Original Research

Real-World Evidence for Safety and Effectiveness of Repeated Courses of Hyaluronic Acid Injections on the Time to Knee Replacement Surgery

Publish date: July 24, 2018

Vinod Dasa, MD

Sooyeol Lim, MSc, MBA

Peter Heeckt, MD, PhD

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TAKE-HOME POINTS

Repeated courses of treatment with HA are safe and are associated with the delay of TKR for up to 3 years.
HA treatment should be considered an important clinical treatment option for patients with knee OA.
Repeated courses of treatment with HA are safe.
Repeated courses of HA treatment pose no greater safety risk than a single course of HA treatment.
Additional research is needed to evaluate the effects of repeated HA courses on delaying TKR beyond a 3-year period.

References

Murphy L, Helmick CG. The impact of osteoarthritis in the United States: a population-health perspective. Am J Nurs. 2012;112(3 Suppl 1):S13-S19.
Arnold W, Fullerton DS, Holder S, May CS. Viscosupplementation: managed care issues for osteoarthritis of the knee. J Manag Care Pharm. 2007;13(4 Suppl):S3-S19.
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(9):859-866.
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(5):350-356.
Strand V, McIntyre LF, Beach WR, Miller LE, Block JE. Safety and efficacy of US-approved viscosupplements for knee osteoarthritis: a systematic review and meta-analysis of randomized, saline-controlled trials. J Pain Res. 2015;8:217-228.
Bannuru RR, Schmid CH, Kent DM, Vaysbrott EE, Wong JB, McAlindon TE. Comparative effectiveness of pharmacologic interventions for knee osteoarthritis: a systematic review and network meta-analysis. Ann Intern Med. 2015;162(1):46-54.
Mandl LA, Losina E. Relative efficacy of knee osteoarthritis treatments: are all placebos created equal? Ann Intern Med. 2015;162(1):71-72.
Kusayama Y, Akamatsu Y, Kumagai K, Kobayashi H, Aratake M, Saito T. Changes in synovial fluid biomarkers and clinical efficacy of intra-articular injections of hyaluronic acid for patients with knee osteoarthritis. J Exp Orthop. 2014;1(1):16. doi:10.1186/s40634-014-0016-7.
Kaneko K, Higuchi C, Kunugiza Y, et al. Hyaluronan inhibits BMP-induced osteoblast differentiation. FEBS Lett. 2015;589(4):447-454. doi:10.1016/j.febslet.2014.
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;16:321. doi:10.1186/s12891-015-0775-z.
Waddell DD, Bricker DC. Total knee replacement delayed with hylan G-F 20 use in patients with grade IV osteoarthritis. J Manag Care Pharm. 2007;13(2):113-121.
Khan T, Nanchanatt G, Farber K, Jan S. Analysis of the effectiveness of hyaluronic acid in prevention of total knee replacement in osteoarthritis patients. J Manag Care Pharm. 2014;20:S49.
Abbott T, Altman RD, Dimeff R, et al. Do hyaluronic acid injections delay total knee replacement surgery? Arthritis Rheum. 2013;65(Suppl 10):2139.
Altman R, Lim S, Steen R, Dasa V. Intra-articular hyaluronic acid delays total knee replacement in patients with knee osteoarthritis: evidence from a large U.S. health claims database. Osteoarthritis Cartilage. 2015;23(Suppl 2):A403-A404.
Mather RC 3rd, Hug KT, Orlando LA, et al. Economic evaluation of access to musculoskeletal care: the case of waiting for total knee arthroplasty. BMC Musculoskelet Disord. 2014;15:22. doi:10.1186/1471-2474-15-22.
Waddell DD, Joseph B. Delayed total knee replacement with Hylan G-F 20. J Knee Surg. 2016;29(2):159-168. doi:10.1055/s-0034-1395281.
Atukorala I, Makovey J, Williams M, Ochoa Albiztegui E, Eyles JP, Hunter DJ. If you have end-stage radiographic knee osteoarthritis can you respond to non-surgical management? Osteoarthritis Cartilage. 2015;23(Suppl 2):A329.
Strand V, Baraf HS, 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(4):297-304. doi:10.1177/1947603512451024.
Riddle DL, Kong X, Jiranek WA. Two-year incidence and predictors of future knee arthroplasty in persons with symptomatic knee osteoarthritis: preliminary analysis of longitudinal data from the osteoarthritis initiative. Knee. 2009;16(6):494-500.
Hawker GA, Guan J, Croxford R, et al. A prospective population-based study of the predictors of undergoing total joint arthroplasty. Arthritis Rheum. 2006;54(10):3212-3220.
Jevsevar DS. Treatment of osteoarthritis of the knee: evidence-based guideline, 2nd edition. J Am Acad Orthop Surg. 2013;21(9):571-576. doi:10.5435/JAAOS-21-09-571.
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.
Jordan KM, Arden NK, Doherty M, et al. EULAR Recommendations 2003: an evidence based approach to the management of knee osteoarthritis: report of a task force of the standing committee for international clinical studies including therapeutic trials (ESCISIT). Ann Rheum Dis. 2003;62(12):1145-1155.
Bannuru RR, Vaysbrot EE, McIntyre LF. Did the American Academy of Orthopaedic Surgeons osteoarthritis guidelines miss the mark? Arthroscopy. 2014;30(1):86-89. doi:10.1016/j.arthro.2013.10.007.
Losina E, Thornhill TS, Rome BN, Wright J, Katz JN. The dramatic increase in total knee replacement utilization rates in the United States cannot be fully explained by growth in population size and the obesity epidemic. J Bone Joint Surg Am. 2012;94(3):201-207. doi:10.2106/JBJS.J.01958.
Weinstein AM, Rome BN, Reichmann WM, et al. Estimating the burden of total knee replacement in the United States. J Bone Joint Surg Am. 2013;95(5):385-392. doi:10.2106/JBJS.L.00206.
Riddle DL, Jiranek WA, Hayes CW. Use of a validated algorithm to judge the appropriateness of total knee arthroplasty in the United States: a multicenter longitudinal cohort study. Arthritis Rheumatol. 2014;66(8):2134-2143. doi:10.1002/art.38685.
NewBerry SJ, Fitzgerald JD, Maglione MA, et al. Agency for Healthcare Research and Quality Web site. Systematic Review for Effectiveness of Hyaluronic Acid in the Treatment of Severe Degenerative Joint Disease (DJD) of the Knee: Technology Assessment Report. http://www.ahrq.gov/research/findings/ta/call-for-public-review.html. Published July 23, 2015. Accessed December 22, 2014.

ABSTRACT

Osteoarthritis (OA) of the knee is a top cause of disability among the elderly. Total knee replacement (TKR) has been available as an effective and definite surgical method to treat severe OA of the knee. However, TKR is a significant procedure with potential risk for serious complications and high costs. Alternative lower risk therapies that can delay or obviate TKR are valuable to those who are poor candidates for surgery or wish to avoid TKR as long as possible. Given the chondroprotective effects of hyaluronic acid (HA) injections, they are a safe and effective treatment to improve pain, function, and longevity of the knee. Thus, HA features the potential to delay or obviate TKR.

We aim to study the safety and effectiveness of repeated courses of HA on the time to TKR over a 3-year period using data from a large US health plan administrative claims database.

Retrospective analyses were conducted by identifying knee OA patients during the selection period (2007-2010). The follow-up period was 36 months, post-index date of initial HA injection. Procedural outcomes and adverse events of interest were tabulated and analyzed. A Cox proportional hazards model was used to model the risk of TKR.

A total of 50,389 patients who received HA for treatment of knee OA and met the study inclusion criteria were analyzed. Successive courses of HA showed a good safety profile and led to high proportions of patients without TKR 3 years after treatment initiation. Multivariate statistical modeling showed that multiple courses of HA injections significantly decreased the rates of TKR (95.0% without TKR for ≥5 courses vs 71.6% without TKR for 1 course; hazard ratio, 0.138; P < .0001).

Repeated courses of treatment with HA are safe and are associated with the delay of TKR for up to 3 years. Additional research is needed to evaluate the effect of repeated HA courses on delaying TKR beyond a 3-year time horizon.

Continue to: Osteoarthritis (OA) of the knee...

References

Murphy L, Helmick CG. The impact of osteoarthritis in the United States: a population-health perspective. Am J Nurs. 2012;112(3 Suppl 1):S13-S19.
Arnold W, Fullerton DS, Holder S, May CS. Viscosupplementation: managed care issues for osteoarthritis of the knee. J Manag Care Pharm. 2007;13(4 Suppl):S3-S19.
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(9):859-866.
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(5):350-356.
Strand V, McIntyre LF, Beach WR, Miller LE, Block JE. Safety and efficacy of US-approved viscosupplements for knee osteoarthritis: a systematic review and meta-analysis of randomized, saline-controlled trials. J Pain Res. 2015;8:217-228.
Bannuru RR, Schmid CH, Kent DM, Vaysbrott EE, Wong JB, McAlindon TE. Comparative effectiveness of pharmacologic interventions for knee osteoarthritis: a systematic review and network meta-analysis. Ann Intern Med. 2015;162(1):46-54.
Mandl LA, Losina E. Relative efficacy of knee osteoarthritis treatments: are all placebos created equal? Ann Intern Med. 2015;162(1):71-72.
Kusayama Y, Akamatsu Y, Kumagai K, Kobayashi H, Aratake M, Saito T. Changes in synovial fluid biomarkers and clinical efficacy of intra-articular injections of hyaluronic acid for patients with knee osteoarthritis. J Exp Orthop. 2014;1(1):16. doi:10.1186/s40634-014-0016-7.
Kaneko K, Higuchi C, Kunugiza Y, et al. Hyaluronan inhibits BMP-induced osteoblast differentiation. FEBS Lett. 2015;589(4):447-454. doi:10.1016/j.febslet.2014.
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;16:321. doi:10.1186/s12891-015-0775-z.
Waddell DD, Bricker DC. Total knee replacement delayed with hylan G-F 20 use in patients with grade IV osteoarthritis. J Manag Care Pharm. 2007;13(2):113-121.
Khan T, Nanchanatt G, Farber K, Jan S. Analysis of the effectiveness of hyaluronic acid in prevention of total knee replacement in osteoarthritis patients. J Manag Care Pharm. 2014;20:S49.
Abbott T, Altman RD, Dimeff R, et al. Do hyaluronic acid injections delay total knee replacement surgery? Arthritis Rheum. 2013;65(Suppl 10):2139.
Altman R, Lim S, Steen R, Dasa V. Intra-articular hyaluronic acid delays total knee replacement in patients with knee osteoarthritis: evidence from a large U.S. health claims database. Osteoarthritis Cartilage. 2015;23(Suppl 2):A403-A404.
Mather RC 3rd, Hug KT, Orlando LA, et al. Economic evaluation of access to musculoskeletal care: the case of waiting for total knee arthroplasty. BMC Musculoskelet Disord. 2014;15:22. doi:10.1186/1471-2474-15-22.
Waddell DD, Joseph B. Delayed total knee replacement with Hylan G-F 20. J Knee Surg. 2016;29(2):159-168. doi:10.1055/s-0034-1395281.
Atukorala I, Makovey J, Williams M, Ochoa Albiztegui E, Eyles JP, Hunter DJ. If you have end-stage radiographic knee osteoarthritis can you respond to non-surgical management? Osteoarthritis Cartilage. 2015;23(Suppl 2):A329.
Strand V, Baraf HS, 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(4):297-304. doi:10.1177/1947603512451024.
Riddle DL, Kong X, Jiranek WA. Two-year incidence and predictors of future knee arthroplasty in persons with symptomatic knee osteoarthritis: preliminary analysis of longitudinal data from the osteoarthritis initiative. Knee. 2009;16(6):494-500.
Hawker GA, Guan J, Croxford R, et al. A prospective population-based study of the predictors of undergoing total joint arthroplasty. Arthritis Rheum. 2006;54(10):3212-3220.
Jevsevar DS. Treatment of osteoarthritis of the knee: evidence-based guideline, 2nd edition. J Am Acad Orthop Surg. 2013;21(9):571-576. doi:10.5435/JAAOS-21-09-571.
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.
Jordan KM, Arden NK, Doherty M, et al. EULAR Recommendations 2003: an evidence based approach to the management of knee osteoarthritis: report of a task force of the standing committee for international clinical studies including therapeutic trials (ESCISIT). Ann Rheum Dis. 2003;62(12):1145-1155.
Bannuru RR, Vaysbrot EE, McIntyre LF. Did the American Academy of Orthopaedic Surgeons osteoarthritis guidelines miss the mark? Arthroscopy. 2014;30(1):86-89. doi:10.1016/j.arthro.2013.10.007.
Losina E, Thornhill TS, Rome BN, Wright J, Katz JN. The dramatic increase in total knee replacement utilization rates in the United States cannot be fully explained by growth in population size and the obesity epidemic. J Bone Joint Surg Am. 2012;94(3):201-207. doi:10.2106/JBJS.J.01958.
Weinstein AM, Rome BN, Reichmann WM, et al. Estimating the burden of total knee replacement in the United States. J Bone Joint Surg Am. 2013;95(5):385-392. doi:10.2106/JBJS.L.00206.
Riddle DL, Jiranek WA, Hayes CW. Use of a validated algorithm to judge the appropriateness of total knee arthroplasty in the United States: a multicenter longitudinal cohort study. Arthritis Rheumatol. 2014;66(8):2134-2143. doi:10.1002/art.38685.
NewBerry SJ, Fitzgerald JD, Maglione MA, et al. Agency for Healthcare Research and Quality Web site. Systematic Review for Effectiveness of Hyaluronic Acid in the Treatment of Severe Degenerative Joint Disease (DJD) of the Knee: Technology Assessment Report. http://www.ahrq.gov/research/findings/ta/call-for-public-review.html. Published July 23, 2015. Accessed December 22, 2014.

Real-World Evidence for Safety and Effectiveness of Repeated Courses of Hyaluronic Acid Injections on the Time to Knee Replacement Surgery

TAKE-HOME POINTS

References

ABSTRACT

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