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Nabiximols discontinuation rate in a large population of patients with multiple sclerosis: a 18-month multicentre study
  1. Clara Grazia Chisari1,
  2. Claudio Solaro2,
  3. Pasquale Annunziata3,
  4. Roberto Bergamaschi4,
  5. Assunta Bianco5,
  6. Simona Bonavita6,
  7. Vincenzo Brescia Morra7,
  8. Roberto Bruno Bossio8,
  9. Elisabetta Capello9,
  10. Letizia Castelli10,
  11. Paola Cavalla11,
  12. Gianfranco Costantino12,
  13. Diego Centonze13,14,
  14. Salvatore Cottone15,
  15. Maura Chiara Danni16,
  16. Federica Esposito17,
  17. Alberto Gajofatto18,
  18. Claudio Gasperini19,
  19. Angelica Guareschi20,
  20. Roberta Lanzillo7,
  21. Giacomo Lus21,
  22. Giorgia Teresa Maniscalco22,
  23. Manuela Matta23,
  24. Damiano Paolicelli24,
  25. Loredana Petrucci25,
  26. Simona Pontecorvo26,
  27. Isabella Righini27,
  28. Marco Rovaris28,
  29. Edoardo Sessa29,
  30. Gabriella Spinicci30,
  31. Daniele Spitaleri31,
  32. Paola Valentino32,
  33. Mauro Zaffaroni33,
  34. Mario Zappia1,
  35. Francesco Patti1
  1. 1Department of Medical, Surgical Science and Advanced Technology "GF Ingrassia", section of neurosciences, Università degli Studi di Catania, Catania, Sicilia, Italy
  2. 2Rehabilitation Unit, "Mons. L. Novarese" Hospital, Moncrivello, Vercelli, Piemonte, Italy
  3. 3Department of Medicine, Surgery and Neurosciences, Università degli Studi di Siena Facoltà di Medicina e Chirurgia, Siena, Toscana, Italy
  4. 4Department of Neurology, Foundation National Neurological Institute C Mondino Institute for Hospitalization and Care Scientific, Pavia, Lombardia, Italy
  5. 5Multiple Sclerosis Unit, University Hospital Agostino Gemelli, Roma, Lazio, Italy
  6. 6Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences, II Clinic of Neurology, University of Campania "Luigi Vanvitelli", Naples, Campania, Italy
  7. 7Multiple Sclerosis Clinical Care and Research Centre, Department of Neuroscience, Reproductive Science and Odontostomatology, Federico II University Hospital, Napoli, Campania, Italy
  8. 8Neurology Operating Unit and Multiple Sclerosis Center, Cosenza Hospital Districts, Cosenza, Calabria, Italy
  9. 9Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genova, Ospedale Policlinico San Martino, Genova, Liguria, Italy
  10. 10IRCCS Fondazione Don Carlo Gnocchi, Milano, Lombardia, Italy
  11. 11Department of Neurosciences, Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino Ospedale San Vito, Torino, Piemonte, Italy
  12. 12Simple Unit Multiple Sclerosis, Ospedali Riuniti di Foggia, Foggia, Puglia, Italy
  13. 13Neuroscience Department, University of Rome Tor Vergata, Roma, Lazio, Italy
  14. 14Unit of Neurology and of Neurorehabilitation, NEUROMED, Pozzilli, Molise, Italy
  15. 15Villa Sofia Cervello United Hospitals, Palermo, Sicilia, Italy
  16. 16Neurological Clinic, Department of Experimental & Clinical Medicine, Università Politecnica delle Marche, Ancona, Marche, Italy
  17. 17Department of Neurology, San Raffaele Hospital, Milano, Lombardia, Italy
  18. 18Department of Neuroscience, Biomedicine and Movement Multiple Sclerosis Centre, Università degli Studi di Verona, Verona, Veneto, Italy
  19. 19Neurology Division, San Camillo Hospital, Roma, Lazio, Italy
  20. 20Multiple Sclerosis Center, Medicine Department, Fidenza Hospital, Fidenza, Emilia Romagna, Italy
  21. 21Multiple Sclerosis Center, II Division of Neurology, Department of Surgical Medical Science, Neurological, Metabolic and Aging, University of Campania Luigi Vanvitelli, Caserta, Campania, Italy
  22. 22Multiple Sclerosis Centre, Antonio Cardarelli Hospital, Napoli, Campania, Italy
  23. 23Multiple Sclerosis Centre (CRESM), San Luigi Gonzaga University Hospital, Orbassano, Italy
  24. 24Department of Basic Medical Sciences, Neuroscience and Sense Organs, Università degli Studi di Bari Aldo Moro, Bari, Puglia, Italy
  25. 25Multiple Sclerosis Centre, Pisa University Hospital, Pisa, Toscana, Italy
  26. 26Department of Human Neuroscience, Multiple Sclerosis Center, Sapienza University of Rome, Roma, Lazio, Italy
  27. 27NEUROFARBA Department, Neuroscience Section, University of Florence, Firenze, Toscana, Italy
  28. 28Multiple Sclerosis Centre, Don Gnocchi Foundation, Milano, Lombardia, Italy
  29. 29Multiple Sclerosis Centre, IRCCS Centro Neurolesi Bonino Pulejo, Messina, Sicilia, Italy
  30. 30Department of Medical Sciences, Università degli Studi di Cagliari, Cagliari, Sardegna, Italy
  31. 31Multiple Sclerosis Centre, Azienda Ospedaliera di Rilievo Nazionale e di Alta Specialità San Giuseppe Moscati, Avellino, Campania, Italy
  32. 32Institute of Neurology, Magna Graecia University of Catanzaro, Catanzaro, Calabria, Italy
  33. 33Multiple Sclerosis Centre, Gallarate Hospital, Azienda Socio Sanitaria Territoriale della Valle Olona, Gallarate, Lombardia, Italy
  1. Correspondence to Professor Francesco Patti, Department of Medical, Surgical Science and Advanced Technology "GF Ingrassia", University of Catania, Catania 95126, Italy; patti{at}unict.it

Abstract

Introduction Delta-δ-tetrahydrocannabinol and cannabidiol (THC:CBD) oromucosal spray is used as an add-on therapy option for moderate to severe multiple sclerosis (MS) spasticity resistant to other medications. Aims of this study were to provide real-life data on long-term clinical outcomes in a large population of Italian patients treated with THC:CBD and to evaluate predictors of THC:CBD therapy continuation.

Materials and methods This prospective observational multicentre Italian study screened all patients with MS consecutively included in the Agenzia Italiana del Farmaco e-registry at the start of THC:CBD treatment (baseline), after 4 weeks (T1), 12±3 weeks (T2), 24±3 weeks (T3), 48±3 weeks (T4) and 72±3 weeks (T5) from baseline.

Results A total of 1845 patients were recruited from 32 MS Italian centres. At T1, 1502 (81.4%) of patients reached a Numerical Rating Scale (NRS) improvement of ≥20%, with an NRS reduction of 26.9% at T1 and of 34.4% at T5. At T5, 725 patients (48.3% of 1502) discontinued treatment with highest discontinuation rate at T2 and T3. Daily number of puffs was generally stable through the observation period. The multivariate analysis showed that higher NRS scores at baseline (OR 2.28, 95% CI 1.15 to 6.36, p<0.01) and higher differences of NRS between T0 and T1 (OR 2.11, 95% CI 1.08 to 8.26, p<0.05) were associated with an increased probability to continue therapy after 18 months.

Discussion THC:CBD effects were sustained for 18 months with a relatively stable number of puffs per day. About 50% of patients abandoned THC:CBD therapy for loss of efficacy or adverse events.

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Footnotes

  • Collaborators Maria Pia Amato, Sebastiano Arena, Maria Donata Benedetti, Eliana Berra, Antonio Bertolotto, Assunta Bianco, Fabio Buttari, Raffaella Cerqua, Ada Francia, Aurora Fuiani, Angelo Ghezzi, Domenico Ippolito, Alfonso Iudice, Salvatore Lo Fermo, Maria Giovanna Marrosu, Enrico Montanari, Carlo Pozzilli, Isabella Righini, Margherita Russo, Francesco Saccà, Giovanna Salamone, Gabriella Spinicci, Eleonora Tavazzi, Simona Toscano, Maria Trojano, Luca Trabucco, Maria Trotta on behalf of the SA.FE. study group.

  • Contributors FP: conceptualisation, supervision, writing—review and editing, validation. CGC: data collection, methodology, statistical analysis, writing—original draft preparation. PA, RB, AB, SB, VBM, RBB, EC, LC, PC, DC, GC, SC, PD, FE, AGa, CG, AGu, RL, GL, GTM, MM, DP, LP, SP, IR, MR, ES, CS, GS, DS, MZaf, PV, MZap: data collection, revision and validation.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests RB reports grants and personal fees from Merck Serono, Almirall, Sanofi Genzyme, Novartis, Bayer, TEVA; grants, personal fees and non-financial support from Roche, Biogen, outside the submitted work. SB reports grants and personal fees from Almirall, Novartis; personal fees and non-financial support from Merck; personal fees from TEVA; grants, personal fees and non-financial support from Biogen, outside the submitted work. VBM reports grants and personal fees from Almirall, Novartis; grants, personal fees and non-financial support from Merck, Biogen; personal fees and non-financial support from TEVA, outside the submitted work. RBB reports grants and personal fees from Almirall, Novartis; grants, personal fees and non-financial support from Merck, Biogen; personal fees and non-financial support from TEVA, outside the submitted work. DC reports grants and personal fees from Merck Serono, Almirall, Sanofi Genzyme, Novartis, Bayer, TEVA; grants, personal fees and non-financial support from Roche, Biogen, outside the submitted work. CGC reports grants from Merck Serono, Roche, Biogen, Almirall, Sanofi Genzyme, Novartis, outside the submitted work. SC reports grants and personal fees from Merck Serono, Almirall, Sanofi Genzyme; grants, personal fees and non-financial support from Roche, Biogen, Novartis, TEVA, outside the submitted work. CG reports grants and personal fees from Almirall, outside the submitted work. GL reports grants and personal fees from Almirall, Novartis; personal fees and non-financial support from Merck; personal fees from TEVA; grants, personal fees and non-financial support from Biogen, outside the submitted work. GTM reports grants and personal fees from Almirall, Novartis; personal fees and non-financial support from Merck; personal fees from TEVA; grants, personal fees and non-financial support from Biogen, outside the submitted work. MM reports grants and personal fees from Almirall, outside the submitted work. FP reports grants and personal fees from Merck Serono, Sanofi Genzyme, Novartis; grants, personal fees and non-financial support from Roche, Biogen, Bayer, TEVA; grants and personal fees from Almiral, outside the submitted work. ES reports grants and personal fees from Almirall, Novartis; personal fees and non-financial support from Merck; personal fees from TEVA; grants, personal fees and non-financial support from Biogen, outside the submitted work. CS reports grants and personal fees from Merck Serono, Almirall, Sanofi Genzyme; grants, personal fees and non-financial support from Roche, Biogen, Bayer, TEVA, outside the submitted work. MZaf reports grants and personal fees from Almirall; non-financial support from Merck; personal fees from Novartis; grants, personal fees and non-financial support from Biogen, outside the submitted work. MZap reports grants and personal fees from Merck Serono, Almirall, Sanofi Genzyme, Novartis, Bayer, TEVA; grants, personal fees and non-financial support from Roche, Biogen, outside the submitted work.

  • Patient consent for publication Obtained.

  • Ethics approval This study protocol was approved by the Policlinico-Vittorio Emanuele (Catania, Italy) Ethics Committee (n 37/2015/PO) and by the Ethics Committees of all participating centres.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available on reasonable request. What the data are: Individual participant's data that underlie the results after deindentification. From whom the data are available from: Investigators who provide a methodologically sound proposal. Proposal may be submitted up to 36 months following the publication to the corresponding author FP.

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