIMAL MODEL; AREA UNDER THE CURVE; ARTICLE; CARTILAGE; CONTROLLED STUDY; CORTICOSTERONE BLOOD LEVEL; DOSE RESPONSE; DRUG BLOOD LEVEL; DRUG EFFICACY; GAIT DISORDER; HISTOLOGY; IC50; KNEE ARTHRITIS; MALE; MAXIMUM PLASMA CONCENTRATION; NONHUMAN; PANNUS; PLASMA CONCENTRATION-TIME CURVE; RAT; SINGLE DRUG DOSE; SUSTAINED DRUG RELEASE; SYNOVITIS; ANIMAL; ARTHRITIS, EXPERIMENTAL; EVALUATION STUDY; INTRAARTICULAR DRUG ADMINISTRATION; KNEE; LEWIS RAT;

ANIMALS; ARTHRITIS, EXPERIMENTAL; GLUCOCORTICOIDS; INJECTIONS, INTRA-ARTICULAR; KNEE JOINT; LACTIC ACID; MALE; MICROSPHERES; POLYGLYCOLIC ACID; RATS; RATS, INBRED LEW; SYNOVITIS; TRIAMCINOLONE ACETONIDE;

EID: 84919400413     PISSN: 10634584     EISSN: 15229653     Source Type: Journal    
DOI: 10.1016/j.joca.2014.09.019     Document Type: Article

References (50)

1. Benito M.J., Veale D.J., FitzGerald O., van den Berg W.B., Bresnihan B. Synovial tissue inflammation in early and late osteoarthritis. Ann Rheum Dis 2005, 64:1263-1267.
2. Sellam J., Berenbaum F. The role of synovitis in pathophysiology and clinical symptoms of osteoarthritis. Nat Rev Rheumatol 2010, 6:625-635.
3. Wenham C.Y.J., Conaghan P.G. The role of synovitis in osteoarthritis. Ther Adv Musculoskelet Dis 2010, 2:349-359.
4. Myers S.L., Brandt K.D., Ehlich J.W., Braunstein E.M., Shelbourne K.D., Heck D.A., et al. Synovial inflammation in patients with early osteoarthritis of the knee. JRheumatol 1990, 17:1662-1669.
5. Smith M.D., Triantafillou S., Parker A., Youssef P.P., Coleman M. Synovial membrane inflammation and cytokine production in patients with early osteoarthritis. JRheumatol 1997, 24:365-371.
6. Schumacher H.R. Synovial inflammation, crystals and osteoarthritis. JRheumatol 1995, 22:101-103.
7. Gordon G.V., Villanueva T., Schumacher H.R., Gohel V. Autopsy study correlating degree of osteoarthritis, synovitis and evidence of articular calcification. JRheumatol 1984, 11:681-686.
8. Fernandez-Madrid F., Karvonen R.L., Teitge R.A., Miller P.R., An T., Negendank W.G. Synovial thickening detected by MR imaging in osteoarthritis of the knee confirmed by biopsy as synovitis. Magn Reson Imaging 1995, 13:177-183.
9. Hill C.L., Hunter D.J., Niu J., Clancy M., Guermazi A., Genant H., et al. Synovitis detected on magnetic resonance imaging and its relation to pain and cartilage loss in knee osteoarthritis. Ann Rheum Dis 2007, 66:1599-1603.
10. Ayral X., Pickering E.H., Woodworth T.G., Mackillop N., Dougados M. Synovitis: a potential predictive factor of structural progression of medial tibiofemoral knee osteoarthritis - results of a 1 year longitudinal arthroscopic study in 422 patients. Osteoarthritis Cartilage 2005, 13:361-367.
11. Pelletier J.P., Raynauld J.P., Abram F., Haraoui B., Choquette D., Martel-Pelletier J. Anew non-invasive method to assess synovitis severity in relation to symptoms and cartilage volume loss in knee osteoarthritis patients using MRI. Osteoarthritis Cartilage 2008, 16(Suppl 3):S8-S13.
12. Lohmander L.S., Felson D. Can we identify a 'high risk' patient profile to determine who will experience rapid progression of osteoarthritis?. Osteoarthritis Cartilage 2004, 12(Suppl A):S49-S52.
13. Loeuille D., Chary-Valckenaere I., Champigneulle J., Rat A.-C., Toussaint F., Pinzano-Watrin A., et al. Macroscopic and microscopic features of synovial membrane inflammation in the osteoarthritic knee: correlating magnetic resonance imaging findings with disease severity. Arthritis Rheum 2005, 52:3492-3501.
14. Roemer F.W., Guermazi A., Felson D.T., Niu J., Nevitt M.C., Crema M.D., et al. Presence of MRI-detected joint effusion and synovitis increases the risk of cartilage loss in knees without osteoarthritis at 30-month follow-up: the MOST study. Ann Rheum Dis 2011, 10.1136/ard.2011.150243.
15. Jones A.R., Flannery C.R. Bioregulation of lubricin expression by growth factors and cytokines. Eur Cell Mater 2007, 13:40-45.
16. Elsaid K.A., Jay G.D., Chichester C.O. Reduced expression and proteolytic susceptibility of lubricin/superficial zone protein may explain early elevation in the coefficient of friction in the joints of rats with antigen-induced arthritis. Arthritis Rheum 2007, 56:108-116.
17. Probert L., Plows D., Kontogeorgos G., Kollias G. The type I interleukin-1 receptor acts in series with tumor necrosis factor (TNF) to induce arthritis in TNF-transgenic mice. Eur J Immunol 1995, 25:1794-1797.
18. van de Loo F.A., Joosten L.A., van Lent P.L., Arntz O.J., van den Berg W.B. Role of interleukin-1, tumor necrosis factor alpha, and interleukin-6 in cartilage proteoglycan metabolism and destruction. Effect of in situ blocking in murine antigen- and zymosan-induced arthritis. Arthritis Rheum 1995, 38:164-172.
19. Pelletier J.P., Faure M.P., DiBattista J.A., Wilhelm S., Visco D., Martel-Pelletier J. Coordinate synthesis of stromelysin, interleukin-1, and oncogene proteins in experimental osteoarthritis. An immunohistochemical study. Am J Pathol 1993, 142:95-105.
20. Okada Y., Shinmei M., Tanaka O., Naka K., Kimura K., Nakanishi I., et al. Localization of matrix metalloproteinase 3 (stromelysin) in osteoarthritic cartilage and synovium. Lab Invest 1992, 66:680-690.
21. Clark I.M., Powell L.K., Ramsey S., Hazleman B.L., Cawston T.E. The measurement of collagenase, tissue inhibitor of metalloproteinases (TIMP), and collagenase-TIMP complex in synovial fluids from patients with osteoarthritis and rheumatoid arthritis. Arthritis Rheum 1993, 36:372-379.
22. Vankemmelbeke M.N., Holen I., Wilson A.G., Ilic M.Z., Handley C.J., Kelner G.S., et al. Expression and activity of ADAMTS-5 in synovium. Eur J Biochem 2001, 268:1259-1268.
23. Bellamy N., Campbell J., Robinson V., Gee T., Bourne R., Wells G. Intraarticular corticosteroid for treatment of osteoarthritis of the knee. Cochrane Database Syst Rev 2006, Issue 2. Art No.: CD005328. 10.1002/1465 1858.
24. Bjordal J.M., Johnson M.I., Lopes-Martins R.A., Bogen B., Chow R., Ljunggren A.E. Short-term efficacy of physical interventions in osteoarthritic knee pain. A systematic review and meta-analysis of randomized placebo-controlled trials. BMC Musculoskelet Disord 2007, 8:51-65.
25. Hepper C.T., Halvorson J.J., Duncan S.T., Gregory A.J.M., Dunn W.R., Spindler K.P. The efficacy and duration of intra-articular corticosteroid injection for knee osteoarthritis: a systematic review of Level I studies. JAm Acad Orthop Surg 2009, 17:638-646.
26. Anderson J.M., Shive M.S. Biodegradation and biocompatibility of PLA and PLGA microspheres. Adv Drug Deliv Rev 1997, 28:5-24.
27. Esser R.E., Stimpson S.A., Cromartie W.J., Schwab J.H. Reactivation of streptococcal cell wall-induced arthritis by homologous and heterologous cell wall polymers. Arthritis Rheum 1985, 28:1402-1411.
28. Schwab J.H., Anderle S.K., Brown R.R., Dalldorf F.G., Thompson R.C. Pr- and anti-inflammatory roles of interleukin-1 in recurrence of bacterial cell wall-induced arthritis in rats. Infect Immun 1991, 59:4436-4442.
29. Derendorf H., Möllmann H., Gruner A., Haack D., Gyselby G. Pharmacokinetics and pharmacodynamics of glucocorticoid suspensions after intra-articular administration. Clin Pharmacol Ther 1986, 39:313-317.
30. Rohatagi S., Hochhaus G., Mollmann H., Barth J., Galia E., Erdmann M., et al. Pharmacokinetic and pharmacodynamics evaluation of triamcinolone acetonide after intravenous, oral, and inhaled administration. JClin Pharmacol 1995, 35:1187-1193.
31. Abramson S.B., Attur M. Developments in the scientific understanding of osteoarthritis. Arthritis Res Ther 2009, 11:227.
32. Wang Q., Rozelle A.L., Lepus C.M., Scanzello C.R., Song J.J., Larsen D.M., et al. Identification of a central role for complement in osteoarthritis. Nat Med 2011, 10.1038/nm.2543.
33. DiBattista J.A., Martel-Pelletier J., Wosu L.O., Sandor T., Antakly T., Pelletier J.P. Glucocorticoid receptor mediated inhibition of interleukin-1 stimulated neutral metalloprotease synthesis in normal human chondrocytes. JClin Endocrinol Metab 1991, 72:316-326.
34. Pelletier J.P., Cloutier J.M., Martel-Pelletier J. Invitro effects of NSAIDs and corticosteroids on the synthesis and secretion of interleukin 1 by human osteoarthritic synovial membranes. Agents Actions Suppl 1993, 39:181-193.
35. Panagides J., Landes M.J., Sloboda A.E. Destruction of articular cartilage by arthritic synovium invitro: mechanism of breakdown and effect of indomethacin and prednisolone. Agents Actions 1980, 10:22-30.
36. Steinberg J., Tsukamoto S., Sledge C.B. Atissue culture model of cartilage breakdown in rheumatoid arthritis. III. Effects of antirheumatic drugs. Arthritis Rheum 1979, 22:877-885.
37. Lu Y.C.S., Evans C.H., Grodzinsky A.J. Effects of short-term glucocorticoid treatment on changes in cartilage matrix degradation and chondrocyte gene expression induced by mechanical injury and inflammatory cytokines. Arthritis Res Ther 2011, 13:R142. 10.1186/ar3456.
38. Pelletier J.P., Martel-Pelletier J. Protective effects of corticosteroids on cartilage lesions and osteophyte formation in the Pond-Nuki dog model of osteoarthritis. Arthritis Rheum 1989, 32:181-193.
39. Pelletier J.P., Mineau F., Raynauld J.P., Woessner J.F., Gunja-Smith Z., Martel-Pelletier J. Intraarticular injections with methylprednisolone acetate reduce osteoarthritic lesions in parallel with chondrocyte stromelysin synthesis in experimental osteoarthritis. Arthritis Rheum 1994, 37:414-423.
40. Pelletier J.P., DiBattista J.A., Raynauld J.P., Wilhelm S., Martel-Pelletier J. The invivo effects of intraarticular corticosteroid injections on cartilage lesions, stromelysin, interleukin-1, and oncogene protein synthesis in experimental osteoarthritis. Lab Invest 1995, 72:578-586.
41. Joosten L.A., Helsen M.M., van den Berg W.B. Protective effect of rimexolone on cartilage damage in arthritic mice: a comparative study with triamcinolone hexacetonide. Agents Actions 1990, 31:135-142.
42. Larsson E., Harris H.E., Larsson A., Mansson B., Saxne T., Klareskog L. Corticosteroid treatment of experimental arthritis retards cartilage destruction as determined by histology and serum COMP. Rheumatology (Oxford) 2004, 43:428-434.
43. Williams J.M., Brandt K.D. Triamcinolone hexacetonide protects against fibrillation and osteophyte formation following chemically induced articular cartilage damage. Arthritis Rheum 1985, 28:1267-1274.
44. Chandler G.N., Wright V. Deleterious effect of intra-articular hydrocortisone. Lancet 1958, 2:661-663.
45. Mankin H.J., Conger K.A. The acute effects of intra-articular hydrocortisone on articular cartilage in rabbits. JBone Joint Surg Am 1966, 48:1383-1388.
46. Chunekamrai S., Krook L.P., Lust G., Maylin G.A. Changes in articular cartilage after intra-articular injections of methylprednisolone acetate in horses. Am J Vet Res 1989, 50:1733-1741.
47. Habib G.S., Saliba W., Nashashibi M. Local effects of intra-articular corticosteroids. Clin Rheumatol 2010, 29:347-356.
48. Raynauld J.-P., Buckland-Wright C., Ward R., Choquette D., Haraoui B., Martel-Pelletier J., et al. Safety and efficacy of long-term intraarticular steroid injections in osteoarthritis of the knee. Arthritis Rheum 2003, 48:370-377.
49. Bodick N., Lufkin J., Willwerth C., Blanks R.C., Inderjeeth C.A., Kumar A., et al. FX006 prolongs the residency of triamcinolone acetonide in the synovial tissues of patients with knee osteoarthritis. Osteoarthritis and Cartilage 2013, 21:S144-S145. #267 (abstr).
50. Bodick N., Lufkin J., Willwerth C., Lachance P., Jasey G., Gupta A., et al. Arandomized, double-blind, dose ranging study comparing FX006, an intra-articular (IA) sustained-release formulation of triamcinolone acetonide (TCA), to an approved injectable suspension of TCA in patients with osteoarthritis of the knee. Arthritis Rheum 2013, 65:S1138. #2668 (abstr).