PMID- 29268731
OWN - NLM
STAT- MEDLINE
DCOM- 20180827
LR  - 20220411
IS  - 1471-2474 (Electronic)
IS  - 1471-2474 (Linking)
VI  - 18
IP  - 1
DP  - 2017 Dec 21
TI  - The efficacy of multiple versus single hyaluronic acid injections: a systematic 
      review and meta-analysis.
PG  - 542
LID - 10.1186/s12891-017-1897-2 [doi]
LID - 542
AB  - BACKGROUND: Intra-articular hyaluronic acid (IA-HA) is a common therapy used to 
      treat knee pain and suppress knee inflammation in knee osteoarthritis (OA), 
      typically prescribed in regimens ranging from a single injection to 5 weekly 
      injections given once weekly. We conducted a systematic review to determine the 
      efficacy of IA-HA, with subgroup analyses to explore the differences in knee pain 
      and adverse events (AEs) across different dosing regimens. METHODS: We conducted 
      a systematic search of the literature to identify studies evaluating IA-HA for 
      the management of knee OA compared to IA-saline. Primary outcome measure was the 
      mean knee pain score at 13 Weeks (3 months) or 26 weeks (6 months). Secondary 
      outcome was the number of treatment-related AEs and treatment-related serious 
      adverse events (SAEs). We evaluated differences in levels of pain and AEs/SAEs 
      between dosing regimens compared to IA-Saline. RESULTS: Thirty articles were 
      included. Overall, IA-HA injections were associated with less knee pain compared 
      to IA-Saline injections for all dosing regimens. 2-4 injections of IA-HA vs. 
      IA-Saline produced the largest effect size at both 3-months and 6-months 
      (Standard mean difference [SMD] = -0.76; -0.98 to -0.53, 95% CI, P < 0.00001, and 
      SMD = -0.36; -0.63 to -0.09 95% CI, P = 0.008, respectively). Additionally, 
      single injection studies yielded a non-significant treatment effect at 3 and 
      6 months, while >/=5 5 injections demonstrated a significant improvement in pain 
      only at 6 months. Five or more injections of IA-HA were associated with a higher 
      risk of treatment-related AEs compared to IA-Saline (Risk ratio [RR] = 1.67; 1.09 
      to 2.56 95% CI, p = 0.02), which was a result not seen within the 1 and 2-4 
      injection subgroups. CONCLUSION: Overall, 2-4 and >/=5 injection regimens provided 
      pain relief over IA-Saline, while single injection did not. Intra-articular 
      injections of HA used in a 2-4 injection treatment regimen provided the greatest 
      benefit when compared to IA-Saline with respect to pain improvement in patients 
      with knee OA, and was generally deemed safe with few to no treatment-related AEs 
      reported across studies. Future research is needed to directly compare these 
      treatment regimens.
FAU - Concoff, Andrew
AU  - Concoff A
AUID- ORCID: 0000-0001-8325-760X
AD  - Departments of Orthopedics and Rheumatology, St. Jude Medical Center, Fullerton, 
      California, USA. Andrew.Concoff@stjoe.org.
FAU - Sancheti, Parag
AU  - Sancheti P
AD  - Sancheti Institute for Orthopaedics and Rehabilitation, Maharashtra, India.
FAU - Niazi, Faizan
AU  - Niazi F
AD  - Ferring Pharmaceuticals Inc., Parsippany, NJ, USA.
FAU - Shaw, Peter
AU  - Shaw P
AD  - Ferring Pharmaceuticals Inc., Parsippany, NJ, USA.
FAU - Rosen, Jeffrey
AU  - Rosen J
AD  - Department of Orthopaedics & Rehabilitation, New York Presbyterian Queens; 
      Department of Clinical Orthopaedic Surgery, Weill Medical College of Cornell 
      University, New York, NY, USA.
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Meta-Analysis
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PT  - Systematic Review
DEP - 20171221
PL  - England
TA  - BMC Musculoskelet Disord
JT  - BMC musculoskeletal disorders
JID - 100968565
RN  - 0 (Viscosupplements)
RN  - 9004-61-9 (Hyaluronic Acid)
SB  - IM
MH  - Humans
MH  - Hyaluronic Acid/*administration & dosage
MH  - Injections, Intra-Articular
MH  - Osteoarthritis, Knee/*diagnosis/*drug therapy
MH  - Pain Management/methods
MH  - Randomized Controlled Trials as Topic/methods
MH  - Treatment Outcome
MH  - Viscosupplements/*administration & dosage
PMC - PMC5740709
OTO - NOTNLM
OT  - Intra-articular hyaluronic acid (IA-HA)
OT  - Knee
OT  - Osteoarthritis (OA)
COIS- ETHICS APPROVAL AND CONSENT TO PARTICIPATE: Not applicable CONSENT FOR 
      PUBLICATION: Not applicable COMPETING INTERESTS: Andrew Concoff: Honorarium 
      received for Ferring Pharmaceuticals advisory board. Parag Sancheti: None. Faizan 
      Niazi: Paid employee of Ferring Pharmaceuticals. Peter Shaw: Paid employee of 
      Ferring Pharmaceuticals. Jeffrey Rosen: Honorarium received for Ferring 
      Pharmaceuticals, Flexion, and Novartis advisory boards. Honorarium received for 
      OrthoGenrx sales force lecture. PUBLISHER'S NOTE: Springer Nature remains neutral 
      with regard to jurisdictional claims in published maps and institutional 
      affiliations.
EDAT- 2017/12/23 06:00
MHDA- 2018/08/28 06:00
PMCR- 2017/12/21
CRDT- 2017/12/23 06:00
PHST- 2017/06/21 00:00 [received]
PHST- 2017/12/08 00:00 [accepted]
PHST- 2017/12/23 06:00 [entrez]
PHST- 2017/12/23 06:00 [pubmed]
PHST- 2018/08/28 06:00 [medline]
PHST- 2017/12/21 00:00 [pmc-release]
AID - 10.1186/s12891-017-1897-2 [pii]
AID - 1897 [pii]
AID - 10.1186/s12891-017-1897-2 [doi]
PST - epublish
SO  - BMC Musculoskelet Disord. 2017 Dec 21;18(1):542. doi: 10.1186/s12891-017-1897-2.