title: Efficacy and safety of tanezumab added on to diclofenac sustained release in patients with knee or hip osteoarthritis: a double-blind, placebo-controlled, parallel-group, multicentre phase III randomised clinical trial.
abstract: OBJECTIVE
  Tanezumab, a monoclonal antibody, inhibits nerve growth factor and reduces chronic pain. This randomised, double-blind, controlled multicentre study was conducted to evaluate the efficacy and safety of tanezumab added to oral diclofenac sustained release (DSR) in patients with hip or knee osteoarthritis (OA) pain.
  
  
  METHODS
  Patients (N=604) with moderate to severe knee or hip OA tolerating stable DSR were randomised and treated with DSR 75 mg twice daily combined with intravenous tanezumab 10, 5 or 2.5 mg or placebo at weeks 0, 8 and 16. Co-primary efficacy endpoints (Western Ontario and McMaster Universities OA Index (WOMAC) Pain and Physical Function subscales and patient's global assessment of OA) were assessed at week 16.
  
  
  RESULTS
  All co-primary endpoints were significantly improved for all tanezumab+DSR groups versus placebo+DSR (p≤0.039). The incidence of adverse events of abnormal peripheral sensation was lower than in previous tanezumab trials. No new safety signals emerged. Overall incidence of adverse events was higher with tanezumab+DSR (45.2%-49.7%) than with placebo+DSR (34.9%); serious adverse event rates were similar across treatments (5.3%-7.6%). Osteonecrosis was reported in six of 452 patients with tanezumab+DSR (1.3%), but an external adjudication committee did not confirm osteonecrosis in any patient.
  
  
  CONCLUSIONS
  Addition of tanezumab to DSR resulted in significant improvements in pain, function and global assessments in patients with OA. Although no new safety signals were observed, the higher incidence of adverse events in the tanezumab+diclofenac group suggests that combination therapy is unfavourable. Further investigations of tanezumab monotherapy for OA pain treatment are required.
  
  
  BACKGROUND
  NCT00864097.
authors.affiliation: Department of Internal Medicine and Rheumatology, Sf. Maria Hospital, University of Medicine and Pharmacy Carol Davila, Bucharest, Romania.
authors.forename: Andra Rodica
authors.initials: AR
authors.lastname: Balanescu
authors.affiliation: Department of Rheumatology and Clinical Immunology, Charité-Universitaetsmedizin, Berlin, Germany.
authors.forename: Eugen
authors.initials: E
authors.lastname: Feist
authors.affiliation: Pfizer Inc, Groton, Connecticut, USA.
authors.forename: Gernot
authors.initials: G
authors.lastname: Wolfram
authors.affiliation: Pfizer Inc, Groton, Connecticut, USA.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Davignon
authors.affiliation: Pfizer Inc, Groton, Connecticut, USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Smith
authors.affiliation: Pfizer Inc, Groton, Connecticut, USA.
authors.forename: Mark T
authors.initials: MT
authors.lastname: Brown
authors.affiliation: Pfizer Inc, Groton, Connecticut, USA.
authors.forename: Christine R
authors.initials: CR
authors.lastname: West
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003692:Delayed-Action Preparations; D004008:Diclofenac / Q000009:adverse effects / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015207:Osteoarthritis, Hip / Q000150:complications / Q000188:drug therapy*; D020370:Osteoarthritis, Knee / Q000150:complications / Q000188:drug therapy*; D010146:Pain / Q000209:etiology / Q000517:prevention & control; D010147:Pain Measurement / Q000379:methods; D020800:Receptor, Nerve Growth Factor / Q000037:antagonists & inhibitors; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D061067:Antibodies, Monoclonal, Humanized; D003692:Delayed-Action Preparations; D020800:Receptor, Nerve Growth Factor; D004008:Diclofenac; C549319:tanezumab
keywords: Arthritis; Knee Osteoarthritis; Osteoarthritis