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Research paper
Efficacy and safety of cannabinoid oromucosal spray for multiple sclerosis spasticity
  1. F Patti1,
  2. S Messina1,
  3. C Solaro2,
  4. M P Amato3,
  5. R Bergamaschi4,
  6. S Bonavita5,
  7. R Bruno Bossio6,
  8. V Brescia Morra7,
  9. G F Costantino8,
  10. P Cavalla9,
  11. D Centonze10,11,
  12. G Comi12,
  13. S Cottone13,
  14. M Danni14,
  15. A Francia15,
  16. A Gajofatto16,
  17. C Gasperini17,
  18. A Ghezzi18,
  19. A Iudice19,
  20. G Lus20,
  21. G T Maniscalco21,
  22. M G Marrosu22,
  23. M Matta23,
  24. M Mirabella24,
  25. E Montanari25,
  26. C Pozzilli26,
  27. M Rovaris27,
  28. E Sessa28,
  29. D Spitaleri29,
  30. M Trojano30,
  31. P Valentino31,
  32. M Zappia1
  33. on behalf of the SA.FE. study group
    1. 1Department of Medical, Surgical Science and Advanced Technology “GF Ingrassia”, University of Catania, Catania, Italy
    2. 2Neurology Unit, Department Head and Neck, ASL3 Genova, Genova, Italy
    3. 3Department NEUROFARBA, University of Florence, Florence, Italy
    4. 4Department of Neurology, Neurology Institute C Mondino, Pavia, Italy
    5. 5I Clinic Neurology, II University of Naples, Naples, Italy
    6. 6Neurology Operating Unit, Multiple Sclerosis Center, Provincial Health Authority of Cosenza, Cosenza, Italy
    7. 7Multiple Sclerosis Centre, University Federico II, Naples, Italy
    8. 8Demyelinating Diseases Centre, Foggia Hospital, Foggia, Italy
    9. 9Multiple Sclerosis Centre, S. Giovanni Battista, Molinette Hospital, Turin, Italy
    10. 10Department of Systems Medicine, Multiple Sclerosis Clinical and Research Center, Tor Vergata University, Rome, Italy
    11. 11Unit of Neurology and of Neurorehabilitation, IRCCS Neuromed, Pozzilli (IS), Italy
    12. 12Department of Neurology, San Raffaele Hospital, Milan, Italy
    13. 13Neuroimmunology Unit, Villa Sofia-Cervello Hospital, Palermo, Italy
    14. 14Neurology Clinic, Ancona Hospital, Ancona, Italy
    15. 15Department Neurol Psich, Multiple Sclerosis Center, Sapienza University, Rome, Italy
    16. 16Multiple Sclerosis Centre, University of Verona, Verona, Italy
    17. 17Neurology Division, San Camillo Hospital, Rome, Italy
    18. 18Multiple Sclerosis Centre, Sant'Antonio Abate Hospital, Gallarate, Italy
    19. 19Multiple Sclerosis Centre, University Hospital Pisa, Pisa, Italy
    20. 20Multiple Sclerosis Center, Second University of Naples, Naples, Italy
    21. 21Multiple Sclerosis Centre, Cardarelli Hospital, Naples, Italy
    22. 22Department of Medical Sciences, University of Cagliari, Cagliari, Italy
    23. 23Multiple Sclerosis Centre (CRESM), San Luigi Gonzaga Hospital, Orbassano, Italy
    24. 24Multiple Sclerosis Centre, Cattolica University, Rome, Italy
    25. 25Multiple Sclerosis Centre, Vaio Hospital, Fidenza, Italy
    26. 26Multiple Sclerosis Centre, S. Andrea Hospital, Rome, Italy
    27. 27Multiple Sclerosis Centre, IRCCS Don Gnocchi Foundation, Milan, Italy
    28. 28Multiple Sclerosis Centre, IRCCS-Bonino Pulejo Centre, Messina, Italy
    29. 29Multiple Sclerosis Centre, San G. Moscati Hospital, Avellino, Italy
    30. 30Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari “Aldo Moro”, Bari, Italy
    31. 31Department of Medical Sciences, Institute of Neurology, University “Magna Graecia”, Catanzaro, Italy
    1. Correspondence to Dr Francesco Patti, Department “G.F.Ingrassia”, Multiple Sclerosis Center, University of Catania, Teaching Hospital Policlinico “G.Rodolico”, Via S. Sofia 78, Catania 95123, Italy; patti{at}


    Background The approval of 9-δ-tetrahydocannabinol and cannabidiol (THC:CBD) oromucosal spray (Sativex) for the management of treatment-resistant multiple sclerosis (MS) spasticity opened a new opportunity for many patients. The aim of our study was to describe Sativex effectiveness and adverse events profile in a large population of Italian patients with MS in the daily practice setting.

    Methods We collected data of all patients starting Sativex between January 2014 and February 2015 from the mandatory Italian medicines agency (AIFA) e-registry. Spasticity assessment by the 0–10 numerical rating scale (NRS) scale is available at baseline, after 1 month of treatment (trial period), and at 3 and 6 months.

    Results A total of 1615 patients were recruited from 30 MS centres across Italy. After one treatment month (trial period), we found 70.5% of patients reaching a ≥20% improvement (initial response, IR) and 28.2% who had already reached a ≥30% improvement (clinically relevant response, CRR), with a mean NRS score reduction of 22.6% (from 7.5 to 5.8). After a multivariate analysis, we found an increased probability to reach IR at the first month among patients with primary and secondary progressive MS, (n=1169, OR 1.4 95% CI 1.04 to 1.9, p=0.025) and among patients with >8 NRS score at baseline (OR 1.8 95% CI 1.3–2.4 p<0.001). During the 6 months observation period, 631(39.5%) patients discontinued treatment. The main reasons for discontinuation were lack of effectiveness (n=375, 26.2%) and/or adverse events (n=268, 18.7%).

    Conclusions Sativex can be a useful and safe option for patients with MS with moderate to severe spasticity resistant to common antispastic drugs.

    This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:

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