title: A Model-Based Meta-analysis to Compare Efficacy and Tolerability of Tramadol and Tapentadol for the Treatment of Chronic Non-Malignant Pain.
abstract: BACKGROUND
  Pain is a major symptom in many medical conditions which can be relieved thanks to analgesics. The goal of this work was to present an indirect comparison of efficacy and tolerability profiles of two analgesics, tramadol and tapentadol, in patients with chronic non-malignant pain.
  
  
  METHODS
  In the absence of a head-to-head comparison between these two opioid drugs, model-based meta-analyses were used to characterize the pain intensity time dynamics and evaluate the proportions of most frequent adverse events (constipation, nausea, vomiting, dizziness, and somnolence) and drop-outs (due to adverse event, as well as due to lack of efficacy) in each treatment group. Using these models, the investigational treatments were compared on the basis of Monte Carlo simulation outcomes.
  
  
  RESULTS
  Data were extracted from 45 Phase II and Phase III studies representing a total of 81 treatment arms, i.e., approximately 13,000 patients. The pain intensity model shows, that after having adjusted for differences in baseline pain intensity and placebo effects, tramadol 300 mg once daily (qd) was slightly more effective in reducing pain than tapentadol 100-250 mg twice daily (bid), with a 46% change from baseline for the former versus 36% for the latter. From a tolerability standpoint, both drugs showed, as expected, increased risks of adverse events compared to placebo. Yet, tapentadol was associated with slightly lower risks of constipation, and nausea than tramadol.
  
  
  CONCLUSIONS
  Overall, the analysis showed that the benefit-risk profiles of tramadol 300 mg qd and tapentadol 100-250 mg bid were approximately even. The amount of data to characterize dose-response relationships was sufficient only in the tramadol group; public access to tapentadol efficacy and tolerability readouts across a wide dose range in chronic non-malignant pain would allow a comparison of therapeutic indices, a straight quantitation of the benefit-risk ratio. Knowing that their side-effects have been identified as potential hindrance to prescription, a broad and open access to clinical trial data in this indication is encouraged in order to facilitate the evaluation of the opiate analgesics clinical utility.
authors.affiliation: Pharsight Consulting Services, a Certara™ Company, St. Louis, MO, USA, francois0mercier@gmail.com.
authors.forename: François
authors.initials: F
authors.lastname: Mercier
authors.forename: Laurent
authors.initials: L
authors.lastname: Claret
authors.forename: Klaas
authors.initials: K
authors.lastname: Prins
authors.forename: René
authors.initials: R
authors.lastname: Bruno