Intra-articular hyaluronan is without clinical effect in knee osteoarthritis: a multicentre, randomised, placebo-controlled, double-blind study of 337 patients followed for 1 year.
OBJECTIVE
To examine the long-term efficacy and safety of five intra-articular injections with hyaluronan in knee osteoarthritis.


METHODS
A multicentre, randomised, placebo-controlled double-blind study of 337 patients fulfilling the American College of Rheumatology (ACR) criteria for knee osteoarthritis (clinical and laboratory) and with a Lequesne algofunctional index score (LFI) of 10 or greater. Patients received a hyaluronan product (sodium hyaluronate; Hyalgan) (n=167) or saline (n=170) intra-articularly weekly for 5 weeks and were followed up to 1 year. Time to recurrence was the primary efficacy parameter. LFI, pain on walking 50 m based on visual analogue scale (VAS pain 50 m), paracetamol consumption, patients' global assessment, Nottingham health profile, joint effusion and number of responders were secondary efficacy parameters. The efficacy parameters were analysed by intention to treat (ITT) and per protocol (PP). All adverse events (AE) were recorded as safety parameters.


RESULTS
Time to recurrence showed no significant treatment effect (ITT analysis, p=0.26). Change from baseline in LFI and VAS pain 50 m for the ITT population showed no treatment effect. Paracetamol consumption, patients' global assessment, responder rates and AE displayed no significant difference between treatment groups, analysed by both ITT and PP. Treatment compliance was 95% in the hyaluronan group and 99% in the placebo group. No safety problems were registered.


CONCLUSIONS
In patients fulfilling the ACR criteria for osteoarthritis of the knee with moderate to severe disease activity (LFI > or = 10), five intra-articular injections of hyaluronan did not improve pain, function, paracetamol consumption or other efficacy parameters 3, 6, 9 and 12 months after the treatment.
Jørgensen
Anette
A
Department of Rheumatology, Aarhus University Hospital, Norrebrogade 44, DK-8000 Aarhus C, Denmark.
Stengaard-Pedersen
Kristian
K
Simonsen
Ole
O
Pfeiffer-Jensen
Mogens
M
Eriksen
Christian
C
Bliddal
Henning
H
Pedersen
Niels Wisbech
NW
Bødtker
Søren
S
Hørslev-Petersen
Kim
K
Snerum
Lennart Ørtoft
LØ
Egund
Niels
N
Frimer-Larsen
Helle
H
D000082:Acetaminophen / Q000008:administration & dosage; D000368:Aged; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage; D004334:Drug Administration Schedule; D004812:Epidemiologic Methods; D005260:Female; D006801:Humans; D006820:Hyaluronic Acid / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D007270:Injections, Intra-Articular; D008297:Male; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000188:drug therapy*; D010147:Pain Measurement; D012008:Recurrence; D016896:Treatment Outcome; D055675:Viscosupplements / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use
D018712:Analgesics, Non-Narcotic; D055675:Viscosupplements; D000082:Acetaminophen; D006820:Hyaluronic Acid