A Pooled Analysis of Two Multicenter, Randomized Controlled Trials of a Single Intra-articular Injection of Gel-200 for Treatment of Osteoarthritis of the Knee

Junko Takamura, Takayuki Seo, Vibeke Strand, Junko Takamura, Takayuki Seo, Vibeke Strand

Abstract

Background and objective: To perform an integrated analysis of 2 randomized controlled trials (RCTs) to assess the efficacy and safety of a single intra-articular injection of Gel-200 compared with phosphate buffered saline (PBS) for treatment of osteoarthritis of the knee.

Methods: Data from the intention-to-treat (ITT) populations of both RCTs were pooled for this integrated analysis. Mean changes from baseline in Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain subscores were assessed using a longitudinal model; treatment differences were compared between intra-articular Gel-200 and PBS injections. Analyses included secondary outcome measures repeated at individual time points. The safety populations of both RCTs were pooled for an integrated safety analysis to compare adverse events (AEs).

Results: The pooled ITT population included 1184 subjects (649 Gel-200; 535 PBS); demographic characteristics were similar between treatment groups. Mean improvements in pain subscores from baseline to week 12 were -24.7 mm in Gel-200 and -21.8 mm in PBS groups, a statistically significant treatment group difference of -2.9 mm (P = .047). From weeks 3 to 26, mean improvements from baseline in pain subscores were -23.8 mm with Gel-200 and -20.8 mm with PBS; this treatment group difference of -3.0 mm was statistically significant (P = .017). The rate of AEs was similar between Gel-200 and PBS treatment groups.

Conclusion: This integrated analysis demonstrated the efficacy of a single intra-articular injection of Gel-200 compared with PBS for treatment of osteoarthritis of the knee over 26 weeks without major safety concerns.

Trial registration: NCT00449696 and NCT00450112.

Keywords: Gel-200; Osteoarthritis; cross-linked HA; intra-articular; knee.

Conflict of interest statement

Declaration Of Conflicting Interests:The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: J.T. and T.S. are employees of Seikagaku Corporation. J.T. is listed as an inventor of a hyaluronate product. V.S. has served as a consultant to Seikagaku Corporation as well as Bioventus, Carbylan, Eupraxia, Flexion, Iroko, and Sanofi.

Figures

Figure 1.
Figure 1.
Overview of clinical studies.

References

    1. Peat G, McCarney R, Croft P. Knee pain and osteoarthritis in older adults: a review of community burden and current use of primary health care. Ann Rheum Dis. 2001;60:91–97.
    1. Altman RD, Manjoo A, Fierlinger A, Niazi F, Nicholls M. The mechanism of action for hyaluronic acid treatment in the osteoarthritic knee: a systematic review. BMC Musculoskelet Disord. 2015;16:1–10.
    1. Migliore A, Procopio S. Effectiveness and utility of hyaluronic acid in osteoarthritis. Clin Cases Miner Bone Metab. 2015;12:31–33.
    1. Goldberg VM, Goldberg L. Intra-articular hyaluronans: the treatment of knee pain in osteoarthritis. J Pain Res. 2010;3:51–56.
    1. Strand V, Conaghan PG, Lohmander LS, et al. An integrated analysis of five double-blind, randomized controlled trials evaluating the safety and efficacy of a hyaluronan product for intra-articular injection in osteoarthritis of the knee. Osteoarthritis Cartilage. 2006;14:859–866.
    1. Trojian TH, Concoff AL, Joy SM, Hatzenbuehler JR, Saulsberry WJ, Coleman CI. AMSSM scientific statement concerning viscosupplementation injections for knee osteoarthritis: importance for individual patient outcomes. BMJ Sports Med. 2016;50:84–92.
    1. American Academy of Orthopaedic Surgeons. Treatment of Osteoarthritis of the Knee Evidence-Based Guideline. 2nd ed. Rosemont, IL: American Academy of Orthopaedic Surgeons; 2013, . Accessed September 22, 2015.
    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. 2012;64:465–474.
    1. Cooper C, Rannou F, Richette P, et al. Use of intra-articular hyaluronic acid in the management of knee osteoarthritis in clinical practice. Arthritis Care Res. 2017;69:1287–1296.
    1. Strand V, Baraf HSB, 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;20:350–356.
    1. Strand V, Baraf HSB, Lavin PT, Lim S, Hosokawa H. Effectiveness and safety of a multicenter extension and retreatment trial of Gel-200 in patients with knee. Osteoarthritis Cartilage. 2012;3:297–304.
    1. Strand V, Lim S, Takamura J. Evidence for safety of retreatment with a single intra-articular injection of Gel-200 for treatment of osteoarthritis of the knee from the double-blind pivotal and open-label retreatment clinical trials. BMC Musculoskelet Disord. 2016;17:240–247.
    1. Food Drug Administration. Summary of safety and effectiveness data, Gel-One®—P080020/S020; 2016, . Accessed June 19, 2017.
    1. Chevalier X, Jerosch J, Goupille P, 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;69:113–119.
    1. Food Drug Administration. Summary of safety and effectiveness data, MonoviscTM—P090031; 2014, . Accessed June 19, 2017.
    1. Dougados M, Leclaire P, van der Heijde D, Bloch DA, Bellamy N, Altman RD. Response criteria for clinical trials on osteoarthritis of the knee and hip: a report of the Osteoarthritis Research Society International Standing Committee for Clinical Trials response criteria initiative. Osteoarthritis Cartilage. 2000;8:395–403.
    1. Pham T, van der Heijde D, Lassare M, et al. Outcome variables for osteoarthritis clinical trials: the OMERACT-OARSI set of responder criteria. J Rheumatol. 2003;30:1648–1654.
    1. Pham T, van der Heijde D, Altman RD, et al. OMERACT-OARSI initiative: Osteoarthritis Research Society International set of responder criteria for osteoarthritis clinical trials revisited. Osteoarthritis Cartilage. 2004;12:389–399.
    1. Tubach F, Ravaud P, Baron G, et al. Evaluation of clinically relevant changes in patient reported outcomes in knee and hip osteoarthritis: the minimal clinically important improvement. Ann Rheum Dis. 2005;64:29–33.
    1. Strand V, Kelman A. Outcome measures in osteoarthritis: randomized controlled trials. Curr Rheumatol Rep. 2004;6:20–30.
    1. Strand V, Boers M, Inzerada L, et al. It’s good to feel better but it’s better to feel good and even better to feel good as soon as possible for as long as possible: response criteria and the importance of change at OMERACT 10. J Rheumatol. 2011;38:1720–1727.
    1. Bellamy N, Campbell J, Robinson V, Gee T, Bourne R, Weels G. Viscosupplementation for the treatment of osteoarthritis of the knee. Cochrane Database Syst Rev. 2006;2:CD005321.
    1. Arrich J, Piribauer F, Mad P, Schmid D, Klaushofer K, Mullner M. Intra-articular hyaluronic acid for the treatment of osteoarthritis of the knee: systematic review and meta-analysis. CMAJ. 2005;172:1039–1043.
    1. Rutjes AW, Jüni P, da Costa BR, Trelle S, Nüesch E, Reichenbach S. Viscosupplementation for osteoarthritis of the knee: a systematic review and meta-analysis. Ann Intern Med. 2012:157:180–191.

Source: PubMed

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