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

Silvia Messina,Francesco Patti,Ada Francia,Roberto Bruno Bossio,Salvatore Cottone,Claudio Gasperini,Diego Centonze,Claudio Solaro,Manuela Matta,Loredana Petrucci,Edoardo Sessa,Elisabetta Signoriello,Mario Zappia,Paola Cavalla,Roberto Bergamaschi,Isabella Righini,Damiano Paolicelli,Alberto Gajofatto,Letizia Castelli,Massimiliano Mirabella,Alfredo Granata,Graziella Pedà,Marco Rovaris,Vincenzo Brescia Morra,Daniele Spitaleri,Giancarlo Comi,Gabriella Spinicci,Mauro Zaffaroni,Simona Bonavita,Gianfranco Costantino,Mauro Maniscalco ,Maura Danni

doi:10.1371/journal.pone.0180651

Abstract

BackgroundThe 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.MethodsWe 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.ResultsDuring 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.ConclusionThese 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.

Highlights

Spasticity is a common symptom in multiple sclerosis(MS) patients [1,2]
We found after adjusted modeling that a higher numerical rating scale (NRS) score at T1 and a lower baseline NRS score were predictive of treatment discontinuation
These data show that the first 6 weeks are useful in identifying those patients in which Sativex could be effective, avoiding the cost of longer term evaluation

Summary

Introduction

Spasticity is a common symptom in multiple sclerosis(MS) patients [1,2]. Spasms, pain, poor sleep quality, and urinary dysfunction are symptoms frequently associated with spasticity in MS [3]. The efficacy of Sativex oromucosal spray as add-on therapy for symptoms improvement in MS patients with moderate to severe spasticity has been demonstrated in several clinical trials [9,10,11,7,12]. Dr Bergamaschi has received honoraria for scientific lectures and travel payment from Biogen, Novartis, Teva, Genzyme, Bayer Schering, Merck Serono, Almirall. Dr Brescia Morra has received honoraria for scientific lectures and travel payment from Biogen, Novartis, Teva, Genzyme, Bayer Schering, Merck Serono, Almirall. Prof Comi has received honoraria for scientific lectures from Biogen, Novartis, Teva, Genzyme, Bayer Schering, Merck Serono, Almirall. Dr Rovaris received honoraria from Biogen, Genzyme, Novartis, Merck Serono, of our study was to describe the Sativex discontinuation profile from a large population of spasticity treated Italian MS patients

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Conclusion