title: Preliminary assessment of the safety and efficacy of tanezumab in Japanese patients with moderate to severe osteoarthritis of the knee: a randomized, double-blind, dose-escalation, placebo-controlled study.
abstract: OBJECTIVE
  To investigate the use of tanezumab, a humanized monoclonal antibody that inhibits nerve growth factor, for the treatment of moderate to severe osteoarthritis in Japanese patients.
  
  
  METHODS
  Patients received tanezumab 10, 25, 50, 100, 200 μg/kg, or placebo and were followed for 92 or 120 days. Endpoints included the incidence of adverse events (AEs) and the change from baseline to week 8 in pain intensity and the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) subscales.
  
  
  RESULTS
  Patients (n = 83) were 69% female, age 44-73 years, with a Kellgren-Lawrence X-ray grade of 2-4. At week 8, compared with placebo, tanezumab 25, 100, and 200 μg/kg improved index knee pain during walking (-18.5, -14.3, and -27.6, respectively), index knee pain in the past 24 h (-19.1, -14.6, and -24.2, respectively), current index knee pain (-16.5, -10.9, and -22.8, respectively), and the WOMAC pain (-11.5, -9.6, and -18.8, respectively), physical function (-8.7, -9.5, and -17.6, respectively), and stiffness (-20.4, -11.2, and -10.2, respectively) subscales. Overall, seven patients reported AEs of abnormal peripheral sensation: allodynia (two in the tanezumab 200 μg/kg group); paresthesia (two in the tanezumab 200 μg/kg group), dysesthesia (one in the tanezumab 200 μg/kg group); thermohypoesthesia (one in the tanezumab 100 μg/kg group), and decreased vibratory sense (one in the placebo group). All of these AEs were mild to moderate in severity and transient in nature.
  
  
  CONCLUSIONS
  Tanezumab was safe and generally well tolerated and may improve pain symptoms in Japanese patients with moderate to severe osteoarthritis of the knee. CLINICALTRIALS.GOV IDENTIFIER: NCT00669409.
authors: Yanagibashi-Clinical Trial Center, Yanagibashi Hospital, Life Extension Research Institute Foundation, Tokyo, Japan.
authors: H
authors: H
authors: Nagashima
authors: M
authors: M
authors: Suzuki
authors: S
authors: S
authors: Araki
authors: T
authors: T
authors: Yamabe
authors: C
authors: C
authors: Muto
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy*; D010147:Pain Measurement / Q000379:methods; D010919:Placebos; D011859:Radiography; D020800:Receptor, Nerve Growth Factor / Q000037:antagonists & inhibitors; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D010919:Placebos; D020800:Receptor, Nerve Growth Factor; C549319:tanezumab