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Effects of THC/CBD oromucosal spray on spasticity-related symptoms in people with multiple sclerosis: results from a retrospective multicenter study

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Abstract

Introduction

The approval of 9-δ-tetrahydocannabinol (THC)+cannabidiol (CBD) oromucosal spray (Sativex®) in Italy as an add-on medication for the management of moderate to severe spasticity in multiple sclerosis (MS) has provided a new opportunity for MS patients with drug-resistant spasticity. We aimed to investigate the improvement of MS spasticity-related symptoms in a large cohort of patients with moderate to severe spasticity in daily clinical practice.

Materials and methods

MS patients with drug-resistant spasticity were recruited from 30 Italian MS centers. All patients were eligible for THC:CBD treatment according to the approved label: ≥ 18 years of age, at least moderate spasticity (MS spasticity numerical rating scale [NRS] score ≥ 4) and not responding to the common antispastic drugs. Patients were evaluated at baseline (T0) and after 4 weeks of treatment (T1) with the spasticity NRS scale and were also asked about meaningful improvements in 6 key spasticity-related symptoms.

Results

Out of 1615 enrolled patients, 1432 reached the end of the first month trial period (T1). Of these, 1010 patients (70.5%) reached a ≥ 20% NRS score reduction compared with baseline (initial responders; IR). We found that 627 (43.8% of 1432) patients showed an improvement in at least one spasticity-related symptom (SRSr group), 543 (86.6%) of them belonging to the IR group and 84 (13.4%) to the spasticity NRS non-responders group.

Conclusion

Our study confirmed that the therapeutic benefit of cannabinoids may extend beyond spasticity, improving spasticity-related symptoms even in non-NRS responder patients.

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Author information

Author notes

  1. Patti Francesco and G Chisari Clara contributed equally to this work.

Authors and Affiliations

  1. Department “G.F. Ingrassia”, section of Neurosciences, University of Catania, Catania, Italy

    Francesco Patti, Clara Grazia Chisari & Mario Zappia

  2. Department of Neurology, ASL3 Genovese, and Department of Rehabilitation, ML Novarese Hospital Moncrivello, Genoa, Italy

    Claudio Solaro

  3. Department of Neuroscience, Biomedicine, and Movement Sciences, Section of Neurology, University of Verona, Verona, Italy

    Maria Donata Benedetti

  4. Neurorehabilitation Unit, Department of Neurology, Neurology Institute C. Mondino, Pavia, Italy

    Eliana Berra

  5. Multiple Sclerosis Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy

    Assunta Bianco

  6. Neurology Operating Unit and Multiple Sclerosis Center, Provincial Health Authority of Cosenza, Cosenza, Italy

    Roberto Bruno Bossio

  7. Synaptic Immunopathology Lab, Department of Systems Medicine, Tor Vergata University, Rome, Italy

    Fabio Buttari

  8. Neurology Unit, IRCCS Fondazione Don Carlo Gnocchi, Milan, Italy

    Letizia Castelli

  9. Department Neuroscience and Mental Health, Multiple Sclerosis Centre, Health and Science City University Hospital of Turin, Turin, Italy

    Paola Cavalla

  10. Department of Experimental and Clinical Medicine, Neurological Clinic, Marche Polytechnic University, Ancona, Italy

    Raffaella Cerqua

  11. Demyelinating Diseases Centre, Foggia Hospital, Foggia, Italy

    Gianfranco Costantino

  12. Multiple Sclerosis Centre, San Camillo-Forlanini Hospital, Rome, Italy

    Claudio Gasperini

  13. Multiple Sclerosis Center, Medicine Department, Fidenza Hospital, Fidenza, PR, Italy

    Angelica Guareschi

  14. Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, Naples, Italy

    Domenico Ippolito

  15. Department of Neurosciences, Reproductive and Odontostomatological Sciences, University Federico II, Naples, Italy

    Roberta Lanzillo & Francesco Saccà

  16. Department of Neurology, Ospedale Cardarelli, Naples, Italy

    Giorgia Teresa Maniscalco

  17. Neurobiology Unit, Neurologia 2, CReSM (Regional Referring Center Multiple Sclerosis), San Luigi Gonzaga University Hospital & Neuroscience Institute Cavalieri Ottolenghi (NICO), Orbassano, TO, Italy

    Manuela Matta

  18. Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari Aldo Moro, Bari, Italy

    Damiano Paolicelli

  19. Multiple Sclerosis Centre, University Hospital Pisa, Pisa, Italy

    Loredana Petrucci

  20. Multiple Sclerosis Center of Department of Neurology and Psychiatry of Sapienza, University of Rome, Rome, Italy

    Simona Pontecorvo

  21. Department of NEUROFARBA, University of Florence, Florence, Italy

    Isabella Righini

  22. Multiple Sclerosis Centre, IRCCS-Bonino Pulejo Centre, Messina, Italy

    Margherita Russo

  23. Neuroimmunology Unit, Villa Sofia-Cervello Hospital, Palermo, Italy

    Giovanna Salamone

  24. Department of Clinical and Experimental Medicine, Multiple Sclerosis Center, II Division of Neurology, University of Campania “Luigi Vanvitelli”, Naples, Italy

    Elisabetta Signoriello

  25. Department of Medical Sciences and Public Health, Multiple Sclerosis Center, University of Cagliari, Cagliari, Italy

    Gabriella Spinicci

  26. Azienda Ospedaliera di Rilievo Nazionale, San Giuseppe Moscati, Avellino, Italy

    Daniele Spitaleri

  27. Multiple Sclerosis Center, Unit of Motor Neurorehabilitation, IRCCS Santa Maria Nascente, Fondazione Don Gnocchi, Milan, Italy

    Eleonora Tavazzi

  28. Institute of Neurology, University “Magna Graecia”, Germaneto, Catanzaro, Italy

    Maria Trotta

  29. Multiple Sclerosis Center, ASST della Valle Olona, Gallarate Hospital, Gallarate, VA, Italy

    Mauro Zaffaroni

Authors
  1. Francesco Patti
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  2. Clara Grazia Chisari
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  3. Claudio Solaro
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  4. Maria Donata Benedetti
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  5. Eliana Berra
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  6. Assunta Bianco
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  7. Roberto Bruno Bossio
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  31. Mauro Zaffaroni
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  32. Mario Zappia
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Consortia

on behalf of the SA.FE. group

Corresponding author

Correspondence to Francesco Patti.

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Conflict of interest

Prof Patti has received honoraria for speaking activities by Bayer Schering, Biogen Idec, Merck Serono, Novartis, and Sanofi Aventis; he also served as advisory board member the following companies: Bayer Schering, Biogen Idec, Merck Serono, and Novartis; he was also funded by Pfeizer and FISM for epidemiological studies; finally, he received grant for congress participation from Bayer Schering, Biogen Idec, Merck Serono, Novartis, Roche, Sanofi Aventis, and TEVA. Dr. Chisari CG received grant for congress participation from Bayer Schering, Biogen Idec, Merck Serono, Novartis, Roche, Sanofi Aventis, and TEVA. Dr. Solaro received honoraria from Biogen, Genzyme, Novartis, Merck Serono, Almirall, Roche, and TEVA. Dr. Bruno Bossio R received grant for advisory board activities from Almirall. Dr. Maniscalco GT received speaking and advisory honoraria from Biogen, Novartis, and TEVA. Dr. Matta M received honoraria for serving in the scientific advisory boards of Almirall, Novartis, Biogen, and Genzyme. Prof. Zappia M has received compensation for consulting services from Boehringer-Ingelheim, Lundbeck, Union Chimique Belge, and scientific grants from AIFA - Agenzia Italiana del Farmaco, Novartis, Lundbeck.

Dr. Benedetti MD, Dr. Berra E, Dr. Bianco A, Dr. Buttari, Dr. Castelli L, Dr. Cavalla P, Dr. Cerqua R, Dr. Costantino GF, Dr. Gasperini C, Dr. Guareschi, Dr. Ippolito D, Dr. Lanzillo R, Dr. Paolicelli D, Dr. Petrucci L, Dr. Pontecorvo S, Dr. Righini I, Dr. Russo M, Dr. Saccà F, Dr. Salamone G, Dr. Signoriello E, Dr. Spinicci G, Dr. Spitaleri D, Dr. Tavazzi E, Dr. Trotta M, and Dr. Zaffaroni M declared that they have no conflict of interest.

Ethics approval

The study was approved by the Policlinico-Vittorio Emanuele (Catania, Italy) Ethics Committee (no. 37/2015/PO) and by the Ethics Committee of the other participating centers.

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Patti, F., Chisari, C., Solaro, C. et al. Effects of THC/CBD oromucosal spray on spasticity-related symptoms in people with multiple sclerosis: results from a retrospective multicenter study. Neurol Sci 41, 2905–2913 (2020). https://doi.org/10.1007/s10072-020-04413-6

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