Safety of Repeated Injections of Sodium Hyaluronate (SUPARTZ) for Knee Osteoarthritis: A Systematic Review and Meta-Analysis.
OBJECTIVE
Though there is no consensus on its efficacy, knee osteoarthritis is symptomatically managed with intra-articular hyaluronic acid (IAHA). Recent reports suggest that IAHA may delay the need for total knee replacement, with the magnitude of delay proportional to the number of injection series. However, the safety of repeated injection series is reported to vary between commercial products. This report describes a systematic review of safety data on repeated treatment courses of SUPARTZ.


METHODS
We performed a systematic search of MEDLINE, Cochrane database, EMBASE, Web of Science, Google Scholar, and unpublished data. We included all human randomized controlled trials or observational studies with adverse event (AE) data for SUPARTZ in knee osteoarthritis. Two independent reviewers extracted data and evaluated study quality. Data were analyzed separately for the first and subsequent series of injections.


RESULTS
The primary sources for repeated-injection data on SUPARTZ were a postmarket registry (N = 7404), 4 prospective studies (N = 127 total), and a retrospective study (N = 220). None of the sources reported increased frequency or severity of AEs with repeated injections. In the registry, 95% of multiple-injection-series patients who reported an AE did so during the first series. None of the AEs was serious, and most resolved spontaneously without medical intervention. The overall adverse event rate after repeat courses of SUPARTZ was 0.008 (95% confidence interval: 0.001-0.055).


CONCLUSIONS
Multiple courses of SUPARTZ injections appear to be at least as safe, and probably safer, than the first course. This study supports the safety of repeat courses of SUPARTZ injections for knee osteoarthritis.
Center for Treatment Comparison and Integrative Analysis, Division of Rheumatology, Tufts Medical Center, Boston, MA, USA.
Raveendhara R
RR
Bannuru
Bioventus LLC, Durham, NC 27703, USA.
Christopher R
CR
Brodie
Center for Treatment Comparison and Integrative Analysis, Division of Rheumatology, Tufts Medical Center, Boston, MA, USA.
Matthew C
MC
Sullivan
Center for Treatment Comparison and Integrative Analysis, Division of Rheumatology, Tufts Medical Center, Boston, MA, USA.
Timothy E
TE
McAlindon
hyaluronic acid; knee osteoarthritis; repeated injection; safety; systematic review
Lancet. 2012 Dec 15;380(9859):2163-96
23245607
J Pain Res. 2015 May 07;8:217-28
26005358
Clin Orthop Relat Res. 2005 May;(434):239-45
15864059
Osteoarthritis Cartilage. 1993 Oct;1(4):233-41
15449510
J Med Econ. 2014 May;17(5):326-37
24625229
Scand J Med Sci Sports. 2000 Feb;10(1):2-11
10693606
Ann Rheum Dis. 1996 Jul;55(7):424-31
8774159
Osteoarthritis Cartilage. 2014 Mar;22(3):363-88
24462672
Clin Med Insights Arthritis Musculoskelet Disord. 2014 Dec 22;7:49-55
25574144
Control Clin Trials. 1986 Sep;7(3):177-88
3802833
Knee Surg Sports Traumatol Arthrosc. 2011 Sep;19(9):1418-32
21833512
Orthopedics. 2012 Apr;35(4):e514-9
22495852
J Rheumatol. 2004 Apr;31(4):775-82
15088306
Arthritis Rheum. 2000 Jun;43(6):1192-203
10857778
Psychol Methods. 2006 Jun;11(2):193-206
16784338
Lancet. 2012 Dec 15;380(9859):2197-223
23245608
Ryumachi. 1983 Aug;23(4):280-90
6364389
J Bone Joint Surg Am. 2002 Sep;84-A(9):1619-23
12208919
Osteoarthritis Cartilage. 2011 Jun;19(6):611-9
21443958
J Bone Joint Surg Am. 2012 Feb 1;94(3):201-7
22298051
Zhonghua Yi Xue Za Zhi (Taipei). 1997 Feb;59(2):99-106
9175299
BMJ. 2011 Mar 08;342:d1165
21385807
Ann Intern Med. 2012 Aug 7;157(3):180-91
22868835
J Knee Surg. 2016 Oct;29(7):564-570
26641076
Drugs Aging. 2010 Nov 1;27(11):925-41
20964466
Osteoarthritis Cartilage. 2011 Oct;19(10):1169-75
21820521
Arthritis Rheum. 1994 Apr;37(4):521-8
8147929
J Bone Joint Surg Am. 2002 Jul;84-A(7):1142-7
12107313
Pain. 2011 Mar;152(3):566-72
21239114
PLoS One. 2015 Dec 22;10(12):e0145776
26694145
Rheumatology (Oxford). 2002 Nov;41(11):1240-8
12421996
J Bone Joint Surg Am. 2007 Jan;89(1):148-57
17200322
Osteoarthritis Cartilage. 2006 Sep;14(9):859-66
16626978
Ann Intern Med. 2015 Jan 6;162(1):46-54
25560713