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Neurological Sciences

, Volume 37, Issue 2, pp 235–242 | Cite as

Efficacy and safety of nabiximols (Sativex®) on multiple sclerosis spasticity in a real-life Italian monocentric study

  • Laura Ferrè
  • Arturo Nuara
  • Giulia Pavan
  • Marta Radaelli
  • Lucia Moiola
  • Mariaemma Rodegher
  • Bruno Colombo
  • Ignacio Juan Keller Sarmiento
  • Vittorio Martinelli
  • Letizia Leocani
  • Filippo Martinelli BoneschiEmail author
  • Giancarlo Comi
  • Federica Esposito
Original Article

Abstract

Multiple sclerosis (MS) patients frequently suffer from limb spasticity and pain despite antispastic treatments. To investigate nabiximols efficacy and safety in a real-world monocentric Italian cohort, the following data were collected at baseline, week 4, 14 and 48: Ambulation Index (AI), 10-min walking test (10MWT), combined Modified Ashworth scale (cMAS), scores at numerical rating scale for spasticity (sNRS) and pain (pNRS). Responder status was defined as a ≥20 % reduction in sNRS after 4 weeks of treatment. 144 MS patients (123 progressive and 21 relapsing-remitting) complaining of moderate-to-severe spasticity (mean sNRS: 7.5) were included: 138 (95.8 %) completed the first month of therapy and were classified as follows—23.2 % were non-responders, 5.1 % were responders but discontinued treatment due to side effects, 71.7 % were responders with a mean 32 % reduction in sNRS (p < 0.001). In responders sNRS further decreased between 4 and 14 weeks (p = 0.03). Similarly, pNRS improvement was seen during the first month and between 4 and 14 weeks (p < 0.001 and p = 0.004, respectively). Moreover, at 4 weeks responders showed a significant (p < 0.05) improvement in cMAS, AI and 10MWT, which was maintained at 14 weeks. At 1-year follow-up, a benefit was still evident on spasticity and painful symptoms with a low drop-out rate. Confusion/ideomotor slowing, fatigue and dizziness were the most frequent side effects; no major adverse events were reported. Shorter disease duration at treatment start was associated with better response. This real-world study confirms nabiximols efficacy and safety in the treatment of MS-related spasticity and pain, which is maintained up to 48 weeks.

Keywords

Multiple sclerosis Nabiximols Spasticity Pain 

Notes

Compliance with ethical standards

The study was approved by the internal ethics committee, in agreement with good clinical practice standards and respecting the confidentiality of the demographic and clinical data collected. All the subjects involved in the study gave their approval before data collection and signed a written informed consent.

Conflict of interest

Dr. Ferrè, Dr. Nuara, Dr. Pavan, Dr. Radaelli, Mr Keller Sarmiento and Prof. Leocani have nothing to disclose. Dr. Moiola reports speaking fees and/or travel expenses from Merck Serono and from Biogen. Dr. Rodegher reports speaking fees and/or travel expenses from Merck Serono and from Novartis. Dr. Colombo reports speaking fees and/or travel expenses from Merck Serono and from Teva Pharmaceuticals. Dr. Martinelli reports consultancy, speaking fees and/or travel expenses from Biogen-Dompè SG, Merck Serono, Bayer Schering, Novartis, Sanofi-Aventis, Genzyme Europe, Teva Pharmaceuticals. Prof. Comi has received consulting fees for participating on advisory boards from Novartis, Teva Pharmaceutical Ind. Ltd, Sanofi-Aventis, Merck Serono, Bayer Schering, Actelion and Geneuro and lecture fees from Novartis, Teva Pharmaceutical Industries Ltd, Sanofi-Aventis, Merck Serono, BiogenDompè, Bayer Schering and Serono Symposia International Foundation. PLDJ received honoraria for consulting, research grant, lecture and clinical trial from TEVA neuroscience, Biogen IDEC, Merck Serono and Vertex. Dr. Martinelli Boneschi received honoraria for consulting, research grant and travel expenses from TEVA neuroscience, Biogen IDEC, Serono Symposia International Foundation and Genzyme Europe. Dr. Esposito received honoraria from Serono Symposia International Foundation.

Supplementary material

10072_2015_2392_MOESM1_ESM.tiff (2.4 mb)
10MWT in responders at different time-point. 10MWT values at baseline, 4-, 14- and 48-week visit in responder patients (TIFF 2503 kb)

References

  1. 1.
    Pandyan AD, Gregoric M, Barnes MP et al (2005) Spasticity clinical perception, neurological realities and meaningful measurement. Disabil Rehabil 27(1–2):2–6CrossRefPubMedGoogle Scholar
  2. 2.
    Balantrapu S, Sosnoff J, Pula J et al. (2014) Leg spasticity and ambulation in multiple sclerosis. Mult Scler Int 649390. doi: 10.1155/2014/649390
  3. 3.
    Rizzo MA, Hadjimichael OC, Preiningerova J et al (2004) Prevalence and treatment of spasticity reported by multiple sclerosis patients. Mult Scler 10:589–595CrossRefPubMedGoogle Scholar
  4. 4.
    Shakespeare DT, Boggild M, Young C (2003) Anti-spasticity agents for multiple sclerosis. Cochrane Database Syst Rev (4):CD001332Google Scholar
  5. 5.
    Beard S, Hunn A, Wight J (2003) Treatments for spasticity and pain in multiple sclerosis: a systematic review. Health Technol Assess 7(40):iii, ix–x, 1–111Google Scholar
  6. 6.
    GW Pharma Ltd (2014) Sativex oromucosal spray: summary of product characteristics. http://www.medicines.org.uk/emc/medicine/23262. Accessed 27 Sep 2014
  7. 7.
    Wade DT, Makela P, Robson P et al (2004) Do cannabis-based medicinal extracts have general or specific effects on symptoms in multiple sclerosis? A double-blind, randomized, placebo-controlled study on 160 patients. Mult Scler 10(4):434–441CrossRefPubMedGoogle Scholar
  8. 8.
    Collin C, Davies P, Mutiboko IK et al (2007) Randomized controlled trial of cannabis-based medicine in spasticity caused by multiple sclerosis. Eur J Neurol 14(3):290–296Google Scholar
  9. 9.
    Collin C, Ehler E, Waberzinek G et al (2010) A double-blind, randomized, placebo-controlled, parallel-group study of Sativex, in subjects with symptoms of spasticity due to multiple sclerosis. Neurol Res 32(5):451–459. doi: 10.1179/016164109X12590518685660 [Epub 2010 Mar 19] CrossRefPubMedGoogle Scholar
  10. 10.
    Novotna A, Mares J, Ratcliffe S et al (2011) A randomized, double-blind, placebo-controlled, parallel-group, enriched-design study of nabiximols* (Sativex®), as add-on therapy, in subjects with refractory spasticity caused by multiple sclerosis. Eur J Neurol 18(9):1122–1131. doi: 10.1111/j.1468-1331.2010.03328.x [Epub 2011 Mar 1] CrossRefPubMedGoogle Scholar
  11. 11.
    Notcutt W, Langford R, Davies P et al (2012) A placebo-controlled, parallel-group, randomized withdrawal study of subjects with symptoms of spasticity due to multiple sclerosis who are receiving long-term Sativex® (nabiximols). Mult Scler 18(2):219–228CrossRefPubMedGoogle Scholar
  12. 12.
    Flachenecker P, Henze T, Zettl UK (2014) Nabiximols (THC/CBD oromucosal spray, Sativex®) in clinical practice–results of a multicenter, non-interventional study (MOVE 2) in patients with multiple sclerosis spasticity. Eur Neurol 71(5–6):271–279. doi: 10.1159/000357427 [Epub 2014 Feb 12] CrossRefPubMedGoogle Scholar
  13. 13.
    Flachenecker P, Henze T, Zettl UK (2014) Long-term effectiveness and safety of nabiximols (tetrahydrocannabinol/cannabidiol oromucosal spray) in clinical practice. Eur Neurol 72(1–2):95–102. doi: 10.1159/000360285 [Epub 2014 Jun 18] CrossRefPubMedGoogle Scholar
  14. 14.
    Koehler J, Feneberg W, Meier M et al (2014) Clinical experience with THC:CBD oromucosal spray in patients with multiple sclerosis-related spasticity. Int J Neurosci 124(9):652–656. doi: 10.3109/00207454.2013.877460 [Epub 2014 Jan 23] CrossRefPubMedGoogle Scholar
  15. 15.
    García-Merino A (2013) Endocannabinoid system modulator use in everyday clinical practice in the UK and Spain. Expert Rev Neurother 13(3 Suppl 1):9–13. doi: 10.1586/ern.13.4 CrossRefPubMedGoogle Scholar
  16. 16.
    Serpell MG, Notcutt W, Collin C (2013) Sativex long-term use: an open-label trial in patients with spasticity due to multiple sclerosis. J Neurol 260(1):285–295CrossRefPubMedGoogle Scholar
  17. 17.
    Polman CH, Reingold SC, Banwell B et al (2011) Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol 69(2):292–302PubMedCentralCrossRefPubMedGoogle Scholar
  18. 18.
    Anwar K, Barnes MP (2009) A pilot study of a comparison between a patient scored numeric rating scale and clinician scored measures of spasticity in multiple sclerosis. NeuroRehabilitation 24(4):333–340. doi: 10.3233/NRE-2009-0487
  19. 19.
    Farrar JT, Troxel AB, Stott C et al (2008) Validity, reliability, and clinical importance of change in a 0–10 numeric rating scale measure of spasticity: a post hoc analysis of a randomized, double-blind, placebo-controlled trial. Clin Ther 30(5):974–985CrossRefPubMedGoogle Scholar
  20. 20.
    Yadav V, Bever C Jr, Bowen J et al (2014) Summary of evidence-based guideline: complementary and alternative medicine in multiple sclerosis: report of the guideline development subcommittee of the American academy of neurology. Neurology 82(12):1083–1092PubMedCentralCrossRefPubMedGoogle Scholar
  21. 21.
    Medicines and Healthcare products regulatory agency. Public assessment report: Sativex oromucosal spray (reference number HK/H/2462/001/DC). http://www.mhra.gov.uk/home/groups/par/documents/websiteresources/con084961.pdf. Accessed July 2015

Copyright information

© Springer-Verlag Italia 2015

Authors and Affiliations

  • Laura Ferrè
    • 1
    • 2
  • Arturo Nuara
    • 1
    • 3
  • Giulia Pavan
    • 1
  • Marta Radaelli
    • 1
  • Lucia Moiola
    • 1
  • Mariaemma Rodegher
    • 1
  • Bruno Colombo
    • 1
  • Ignacio Juan Keller Sarmiento
    • 1
    • 2
  • Vittorio Martinelli
    • 1
  • Letizia Leocani
    • 1
    • 3
  • Filippo Martinelli Boneschi
    • 1
    • 2
    Email author
  • Giancarlo Comi
    • 1
  • Federica Esposito
    • 1
    • 2
  1. 1.Department of NeurologySan Raffaele Scientific InstituteMilanItaly
  2. 2.Laboratory of Genetics of Complex Neurological Disorders, Institute of Experimental Neurology (INSPE), Division of NeuroscienceSan Raffaele Scientific InstituteMilanItaly
  3. 3.Experimental Neurophysiology Unit, Institute of Experimental Neurology (INSPE)San Raffaele Scientific InstituteMilanItaly

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