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Nabiximols, a cannabis-based oral spray containing delta-9 tetrahydrocannabinol and cannabidiol, significantly improved spasticity symptoms in combination with antispasticity drugs in patients with motor neuron disease in a randomized, double-blind, placebo-controlled, parallel-group, phase 2 clinical trial.
Nabiximols proved superior to a placebo spray when both were given to patients with either amyotrophic lateral sclerosis or primary lateral sclerosis as part of an antispasticity regimen in the 6-week, CANALS (Cannabis Sativa Extract in Amyotrophic Lateral Sclerosis and other Motor Neuron Disease) study at four Italian centers, Nilo Riva, MD, PhD, of the San Raffaele Scientific Institute in Milan and his colleagues reported in The Lancet Neurology. Nabiximols is approved for the treatment of spasticity due to multiple sclerosis in multiple countries, but not in the United States.
“There is no cure for motor neuron disease, so improved symptom control and quality of life are important for patients,” Dr. Riva stated in a press release. “Our proof-of-concept trial showed a beneficial effect of THC-CBD [delta-9 tetrahydrocannabinol and cannabidiol] spray in people on treatment-resistant spasticity and pain.
“Despite these encouraging findings, we must first confirm that THC-CBD spray is effective and safe in larger, longer-term phase 3 trials,” Dr. Riva added.
The patients enrolled in the phase 2 trial between January 2013 and December 2014 and were between 18 and 80 years old with a probable diagnosis of amyotrophic lateral sclerosis or primary lateral sclerosis, were on an antispasticity regimen for at least 30 days, and had a spasticity score of at least 1 in two muscle groups on the 5-point Modified Ashworth Scale. Participants titrated for the first 2 weeks before maintaining their treatment for 4 weeks.
Of 59 participants at final follow-up, Modified Ashworth Scale scores improved in the nabiximols group (29 participants) by a mean of –0.11 points, compared with worsening by a mean of 0.16 points in the placebo group (30 participants). The researchers noted that there were no participants who withdrew from the study, nabiximols was well-tolerated, and there were no serious adverse events in the nabiximols group; however, there were 22 participants in the nabiximols group and 8 participants in the placebo group who experienced an adverse event from any cause.
“This study is, to our knowledge, the first randomized controlled trial of safety and efficacy of a pharmacological treatment for spasticity and the first trial of nabiximols in motor neuron disease,” Dr. Riva and his colleagues wrote. “Our results suggest that the study drug is well tolerated and provides first evidence of efficacy in terms of controlling spasticity in patients with motor neuron disease.”
The study was funded by the Italian Research Foundation for Amyotrophic Lateral Sclerosis. GW Pharma, which developed nabiximols, provided the study drug and placebo. Many of the authors reported financial disclosures with pharmaceutical companies.
SOURCE: Riva N et al. Lancet Neurol. 2018 Dec 13. doi: 10.1016/S1474-4422(18)30406-X.
Although the results of Riva et al. are encouraging, the study had several major limitations and future research in the form of larger, multicenter, randomized controlled trials is needed, Marianne de Visser, MD, PhD, wrote in a related editorial.
Dr. de Visser noted a bias in the study as it randomized 16 patients with predominantly upper motor neuron involvement to the nabiximols group. The treatment could potentially have benefited those patients, for whom spasticity is the prevailing symptom, more than the 13 patients randomized to the nabiximols group who had classic amyotrophic lateral sclerosis involving both upper and lower neurons. In addition, Riva et al. did not differentiate between patients with upper and lower limb spasticity or patients with bulbar spasticity and those without, she said.
The use of the Modified Ashworth Scale was also a potential issue, because while it has been used in previous studies examining antispastic treatment efficacy, “it lacked sensitivity in studies of the efficacy of cannabinoids in patients with multiple sclerosis–related spasticity, and new spasticity numeric rating or visual analogue scales are being adopted,” Dr. de Visser wrote.
The number of adverse effects in the treatment group could have also unblinded researchers, which may have affected the significant findings, she said.
“Before asking for approval of cannabinoids for symptomatic treatment of spasticity in patients with amyotrophic lateral sclerosis, further studies are needed to establish the frequency of spasticity in the various presentations of motor neuron disease, and also whether reductions in spasticity improve quality of life,” Dr. de Visser said in a press release. “Natural history studies including all subtypes of motor neuron disease and better outcome measures aimed at assessment of spasticity are required. Dr. Riva and colleagues’ data are encouraging, and larger multicenter, randomized controlled trials should be done to identify which subgroups of patients derive clinically significant benefits from nabiximols.”
Marianne de Visser, MD, PhD, is with the department of neurology at Amsterdam University Medical Center. She reported no relevant conflicts of interest. Her remarks are taken from an editorial accompanying the study by Dr. Riva and associates (Lancet Neurol. 2018 Dec 13. doi: 10.1016/S1474-4422[18]30493-9 ).
Although the results of Riva et al. are encouraging, the study had several major limitations and future research in the form of larger, multicenter, randomized controlled trials is needed, Marianne de Visser, MD, PhD, wrote in a related editorial.
Dr. de Visser noted a bias in the study as it randomized 16 patients with predominantly upper motor neuron involvement to the nabiximols group. The treatment could potentially have benefited those patients, for whom spasticity is the prevailing symptom, more than the 13 patients randomized to the nabiximols group who had classic amyotrophic lateral sclerosis involving both upper and lower neurons. In addition, Riva et al. did not differentiate between patients with upper and lower limb spasticity or patients with bulbar spasticity and those without, she said.
The use of the Modified Ashworth Scale was also a potential issue, because while it has been used in previous studies examining antispastic treatment efficacy, “it lacked sensitivity in studies of the efficacy of cannabinoids in patients with multiple sclerosis–related spasticity, and new spasticity numeric rating or visual analogue scales are being adopted,” Dr. de Visser wrote.
The number of adverse effects in the treatment group could have also unblinded researchers, which may have affected the significant findings, she said.
“Before asking for approval of cannabinoids for symptomatic treatment of spasticity in patients with amyotrophic lateral sclerosis, further studies are needed to establish the frequency of spasticity in the various presentations of motor neuron disease, and also whether reductions in spasticity improve quality of life,” Dr. de Visser said in a press release. “Natural history studies including all subtypes of motor neuron disease and better outcome measures aimed at assessment of spasticity are required. Dr. Riva and colleagues’ data are encouraging, and larger multicenter, randomized controlled trials should be done to identify which subgroups of patients derive clinically significant benefits from nabiximols.”
Marianne de Visser, MD, PhD, is with the department of neurology at Amsterdam University Medical Center. She reported no relevant conflicts of interest. Her remarks are taken from an editorial accompanying the study by Dr. Riva and associates (Lancet Neurol. 2018 Dec 13. doi: 10.1016/S1474-4422[18]30493-9 ).
Although the results of Riva et al. are encouraging, the study had several major limitations and future research in the form of larger, multicenter, randomized controlled trials is needed, Marianne de Visser, MD, PhD, wrote in a related editorial.
Dr. de Visser noted a bias in the study as it randomized 16 patients with predominantly upper motor neuron involvement to the nabiximols group. The treatment could potentially have benefited those patients, for whom spasticity is the prevailing symptom, more than the 13 patients randomized to the nabiximols group who had classic amyotrophic lateral sclerosis involving both upper and lower neurons. In addition, Riva et al. did not differentiate between patients with upper and lower limb spasticity or patients with bulbar spasticity and those without, she said.
The use of the Modified Ashworth Scale was also a potential issue, because while it has been used in previous studies examining antispastic treatment efficacy, “it lacked sensitivity in studies of the efficacy of cannabinoids in patients with multiple sclerosis–related spasticity, and new spasticity numeric rating or visual analogue scales are being adopted,” Dr. de Visser wrote.
The number of adverse effects in the treatment group could have also unblinded researchers, which may have affected the significant findings, she said.
“Before asking for approval of cannabinoids for symptomatic treatment of spasticity in patients with amyotrophic lateral sclerosis, further studies are needed to establish the frequency of spasticity in the various presentations of motor neuron disease, and also whether reductions in spasticity improve quality of life,” Dr. de Visser said in a press release. “Natural history studies including all subtypes of motor neuron disease and better outcome measures aimed at assessment of spasticity are required. Dr. Riva and colleagues’ data are encouraging, and larger multicenter, randomized controlled trials should be done to identify which subgroups of patients derive clinically significant benefits from nabiximols.”
Marianne de Visser, MD, PhD, is with the department of neurology at Amsterdam University Medical Center. She reported no relevant conflicts of interest. Her remarks are taken from an editorial accompanying the study by Dr. Riva and associates (Lancet Neurol. 2018 Dec 13. doi: 10.1016/S1474-4422[18]30493-9 ).
Nabiximols, a cannabis-based oral spray containing delta-9 tetrahydrocannabinol and cannabidiol, significantly improved spasticity symptoms in combination with antispasticity drugs in patients with motor neuron disease in a randomized, double-blind, placebo-controlled, parallel-group, phase 2 clinical trial.
Nabiximols proved superior to a placebo spray when both were given to patients with either amyotrophic lateral sclerosis or primary lateral sclerosis as part of an antispasticity regimen in the 6-week, CANALS (Cannabis Sativa Extract in Amyotrophic Lateral Sclerosis and other Motor Neuron Disease) study at four Italian centers, Nilo Riva, MD, PhD, of the San Raffaele Scientific Institute in Milan and his colleagues reported in The Lancet Neurology. Nabiximols is approved for the treatment of spasticity due to multiple sclerosis in multiple countries, but not in the United States.
“There is no cure for motor neuron disease, so improved symptom control and quality of life are important for patients,” Dr. Riva stated in a press release. “Our proof-of-concept trial showed a beneficial effect of THC-CBD [delta-9 tetrahydrocannabinol and cannabidiol] spray in people on treatment-resistant spasticity and pain.
“Despite these encouraging findings, we must first confirm that THC-CBD spray is effective and safe in larger, longer-term phase 3 trials,” Dr. Riva added.
The patients enrolled in the phase 2 trial between January 2013 and December 2014 and were between 18 and 80 years old with a probable diagnosis of amyotrophic lateral sclerosis or primary lateral sclerosis, were on an antispasticity regimen for at least 30 days, and had a spasticity score of at least 1 in two muscle groups on the 5-point Modified Ashworth Scale. Participants titrated for the first 2 weeks before maintaining their treatment for 4 weeks.
Of 59 participants at final follow-up, Modified Ashworth Scale scores improved in the nabiximols group (29 participants) by a mean of –0.11 points, compared with worsening by a mean of 0.16 points in the placebo group (30 participants). The researchers noted that there were no participants who withdrew from the study, nabiximols was well-tolerated, and there were no serious adverse events in the nabiximols group; however, there were 22 participants in the nabiximols group and 8 participants in the placebo group who experienced an adverse event from any cause.
“This study is, to our knowledge, the first randomized controlled trial of safety and efficacy of a pharmacological treatment for spasticity and the first trial of nabiximols in motor neuron disease,” Dr. Riva and his colleagues wrote. “Our results suggest that the study drug is well tolerated and provides first evidence of efficacy in terms of controlling spasticity in patients with motor neuron disease.”
The study was funded by the Italian Research Foundation for Amyotrophic Lateral Sclerosis. GW Pharma, which developed nabiximols, provided the study drug and placebo. Many of the authors reported financial disclosures with pharmaceutical companies.
SOURCE: Riva N et al. Lancet Neurol. 2018 Dec 13. doi: 10.1016/S1474-4422(18)30406-X.
Nabiximols, a cannabis-based oral spray containing delta-9 tetrahydrocannabinol and cannabidiol, significantly improved spasticity symptoms in combination with antispasticity drugs in patients with motor neuron disease in a randomized, double-blind, placebo-controlled, parallel-group, phase 2 clinical trial.
Nabiximols proved superior to a placebo spray when both were given to patients with either amyotrophic lateral sclerosis or primary lateral sclerosis as part of an antispasticity regimen in the 6-week, CANALS (Cannabis Sativa Extract in Amyotrophic Lateral Sclerosis and other Motor Neuron Disease) study at four Italian centers, Nilo Riva, MD, PhD, of the San Raffaele Scientific Institute in Milan and his colleagues reported in The Lancet Neurology. Nabiximols is approved for the treatment of spasticity due to multiple sclerosis in multiple countries, but not in the United States.
“There is no cure for motor neuron disease, so improved symptom control and quality of life are important for patients,” Dr. Riva stated in a press release. “Our proof-of-concept trial showed a beneficial effect of THC-CBD [delta-9 tetrahydrocannabinol and cannabidiol] spray in people on treatment-resistant spasticity and pain.
“Despite these encouraging findings, we must first confirm that THC-CBD spray is effective and safe in larger, longer-term phase 3 trials,” Dr. Riva added.
The patients enrolled in the phase 2 trial between January 2013 and December 2014 and were between 18 and 80 years old with a probable diagnosis of amyotrophic lateral sclerosis or primary lateral sclerosis, were on an antispasticity regimen for at least 30 days, and had a spasticity score of at least 1 in two muscle groups on the 5-point Modified Ashworth Scale. Participants titrated for the first 2 weeks before maintaining their treatment for 4 weeks.
Of 59 participants at final follow-up, Modified Ashworth Scale scores improved in the nabiximols group (29 participants) by a mean of –0.11 points, compared with worsening by a mean of 0.16 points in the placebo group (30 participants). The researchers noted that there were no participants who withdrew from the study, nabiximols was well-tolerated, and there were no serious adverse events in the nabiximols group; however, there were 22 participants in the nabiximols group and 8 participants in the placebo group who experienced an adverse event from any cause.
“This study is, to our knowledge, the first randomized controlled trial of safety and efficacy of a pharmacological treatment for spasticity and the first trial of nabiximols in motor neuron disease,” Dr. Riva and his colleagues wrote. “Our results suggest that the study drug is well tolerated and provides first evidence of efficacy in terms of controlling spasticity in patients with motor neuron disease.”
The study was funded by the Italian Research Foundation for Amyotrophic Lateral Sclerosis. GW Pharma, which developed nabiximols, provided the study drug and placebo. Many of the authors reported financial disclosures with pharmaceutical companies.
SOURCE: Riva N et al. Lancet Neurol. 2018 Dec 13. doi: 10.1016/S1474-4422(18)30406-X.
FROM THE LANCET NEUROLOGY
Key clinical point:
Major finding: In the nabiximols group, Modified Ashworth Scale scores improved by mean of –0.11 points, compared with worsening by a mean of 0.16 points in the placebo group.
Study details: A multicenter, double-blinded, randomized, placebo-controlled, phase 2 trial of 59 participants with spasticity symptoms from motor neuron disease from four tertiary motor neuron centers in Italy.
Disclosures: The study was funded by the Italian Research Foundation for Amyotrophic Lateral Sclerosis. GW Pharma, which developed nabiximols, provided the study drug and placebo. Many of the authors reported financial disclosures with pharmaceutical companies.
Source: Riva N et al. Lancet Neurol. 2018 Dec 13. doi: 10.1016/S1474-4422(18)30406-X