title: Onset of response with duloxetine treatment in patients with osteoarthritis knee pain and chronic low back pain: a post hoc analysis of placebo-controlled trials.
abstract: BACKGROUND
  Knowing when to change pain-medication strategy is not well researched and remains a gap in treating chronic pain.
  
  
  OBJECTIVE
  Our aim was to determine how long to treat osteoarthritis (OA) knee pain and chronic low back pain (CLBP) with duloxetine before considering a change in medication strategy.
  
  
  METHODS
  We employed a post hoc analysis of changes in pain-severity data from placebo-controlled studies of duloxetine treatment in nondepressed patients with OA knee pain and CLBP. The studies were selected for inclusion in the analyses based on similarity of study design. Pain severity was recorded daily in patient diaries using an ordinal 11-point numerical rating scale (0 = no pain to 10 = most severe pain). The weekly means of the daily 24-hour average pain severity ratings from these diaries were pooled within disease states. Moderate response was defined as at least a 30% reduction from baseline in pain severity, and minimal improvement was defined as <10% reduction from baseline. The probability of achieving at least moderate pain reduction during 3 months treatment with duloxetine was estimated by Kaplan-Meier methods in patients with no or minimal improvement after 2, 4, and 6 weeks of treatment, as well as in all patients who had not yet achieved a moderate response (<30% reduction in pain severity).
  
  
  RESULTS
  There were 239 OA patients and 541 CLBP patients who were randomly assigned to treatment with duloxetine 60/120 mg/d. OA and CLBP patients with minimal improvement at 2 weeks of treatment had <40% probability of achieving a moderate response, and at 4 weeks of treatment their chances were reduced to <30% in OA patients and <25% in CLBP patients. In patients showing <30% improvement at week 2 of treatment, OA patients had a 62% probability of achieving a moderate response, and CLBP patients had a 52% probability for a moderate response, and at 4 weeks of treatment, their chances were reduced to <50% in OA patients and <40% in CLBP patients.
  
  
  CONCLUSIONS
  Patients taking duloxetine for OA or CLBP who have <10% reduction in pain after 4 weeks of treatment have limited possibility for eventually achieving even moderate pain reduction by the end of 12 weeks. ClinicalTrials.gov identifier: NCT00433290, NCT00408421, NCT00424593, NCT00408876, NCT00767806.
authors.affiliation: JPOCSC Pain Management Clinic, Fraser Health Authority, Surrey, British Columbia, Canada; Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Victoria, Australia.
authors.forename: Owen D
authors.initials: OD
authors.lastname: Williamson
authors.affiliation: Mercy Health, Cincinnati, Ohio.
authors.forename: Melissa
authors.initials: M
authors.lastname: Schroer
authors.affiliation: Lilly USA, LLC, Indianapolis, Indiana.
authors.forename: Dustin D
authors.initials: DD
authors.lastname: Ruff
authors.affiliation: Lilly USA, LLC, Indianapolis, Indiana.
authors.forename: Jonna
authors.initials: J
authors.lastname: Ahl
authors.affiliation: Medical Solutions, St Louis, Missouri.
authors.forename: Anthony
authors.initials: A
authors.lastname: Margherita
authors.affiliation: Eli Lilly Canada, Inc, Toronto, Canada.
authors.forename: Doron
authors.initials: D
authors.lastname: Sagman
authors.affiliation: Lilly USA, LLC, Indianapolis, Indiana. Electronic address: mwmd@lilly.com.
authors.forename: Madelaine M
authors.initials: MM
authors.lastname: Wohlreich
mesh_terms: D000700:Analgesics / Q000008:administration & dosage / Q000627:therapeutic use*; D059350:Chronic Pain / Q000188:drug therapy*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D000068736:Duloxetine Hydrochloride / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D017116:Low Back Pain / Q000188:drug therapy*; D008297:Male; D020370:Osteoarthritis, Knee / Q000188:drug therapy*; D010147:Pain Measurement
chemical_list: D000700:Analgesics; D000068736:Duloxetine Hydrochloride
keywords: back; chronic pain; duloxetine; minimal response; osteoarthritis