OBJECTIVE: To evaluate the efficacy and safety of an intraarticular injection of Cingal (Anika Therapeutics, Inc., Bedford, MA) compared with Monovisc (Anika Therapeutics, Inc., Bedford, MA) or saline for the treatment of knee osteoarthritis. DESIGN: This multicenter, double-blind, saline-controlled clinical trial randomized subjects with knee osteoarthritis (Kellgren-Lawrence grades I-III) to a single injection of Cingal (4 mL, 88 mg hyaluronic acid [HA] plus 18 mg triamcinolone hexacetonide [TH]), Monovisc (4 mL, 88 mg HA), or saline (4 mL, 0.9%). The primary efficacy outcome was change in WOMAC (Western Ontario and McMaster Universities Arthritis Index) Pain Score through 12 weeks with Cingal versus saline. Secondary outcomes included Patient and Evaluator Global Assessments, OMERACT-OARSI Responder index, and WOMAC Total, Stiffness, and Physical Function scores through 26 weeks. RESULTS: A total of 368 patients were treated (Cingal, n = 149; Monovisc, n = 150; saline, n = 69). Cingal improvement from baseline was significantly greater than saline through 12 weeks ( P = 0.0099) and 26 weeks ( P = 0.0072). WOMAC Pain was reduced by 70% at 12 weeks and by 72% at 26 weeks with Cingal. Significant improvements were found in most secondary endpoints for pain and function at most time points through 26 weeks. At 1 and 3 weeks, Cingal was significantly better than Monovisc for most endpoints; Cingal and Monovisc were similar from 6 weeks through 26 weeks. A low incidence of related adverse events was reported. CONCLUSIONS: Cingal provides immediate and long-term relief of osteoarthritis-related pain, stiffness, and function, significant through 26 weeks compared to saline. Cingal had similar immediate advantages compared with HA alone, while showing benefit comparable to HA at 6 weeks and beyond.

ARTIMED Niepubliczny Zakład Opieki Zdrowotnej Kielce Poland

Consultative Outpatients' Medical Office for Rheumatologic Diseases Sofia Bulgaria

Department of Orthopaedics Uzsoki Hospital Budapest Hungary

Dynastat Biostatistical Consulting Austin TX USA

Health Center of Downtown Lipotvaros Orthopedic Outpatient Clinic Budapest Hungary

Jutrix Medical LLC Kecskémet Hungary

Medical Plus s r o Uherske Hradiste Czech Republic

NZOZ Medi SPATZ Gilwice Poland

Semmelweis Egyetem Orthopaedic Clinic Budapest Hungary

Zobrazit více v PubMed

Zhang Y, Jordan JM. Epidemiology of osteoarthritis. Clin Geriatr Med. 2010;26:355-69. PubMed PMC

Kotlarz H, Gunnarsson CL, Fang H, Rizzo JA. Insurer and out-of-pocket costs of osteoarthritis in the US: evidence from national survey data. Arthritis Rheum. 2009;60:3546-53. PubMed

Conaghan PG, Kloppenburg M, Schett G, Bijlsma JW; EULAR Osteoarthritis Ad Hoc Committee. Osteoarthritis research priorities: a report from a EULAR ad hoc expert committee. Ann Rheum Dis. 2014;73:1442-5. PubMed

Moreland LW. Intra-articular hyaluronan (hyaluronic acid) and hylans for the treatment of osteoarthritis: mechanism of action. Arthritis Res Ther. 2003;5:54-67. PubMed PMC

Stitik TP, Levy JA. Viscosupplementation (biosupplementation) for osteoarthritis. Am J Phys Med Rehabil. 2006;85(Suppl):S32-S50. PubMed

Chevalier X, Jerosch J, Goupille P, van Dijk N, Luyten FP, Scott DL, et al. Single, intra-articular treatment with 6 ml hylan G-F 20 in patients with symptomatic primary osteoarthritis of the knee: a randomised, multicentre, double-blind, placebo controlled trial. Ann Rheum Dis. 2010;69:113-9. PubMed PMC

Murphy L, Schwartz TA, Helmick CG, Renner JB, Tudor G, Koch G, et al. Lifetime risk of symptomatic knee osteoarthritis. Arthritis Rheum. 2008;59:1207-13. PubMed PMC

Kurtz S, Ong K, Lau E, Mowat F, Halpern M. Projections of primary and revision hip and knee arthroplasty in the United States from 2005 to 2030. J Bone Joint Surg Am. 2007;89:780-5. PubMed

McAlindon TE, Bannuru RR, Sullivan MC, Arden NK, Berenbaum F, Bierma-Zeinstra SM, et al. OARSI guidelines for the non-surgical management of knee osteoarthritis. Osteoarthritis Cartilage. 2014;22:363-88. PubMed

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;(2):CD005328. PubMed

Bannuru RR, Natov NS, Dasi UR, Schmid CH, McAlindon TE. Therapeutic trajectory following intra-articular hyaluronic acid injection in knee osteoarthritis—meta-analysis. Osteoarthritis Cartilage. 2011;19:611-9. PubMed

de Campos GC, Rezende MU, Pailo AF, Frucchi R, Camargo OP. Adding triamcinolone improves viscosupplementation: a randomized clinical trial. Clin Orthop Relat Res. 2013;471:613-20. PubMed PMC

Ozturk C, Atamaz F, Hepguler S, Argin M, Arkun R. The safety and efficacy of intraarticular hyaluronan with/without corticosteroid in knee osteoarthritis: 1-year, single-blind, randomized study. Rheumatol Int. 2006;26:314-9. PubMed

Caborn D, Rush J, Lanzer W, Parenti D, Murray C. A randomized, single-blind comparison of the efficacy and tolerability of hylan G-F 20 and triamcinolone hexacetonide in patients with osteoarthritis of the knee. J Rheumatol. 2004;31:333-43. PubMed

Kellgren JH, Lawrence JS. Radiological assessment of osteo-arthrosis. Ann Rheum Dis. 1957;16:494-502. PubMed PMC

Bellamy N, Buchanan WW, Goldsmith CH, Campbell J, Stitt LW. Validation study of WOMAC: a health status instrument for measuring clinically important patient relevant outcomes to antirheumatic drug therapy in patients with osteoarthritis of the hip or knee. J Rheumatol. 1988;15:1833-40. PubMed

Pham T, Van Der Heijde D, Lassere M, Altman RD, Anderson JJ, Bellamy N, et al. Outcome variables for osteoarthritis clinical trials: the OMERACT-OARSI set of responder criteria. J Rheumatol. 2003;30:1648-54. PubMed

Fransen M, Edmonds J. Reliability and validity of the EuroQol in patients with osteoarthritis of the knee. Rheumatology (Oxford). 1999;38:807-13. PubMed

Strand V, Baraf HS, Lavin PT, Lim S, Hosokawa H. A multicenter, randomized controlled trial comparing a single intra-articular injection of Gel-200, a new cross-linked formulation of hyaluronic acid, to phosphate buffered saline for treatment of osteoarthritis of the knee. Osteoarthritis Cartilage. 2012;20:350-6. PubMed

Karlsson J, Sjogren LS, Lohmander LS. Comparison of two hyaluronan drugs and placebo in patients with knee osteoarthritis. A controlled, randomized, double-blind, parallel-design multicentre study. Rheumatology. 2002;41:1240-8. PubMed

Neustadt D, Caldwell J, Bell M, Wade J, Gimbel J. Clinical effects of intraarticular injection of high molecular weight hyaluronan (Orthovisc) in osteoarthritis of the knee: a randomized, controlled, multicenter trial. J Rheumatol. 2005;32:1928-36. PubMed

Pyne D, Ioannou Y, Mootoo R, Bhanji A. Intra-articular steroids in knee osteoarthritis: a comparative study of triamcinolone hexacetonide and methylprednisolone acetate. Clin Rheumatol. 2004;23:116-20. PubMed

Frias G, Caracuel MA, Escudero A, Rumbao J, Perez-Gujo V, del Carmen CM, et al. Assessment of the efficacy of joint lavage versus joint lavage plus corticoids in patients with osteoarthritis of the knee. Curr Med Res Opin. 2004;20:861-7. PubMed

Dworkin RH, Turk DC, McDermott MP, Peirce-Sandner S, Burke LB, Cowan P, et al. Interpreting the clinical importance of group differences in chronic pain clinical trials: IMMPACT recommendations. Pain. 2009;146:238-44. PubMed

Rosseland LA, Helgesen KG, Breivik H, Stubhaug A. Moderate-to-severe pain after knee arthroscopy is relieved by intraarticular saline: a randomized controlled trial. Anesth Analg. 2004;98:1546-51. PubMed

What We Should Expect from an Innovative Intra-Articular Hyaluronic Acid Product: Expert Opinion Based on a Comprehensive Review of the Literature

An Effective Translation: The Development of Hyaluronan-Based Medical Products From the Physicochemical, and Preclinical Aspects