Sativex in resistant multiple sclerosis spasticity: Discontinuation study in a large population of Italian patients (SA.FE. study)

PLoS One. 2017 Aug 1;12(8):e0180651. doi: 10.1371/journal.pone.0180651. eCollection 2017.


Background: The approval of Sativex for the management of multiple sclerosis (MS) spasticity opened a new opportunity to many patients. In Italy, the healthcare payer can be fully reimbursed by the involved pharma company with the cost of treatment for patients not responding after a 4 week (28 days) trial period (Payment by Results, PbR), and 50% reimbursed with the cost of 6 weeks (42 days) treatment for other patients discontinuing (Cost Sharing, CS). The aim of our study was to describe the Sativex discontinuation profile from a large population of spasticity treated Italian MS patients.

Methods: We collected data of patients from 30 MS centres across the country starting Sativex between January 2014 and February 2015. Data were collected from the mandatory Italian Medicines Agency (AIFA) web-registry. Predictors of treatment discontinuation were assessed using a multivariate Cox proportional regression analysis.

Results: During the observation period 631 out of 1597 (39.5%) patients discontinued Sativex. The Kaplan-Meier estimates curve showed that 333 patients (20.8%) discontinued treatment at 4 weeks while 422 patients (26.4%) discontinued at 6 weeks. We found after adjusted modeling that a higher NRS score at T1 (adjHR 2.23, 95% 2.07-2.41, p<0.001) and a lower baseline NRS score (adjHR 0.51 95% CI 0.46-0.56, p<0.001) were predictive of treatment discontinuation.

Conclusion: These data show that the first 6 weeks are useful in identifying those patients in which Sativex could be effective, thus avoiding the cost of longer term evaluation.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Cannabidiol
  • Cost Sharing
  • Dronabinol
  • Drug Approval
  • Drug Combinations
  • Drug Costs
  • Drug Industry
  • Female
  • Humans
  • Italy
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Multiple Sclerosis / drug therapy*
  • Multivariate Analysis
  • Muscle Spasticity / drug therapy*
  • Parasympatholytics / economics
  • Parasympatholytics / therapeutic use*
  • Plant Extracts / economics
  • Plant Extracts / therapeutic use*
  • Proportional Hazards Models
  • Registries
  • Regression Analysis
  • Severity of Illness Index
  • Young Adult


  • Drug Combinations
  • Parasympatholytics
  • Plant Extracts
  • Cannabidiol
  • Dronabinol
  • nabiximols

Grant support

The authors received no specific funding for this work.