title: Transdermal buprenorphine plus oral paracetamol vs an oral codeine-paracetamol combination for osteoarthritis of hip and/or knee: a randomised trial.
abstract: OBJECTIVE
  Low-dose transdermal opioids offer a new therapeutic option for osteoarthritis (OA). This study compared symptom relief obtained with buprenorphine patches plus oral paracetamol with that obtained with an oral codeine-paracetamol combination tablet (co-codamol) in older adults with OA.
  
  
  METHODS
  Two hundred and twenty people (aged ≥60 years) with OA hip and/or knee pain were randomised to treatment with 7-day buprenorphine patches plus oral paracetamol (5-25 μg/h buprenorphine patches plus 1000 mg oral paracetamol q.i.d. (4 times daily); n=110) or co-codamol tablets (two 8/500-two 30/500 mg tablets q.i.d.; n=110). They entered a titration period of up to 10 weeks, during which their dose of study medication was adjusted until they reached optimum pain control. Patients who achieved optimum pain control entered a 12-week assessment period. The primary outcome was average daily pain scores recorded using the box scale-11 (BS-11) pain scale.
  
  
  RESULTS
  Both treatments significantly reduced patient pain scores. The estimated treatment difference [95% confidence interval (CI)] was -0.02 (-0.64, 0.60) for the per protocol (PP) population. The results were similar for the full analysis population. Patients receiving 7-day buprenorphine patches plus oral paracetamol needed significantly less escape medication (ibuprofen) than those receiving co-codamol tablets (P=0.002; PP population). Less than 10% of patients in the 7-day buprenorphine patches plus oral paracetamol group were receiving the highest dose level at the end of the study, compared with 34% in the co-codamol group. Withdrawal rates were high in both groups. The incidence of adverse events (AEs) was comparable between the groups (86.4% of patients in the 7-day buprenorphine patches plus oral paracetamol group; 81.7% in the co-codamol group). Six serious AEs were reported in three patients (2.7%) in the 7-day buprenorphine patches plus oral paracetamol group and one (0.9%) in the co-codamol group.
  
  
  CONCLUSIONS
  7-day buprenorphine patches plus oral paracetamol were non-inferior to co-codamol tablets with respect to analgesic efficacy in older adults with OA pain in the hip/knee.
authors.affiliation: Section of Musculoskeletal Disease, University of Leeds & NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds, UK. p.conaghan@leeds.ac.uk
authors.forename: P G
authors.initials: PG
authors.lastname: Conaghan
authors.forename: C M
authors.initials: CM
authors.lastname: O'Brien
authors.forename: M
authors.initials: M
authors.lastname: Wilson
authors.forename: J P
authors.initials: JP
authors.lastname: Schofield
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage*; D000279:Administration, Cutaneous; D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D000700:Analgesics / Q000008:administration & dosage*; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage; D000701:Analgesics, Opioid / Q000008:administration & dosage; D002047:Buprenorphine / Q000008:administration & dosage*; D003061:Codeine / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015207:Osteoarthritis, Hip / Q000188:drug therapy*; D020370:Osteoarthritis, Knee / Q000188:drug therapy*; D010147:Pain Measurement; D016896:Treatment Outcome
chemical_list: D000700:Analgesics; D018712:Analgesics, Non-Narcotic; D000701:Analgesics, Opioid; D004338:Drug Combinations; C526278:acetaminophen, codeine drug combination; D000082:Acetaminophen; D002047:Buprenorphine; D003061:Codeine