title: NASHA hyaluronic acid vs. methylprednisolone for knee osteoarthritis: a prospective, multi-centre, randomized, non-inferiority trial.
abstract: OBJECTIVE
  To compare NASHA hyaluronic acid gel as single-injection intra-articular (IA) treatment for knee osteoarthritis (OA) against methylprednisolone acetate (MPA).
  
  
  METHODS
  This was a prospective, multi-centre, randomized, active-controlled, double-blind, non-inferiority clinical trial. A unique, open-label extension phase (OLE) was undertaken to answer further important clinical questions. Subjects with painful unilateral knee OA were treated and followed for 26 weeks (blinded phase). All patients attending the clinic at 26 weeks were offered NASHA treatment, with a subsequent 26-week follow-up period (extension phase). The primary objective was to show non-inferiority of NASHA vs MPA in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain responder rate (percentage of patients with ≥40% improvement from baseline in WOMAC pain score and an absolute improvement of ≥5 points) at 12 weeks.
  
  
  RESULTS
  In total, 442 participants were enrolled. The primary objective was met, with NASHA producing a non-inferior response rate vs MPA at 12 weeks (NASHA: 44.6%; MPA: 46.2%; difference [95% CI]: 1.6% [-11.2%; +7.9%]). Effect size for WOMAC pain, physical function and stiffness scores favoured NASHA over MPA from 12 to 26 weeks. In response to NASHA treatment at 26 weeks, sustained improvements were seen in WOMAC outcomes irrespective of initial treatment. No serious device-related adverse events (AEs) were reported.
  
  
  CONCLUSIONS
  This study shows that single-injection NASHA was well tolerated and non-inferior to MPA at 12 weeks. The benefit of NASHA was maintained to 26 weeks while that of MPA declined. An injection of NASHA at 26 weeks conferred long-term improvements without increased sensitivity or risk of complications. STUDY IDENTIFIER: NCT01209364 (www.clinicaltrials.gov).
authors.affiliation: QEII Health Sciences Centre, New Halifax Infirmary, Halifax, NS, Canada. Electronic address: r.k.leighton@ns.sympatico.ca.
authors.forename: R
authors.initials: R
authors.lastname: Leighton
authors.affiliation: Sport Med, Birger Jarlsgatan 106A, SE-11420 Stockholm, Sweden.
authors.forename: C
authors.initials: C
authors.lastname: Akermark
authors.affiliation: Centre de Rhumatologie St-Louis, Saint-Foy, Quebec, Canada G1W4R4.
authors.forename: R
authors.initials: R
authors.lastname: Therrien
authors.affiliation: Robert Jones and Agnes Hunt Orthopaedic & District Hospital, Institute of Orthopaedics Oswestry, SY10 7AG, UK.
authors.forename: J B
authors.initials: JB
authors.lastname: Richardson
authors.affiliation: Q-Med AB, Seminariegatan 21, 752 28 Uppsala, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Andersson
authors.affiliation: Smith & Nephew UK Ltd, Research Centre, York Science Park, York, UK.
authors.forename: M G
authors.initials: MG
authors.lastname: Todman
authors.affiliation: NIHR Musculoskeletal Biomedical Research Unit, University of Oxford, UK.
authors.forename: N K
authors.initials: NK
authors.lastname: Arden
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004311:Double-Blind Method; D005260:Female; D005938:Glucocorticoids / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D006820:Hyaluronic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007270:Injections, Intra-Articular; D008297:Male; D008775:Methylprednisolone / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000077555:Methylprednisolone Acetate; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000188:drug therapy*; D010147:Pain Measurement / Q000379:methods; D011446:Prospective Studies; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D005938:Glucocorticoids; D000077555:Methylprednisolone Acetate; D006820:Hyaluronic Acid; D008775:Methylprednisolone
keywords: Knee; Methylprednisolone acetate; NASHA hyaluronic acid gel; Osteoarthritis