Tweet
A few studies were released at the just-completed ECTRIMS conference. - D
Effect of THC/CBD oromucosal spray on spasticity in MS: an open label clinical-neurophysiological study
A. Nuara, A. Giordano, L. Ferrè, V. Martinelli, F. Martinelli Boneschi, F. Esposito, G. Comi, L. Leocani Ospedale San Raffaele, Milan, Italy
Background: Spasticity, manifesting as muscle stiffness, spasms and pain, is a frequent symptom of multiple sclerosis (MS), with a strong impact on quality on life of patients. Cannabis derivatives and endocannabinoid system modulator (such as Sativex, a THC/CBD oromucosal spray) have been reported to relieve symptoms of spasticity in MS. Despite demonstrated symptomatic relief of MS spasticity, few studies have investigated neurophysiological baseline characteristics on predicting treatment response, as well as the neurophysiological changes induced by theraphy with cannabinoids in MS.
Objectives: To assess the clinical-neurophysiological correlates of Sativex effect on spasticity in MS and the predictive value of neurophysiological baseline features on treatment response.
Methods: 20 outpatients affected by multiple sclerosis (6M, 14F, age 31-64, EDSS 4.0-7.5) with spasticity-associated symptoms (baseline spasticity NRS>4) underwent the following clinical evaluations at baseline (T0) and after a 4-week (T4) Sativex titration period: EDSS, 10 meters walking test, Ambulation Index (AI), Modified Ashworth Scale (MAS), spasticity and pain numerical-rating-scale (NRS). Neurophysiological baseline features (resting motor threshold [RMT], Motor-evoked-potentials [MEP's] amplitude of First Digital Interosseus [FDI] at 120% of RMT, intracortical inhibition/facilitation [ICI/ICF] were collected at T0 in the whole group ad in 10 patients at T4.
Results: From T0 to T4, a significant improvement of spasticity was observed, considering both subjective (NRS 7+1.45 vs 5.15+1.38, p=0.0001) and physician-reported (MAS 3.3+1.94 2.93+1.70) spasticity. No significant changes in neurophysiological measures were observed. Grouping patients according to treatment responsiveness (NRS improvement >20%, 9 responder), no significant differences were found in neurophysiological baseline features.
Conclusion: Our findings confirm the clinical benefit of Sativex on MS spasticity. The lack of both corresponding changes in corticospinal excitability and baseline neurophysiological predictors of efficacy, suggest the involvement of other neurophysiological mechanisms underlying Sativex effect on spasticity.
-------------------
The use of medical-grade Cannabis (Bedrocan®) in patients non-responders to nabiximols (sativex®)
F. Saccà1, C. Pane1, A. Carotenuto1, M. Massarelli1, R. Lanzillo1, E.B. Florio2, V. Brescia Morra1 1Department of Neuroscience, Reproductive, and Odontostomatological Sciences, Federico II University, 2Farmacia Florio Dr. Ettore SNC, Napoli, Italy
Introduction: Spasticity is one of the most common symptoms in Multiple sclerosis (MS). It causes disability, and is chronically present. Historical treatment includes several drugs with very limited patient and physician satisfaction. Nabiximols (Sativex®) is a cannabis extract containing a 1:1 ratio of delta-9-tetrahydrocannabinol to Cannabidiol. Several studies showed its superiority over placebo in reducing the Numeric Rating Scale (NRS). Unfortunately, half of treated patients do not respond to Nabiximols and for them therapeutic options are absent.
Methods: We retrospectively enrolled patients that had been treated with Nabiximols (Sativex®) for 28 days and were judged non-responders (reduction < 20% from baseline NRS), and were subsequently treated with medical-grade cannabis (Bedrocan®) for at least 28 days. Bedrocan was fractionized at authorized ISO 9001:2008 pharmacies into 50 mg sachets. Patients were instructed to take Bedrocan at a dose of 50-100 mg /day.
Results: We found 13 patients (Table 1) corresponding to our inclusion criteria. Non-response to Nabiximols was caused by insufficient NRS reduction for all patients. Bedrocan was administered orally to eleven patients, and through smoking for two. Mean NRS for Nabiximols Baseline was 7.6±1.5 and 7.4±1.6 after 28 days (-0.2; CI -0.65, +0.15; p=0.493). Mean NRS for Bedrocan baseline was 7.6±1.8 and 5.3±2.4 after 28 days (-2.3; CI -3.58, -1.12; p< 0.001). Patients continued Bedrocan administration for 205±182 days (range 46-700). Two patients suspended therapy, one for the onset of dizziness, and the other for the drug's cost. Mean NRS at follow-up was 5.6±2.3, resulting in a significant reduction as compared to baseline (-2.0; CI -.2.9, -1.2; p< 0.001). During Bedrocan therapy, only 3 AEs were reported in three patients, as compared to 15 AEs in 11 patients during Nabiximols treatment (Odds Ratio 5.0; CI 1.45, 17.27; p< 0.02).
Discussion: This is the first study that investigates rescue strategies for Nabiximols non-responders. Bedrocan was very well tolerated with 85% responders at 28 days and 70% at the end of the individual follow-up. This is a high response rate if compared to previous trials. Future randomized, placebo-controlled studies are necessary to conclude, at a higher class of evidence, that medicinal-grade cannabis is a good option for Nabiximols non-responders.
-------------------------
Nabixol (Sativex) in spasticity responders multiple sclerosis patients is effective on subjective but not on objective measures of walking ability
C. Solaro1, E. Trabucco2, M. Cella1, A. Mattioda3, S. Masera3, P. Cavalla3 1ASL3 Genovese, genova, 2Università di genova, of Experimental Medicine, Section of Diagnostic Radiology, 3Centro SM, Dep. of Neuroscience, AOU Città della Salute e della scienza, torino, Italy
Background: Delta-9-tetrahydrocannabinol (THC)/cannabidiol (CBD) [Sativex(®)] is an oromucosal spray formulation is approved in a number of countries, included Italy, as add-on therapy for moderate-to-severe multiple sclerosis (MS) treatment-resistant spasticity symptoms.
Objective: The aim of the study is to provide real- life observational data of effect of Sativex on walking objective measures and patients' perceptions of the impact of MS on walking ability
Materials and methods: This was an observational, prospective study conducted in 2 italian MS centres. Patients with moderate to severe spasticity, with a score at the numerical rating scale (NRS) greater than 4 were included in the study. A battery of tests including Symbol Digit (SDT), Nine Hole Peg Test (9HPT), Fatigue Severity Scale (FSS), 12-item Multiple Sclerosis Walking Scale (MSWS-12), Two Minutes Walking Test (2MWT) and Timed 25-foot Walk (T25FW) was performed at baseline (T0) and 30 days later (T1). Responders had been defined by the literature as subjects with an improvement at the NRS score for spasticity greater than 20%
Results: Out of 75 subjects enrolled 33 were female and 42 male. Mean age was 53.7 years (range 28.26 - 81.43) , mean disease duration 13 years (range 0.7 - 39), 25 (29.3%) subjects had relapsing remitting, 34 (45.3%) secondary progressive and 19 (25.4%) had primary progressive disease course. Mean EDSS score was 6.2 (range 4 - 8.5).
A significant improvement (>20%) at NRS was observed in 49 patients (responders), 26 patients were classified as “no responders”.
Considering patients able to walk (EDSS < = 6.5, n°32) mean NRS for spasticity at T0 was 7.9 (range 1-10) in 20/32 patients mean score decreased greater than >40%. MSWS-12 score decreased more than 6 points in 19/32 patients and an improvement (>20%) in FSS was reported in 5/32 subjects.
An improvement (>20%) in walking speed (T25FW) was observed in 2/32 patient and in endurance (2MWT) in only 1/32 patients. No patients improved in 9HPT and SDT
Conclusions: Real-life data confirm Sativex(®) as an effective on spasticity (65.3% responders) and well tolerated treatment option for MS patients. A positive effect was highlighted on measuring patients' perceptions of walking scale such as fatigue and MS12 while an effect on objective measures on walking performance was not found.
Effect of THC/CBD oromucosal spray on spasticity in MS: an open label clinical-neurophysiological study
A. Nuara, A. Giordano, L. Ferrè, V. Martinelli, F. Martinelli Boneschi, F. Esposito, G. Comi, L. Leocani Ospedale San Raffaele, Milan, Italy
Background: Spasticity, manifesting as muscle stiffness, spasms and pain, is a frequent symptom of multiple sclerosis (MS), with a strong impact on quality on life of patients. Cannabis derivatives and endocannabinoid system modulator (such as Sativex, a THC/CBD oromucosal spray) have been reported to relieve symptoms of spasticity in MS. Despite demonstrated symptomatic relief of MS spasticity, few studies have investigated neurophysiological baseline characteristics on predicting treatment response, as well as the neurophysiological changes induced by theraphy with cannabinoids in MS.
Objectives: To assess the clinical-neurophysiological correlates of Sativex effect on spasticity in MS and the predictive value of neurophysiological baseline features on treatment response.
Methods: 20 outpatients affected by multiple sclerosis (6M, 14F, age 31-64, EDSS 4.0-7.5) with spasticity-associated symptoms (baseline spasticity NRS>4) underwent the following clinical evaluations at baseline (T0) and after a 4-week (T4) Sativex titration period: EDSS, 10 meters walking test, Ambulation Index (AI), Modified Ashworth Scale (MAS), spasticity and pain numerical-rating-scale (NRS). Neurophysiological baseline features (resting motor threshold [RMT], Motor-evoked-potentials [MEP's] amplitude of First Digital Interosseus [FDI] at 120% of RMT, intracortical inhibition/facilitation [ICI/ICF] were collected at T0 in the whole group ad in 10 patients at T4.
Results: From T0 to T4, a significant improvement of spasticity was observed, considering both subjective (NRS 7+1.45 vs 5.15+1.38, p=0.0001) and physician-reported (MAS 3.3+1.94 2.93+1.70) spasticity. No significant changes in neurophysiological measures were observed. Grouping patients according to treatment responsiveness (NRS improvement >20%, 9 responder), no significant differences were found in neurophysiological baseline features.
Conclusion: Our findings confirm the clinical benefit of Sativex on MS spasticity. The lack of both corresponding changes in corticospinal excitability and baseline neurophysiological predictors of efficacy, suggest the involvement of other neurophysiological mechanisms underlying Sativex effect on spasticity.
-------------------
The use of medical-grade Cannabis (Bedrocan®) in patients non-responders to nabiximols (sativex®)
F. Saccà1, C. Pane1, A. Carotenuto1, M. Massarelli1, R. Lanzillo1, E.B. Florio2, V. Brescia Morra1 1Department of Neuroscience, Reproductive, and Odontostomatological Sciences, Federico II University, 2Farmacia Florio Dr. Ettore SNC, Napoli, Italy
Introduction: Spasticity is one of the most common symptoms in Multiple sclerosis (MS). It causes disability, and is chronically present. Historical treatment includes several drugs with very limited patient and physician satisfaction. Nabiximols (Sativex®) is a cannabis extract containing a 1:1 ratio of delta-9-tetrahydrocannabinol to Cannabidiol. Several studies showed its superiority over placebo in reducing the Numeric Rating Scale (NRS). Unfortunately, half of treated patients do not respond to Nabiximols and for them therapeutic options are absent.
Methods: We retrospectively enrolled patients that had been treated with Nabiximols (Sativex®) for 28 days and were judged non-responders (reduction < 20% from baseline NRS), and were subsequently treated with medical-grade cannabis (Bedrocan®) for at least 28 days. Bedrocan was fractionized at authorized ISO 9001:2008 pharmacies into 50 mg sachets. Patients were instructed to take Bedrocan at a dose of 50-100 mg /day.
Results: We found 13 patients (Table 1) corresponding to our inclusion criteria. Non-response to Nabiximols was caused by insufficient NRS reduction for all patients. Bedrocan was administered orally to eleven patients, and through smoking for two. Mean NRS for Nabiximols Baseline was 7.6±1.5 and 7.4±1.6 after 28 days (-0.2; CI -0.65, +0.15; p=0.493). Mean NRS for Bedrocan baseline was 7.6±1.8 and 5.3±2.4 after 28 days (-2.3; CI -3.58, -1.12; p< 0.001). Patients continued Bedrocan administration for 205±182 days (range 46-700). Two patients suspended therapy, one for the onset of dizziness, and the other for the drug's cost. Mean NRS at follow-up was 5.6±2.3, resulting in a significant reduction as compared to baseline (-2.0; CI -.2.9, -1.2; p< 0.001). During Bedrocan therapy, only 3 AEs were reported in three patients, as compared to 15 AEs in 11 patients during Nabiximols treatment (Odds Ratio 5.0; CI 1.45, 17.27; p< 0.02).
Discussion: This is the first study that investigates rescue strategies for Nabiximols non-responders. Bedrocan was very well tolerated with 85% responders at 28 days and 70% at the end of the individual follow-up. This is a high response rate if compared to previous trials. Future randomized, placebo-controlled studies are necessary to conclude, at a higher class of evidence, that medicinal-grade cannabis is a good option for Nabiximols non-responders.
-------------------------
Nabixol (Sativex) in spasticity responders multiple sclerosis patients is effective on subjective but not on objective measures of walking ability
C. Solaro1, E. Trabucco2, M. Cella1, A. Mattioda3, S. Masera3, P. Cavalla3 1ASL3 Genovese, genova, 2Università di genova, of Experimental Medicine, Section of Diagnostic Radiology, 3Centro SM, Dep. of Neuroscience, AOU Città della Salute e della scienza, torino, Italy
Background: Delta-9-tetrahydrocannabinol (THC)/cannabidiol (CBD) [Sativex(®)] is an oromucosal spray formulation is approved in a number of countries, included Italy, as add-on therapy for moderate-to-severe multiple sclerosis (MS) treatment-resistant spasticity symptoms.
Objective: The aim of the study is to provide real- life observational data of effect of Sativex on walking objective measures and patients' perceptions of the impact of MS on walking ability
Materials and methods: This was an observational, prospective study conducted in 2 italian MS centres. Patients with moderate to severe spasticity, with a score at the numerical rating scale (NRS) greater than 4 were included in the study. A battery of tests including Symbol Digit (SDT), Nine Hole Peg Test (9HPT), Fatigue Severity Scale (FSS), 12-item Multiple Sclerosis Walking Scale (MSWS-12), Two Minutes Walking Test (2MWT) and Timed 25-foot Walk (T25FW) was performed at baseline (T0) and 30 days later (T1). Responders had been defined by the literature as subjects with an improvement at the NRS score for spasticity greater than 20%
Results: Out of 75 subjects enrolled 33 were female and 42 male. Mean age was 53.7 years (range 28.26 - 81.43) , mean disease duration 13 years (range 0.7 - 39), 25 (29.3%) subjects had relapsing remitting, 34 (45.3%) secondary progressive and 19 (25.4%) had primary progressive disease course. Mean EDSS score was 6.2 (range 4 - 8.5).
A significant improvement (>20%) at NRS was observed in 49 patients (responders), 26 patients were classified as “no responders”.
Considering patients able to walk (EDSS < = 6.5, n°32) mean NRS for spasticity at T0 was 7.9 (range 1-10) in 20/32 patients mean score decreased greater than >40%. MSWS-12 score decreased more than 6 points in 19/32 patients and an improvement (>20%) in FSS was reported in 5/32 subjects.
An improvement (>20%) in walking speed (T25FW) was observed in 2/32 patient and in endurance (2MWT) in only 1/32 patients. No patients improved in 9HPT and SDT
Conclusions: Real-life data confirm Sativex(®) as an effective on spasticity (65.3% responders) and well tolerated treatment option for MS patients. A positive effect was highlighted on measuring patients' perceptions of walking scale such as fatigue and MS12 while an effect on objective measures on walking performance was not found.
Comment