Long-term Effectiveness of 9-δ-tetrahydrocannabinol:Cannabidiol Oromucosal Spray in Clinical Practice: results from a 18-months Multicenter Italian Study (P5.2-085)

Objective: We aimed to provide real life data on clinical outcomes of a large population of Italian patients with treatment-resistant multiple sclerosis (MS) spasticity receiving 9-δ-tetrahydocannabinol and cannabidiol (THC:CBD) oromucosal spray (Sativex®). Background: THC:CBD oromucosal spray is used as mono or add-on therapy for moderate to severe MS spasticity resistant to other medications. Design/Methods: This 18-months observational, prospective, multicentre study evaluated patients with resistant MS spasticity treated with THC:CBD according to approved labelling. Data were collected from the mandatory Italian medicines agency (AIFA) e-registry from January 2015 to June 2018. Spasticity assessment with the 0–10 numerical rating scale (NRS) was performed at baseline, after 1 month of treatment (T1) and every 6 months until 18 months (T4) from the treatment initiation. Results: A total of 1845 patients were recruited from 32 Italian MS centres. At T1, 1502 (81.4%) of patients reached an NRS improvement of ≥20% and 814 (40.2%) a of ≥30%, with a mean NRS score reduction of 28.9% at T1 and of 36.8% at T4. Daily number of puffs was generally stable through the observation period (6.9±2.4 at T1 vs 6.3±3.1 at T4, p=0.8). At T4, 727 (39.4%) patients have discontinued treatment; 388 (53.4%) because of lack of effectiveness and 339 (46.6%) for adverse events: 127 (37.5%) reported vertigo, 118 (34.8%) sleepiness, 96 (28.3%) worsening of fatigue, and 54 (15.9%) cognitive symptoms. The multivariate analysis showed that higher NRS score at baseline (OR 2.21 95%CI 1.12–6.28, p<0.01) and higher difference of NRS between T1 and baseline (OR 2.03 95%CI 1.04–8.14, p<0.05) were associated to an increased probability to stay on therapy after 18 months. Conclusions: Real-life data from a large Italian MS population confirmed the long-term effectiveness of THC:CBD for the treatment of resistant MS spasticity in everyday clinical practice. Treatment effects were sustained for 18-months with a relatively stable number of puffs/day. Disclosure: Dr. Patti has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Almirall, Bayer, Biogen, Celgene, Merck, Myalin, Novartis, Roche, Sanofi-Genzyme and Teva. Dr. Patti has received research support from MIUR (Ministero Italiano della Universita della Ricerca Scientifica), FISM (Fondazione Italiana Sclerosi Multipla), Biogen and Merck. Dr. Chisari has nothing to disclose. Dr. D’Amico has nothing to disclose. Dr. Solaro has nothing to disclose. Dr. Arena has nothing to disclose. Dr. Annunziata has nothing to disclose. Dr. Benedetti has nothing to disclose. Dr. Berra has nothing to disclose. Dr. Bianco has nothing to disclose. Dr. Bruno Bossio has nothing to disclose. Dr. Buttari has nothing to disclose. Dr. Castelli has nothing to disclose. Dr. Cavalla has nothing to disclose. Dr. Cerqua has nothing to disclose. Dr. Costantino has nothing to disclose. Dr. Esposito has nothing to disclose. Dr. Gasperini has nothing to disclose. Dr. Guareschi has nothing to disclose. Dr. Inglese has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Dr. Inglese reports grants from Novartis Pharmaceuticals, National Multiple Sclerosis Society, Noto Foundation, NIH and Teva Neuroscience. Dr. Ippolito has nothing to disclose. Dr. Lanzillo has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Merck, Novartis, Biogen, Genzyme, Teva and Almirall. Dr. Maniscalco has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Merck Serono, Biogen and TEVA. Dr. Matta has nothing to disclose. Dr. Pietruszewski has nothing to disclose. Dr. Petrucci has nothing to disclose. Dr. Pontecorvo has nothing to disclose. Dr. Righini has nothing to disclose. Dr. Sessa has nothing to disclose. Dr. Sacca has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Alrmirall, Biogen, Forward Pharma, Merck, Mylan, Novartis Pharmaceuticals, Pomona, Sanofi Genzyme, Roche, and Teva. Dr. Salamone has nothing to disclose. Dr. Signoriello has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Almirall, Biogen, Genzyme, Novartis and Teva. Dr. Spinicci has nothing to disclose. Dr. Spitaleri has nothing to disclose. Dr. Tavazzi has nothing to disclose. Dr. Trotta has nothing to disclose. Dr. Zaffaroni has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Genzyme, Merck-Serono and Biogen Italia. Dr. Zappia has nothing to disclose.