PMID- 31073925
OWN - NLM
STAT- MEDLINE
DCOM- 20190708
LR  - 20210317
IS  - 1179-1969 (Electronic)
IS  - 1170-229X (Print)
IS  - 1170-229X (Linking)
VI  - 36
IP  - Suppl 1
DP  - 2019 Apr
TI  - Safety of Intra-articular Hyaluronic Acid Injections in Osteoarthritis: Outcomes 
      of a Systematic Review and Meta-Analysis.
PG  - 101-127
LID - 10.1007/s40266-019-00657-w [doi]
AB  - BACKGROUND: Some controversy exists regarding the safety of intra-articular 
      hyaluronic acid (IAHA) in the management of osteoarthritis (OA). OBJECTIVE: The 
      objective of this study was to re-assess the safety profile of IAHA in patients 
      with OA, through a comprehensive meta-analysis of randomized, placebo-controlled 
      trials. METHODS: A comprehensive literature search was undertaken in the 
      databases MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), and 
      Scopus. Randomized, double-blind, placebo-controlled, parallel-group trials that 
      assessed adverse events (AEs) with IAHA in patients with OA were eligible for 
      inclusion. Authors and/or study sponsors were contacted to obtain the full report 
      of AEs. The primary outcomes were overall severe and serious AEs, as well as the 
      following MedDRA System Organ Class (SOC)-related AEs: gastrointestinal, cardiac, 
      vascular, respiratory, nervous system, skin and subcutaneous tissue disorders, 
      musculoskeletal, renal and urinary disorders, infections and infestations, and 
      hypersensitivity reaction. RESULTS: Database searches initially identified 1481 
      records. After exclusions according to the selection criteria, 22 studies were 
      included in the qualitative synthesis, and nine studies having adequate data were 
      ultimately included in the meta-analysis. From the studies excluded according to 
      the pre-specified selection criteria, 21 with other pharmacological OA treatments 
      permitted during the trials were a posteriori included in a parallel qualitative 
      synthesis, from which eight studies with adequate data were finally included in a 
      parallel meta-analysis. Since this meta-analysis was designed to assess safety, 
      the exclusion criterion on concomitant anti-OA medication was crucial. However, 
      due to the high number of studies that allowed mainly concomitant oral 
      non-steroidal anti-inflammatory drugs (NSAIDs), we decided to include them in a 
      post hoc parallel analysis in order to compare the results from the two analyses. 
      No statistically significant difference in odds was found between IAHA and 
      placebo for all types of SOC-related disorders, except for infections and 
      infestations, for which significantly lower odds were found with IAHA compared 
      with placebo, both overall (odds ratio [OR] = 0.61, 95% confidence interval [CI] 
      0.40-0.93; I(2) = 0%) and in studies without concomitant anti-OA medication 
      (OR = 0.49, 95% CI 0.27-0.89). There were significant increased odds of reporting 
      serious AEs with IAHA compared with placebo, both overall (OR = 1.78, 95% CI 
      1.21-2.63; I(2) = 0%) and in studies with concomitant anti-OA medication 
      (OR = 1.78, 95% CI 1.10-2.89), but not in studies without concomitant anti-OA 
      medication (OR = 1.78, 95% CI 0.92-3.47). CONCLUSIONS: Using the available data 
      on studies without any concomitant anti-OA medication permitted during clinical 
      trials, IAHA seems not to be associated with any safety issue in the management 
      of OA. However, this evidence was associated with only a "low" to "moderate" 
      certainty. A possible association with increased risk of serious AEs, 
      particularly when used with concomitant OA medications, requires further 
      investigation.
FAU - Honvo, Germain
AU  - Honvo G
AUID- ORCID: 0000-0002-6992-6712
AD  - Department of Public Health, Epidemiology and Health Economics, University of 
      Liege, Liege, Belgium. germain.honvo@uliege.be.
AD  - WHO Collaborating Centre for Public Heath Aspects of Musculoskeletal Health and 
      Aging, Liege, Belgium. germain.honvo@uliege.be.
FAU - Reginster, Jean-Yves
AU  - Reginster JY
AUID- ORCID: 0000-0001-6290-752X
AD  - Department of Public Health, Epidemiology and Health Economics, University of 
      Liege, Liege, Belgium.
AD  - WHO Collaborating Centre for Public Heath Aspects of Musculoskeletal Health and 
      Aging, Liege, Belgium.
AD  - Biochemistry Department, College of Science, King Saud University, Riyadh, 
      Kingdom of Saudi Arabia.
FAU - Rannou, Francois
AU  - Rannou F
AD  - Division of Physical Medicine and Rehabilitation, Department of Rheumatology, 
      AP-HP Cochin Hospital, Universite Paris Descartes Sorbonne Paris Cite, Paris, 
      France.
AD  - INSERM U1124, Paris, France.
FAU - Rygaert, Xavier
AU  - Rygaert X
AD  - Department of Public Health, Epidemiology and Health Economics, University of 
      Liege, Liege, Belgium.
AD  - WHO Collaborating Centre for Public Heath Aspects of Musculoskeletal Health and 
      Aging, Liege, Belgium.
FAU - Geerinck, Anton
AU  - Geerinck A
AD  - Department of Public Health, Epidemiology and Health Economics, University of 
      Liege, Liege, Belgium.
AD  - WHO Collaborating Centre for Public Heath Aspects of Musculoskeletal Health and 
      Aging, Liege, Belgium.
FAU - Rabenda, Veronique
AU  - Rabenda V
AD  - Department of Public Health, Epidemiology and Health Economics, University of 
      Liege, Liege, Belgium.
AD  - WHO Collaborating Centre for Public Heath Aspects of Musculoskeletal Health and 
      Aging, Liege, Belgium.
FAU - McAlindon, Tim
AU  - McAlindon T
AD  - Division of Rheumatology, Tufts Medical Center, Boston, MA, USA.
FAU - Charles, Alexia
AU  - Charles A
AD  - Department of Public Health, Epidemiology and Health Economics, University of 
      Liege, Liege, Belgium.
AD  - WHO Collaborating Centre for Public Heath Aspects of Musculoskeletal Health and 
      Aging, Liege, Belgium.
FAU - Fuggle, Nicholas
AU  - Fuggle N
AD  - MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General 
      Hospital, Southampton, UK.
FAU - Cooper, Cyrus
AU  - Cooper C
AD  - WHO Collaborating Centre for Public Heath Aspects of Musculoskeletal Health and 
      Aging, Liege, Belgium.
AD  - MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General 
      Hospital, Southampton, UK.
AD  - National Institute for Health Research (NIHR), Musculoskeletal Biomedical 
      Research Unit, University of Oxford, Oxford, UK.
FAU - Curtis, Elizabeth
AU  - Curtis E
AD  - MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General 
      Hospital, Southampton, UK.
FAU - Arden, Nigel
AU  - Arden N
AD  - MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General 
      Hospital, Southampton, UK.
AD  - Arthritis Research UK Centre for Sport, Exercise and Osteoarthritis, University 
      of Oxford, Oxford, UK.
FAU - Avouac, Bernard
AU  - Avouac B
AD  - Department of Public Health, Epidemiology and Health Economics, University of 
      Liege, Liege, Belgium.
FAU - Bruyere, Olivier
AU  - Bruyere O
AUID- ORCID: 0000-0003-4269-9393
AD  - Department of Public Health, Epidemiology and Health Economics, University of 
      Liege, Liege, Belgium.
AD  - WHO Collaborating Centre for Public Heath Aspects of Musculoskeletal Health and 
      Aging, Liege, Belgium.
LA  - eng
GR  - 21231/VAC_/Versus Arthritis/United Kingdom
GR  - MC_U147585819/MRC_/Medical Research Council/United Kingdom
GR  - MC_UP_A620_1014/MRC_/Medical Research Council/United Kingdom
GR  - G0400491/MRC_/Medical Research Council/United Kingdom
GR  - MC_U147585824/MRC_/Medical Research Council/United Kingdom
GR  - 10/33/04/DH_/Department of Health/United Kingdom
GR  - MC_UU_12011/1/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Meta-Analysis
PT  - Research Support, Non-U.S. Gov't
PT  - Systematic Review
PL  - New Zealand
TA  - Drugs Aging
JT  - Drugs & aging
JID - 9102074
RN  - 0 (Anti-Inflammatory Agents, Non-Steroidal)
RN  - 9004-61-9 (Hyaluronic Acid)
SB  - IM
MH  - Anti-Inflammatory Agents, Non-Steroidal/*administration & dosage/*adverse 
      effects/therapeutic use
MH  - Drug-Related Side Effects and Adverse Reactions/epidemiology/*etiology
MH  - Humans
MH  - Hyaluronic Acid/*administration & dosage/*adverse effects/therapeutic use
MH  - Injections, Intra-Articular
MH  - Osteoarthritis/*drug therapy
MH  - Randomized Controlled Trials as Topic
MH  - Treatment Outcome
PMC - PMC6509101
COIS- O. Bruyere reports grants from Biophytis, IBSA, MEDA, Servier, SMB, and Theramex, 
      outside of the submitted work. C. Cooper reports personal fees from Alliance for 
      Better Bone Health, Amgen, Eli Lilly, GSK, Medtronic, Merck, Novartis, Pfizer, 
      Roche, Servier, Takeda and UCB, outside of the submitted work. J.-Y. Reginster 
      reports grants from IBSA-Genevrier, Mylan, CNIEL, and Radius Health (through 
      institution); consulting fees from IBSA-Genevrier, Mylan, CNIEL, Radius Health, 
      and Pierre Fabre; fees for participation in review activities from 
      IBSA-Genevrier, Mylan, CNIEL, Radius Health, and Teva; payment for lectures from 
      AgNovos, CERIN, CNIEL, Dairy Research Council (DRC), Echolight, IBSA-Genevrier, 
      Mylan, Pfizer Consumer Health, Teva, and Theramex, outside of the submitted work. 
      B. Avouac reports consulting fees from Novartis, BMS, Roche, Janssen Cilag, 
      Expanscience, and IRIS, and fees for participating in research activities from 
      Sanofi, Amgen, Takeda, Allegan, AbbVie, Vertex, AstraZeneca, Ipsen, Leadiant, 
      Otsuka, Jazz, Leo and Alexion, outside of the submitted work. E. Curtis reports 
      lecture fees and travel support from Eli Lilly, Pfizer and UCB, outside of the 
      submitted work. N. Fuggle reports travel support from Eli Lilly and Pfizer, 
      outside of the submitted work. N. Arden reports personal fees from Bioventus, 
      Flexion, Merck, Pfizer/Lilly, Regeneron, Smith & Nephew, and Freshfields 
      Bruckhaus Deringer and grants from Bioiberica and Merck, outside the submitted 
      work. F. Rannou reports grants from APHP, INSERM, University Paris Descartes, and 
      Arthritis (Road Network), and consulting fees from Pierre Fabre, Expanscience, 
      Thuasne, Servier, Genevrier, Sanofi Aventis, and Genzyme, outside of the 
      submitted work. T. McAlindon reports fees for participation in review activities 
      from Pfizer and fees for consulting activities with Flexion, Samumed, Sanofi, 
      Visgo, Roche, Astellas, Pfizer, Seikayaku, Regeneron, and Anika, outside of the 
      submitted work. G. Honvo, X. Rygaert, A. Geerinck, V. Rabenda and A. Charles 
      report nothing to disclose.
EDAT- 2019/05/11 06:00
MHDA- 2019/07/10 06:00
PMCR- 2019/05/09
CRDT- 2019/05/11 06:00
PHST- 2019/05/11 06:00 [entrez]
PHST- 2019/05/11 06:00 [pubmed]
PHST- 2019/07/10 06:00 [medline]
PHST- 2019/05/09 00:00 [pmc-release]
AID - 10.1007/s40266-019-00657-w [pii]
AID - 657 [pii]
AID - 10.1007/s40266-019-00657-w [doi]
PST - ppublish
SO  - Drugs Aging. 2019 Apr;36(Suppl 1):101-127. doi: 10.1007/s40266-019-00657-w.