Multiple Sclerosis

The selective B-cell–targeting monoclonal antibody ocrelizumab became the first drug to improve outcomes in primary progressive multiple sclerosis based on results from the randomized, placebo-controlled, phase III ORATORIO trial.

After 24 weeks of treatment, ocrelizumab reduced the risk of progression in clinical disability by 25%, compared with placebo. Over 2 years, the antibody also reduced the volume of hyperintense T2 lesions by 3.4%, whereas patients taking placebo experienced a 7% increase. The rate of whole brain volume loss was also significantly reduced.

The findings confer the first really good news in how to treat patients with this very difficult condition, said Dr. Xavier Montalbán, who presented the results at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis, held in Barcelona.

“We’ve been looking for something positive for these patients for years and have never found this,” said Dr. Montalbán, director of clinical neuroimmunology at Vall d’Hebron University Hospital, Barcelona. “We can discuss the magnitude of the effect, but I have to say I am very, very happy with this.”

The results are certainly encouraging, said Dr. Peter Calabresi, director of the Johns Hopkins Multiple Sclerosis Center and the division of neuroimmunology at The Johns Hopkins Hospital, Baltimore, although he tempered his enthusiasm a bit regarding patient selection and safety. In the entire cohort of 732 patients, 13 malignancies occurred over 3 years and occurred more than twice as often in the ocrelizumab arm than in the placebo arm (2.3% vs. 0.8%). These included four breast cancers in the active arm and none in the placebo arm.

“The data in general look very strong but with a possible safety signal related to cancers and deaths,” Dr. Calabresi said in an interview. “I’d need to see more detail in this regard, but overall I am very happy to see something work for primary progressive MS, where we have no approved drugs, so this is very important in that regard.

“As others have pointed out, though, the study was designed to target young people with inflammation (active MRIs) in which cases the drug works well. But many of our people with progressive MS are older and have no inflammation, so I’m guessing there is no effect in that group.”

Ocrelizumab, a humanized monoclonal antibody, selectively targets CD20-positive B cells. Since not all B cells are positive for the marker, ocrelizumab leaves intact the patient’s immune memory, as well as the ability to create more B cells. Its success bolsters the emerging idea that B cells may be even more important than T cells in the pathophysiology of MS.

ORATORIO was a 2:1 randomization of 732 patients with primary progressive MS to infusions of either 600 mg ocrelizumab or placebo every 24 weeks for 120 months.

Most patients finished the trial (80% active, 66% placebo). The withdrawals in the placebo arm were primarily due to lack of efficacy. Patients were a mean of 44 years old, with a mean 6.5 years since symptom onset. Most (88%) were treatment-naive. The Expanded Disability Status Score (EDSS) at baseline was 4.7 in both groups. At baseline, about a quarter of patients had gadolinium-enhancing lesions (mean number, 1) with a mean T2 lesion volume of 11 cm³, and their mean whole-brain volume was 1,467 cm³. All patients had either elevated immunoglobulin in cerebrospinal fluid or oligoclonal bands.

The primary endpoint of ORATORIO was 12-week confirmed disability progression (CDP). Secondary endpoints included 24-week CDP; timed 25-foot walk; and T2 lesion and whole brain volume.

By 120 weeks, patients taking the study drug experienced a mean 24% reduction in the risk of CDP (hazard ratio, 0.76; P = .0321). The treatment curves began to separate at week 24, and the differences in the risk of CDP were statistically significant at every evaluation. The benefit has been maintained in a safety evaluation that is extending treatment to 216 weeks in a subset of patients.

*Ocrelizumab significantly slowed the worsening of patients’ 25-foot walking time by 29% at 120 weeks when compared against placebo. Walking times increased by 39% from baseline on ocrelizumab, compared with a 55% rise for those on placebo (P = .0404).

On the imaging endpoints, the drug was associated with a highly significant difference in T2 lesion volume, decreasing the load by 3.4%, while the placebo arm experienced an increase of 7.4% from baseline (P = .0001).

Those taking the drug also experienced a small but significantly lower amount of whole-brain volume loss (–0.9% vs. –1.1%; P = .02).

Infusion reactions were most common with the first dose (27% active vs. 7% placebo). One patient taking the study drug withdrew at that time from a serious reaction, but the remainder were mild to moderate in severity. Reactions decreased over time, and all remained at the mild-moderate level.

Overall adverse events occurred at similar rates between those taking the drug and those taking placebo (95% vs. 90%). Infections were similar (70% vs. 68%) overall, although upper respiratory infections were more common among the active group (11% vs. 6%).

There were five deaths: one in the placebo arm (a motor vehicle accident) and four in the active arm (pulmonary embolism, pneumonia, pancreatic cancer, and pneumonia aspiration). These, as well as the malignancy findings, are still being evaluated, Dr. Montalbán said.

Based on the positive results, Genentech will be submitting the drug for approval in both the United States and Europe in the first quarter of 2016.

Dr. Montalbán disclosed ties with Genentech – the trial’s sponsor – and other pharmaceutical companies.

*Correction, 10/14/15: The timed 25-foot walk test results were previously misstated.

msullivan@frontlinemedcom.com

The selective B-cell–targeting monoclonal antibody ocrelizumab became the first drug to improve outcomes in primary progressive multiple sclerosis based on results from the randomized, placebo-controlled, phase III ORATORIO trial.

After 24 weeks of treatment, ocrelizumab reduced the risk of progression in clinical disability by 25%, compared with placebo. Over 2 years, the antibody also reduced the volume of hyperintense T2 lesions by 3.4%, whereas patients taking placebo experienced a 7% increase. The rate of whole brain volume loss was also significantly reduced.

The findings confer the first really good news in how to treat patients with this very difficult condition, said Dr. Xavier Montalbán, who presented the results at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis, held in Barcelona.

“We’ve been looking for something positive for these patients for years and have never found this,” said Dr. Montalbán, director of clinical neuroimmunology at Vall d’Hebron University Hospital, Barcelona. “We can discuss the magnitude of the effect, but I have to say I am very, very happy with this.”

The results are certainly encouraging, said Dr. Peter Calabresi, director of the Johns Hopkins Multiple Sclerosis Center and the division of neuroimmunology at The Johns Hopkins Hospital, Baltimore, although he tempered his enthusiasm a bit regarding patient selection and safety. In the entire cohort of 732 patients, 13 malignancies occurred over 3 years and occurred more than twice as often in the ocrelizumab arm than in the placebo arm (2.3% vs. 0.8%). These included four breast cancers in the active arm and none in the placebo arm.

“The data in general look very strong but with a possible safety signal related to cancers and deaths,” Dr. Calabresi said in an interview. “I’d need to see more detail in this regard, but overall I am very happy to see something work for primary progressive MS, where we have no approved drugs, so this is very important in that regard.

“As others have pointed out, though, the study was designed to target young people with inflammation (active MRIs) in which cases the drug works well. But many of our people with progressive MS are older and have no inflammation, so I’m guessing there is no effect in that group.”

Ocrelizumab, a humanized monoclonal antibody, selectively targets CD20-positive B cells. Since not all B cells are positive for the marker, ocrelizumab leaves intact the patient’s immune memory, as well as the ability to create more B cells. Its success bolsters the emerging idea that B cells may be even more important than T cells in the pathophysiology of MS.

ORATORIO was a 2:1 randomization of 732 patients with primary progressive MS to infusions of either 600 mg ocrelizumab or placebo every 24 weeks for 120 months.

Most patients finished the trial (80% active, 66% placebo). The withdrawals in the placebo arm were primarily due to lack of efficacy. Patients were a mean of 44 years old, with a mean 6.5 years since symptom onset. Most (88%) were treatment-naive. The Expanded Disability Status Score (EDSS) at baseline was 4.7 in both groups. At baseline, about a quarter of patients had gadolinium-enhancing lesions (mean number, 1) with a mean T2 lesion volume of 11 cm³, and their mean whole-brain volume was 1,467 cm³. All patients had either elevated immunoglobulin in cerebrospinal fluid or oligoclonal bands.

The primary endpoint of ORATORIO was 12-week confirmed disability progression (CDP). Secondary endpoints included 24-week CDP; timed 25-foot walk; and T2 lesion and whole brain volume.

By 120 weeks, patients taking the study drug experienced a mean 24% reduction in the risk of CDP (hazard ratio, 0.76; P = .0321). The treatment curves began to separate at week 24, and the differences in the risk of CDP were statistically significant at every evaluation. The benefit has been maintained in a safety evaluation that is extending treatment to 216 weeks in a subset of patients.

*Ocrelizumab significantly slowed the worsening of patients’ 25-foot walking time by 29% at 120 weeks when compared against placebo. Walking times increased by 39% from baseline on ocrelizumab, compared with a 55% rise for those on placebo (P = .0404).

On the imaging endpoints, the drug was associated with a highly significant difference in T2 lesion volume, decreasing the load by 3.4%, while the placebo arm experienced an increase of 7.4% from baseline (P = .0001).

Those taking the drug also experienced a small but significantly lower amount of whole-brain volume loss (–0.9% vs. –1.1%; P = .02).

Infusion reactions were most common with the first dose (27% active vs. 7% placebo). One patient taking the study drug withdrew at that time from a serious reaction, but the remainder were mild to moderate in severity. Reactions decreased over time, and all remained at the mild-moderate level.

Overall adverse events occurred at similar rates between those taking the drug and those taking placebo (95% vs. 90%). Infections were similar (70% vs. 68%) overall, although upper respiratory infections were more common among the active group (11% vs. 6%).

There were five deaths: one in the placebo arm (a motor vehicle accident) and four in the active arm (pulmonary embolism, pneumonia, pancreatic cancer, and pneumonia aspiration). These, as well as the malignancy findings, are still being evaluated, Dr. Montalbán said.

Based on the positive results, Genentech will be submitting the drug for approval in both the United States and Europe in the first quarter of 2016.

Dr. Montalbán disclosed ties with Genentech – the trial’s sponsor – and other pharmaceutical companies.

*Correction, 10/14/15: The timed 25-foot walk test results were previously misstated.

msullivan@frontlinemedcom.com

The selective B-cell–targeting monoclonal antibody ocrelizumab became the first drug to improve outcomes in primary progressive multiple sclerosis based on results from the randomized, placebo-controlled, phase III ORATORIO trial.

After 24 weeks of treatment, ocrelizumab reduced the risk of progression in clinical disability by 25%, compared with placebo. Over 2 years, the antibody also reduced the volume of hyperintense T2 lesions by 3.4%, whereas patients taking placebo experienced a 7% increase. The rate of whole brain volume loss was also significantly reduced.

The findings confer the first really good news in how to treat patients with this very difficult condition, said Dr. Xavier Montalbán, who presented the results at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis, held in Barcelona.

“We’ve been looking for something positive for these patients for years and have never found this,” said Dr. Montalbán, director of clinical neuroimmunology at Vall d’Hebron University Hospital, Barcelona. “We can discuss the magnitude of the effect, but I have to say I am very, very happy with this.”

The results are certainly encouraging, said Dr. Peter Calabresi, director of the Johns Hopkins Multiple Sclerosis Center and the division of neuroimmunology at The Johns Hopkins Hospital, Baltimore, although he tempered his enthusiasm a bit regarding patient selection and safety. In the entire cohort of 732 patients, 13 malignancies occurred over 3 years and occurred more than twice as often in the ocrelizumab arm than in the placebo arm (2.3% vs. 0.8%). These included four breast cancers in the active arm and none in the placebo arm.

“The data in general look very strong but with a possible safety signal related to cancers and deaths,” Dr. Calabresi said in an interview. “I’d need to see more detail in this regard, but overall I am very happy to see something work for primary progressive MS, where we have no approved drugs, so this is very important in that regard.

“As others have pointed out, though, the study was designed to target young people with inflammation (active MRIs) in which cases the drug works well. But many of our people with progressive MS are older and have no inflammation, so I’m guessing there is no effect in that group.”

Ocrelizumab, a humanized monoclonal antibody, selectively targets CD20-positive B cells. Since not all B cells are positive for the marker, ocrelizumab leaves intact the patient’s immune memory, as well as the ability to create more B cells. Its success bolsters the emerging idea that B cells may be even more important than T cells in the pathophysiology of MS.

ORATORIO was a 2:1 randomization of 732 patients with primary progressive MS to infusions of either 600 mg ocrelizumab or placebo every 24 weeks for 120 months.

Most patients finished the trial (80% active, 66% placebo). The withdrawals in the placebo arm were primarily due to lack of efficacy. Patients were a mean of 44 years old, with a mean 6.5 years since symptom onset. Most (88%) were treatment-naive. The Expanded Disability Status Score (EDSS) at baseline was 4.7 in both groups. At baseline, about a quarter of patients had gadolinium-enhancing lesions (mean number, 1) with a mean T2 lesion volume of 11 cm³, and their mean whole-brain volume was 1,467 cm³. All patients had either elevated immunoglobulin in cerebrospinal fluid or oligoclonal bands.

The primary endpoint of ORATORIO was 12-week confirmed disability progression (CDP). Secondary endpoints included 24-week CDP; timed 25-foot walk; and T2 lesion and whole brain volume.

By 120 weeks, patients taking the study drug experienced a mean 24% reduction in the risk of CDP (hazard ratio, 0.76; P = .0321). The treatment curves began to separate at week 24, and the differences in the risk of CDP were statistically significant at every evaluation. The benefit has been maintained in a safety evaluation that is extending treatment to 216 weeks in a subset of patients.

*Ocrelizumab significantly slowed the worsening of patients’ 25-foot walking time by 29% at 120 weeks when compared against placebo. Walking times increased by 39% from baseline on ocrelizumab, compared with a 55% rise for those on placebo (P = .0404).

On the imaging endpoints, the drug was associated with a highly significant difference in T2 lesion volume, decreasing the load by 3.4%, while the placebo arm experienced an increase of 7.4% from baseline (P = .0001).

Those taking the drug also experienced a small but significantly lower amount of whole-brain volume loss (–0.9% vs. –1.1%; P = .02).

Infusion reactions were most common with the first dose (27% active vs. 7% placebo). One patient taking the study drug withdrew at that time from a serious reaction, but the remainder were mild to moderate in severity. Reactions decreased over time, and all remained at the mild-moderate level.

Overall adverse events occurred at similar rates between those taking the drug and those taking placebo (95% vs. 90%). Infections were similar (70% vs. 68%) overall, although upper respiratory infections were more common among the active group (11% vs. 6%).

There were five deaths: one in the placebo arm (a motor vehicle accident) and four in the active arm (pulmonary embolism, pneumonia, pancreatic cancer, and pneumonia aspiration). These, as well as the malignancy findings, are still being evaluated, Dr. Montalbán said.

Based on the positive results, Genentech will be submitting the drug for approval in both the United States and Europe in the first quarter of 2016.

Dr. Montalbán disclosed ties with Genentech – the trial’s sponsor – and other pharmaceutical companies.

*Correction, 10/14/15: The timed 25-foot walk test results were previously misstated.

msullivan@frontlinemedcom.com

Two to three years of monthly subcutaneous injections of daclizumab HYP were more effective at reducing the relapse rate and the number of new or worsening brain lesions in patients with relapsing-remitting multiple sclerosis than were weekly intramuscular injections of interferon beta-1a in the phase III, randomized DECIDE trial.

However, the percentage of patients whose disability progressed after 12 weeks of treatment did not differ significantly between the group given daclizumab HYP and that given intramuscular interferon beta-1a (Avonex), and the rates of infection, cutaneous adverse effects, and liver-test abnormalities were higher with daclizumab HYP. “The enhanced efficacy was accompanied by an increased frequency of adverse events, such that the net clinical benefit will need to be carefully considered by patients and their providers,” wrote Dr. Ludwig Kappos of the Neurologic Clinic and Policlinic, departments of medicine, clinical research, and biomedicine and biomedical engineering, University Hospital Basel (Switzerland), and his associates.

Daclizumab HYP (high-yield process), a formulation of daclizumab developed for long-term subcutaneous administration, has less antibody-dependent cytotoxicity than do earlier formulations of the drug. The researchers compared the two therapies in 1,841 patients aged 18-55 years who were treated at 244 sites in 28 countries. These patients were randomly assigned in a double-blind fashion to receive either 150 mg daclizumab HYP every 4 weeks and intramuscular placebo once weekly (919 patients) or 30 mcg intramuscular interferon beta-1a once weekly and subcutaneous placebo every 4 weeks (922 patients) for 2-3 years. The median duration of treatment was 108.7 weeks for daclizumab HYP and 111.4 weeks for interferon beta-1a. Overall rates of treatment discontinuation and withdrawal from the study were similar between the two groups.

The primary endpoint of the study – the annualized relapse rate over 144 weeks – was significantly lower (by 45%) with daclizumab HYP (0.22) than with interferon beta-1a (0.39). This result was confirmed in two sensitivity analyses. In addition, the number of new or newly enlarged lesions on cranial MRI at week 96 was a significant 54% lower with daclizumab HYP than with interferon beta-1a, Dr. Kappos and his associates noted (N Engl J Med. 2015;373:1418-28. doi: 10.1056/NEJMoa1501481).

However, the percentage of patients whose disability progressed at 12 weeks, as measured by scores on the Expanded Disability Status Scale, was not significantly different between the daclizumab HYP group (16%) and the interferon beta-1a group (20%), nor was the percentage of patients free from relapse at week 144 (67% vs. 51%). The proportion of patients who reported clinically meaningful worsening of the physical impact of MS, as measured by the physical subscale score of the 29-item Multiple Sclerosis Impact Scale, also was not significantly different between the two study groups (19% vs. 23%).

The overall incidence of adverse events was 91% in both groups, and there was no between-group difference in the rate of clinically significant hematologic abnormalities. However, patients receiving daclizumab HYP were significantly more likely to report developing infections (65% vs. 57%); serious infections (4% vs. 2%); or cutaneous events such as rash, eczema, seborrheic dermatitis, acne, erythema, and pruritus (37% vs. 19%). More patients discontinued daclizumab HYP because of adverse events, excluding MS relapses (14% vs. 9%).

In addition, hepatobiliary disorders developed in 3% of patients given daclizumab HYP and 2% of those given interferon beta-1a. Liver enzyme elevations more than five times the upper limit of normal occurred in twice as many patients taking daclizumab HYP (6%) than in patients taking interferon beta-1a (3%).

“Long-term follow-up studies will continue to be important in assessing the treatment effects of MS therapies on disability progression, because studies of even 2-3 years’ duration capture only a small fraction of the lifelong treatment that most patients with MS will require,” Dr. Kappos and his associates added.

Two to three years of monthly subcutaneous injections of daclizumab HYP were more effective at reducing the relapse rate and the number of new or worsening brain lesions in patients with relapsing-remitting multiple sclerosis than were weekly intramuscular injections of interferon beta-1a in the phase III, randomized DECIDE trial.

However, the percentage of patients whose disability progressed after 12 weeks of treatment did not differ significantly between the group given daclizumab HYP and that given intramuscular interferon beta-1a (Avonex), and the rates of infection, cutaneous adverse effects, and liver-test abnormalities were higher with daclizumab HYP. “The enhanced efficacy was accompanied by an increased frequency of adverse events, such that the net clinical benefit will need to be carefully considered by patients and their providers,” wrote Dr. Ludwig Kappos of the Neurologic Clinic and Policlinic, departments of medicine, clinical research, and biomedicine and biomedical engineering, University Hospital Basel (Switzerland), and his associates.

Daclizumab HYP (high-yield process), a formulation of daclizumab developed for long-term subcutaneous administration, has less antibody-dependent cytotoxicity than do earlier formulations of the drug. The researchers compared the two therapies in 1,841 patients aged 18-55 years who were treated at 244 sites in 28 countries. These patients were randomly assigned in a double-blind fashion to receive either 150 mg daclizumab HYP every 4 weeks and intramuscular placebo once weekly (919 patients) or 30 mcg intramuscular interferon beta-1a once weekly and subcutaneous placebo every 4 weeks (922 patients) for 2-3 years. The median duration of treatment was 108.7 weeks for daclizumab HYP and 111.4 weeks for interferon beta-1a. Overall rates of treatment discontinuation and withdrawal from the study were similar between the two groups.

The primary endpoint of the study – the annualized relapse rate over 144 weeks – was significantly lower (by 45%) with daclizumab HYP (0.22) than with interferon beta-1a (0.39). This result was confirmed in two sensitivity analyses. In addition, the number of new or newly enlarged lesions on cranial MRI at week 96 was a significant 54% lower with daclizumab HYP than with interferon beta-1a, Dr. Kappos and his associates noted (N Engl J Med. 2015;373:1418-28. doi: 10.1056/NEJMoa1501481).

However, the percentage of patients whose disability progressed at 12 weeks, as measured by scores on the Expanded Disability Status Scale, was not significantly different between the daclizumab HYP group (16%) and the interferon beta-1a group (20%), nor was the percentage of patients free from relapse at week 144 (67% vs. 51%). The proportion of patients who reported clinically meaningful worsening of the physical impact of MS, as measured by the physical subscale score of the 29-item Multiple Sclerosis Impact Scale, also was not significantly different between the two study groups (19% vs. 23%).

The overall incidence of adverse events was 91% in both groups, and there was no between-group difference in the rate of clinically significant hematologic abnormalities. However, patients receiving daclizumab HYP were significantly more likely to report developing infections (65% vs. 57%); serious infections (4% vs. 2%); or cutaneous events such as rash, eczema, seborrheic dermatitis, acne, erythema, and pruritus (37% vs. 19%). More patients discontinued daclizumab HYP because of adverse events, excluding MS relapses (14% vs. 9%).

In addition, hepatobiliary disorders developed in 3% of patients given daclizumab HYP and 2% of those given interferon beta-1a. Liver enzyme elevations more than five times the upper limit of normal occurred in twice as many patients taking daclizumab HYP (6%) than in patients taking interferon beta-1a (3%).

“Long-term follow-up studies will continue to be important in assessing the treatment effects of MS therapies on disability progression, because studies of even 2-3 years’ duration capture only a small fraction of the lifelong treatment that most patients with MS will require,” Dr. Kappos and his associates added.

Two to three years of monthly subcutaneous injections of daclizumab HYP were more effective at reducing the relapse rate and the number of new or worsening brain lesions in patients with relapsing-remitting multiple sclerosis than were weekly intramuscular injections of interferon beta-1a in the phase III, randomized DECIDE trial.

However, the percentage of patients whose disability progressed after 12 weeks of treatment did not differ significantly between the group given daclizumab HYP and that given intramuscular interferon beta-1a (Avonex), and the rates of infection, cutaneous adverse effects, and liver-test abnormalities were higher with daclizumab HYP. “The enhanced efficacy was accompanied by an increased frequency of adverse events, such that the net clinical benefit will need to be carefully considered by patients and their providers,” wrote Dr. Ludwig Kappos of the Neurologic Clinic and Policlinic, departments of medicine, clinical research, and biomedicine and biomedical engineering, University Hospital Basel (Switzerland), and his associates.

Daclizumab HYP (high-yield process), a formulation of daclizumab developed for long-term subcutaneous administration, has less antibody-dependent cytotoxicity than do earlier formulations of the drug. The researchers compared the two therapies in 1,841 patients aged 18-55 years who were treated at 244 sites in 28 countries. These patients were randomly assigned in a double-blind fashion to receive either 150 mg daclizumab HYP every 4 weeks and intramuscular placebo once weekly (919 patients) or 30 mcg intramuscular interferon beta-1a once weekly and subcutaneous placebo every 4 weeks (922 patients) for 2-3 years. The median duration of treatment was 108.7 weeks for daclizumab HYP and 111.4 weeks for interferon beta-1a. Overall rates of treatment discontinuation and withdrawal from the study were similar between the two groups.

The primary endpoint of the study – the annualized relapse rate over 144 weeks – was significantly lower (by 45%) with daclizumab HYP (0.22) than with interferon beta-1a (0.39). This result was confirmed in two sensitivity analyses. In addition, the number of new or newly enlarged lesions on cranial MRI at week 96 was a significant 54% lower with daclizumab HYP than with interferon beta-1a, Dr. Kappos and his associates noted (N Engl J Med. 2015;373:1418-28. doi: 10.1056/NEJMoa1501481).

However, the percentage of patients whose disability progressed at 12 weeks, as measured by scores on the Expanded Disability Status Scale, was not significantly different between the daclizumab HYP group (16%) and the interferon beta-1a group (20%), nor was the percentage of patients free from relapse at week 144 (67% vs. 51%). The proportion of patients who reported clinically meaningful worsening of the physical impact of MS, as measured by the physical subscale score of the 29-item Multiple Sclerosis Impact Scale, also was not significantly different between the two study groups (19% vs. 23%).

The overall incidence of adverse events was 91% in both groups, and there was no between-group difference in the rate of clinically significant hematologic abnormalities. However, patients receiving daclizumab HYP were significantly more likely to report developing infections (65% vs. 57%); serious infections (4% vs. 2%); or cutaneous events such as rash, eczema, seborrheic dermatitis, acne, erythema, and pruritus (37% vs. 19%). More patients discontinued daclizumab HYP because of adverse events, excluding MS relapses (14% vs. 9%).

In addition, hepatobiliary disorders developed in 3% of patients given daclizumab HYP and 2% of those given interferon beta-1a. Liver enzyme elevations more than five times the upper limit of normal occurred in twice as many patients taking daclizumab HYP (6%) than in patients taking interferon beta-1a (3%).

“Long-term follow-up studies will continue to be important in assessing the treatment effects of MS therapies on disability progression, because studies of even 2-3 years’ duration capture only a small fraction of the lifelong treatment that most patients with MS will require,” Dr. Kappos and his associates added.

BARCELONA—In addition to its neuroprotective effect on the peripapillary retinal nerve fiber layer, sodium channel blockade with phenytoin also appears to prevent degeneration of the macular ganglion cell complex after acute optic neuritis, according to data presented at the 31st Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).

Rhian E. Raftopoulos, MbChb, of University College London, and colleagues previously reported in a phase II trial that sodium channel blockade with phenytoin is neuroprotective in acute optic neuritis. The primary outcome measurements were the thickness of the peripapillary retinal nerve fiber layer and macular volume, measured using optical coherence tomography (OCT).

In the present study, the researchers sought to determine whether this neuroprotective effect is selective for particular anatomical layers of the retina. They enrolled patients with acute optic neuritis and randomized them within two weeks of symptom onset to receive phenytoin or placebo for three months. Spectral domain fast macular and papillomacular bundle (PMB) OCT scans were performed at baseline and after six months. Masked automated retinal layer segmentation was performed to obtain average thickness measures of retinal nerve fiber layer, ganglion cell and inner plexiform layer (GC/IPL), and the composite ganglion cell complex. The ganglion cell complex (GCC) encompassed the retinal nerve fiber layer plus GC/IPL. Active versus placebo differences in mean six-month affected eye retinal nerve fiber layer, GC/IPL, and GCC were calculated from macular (n=60) and PMB (n=48) scans, adjusted for the corresponding baseline measurements in the unaffected eye.

At baseline, the mean thicknesses of the retinal nerve fiber layer, GC/IPL, and GCC were similar in the active and placebo groups in the macula and papillomacular bundle. In the intention to treat comparison, mean adjusted affected eye macular retinal nerve fiber layer thickness at six months was 4.67 μm greater in the active group (a 42% treatment effect). Mean adjusted macular GCC thickness was 5.63 μm greater in the active group (a 28% treatment effect). Treatment had no significant effect on macular GC/IPL when measured alone.

In the papillomacular bundle, mean adjusted retinal nerve fiber layer thickness was 2.49 μm greater in the active group at six months, mean GC/IPL thickness 2.79 μm greater, and mean GCC thickness 5.41 μm greater.

BARCELONA—In addition to its neuroprotective effect on the peripapillary retinal nerve fiber layer, sodium channel blockade with phenytoin also appears to prevent degeneration of the macular ganglion cell complex after acute optic neuritis, according to data presented at the 31st Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).

Rhian E. Raftopoulos, MbChb, of University College London, and colleagues previously reported in a phase II trial that sodium channel blockade with phenytoin is neuroprotective in acute optic neuritis. The primary outcome measurements were the thickness of the peripapillary retinal nerve fiber layer and macular volume, measured using optical coherence tomography (OCT).

In the present study, the researchers sought to determine whether this neuroprotective effect is selective for particular anatomical layers of the retina. They enrolled patients with acute optic neuritis and randomized them within two weeks of symptom onset to receive phenytoin or placebo for three months. Spectral domain fast macular and papillomacular bundle (PMB) OCT scans were performed at baseline and after six months. Masked automated retinal layer segmentation was performed to obtain average thickness measures of retinal nerve fiber layer, ganglion cell and inner plexiform layer (GC/IPL), and the composite ganglion cell complex. The ganglion cell complex (GCC) encompassed the retinal nerve fiber layer plus GC/IPL. Active versus placebo differences in mean six-month affected eye retinal nerve fiber layer, GC/IPL, and GCC were calculated from macular (n=60) and PMB (n=48) scans, adjusted for the corresponding baseline measurements in the unaffected eye.

At baseline, the mean thicknesses of the retinal nerve fiber layer, GC/IPL, and GCC were similar in the active and placebo groups in the macula and papillomacular bundle. In the intention to treat comparison, mean adjusted affected eye macular retinal nerve fiber layer thickness at six months was 4.67 μm greater in the active group (a 42% treatment effect). Mean adjusted macular GCC thickness was 5.63 μm greater in the active group (a 28% treatment effect). Treatment had no significant effect on macular GC/IPL when measured alone.

In the papillomacular bundle, mean adjusted retinal nerve fiber layer thickness was 2.49 μm greater in the active group at six months, mean GC/IPL thickness 2.79 μm greater, and mean GCC thickness 5.41 μm greater.

BARCELONA—In addition to its neuroprotective effect on the peripapillary retinal nerve fiber layer, sodium channel blockade with phenytoin also appears to prevent degeneration of the macular ganglion cell complex after acute optic neuritis, according to data presented at the 31st Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).

Rhian E. Raftopoulos, MbChb, of University College London, and colleagues previously reported in a phase II trial that sodium channel blockade with phenytoin is neuroprotective in acute optic neuritis. The primary outcome measurements were the thickness of the peripapillary retinal nerve fiber layer and macular volume, measured using optical coherence tomography (OCT).

In the present study, the researchers sought to determine whether this neuroprotective effect is selective for particular anatomical layers of the retina. They enrolled patients with acute optic neuritis and randomized them within two weeks of symptom onset to receive phenytoin or placebo for three months. Spectral domain fast macular and papillomacular bundle (PMB) OCT scans were performed at baseline and after six months. Masked automated retinal layer segmentation was performed to obtain average thickness measures of retinal nerve fiber layer, ganglion cell and inner plexiform layer (GC/IPL), and the composite ganglion cell complex. The ganglion cell complex (GCC) encompassed the retinal nerve fiber layer plus GC/IPL. Active versus placebo differences in mean six-month affected eye retinal nerve fiber layer, GC/IPL, and GCC were calculated from macular (n=60) and PMB (n=48) scans, adjusted for the corresponding baseline measurements in the unaffected eye.

At baseline, the mean thicknesses of the retinal nerve fiber layer, GC/IPL, and GCC were similar in the active and placebo groups in the macula and papillomacular bundle. In the intention to treat comparison, mean adjusted affected eye macular retinal nerve fiber layer thickness at six months was 4.67 μm greater in the active group (a 42% treatment effect). Mean adjusted macular GCC thickness was 5.63 μm greater in the active group (a 28% treatment effect). Treatment had no significant effect on macular GC/IPL when measured alone.

In the papillomacular bundle, mean adjusted retinal nerve fiber layer thickness was 2.49 μm greater in the active group at six months, mean GC/IPL thickness 2.79 μm greater, and mean GCC thickness 5.41 μm greater.

BARCELONA—The anti-JCV antibody index and L-selectin (CD62L) have merit for risk stratification and share a potential biological relationship with implications for general progressive multifocal leukoencephalopathy (PML) etiology, according to research presented at the 31st Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). “A risk algorithm incorporating both biomarkers could strongly reduce PML incidence,” said Nicholas Schwab, PhD, of the Department of Neurology at the University of Münster in Germany.

Natalizumab treatment is associated with PML development, with more than 541 cases as of March 3, 2015. Treatment duration, prior immunosuppressant use, and JCV serostatus are currently used for categorical risk stratification, but PML incidence continues to rise steadily. Anti-JCV antibody index and CD62L have previously been proposed as additional risk stratification parameters. Dr. Schwab and his research colleagues aimed at verifying and integrating both parameters into one applicable algorithm for risk stratification.

The research team gathered international cohorts of patients with multiple sclerosis who were treated with natalizumab. The participants were assessed for JCV index (1,921 control patients and nine pre-PML patients) and CD62L (1,257 control patients and 17 pre-PML patients).

Low CD62L in natalizumab-treated patients was retrospectively confirmed and prospectively validated as a biomarker for PML risk. The risk factor “CD62L low” increased a patient’s relative risk 55-fold. Validation efforts established an 86% sensitivity and 91% specificity for CD62L and 100% sensitivity and 59% specificity for JCV index as predictors of PML.

Low CD62L values were also found in various other PML associations and stages (ie, lupus, lymphopenia, HIV, acute natalizumab-PML). CD62L values correlated with JCV serostatus, so the lower the CD62L value of a patient was, the higher the probability that they were JCV positive. The researchers ultimately found that 26 out of 27 (96%) patients with low CD62L were JCV positive. Additionally, CD62L values negatively correlated with JCV index values.

“The combined use of JCV serology and CD62L level found 2% of patients studied to be at highest risk,” Dr. Schwab reported. “Adherence to the risk-stratification algorithm might prevent up to or over 85% of PML cases,” he said.

BARCELONA—The anti-JCV antibody index and L-selectin (CD62L) have merit for risk stratification and share a potential biological relationship with implications for general progressive multifocal leukoencephalopathy (PML) etiology, according to research presented at the 31st Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). “A risk algorithm incorporating both biomarkers could strongly reduce PML incidence,” said Nicholas Schwab, PhD, of the Department of Neurology at the University of Münster in Germany.

Natalizumab treatment is associated with PML development, with more than 541 cases as of March 3, 2015. Treatment duration, prior immunosuppressant use, and JCV serostatus are currently used for categorical risk stratification, but PML incidence continues to rise steadily. Anti-JCV antibody index and CD62L have previously been proposed as additional risk stratification parameters. Dr. Schwab and his research colleagues aimed at verifying and integrating both parameters into one applicable algorithm for risk stratification.

The research team gathered international cohorts of patients with multiple sclerosis who were treated with natalizumab. The participants were assessed for JCV index (1,921 control patients and nine pre-PML patients) and CD62L (1,257 control patients and 17 pre-PML patients).

Low CD62L in natalizumab-treated patients was retrospectively confirmed and prospectively validated as a biomarker for PML risk. The risk factor “CD62L low” increased a patient’s relative risk 55-fold. Validation efforts established an 86% sensitivity and 91% specificity for CD62L and 100% sensitivity and 59% specificity for JCV index as predictors of PML.

Low CD62L values were also found in various other PML associations and stages (ie, lupus, lymphopenia, HIV, acute natalizumab-PML). CD62L values correlated with JCV serostatus, so the lower the CD62L value of a patient was, the higher the probability that they were JCV positive. The researchers ultimately found that 26 out of 27 (96%) patients with low CD62L were JCV positive. Additionally, CD62L values negatively correlated with JCV index values.

“The combined use of JCV serology and CD62L level found 2% of patients studied to be at highest risk,” Dr. Schwab reported. “Adherence to the risk-stratification algorithm might prevent up to or over 85% of PML cases,” he said.

BARCELONA—The anti-JCV antibody index and L-selectin (CD62L) have merit for risk stratification and share a potential biological relationship with implications for general progressive multifocal leukoencephalopathy (PML) etiology, according to research presented at the 31st Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). “A risk algorithm incorporating both biomarkers could strongly reduce PML incidence,” said Nicholas Schwab, PhD, of the Department of Neurology at the University of Münster in Germany.

Natalizumab treatment is associated with PML development, with more than 541 cases as of March 3, 2015. Treatment duration, prior immunosuppressant use, and JCV serostatus are currently used for categorical risk stratification, but PML incidence continues to rise steadily. Anti-JCV antibody index and CD62L have previously been proposed as additional risk stratification parameters. Dr. Schwab and his research colleagues aimed at verifying and integrating both parameters into one applicable algorithm for risk stratification.

The research team gathered international cohorts of patients with multiple sclerosis who were treated with natalizumab. The participants were assessed for JCV index (1,921 control patients and nine pre-PML patients) and CD62L (1,257 control patients and 17 pre-PML patients).

Low CD62L in natalizumab-treated patients was retrospectively confirmed and prospectively validated as a biomarker for PML risk. The risk factor “CD62L low” increased a patient’s relative risk 55-fold. Validation efforts established an 86% sensitivity and 91% specificity for CD62L and 100% sensitivity and 59% specificity for JCV index as predictors of PML.

Low CD62L values were also found in various other PML associations and stages (ie, lupus, lymphopenia, HIV, acute natalizumab-PML). CD62L values correlated with JCV serostatus, so the lower the CD62L value of a patient was, the higher the probability that they were JCV positive. The researchers ultimately found that 26 out of 27 (96%) patients with low CD62L were JCV positive. Additionally, CD62L values negatively correlated with JCV index values.

“The combined use of JCV serology and CD62L level found 2% of patients studied to be at highest risk,” Dr. Schwab reported. “Adherence to the risk-stratification algorithm might prevent up to or over 85% of PML cases,” he said.

BARCELONA—When added to other antispasticity treatments, an oromucosal spray containing approximately equal amounts of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) provides effective symptomatic relief of treatment-resistant MS spasticity, according to a study presented at the 31st Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). The drug also is well tolerated in clinical practice.

“The results for spasticity evolution and tolerability in this patient cohort … compare favorably with results reported in randomized controlled trials and other observational studies of THC:CBD oromucosal spray,” said Maria Trojano, MD, Director of the Department of Basic Medical Sciences, Neurosciences, and Sensory Organs at the University of Bari in Italy, and her colleagues.

Randomized controlled trials indicate that THC:CBD oromucosal spray significantly reduces MS spasticity, compared with placebo, and does not raise significant tolerability concerns. German investigators initiated the prospective, noninterventional Mobility Improvement (MOVE) 2 study to examine the spray’s efficacy and tolerability in everyday clinical practice. Patients received treatment with the spray according to its approved use label in the outpatient setting in Europe.

Several Italian centers joined the MOVE 2 study, and Italy became the first country to reach the recruitment target of 300 or more patients for a preplanned interim analysis. Specialist MS centers in Italy are collecting data on MS spasticity from electronic case record forms and patients’ diaries at baseline and after one month (ie, Visit 1) and three months (ie, Visit 3) of treatment with THC:CBD oromucosal spray. The researchers are measuring effectiveness by rates of treatment continuation and changes from baseline in scores on the spasticity numerical rating scale (NRS) and modified Ashworth scale. The researchers also are inquiring about tolerability and adverse events.

In all, 322 patients (58.3% female, mean age 51.1) with treatment-resistant MS spasticity were recruited at 34 Italian MS centers. Baseline antispasticity medicines included baclofen (71.1%), gabapentin–pregabalin (10.9%), benzodiazepines (6.8%), and tizanidine (5.9%). About half of patients were receiving concomitant physiotherapy.

Mean doses of the spray were 6.1 sprays/day at Visit 1 and 5.1 sprays/day at Visit 3. At Visit 1, 82.9% of patients had an initial response to the THC:CBD oromucosal spray (ie, an improvement from baseline NRS score of at least 20%) and continued with treatment. At Visit 3, 24.6% of patients with available data had a clinically relevant response to the spray (ie, improvement from baseline NRS score of at least 30%) and continued with treatment. An additional 53.2% of patients continued to use the spray after Visit 3 although their improvement on the spasticity NRS was less than 30%.

Mean spasticity NRS score was 6.8 at baseline. The score decreased to 5.5 in patients with available data at Visit 3, representing a significant 19.1% improvement. Mean modified Ashworth scale score was 2.6 at baseline. The score decreased to 2.2 at Visit 1 and was 2.3 in patients with available data at Visit 3.

Rates of treatment discontinuation were 8.7% at Visit 1 and 22.2% at Visit 3. The main reasons for treatment discontinuation were lack of effectiveness (42%), lack of tolerability (42%), and pregnancy or other reasons (16%). Approximately 13% of patients reported at least one adverse event. All nonserious adverse events were mild to moderate. Adverse events with an incidence of 1% or greater included dizziness, confusion, nausea, and somnolence. Two serious adverse events, mental impairment and suicidal ideation, were considered as possibly related to treatment. One death was considered unrelated to treatment.

BARCELONA—When added to other antispasticity treatments, an oromucosal spray containing approximately equal amounts of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) provides effective symptomatic relief of treatment-resistant MS spasticity, according to a study presented at the 31st Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). The drug also is well tolerated in clinical practice.

“The results for spasticity evolution and tolerability in this patient cohort … compare favorably with results reported in randomized controlled trials and other observational studies of THC:CBD oromucosal spray,” said Maria Trojano, MD, Director of the Department of Basic Medical Sciences, Neurosciences, and Sensory Organs at the University of Bari in Italy, and her colleagues.

Randomized controlled trials indicate that THC:CBD oromucosal spray significantly reduces MS spasticity, compared with placebo, and does not raise significant tolerability concerns. German investigators initiated the prospective, noninterventional Mobility Improvement (MOVE) 2 study to examine the spray’s efficacy and tolerability in everyday clinical practice. Patients received treatment with the spray according to its approved use label in the outpatient setting in Europe.

Several Italian centers joined the MOVE 2 study, and Italy became the first country to reach the recruitment target of 300 or more patients for a preplanned interim analysis. Specialist MS centers in Italy are collecting data on MS spasticity from electronic case record forms and patients’ diaries at baseline and after one month (ie, Visit 1) and three months (ie, Visit 3) of treatment with THC:CBD oromucosal spray. The researchers are measuring effectiveness by rates of treatment continuation and changes from baseline in scores on the spasticity numerical rating scale (NRS) and modified Ashworth scale. The researchers also are inquiring about tolerability and adverse events.

In all, 322 patients (58.3% female, mean age 51.1) with treatment-resistant MS spasticity were recruited at 34 Italian MS centers. Baseline antispasticity medicines included baclofen (71.1%), gabapentin–pregabalin (10.9%), benzodiazepines (6.8%), and tizanidine (5.9%). About half of patients were receiving concomitant physiotherapy.

Mean doses of the spray were 6.1 sprays/day at Visit 1 and 5.1 sprays/day at Visit 3. At Visit 1, 82.9% of patients had an initial response to the THC:CBD oromucosal spray (ie, an improvement from baseline NRS score of at least 20%) and continued with treatment. At Visit 3, 24.6% of patients with available data had a clinically relevant response to the spray (ie, improvement from baseline NRS score of at least 30%) and continued with treatment. An additional 53.2% of patients continued to use the spray after Visit 3 although their improvement on the spasticity NRS was less than 30%.

Mean spasticity NRS score was 6.8 at baseline. The score decreased to 5.5 in patients with available data at Visit 3, representing a significant 19.1% improvement. Mean modified Ashworth scale score was 2.6 at baseline. The score decreased to 2.2 at Visit 1 and was 2.3 in patients with available data at Visit 3.

Rates of treatment discontinuation were 8.7% at Visit 1 and 22.2% at Visit 3. The main reasons for treatment discontinuation were lack of effectiveness (42%), lack of tolerability (42%), and pregnancy or other reasons (16%). Approximately 13% of patients reported at least one adverse event. All nonserious adverse events were mild to moderate. Adverse events with an incidence of 1% or greater included dizziness, confusion, nausea, and somnolence. Two serious adverse events, mental impairment and suicidal ideation, were considered as possibly related to treatment. One death was considered unrelated to treatment.

BARCELONA—When added to other antispasticity treatments, an oromucosal spray containing approximately equal amounts of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) provides effective symptomatic relief of treatment-resistant MS spasticity, according to a study presented at the 31st Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). The drug also is well tolerated in clinical practice.

“The results for spasticity evolution and tolerability in this patient cohort … compare favorably with results reported in randomized controlled trials and other observational studies of THC:CBD oromucosal spray,” said Maria Trojano, MD, Director of the Department of Basic Medical Sciences, Neurosciences, and Sensory Organs at the University of Bari in Italy, and her colleagues.

Randomized controlled trials indicate that THC:CBD oromucosal spray significantly reduces MS spasticity, compared with placebo, and does not raise significant tolerability concerns. German investigators initiated the prospective, noninterventional Mobility Improvement (MOVE) 2 study to examine the spray’s efficacy and tolerability in everyday clinical practice. Patients received treatment with the spray according to its approved use label in the outpatient setting in Europe.

Several Italian centers joined the MOVE 2 study, and Italy became the first country to reach the recruitment target of 300 or more patients for a preplanned interim analysis. Specialist MS centers in Italy are collecting data on MS spasticity from electronic case record forms and patients’ diaries at baseline and after one month (ie, Visit 1) and three months (ie, Visit 3) of treatment with THC:CBD oromucosal spray. The researchers are measuring effectiveness by rates of treatment continuation and changes from baseline in scores on the spasticity numerical rating scale (NRS) and modified Ashworth scale. The researchers also are inquiring about tolerability and adverse events.

In all, 322 patients (58.3% female, mean age 51.1) with treatment-resistant MS spasticity were recruited at 34 Italian MS centers. Baseline antispasticity medicines included baclofen (71.1%), gabapentin–pregabalin (10.9%), benzodiazepines (6.8%), and tizanidine (5.9%). About half of patients were receiving concomitant physiotherapy.

Mean doses of the spray were 6.1 sprays/day at Visit 1 and 5.1 sprays/day at Visit 3. At Visit 1, 82.9% of patients had an initial response to the THC:CBD oromucosal spray (ie, an improvement from baseline NRS score of at least 20%) and continued with treatment. At Visit 3, 24.6% of patients with available data had a clinically relevant response to the spray (ie, improvement from baseline NRS score of at least 30%) and continued with treatment. An additional 53.2% of patients continued to use the spray after Visit 3 although their improvement on the spasticity NRS was less than 30%.

Mean spasticity NRS score was 6.8 at baseline. The score decreased to 5.5 in patients with available data at Visit 3, representing a significant 19.1% improvement. Mean modified Ashworth scale score was 2.6 at baseline. The score decreased to 2.2 at Visit 1 and was 2.3 in patients with available data at Visit 3.

Rates of treatment discontinuation were 8.7% at Visit 1 and 22.2% at Visit 3. The main reasons for treatment discontinuation were lack of effectiveness (42%), lack of tolerability (42%), and pregnancy or other reasons (16%). Approximately 13% of patients reported at least one adverse event. All nonserious adverse events were mild to moderate. Adverse events with an incidence of 1% or greater included dizziness, confusion, nausea, and somnolence. Two serious adverse events, mental impairment and suicidal ideation, were considered as possibly related to treatment. One death was considered unrelated to treatment.

BARCELONA—Patients with relapsing-remitting multiple sclerosis (MS) who receive daclizumab high-yield process (DAC HYP) for two years have significantly less brain volume loss than patients who receive intramuscular interferon beta-1a for two years, according to research presented at the 31st Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). The effects of daclizumab, compared with those of interferon beta-1a, are not related to pseudoatrophy during the first 24 weeks of treatment, according to the investigators.

“These results are consistent with other MRI outcomes from DECIDE that showed significantly lower inflammatory and chronic brain MRI lesion activity for DAC HYP, compared with intramuscular interferon beta-1a,” said Douglas Arnold, MD, a neurologist at Montreal Neurological Institute and Hospital, and colleagues.

Compared with the general population, people with MS have more rapid brain volume loss that may lead to the accumulation of disability. Previous data suggest that intramuscular interferon beta-1a reduces brain volume loss at year 2.

To compare the effects of DAC HYP and intramuscular interferon beta-1a on brain volume change, Dr. Arnold and colleagues examined data from the DECIDE study, which compared these two drugs in people with relapsing-remitting MS. Participants in the randomized, double-blind trial received 150 mg of subcutaneous DAC HYP every four weeks or 30 mg of intramuscular interferon beta-1a once weekly for at least 96 weeks. Some participants continued in the study for as long as 144 weeks. Whole brain volume change was evaluated as the percentage brain volume change (PBVC) over the prespecified intervals of weeks 0 to 24, 24 to 96, and 0 to 96 using the structural image evaluation using normalization of atrophy (SIENA) method. The researchers performed subgroup analyses according to patients’ baseline demographics and clinical characteristics.

A total of 1,841 patients were enrolled in DECIDE. Patients’ mean age was 36, and 68% of participants were female. Mean duration of disease was approximately four years, the mean number of relapses in the previous year was approximately 1.5, and mean Expanded Disability Status Scale score was 2.5. Median brain volume was 1,498 cm³.

Annualized PBVC was significantly reduced in the DAC HYP group between baseline and Week 96, compared with the intramuscular interferon beta-1a group. The median annualized PBVC from baseline to Week 96 was -0.580 for interferon beta-1a and -0.553 for DAC HYP. Subgroup analyses indicated that annualized percentage brain volume loss between baseline and Week 96 was lower in the DAC HYP group than in the interferon beta-1a group across all subgroups, except in subgroups of patients who were male, had baseline T2 lesion volume equal to or above the median, and with MS diagnosis within three to 10 years.

Annualized percentage brain volume loss also was lower in the DAC HYP group, compared with the interferon beta-1a group in the period from baseline to Week 24 (-0.674 vs -0.745). Annualized PBVC also was reduced between weeks 24 and 96 for DAC HYP, compared with interferon beta-1a (-0.511 vs -0.549).

BARCELONA—Patients with relapsing-remitting multiple sclerosis (MS) who receive daclizumab high-yield process (DAC HYP) for two years have significantly less brain volume loss than patients who receive intramuscular interferon beta-1a for two years, according to research presented at the 31st Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). The effects of daclizumab, compared with those of interferon beta-1a, are not related to pseudoatrophy during the first 24 weeks of treatment, according to the investigators.

“These results are consistent with other MRI outcomes from DECIDE that showed significantly lower inflammatory and chronic brain MRI lesion activity for DAC HYP, compared with intramuscular interferon beta-1a,” said Douglas Arnold, MD, a neurologist at Montreal Neurological Institute and Hospital, and colleagues.

Compared with the general population, people with MS have more rapid brain volume loss that may lead to the accumulation of disability. Previous data suggest that intramuscular interferon beta-1a reduces brain volume loss at year 2.

To compare the effects of DAC HYP and intramuscular interferon beta-1a on brain volume change, Dr. Arnold and colleagues examined data from the DECIDE study, which compared these two drugs in people with relapsing-remitting MS. Participants in the randomized, double-blind trial received 150 mg of subcutaneous DAC HYP every four weeks or 30 mg of intramuscular interferon beta-1a once weekly for at least 96 weeks. Some participants continued in the study for as long as 144 weeks. Whole brain volume change was evaluated as the percentage brain volume change (PBVC) over the prespecified intervals of weeks 0 to 24, 24 to 96, and 0 to 96 using the structural image evaluation using normalization of atrophy (SIENA) method. The researchers performed subgroup analyses according to patients’ baseline demographics and clinical characteristics.

A total of 1,841 patients were enrolled in DECIDE. Patients’ mean age was 36, and 68% of participants were female. Mean duration of disease was approximately four years, the mean number of relapses in the previous year was approximately 1.5, and mean Expanded Disability Status Scale score was 2.5. Median brain volume was 1,498 cm³.

Annualized PBVC was significantly reduced in the DAC HYP group between baseline and Week 96, compared with the intramuscular interferon beta-1a group. The median annualized PBVC from baseline to Week 96 was -0.580 for interferon beta-1a and -0.553 for DAC HYP. Subgroup analyses indicated that annualized percentage brain volume loss between baseline and Week 96 was lower in the DAC HYP group than in the interferon beta-1a group across all subgroups, except in subgroups of patients who were male, had baseline T2 lesion volume equal to or above the median, and with MS diagnosis within three to 10 years.

Annualized percentage brain volume loss also was lower in the DAC HYP group, compared with the interferon beta-1a group in the period from baseline to Week 24 (-0.674 vs -0.745). Annualized PBVC also was reduced between weeks 24 and 96 for DAC HYP, compared with interferon beta-1a (-0.511 vs -0.549).

BARCELONA—Patients with relapsing-remitting multiple sclerosis (MS) who receive daclizumab high-yield process (DAC HYP) for two years have significantly less brain volume loss than patients who receive intramuscular interferon beta-1a for two years, according to research presented at the 31st Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). The effects of daclizumab, compared with those of interferon beta-1a, are not related to pseudoatrophy during the first 24 weeks of treatment, according to the investigators.

“These results are consistent with other MRI outcomes from DECIDE that showed significantly lower inflammatory and chronic brain MRI lesion activity for DAC HYP, compared with intramuscular interferon beta-1a,” said Douglas Arnold, MD, a neurologist at Montreal Neurological Institute and Hospital, and colleagues.

Compared with the general population, people with MS have more rapid brain volume loss that may lead to the accumulation of disability. Previous data suggest that intramuscular interferon beta-1a reduces brain volume loss at year 2.

To compare the effects of DAC HYP and intramuscular interferon beta-1a on brain volume change, Dr. Arnold and colleagues examined data from the DECIDE study, which compared these two drugs in people with relapsing-remitting MS. Participants in the randomized, double-blind trial received 150 mg of subcutaneous DAC HYP every four weeks or 30 mg of intramuscular interferon beta-1a once weekly for at least 96 weeks. Some participants continued in the study for as long as 144 weeks. Whole brain volume change was evaluated as the percentage brain volume change (PBVC) over the prespecified intervals of weeks 0 to 24, 24 to 96, and 0 to 96 using the structural image evaluation using normalization of atrophy (SIENA) method. The researchers performed subgroup analyses according to patients’ baseline demographics and clinical characteristics.

A total of 1,841 patients were enrolled in DECIDE. Patients’ mean age was 36, and 68% of participants were female. Mean duration of disease was approximately four years, the mean number of relapses in the previous year was approximately 1.5, and mean Expanded Disability Status Scale score was 2.5. Median brain volume was 1,498 cm³.

Annualized PBVC was significantly reduced in the DAC HYP group between baseline and Week 96, compared with the intramuscular interferon beta-1a group. The median annualized PBVC from baseline to Week 96 was -0.580 for interferon beta-1a and -0.553 for DAC HYP. Subgroup analyses indicated that annualized percentage brain volume loss between baseline and Week 96 was lower in the DAC HYP group than in the interferon beta-1a group across all subgroups, except in subgroups of patients who were male, had baseline T2 lesion volume equal to or above the median, and with MS diagnosis within three to 10 years.

Annualized percentage brain volume loss also was lower in the DAC HYP group, compared with the interferon beta-1a group in the period from baseline to Week 24 (-0.674 vs -0.745). Annualized PBVC also was reduced between weeks 24 and 96 for DAC HYP, compared with interferon beta-1a (-0.511 vs -0.549).

BARCELONA—The tetracycline antibiotic minocycline reduces the relative risk of multiple sclerosis (MS) in patients experiencing their first clinical demyelinating event by 44.6%, according to the results of a phase III double-blind placebo-controlled Canadian multicenter clinical trial reported at the 31st Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).

“Current proven therapies for patients experiencing their first clinical demyelinating event show benefit the earlier they are introduced. However, payment coverage varies throughout the world, often delaying treatment until patients have demonstrated a second clinical attack,” said Luanne M. Metz, MD, Professor and Head of the Division of Neurology and Director of the MS Program at the University of Calgary in Canada, and her research colleagues. “Current oral therapies may not be ideal options because of safety concerns. Minocycline is an inexpensive oral antibiotic with a recognized safety profile. It is widely available, often in generic formulation. Preclinical and preliminary clinical studies suggest it may be a therapeutic option in MS as both monotherapy and as an add-on treatment.”

Dr. Metz and colleagues enrolled subjects between ages 18 and 60, with onset of their first demyelinating symptoms within the previous 180 days and at least two T2 hyperintense lesions on brain MRI. The study subjects were randomized to oral minocycline 100 mg bid or identical placebo. Treatment continued for 24 months or until MS diagnosis by 2005 McDonald criteria was confirmed. Follow-up visits were scheduled at one, three, six, nine, 12, 15, 18, 21, and 24 months. MRI scans were scheduled at screen, months three, six, 12, and 24 and at early end of study. The primary outcome was the proportion of participants who developed MS by six months. Risk estimates, absolute risk reductions, and relative risk reductions were calculated from actuarial life table analysis.

Starting in December 2008, 236 patients were screened at 12 Canadian sites; 143 were randomized. Intention to treat analysis included 142 subjects, as one subject was randomized in error; 72 received minocycline. Mean age was 35.8; 68.3% were women. Onset was monofocal in 76.8%, median Expanded Disability Status Scale score was 1.5, mean duration since onset of demyelinating symptoms was 84.5 days, 69% had more than eight T2 lesions, and 34.5% had enhancing lesions at screen. The risk of conversion to MS by six months was 61.4% in the placebo group and 34.0% in the minocycline group. The absolute risk reduction was 27.4%, the relative risk reduction was 44.6%, and the number needed to treat (NNT) was four. At 12 months, the absolute risk reduction was 25.1%, the relative risk reduction was 37.6%, and the NNT was four.

Based on their findings, the researchers concluded that minocycline 100 mg bid reduces conversion of the first clinical demyelinating event to MS. “Given its known safety and low cost, minocycline should be considered for initial treatment as well as for combination therapy trials.”

BARCELONA—The tetracycline antibiotic minocycline reduces the relative risk of multiple sclerosis (MS) in patients experiencing their first clinical demyelinating event by 44.6%, according to the results of a phase III double-blind placebo-controlled Canadian multicenter clinical trial reported at the 31st Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).

“Current proven therapies for patients experiencing their first clinical demyelinating event show benefit the earlier they are introduced. However, payment coverage varies throughout the world, often delaying treatment until patients have demonstrated a second clinical attack,” said Luanne M. Metz, MD, Professor and Head of the Division of Neurology and Director of the MS Program at the University of Calgary in Canada, and her research colleagues. “Current oral therapies may not be ideal options because of safety concerns. Minocycline is an inexpensive oral antibiotic with a recognized safety profile. It is widely available, often in generic formulation. Preclinical and preliminary clinical studies suggest it may be a therapeutic option in MS as both monotherapy and as an add-on treatment.”

Dr. Metz and colleagues enrolled subjects between ages 18 and 60, with onset of their first demyelinating symptoms within the previous 180 days and at least two T2 hyperintense lesions on brain MRI. The study subjects were randomized to oral minocycline 100 mg bid or identical placebo. Treatment continued for 24 months or until MS diagnosis by 2005 McDonald criteria was confirmed. Follow-up visits were scheduled at one, three, six, nine, 12, 15, 18, 21, and 24 months. MRI scans were scheduled at screen, months three, six, 12, and 24 and at early end of study. The primary outcome was the proportion of participants who developed MS by six months. Risk estimates, absolute risk reductions, and relative risk reductions were calculated from actuarial life table analysis.

Starting in December 2008, 236 patients were screened at 12 Canadian sites; 143 were randomized. Intention to treat analysis included 142 subjects, as one subject was randomized in error; 72 received minocycline. Mean age was 35.8; 68.3% were women. Onset was monofocal in 76.8%, median Expanded Disability Status Scale score was 1.5, mean duration since onset of demyelinating symptoms was 84.5 days, 69% had more than eight T2 lesions, and 34.5% had enhancing lesions at screen. The risk of conversion to MS by six months was 61.4% in the placebo group and 34.0% in the minocycline group. The absolute risk reduction was 27.4%, the relative risk reduction was 44.6%, and the number needed to treat (NNT) was four. At 12 months, the absolute risk reduction was 25.1%, the relative risk reduction was 37.6%, and the NNT was four.

Based on their findings, the researchers concluded that minocycline 100 mg bid reduces conversion of the first clinical demyelinating event to MS. “Given its known safety and low cost, minocycline should be considered for initial treatment as well as for combination therapy trials.”

BARCELONA—The tetracycline antibiotic minocycline reduces the relative risk of multiple sclerosis (MS) in patients experiencing their first clinical demyelinating event by 44.6%, according to the results of a phase III double-blind placebo-controlled Canadian multicenter clinical trial reported at the 31st Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).

“Current proven therapies for patients experiencing their first clinical demyelinating event show benefit the earlier they are introduced. However, payment coverage varies throughout the world, often delaying treatment until patients have demonstrated a second clinical attack,” said Luanne M. Metz, MD, Professor and Head of the Division of Neurology and Director of the MS Program at the University of Calgary in Canada, and her research colleagues. “Current oral therapies may not be ideal options because of safety concerns. Minocycline is an inexpensive oral antibiotic with a recognized safety profile. It is widely available, often in generic formulation. Preclinical and preliminary clinical studies suggest it may be a therapeutic option in MS as both monotherapy and as an add-on treatment.”

Dr. Metz and colleagues enrolled subjects between ages 18 and 60, with onset of their first demyelinating symptoms within the previous 180 days and at least two T2 hyperintense lesions on brain MRI. The study subjects were randomized to oral minocycline 100 mg bid or identical placebo. Treatment continued for 24 months or until MS diagnosis by 2005 McDonald criteria was confirmed. Follow-up visits were scheduled at one, three, six, nine, 12, 15, 18, 21, and 24 months. MRI scans were scheduled at screen, months three, six, 12, and 24 and at early end of study. The primary outcome was the proportion of participants who developed MS by six months. Risk estimates, absolute risk reductions, and relative risk reductions were calculated from actuarial life table analysis.

Starting in December 2008, 236 patients were screened at 12 Canadian sites; 143 were randomized. Intention to treat analysis included 142 subjects, as one subject was randomized in error; 72 received minocycline. Mean age was 35.8; 68.3% were women. Onset was monofocal in 76.8%, median Expanded Disability Status Scale score was 1.5, mean duration since onset of demyelinating symptoms was 84.5 days, 69% had more than eight T2 lesions, and 34.5% had enhancing lesions at screen. The risk of conversion to MS by six months was 61.4% in the placebo group and 34.0% in the minocycline group. The absolute risk reduction was 27.4%, the relative risk reduction was 44.6%, and the number needed to treat (NNT) was four. At 12 months, the absolute risk reduction was 25.1%, the relative risk reduction was 37.6%, and the NNT was four.

Based on their findings, the researchers concluded that minocycline 100 mg bid reduces conversion of the first clinical demyelinating event to MS. “Given its known safety and low cost, minocycline should be considered for initial treatment as well as for combination therapy trials.”

BARCELONA—Data presented at the 31st Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) show that 31.2% to 44.8% of patients continuously treated with fingolimod in the FREEDOMS core and extension trials achieved NEDA-4 in each of the years three to seven. NEDA-4—no evidence of disease activity in the four areas of relapses, MRI lesions, brain atrophy, and disability progression—is a comprehensive measure of MS disease control. A separate analysis confirmed that NEDA-4 status in the first year is a better predictor of long-term outcomes than an assessment of three parameters (relapses, MRI lesions, and disability progression).

A follow-up analysis of pooled data from the FREEDOMS and FREEDOMS II core and extension trials was conducted to assess NEDA-4 each year for seven years in patients with relapsing-remitting multiple sclerosis (MS). Bruce Cree, PhD, MD, of the University of California San Francisco, and colleagues found that in the first year, 27.1% of patients on fingolimod achieved NEDA-4, compared with 9.1% on placebo. Switching from placebo to fingolimod after year two doubled the proportion of patients achieving NEDA-4 (12.7% to 27.4%) in year three. Of those patients on continuous fingolimod treatment, 31.2% to 44.8% reached NEDA-4 status in each of the years three to seven.

“Fingolimod showed sustained efficacy in achieving NEDA-3 and NEDA-4 over seven years,” Dr. Cree and colleagues reported. “Patients who were on placebo for the first two years demonstrated substantial improvements in NEDA-3 and NEDA-4 outcomes after switching to fingolimod. However, patients who received fingolimod from the start appeared to derive more benefit throughout the first five years.”

A separate follow-up analysis of data from the FREEDOMS and FREEDOMS II trials also confirmed for the first time that assessment of relapsing-remitting MS based on NEDA-4 allowed physicians to better predict long-term disability and brain shrinkage outcomes than just assessing relapses, MRI lesions, and disability progression. Ludwig Kappos, MD, of University Hospital in Basel, Switzerland, and colleagues found that NEDA-4 status over the first year was a significantly better predictor of disability and brain atrophy over the subsequent five years, as measured by patients reaching a stage of severe disability (EDSS of 6 or more) or having more than 0.4% mean annual brain volume loss. According to the researchers, these findings support the importance of assessing relapsing-remitting MS with NEDA-4 to enable a more reliable prediction of long-term disease outcomes.

“NEDA-3 status seems to correlate more with subsequent relapse and focal inflammatory MRI activity, while NEDA-4, which adds an imaging outcome that captures tissue destruction as a result of both focal and diffuse pathology, tended to be a better predictor of subsequent disability-related outcomes and brain volume loss,” Dr. Kappos and colleagues said. “These findings support use of NEDA-4 as a more comprehensive and balanced measure for relapsing-remitting MS.”

BARCELONA—Data presented at the 31st Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) show that 31.2% to 44.8% of patients continuously treated with fingolimod in the FREEDOMS core and extension trials achieved NEDA-4 in each of the years three to seven. NEDA-4—no evidence of disease activity in the four areas of relapses, MRI lesions, brain atrophy, and disability progression—is a comprehensive measure of MS disease control. A separate analysis confirmed that NEDA-4 status in the first year is a better predictor of long-term outcomes than an assessment of three parameters (relapses, MRI lesions, and disability progression).

A follow-up analysis of pooled data from the FREEDOMS and FREEDOMS II core and extension trials was conducted to assess NEDA-4 each year for seven years in patients with relapsing-remitting multiple sclerosis (MS). Bruce Cree, PhD, MD, of the University of California San Francisco, and colleagues found that in the first year, 27.1% of patients on fingolimod achieved NEDA-4, compared with 9.1% on placebo. Switching from placebo to fingolimod after year two doubled the proportion of patients achieving NEDA-4 (12.7% to 27.4%) in year three. Of those patients on continuous fingolimod treatment, 31.2% to 44.8% reached NEDA-4 status in each of the years three to seven.

“Fingolimod showed sustained efficacy in achieving NEDA-3 and NEDA-4 over seven years,” Dr. Cree and colleagues reported. “Patients who were on placebo for the first two years demonstrated substantial improvements in NEDA-3 and NEDA-4 outcomes after switching to fingolimod. However, patients who received fingolimod from the start appeared to derive more benefit throughout the first five years.”

A separate follow-up analysis of data from the FREEDOMS and FREEDOMS II trials also confirmed for the first time that assessment of relapsing-remitting MS based on NEDA-4 allowed physicians to better predict long-term disability and brain shrinkage outcomes than just assessing relapses, MRI lesions, and disability progression. Ludwig Kappos, MD, of University Hospital in Basel, Switzerland, and colleagues found that NEDA-4 status over the first year was a significantly better predictor of disability and brain atrophy over the subsequent five years, as measured by patients reaching a stage of severe disability (EDSS of 6 or more) or having more than 0.4% mean annual brain volume loss. According to the researchers, these findings support the importance of assessing relapsing-remitting MS with NEDA-4 to enable a more reliable prediction of long-term disease outcomes.

“NEDA-3 status seems to correlate more with subsequent relapse and focal inflammatory MRI activity, while NEDA-4, which adds an imaging outcome that captures tissue destruction as a result of both focal and diffuse pathology, tended to be a better predictor of subsequent disability-related outcomes and brain volume loss,” Dr. Kappos and colleagues said. “These findings support use of NEDA-4 as a more comprehensive and balanced measure for relapsing-remitting MS.”

BARCELONA—Data presented at the 31st Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) show that 31.2% to 44.8% of patients continuously treated with fingolimod in the FREEDOMS core and extension trials achieved NEDA-4 in each of the years three to seven. NEDA-4—no evidence of disease activity in the four areas of relapses, MRI lesions, brain atrophy, and disability progression—is a comprehensive measure of MS disease control. A separate analysis confirmed that NEDA-4 status in the first year is a better predictor of long-term outcomes than an assessment of three parameters (relapses, MRI lesions, and disability progression).

A follow-up analysis of pooled data from the FREEDOMS and FREEDOMS II core and extension trials was conducted to assess NEDA-4 each year for seven years in patients with relapsing-remitting multiple sclerosis (MS). Bruce Cree, PhD, MD, of the University of California San Francisco, and colleagues found that in the first year, 27.1% of patients on fingolimod achieved NEDA-4, compared with 9.1% on placebo. Switching from placebo to fingolimod after year two doubled the proportion of patients achieving NEDA-4 (12.7% to 27.4%) in year three. Of those patients on continuous fingolimod treatment, 31.2% to 44.8% reached NEDA-4 status in each of the years three to seven.

“Fingolimod showed sustained efficacy in achieving NEDA-3 and NEDA-4 over seven years,” Dr. Cree and colleagues reported. “Patients who were on placebo for the first two years demonstrated substantial improvements in NEDA-3 and NEDA-4 outcomes after switching to fingolimod. However, patients who received fingolimod from the start appeared to derive more benefit throughout the first five years.”

A separate follow-up analysis of data from the FREEDOMS and FREEDOMS II trials also confirmed for the first time that assessment of relapsing-remitting MS based on NEDA-4 allowed physicians to better predict long-term disability and brain shrinkage outcomes than just assessing relapses, MRI lesions, and disability progression. Ludwig Kappos, MD, of University Hospital in Basel, Switzerland, and colleagues found that NEDA-4 status over the first year was a significantly better predictor of disability and brain atrophy over the subsequent five years, as measured by patients reaching a stage of severe disability (EDSS of 6 or more) or having more than 0.4% mean annual brain volume loss. According to the researchers, these findings support the importance of assessing relapsing-remitting MS with NEDA-4 to enable a more reliable prediction of long-term disease outcomes.

“NEDA-3 status seems to correlate more with subsequent relapse and focal inflammatory MRI activity, while NEDA-4, which adds an imaging outcome that captures tissue destruction as a result of both focal and diffuse pathology, tended to be a better predictor of subsequent disability-related outcomes and brain volume loss,” Dr. Kappos and colleagues said. “These findings support use of NEDA-4 as a more comprehensive and balanced measure for relapsing-remitting MS.”

BARCELONA—Among people with multiple sclerosis (MS), more men than women report current and past use of marijuana, according to the results of a survey presented at the 31st Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).

More men have spoken to their doctor about marijuana use than women, but fewer men thought that marijuana improves symptoms associated with MS.

“Gender differences in [marijuana] use and perceptions about use should be considered in discussions about use,” said Stacey Cofield, PhD, Associate Professor of Biostatistics at the University of Alabama at Birmingham and North American Research Committee on MS (NARCOMS) Coordinating Center Deputy Director. NARCOMS conducted the survey to investigate patients’ perceptions about the effectiveness of marijuana for treating MS symptoms.

NARCOMS is a participant-driven registry with semiannual, self-reported information about MS treatments and symptomatic therapies, financial status, insurance status, and MS disease status.

Participants in NARCOMS are invited to take part in additional research separate from the semiannual updates.

In August 2014, Dr. Cofield and colleagues invited 12,260 active participants in NARCOMS to complete an anonymous online questionnaire about current behaviors and attitudes toward marijuana use and legality. For the purpose of the survey, “marijuana” referred to smoked and ingested forms of the drug, as well as any controlled substance derived from marijuana or synthetic marijuana. Questions included whether participants had used marijuana before their MS diagnosis, whether they used or considered using marijuana to treat MS symptoms, and whether they had discussed marijuana with their doctor. In addition, participants were asked what symptoms they thought marijuana might improve in MS and whether they had any of those symptoms.

A total of 5,665 participants responded to the survey, and 78.3% of respondents were women. Men were older than women at the time of the survey, but the researchers found no difference in age at diagnosis between genders. A higher proportion of men than women described their MS status as progressive without a history of relapse.

More men than women reported having used marijuana before their MS diagnosis. When examining data for marijuana users, the researchers saw no difference between genders in the number of days of marijuana use in the previous 30 days. The median number of days of use was 20 for both genders. Similarly, the researchers found no gender difference in the proportion of respondents who thought that marijuana should be legal. Overall, 91.5% of respondents supported the drug’s legality.

A higher proportion of men than women reported having muscle spasms, cramps, and spasticity, but a lower proportion of men thought that marijuana was effective for treating these symptoms. Similarly, a higher proportion of men than women reported tremor, but the researchers found no difference between genders in the perceived improvement of tremor with marijuana treatment. Also, more men than women (9.5% vs 5.9%) thought that marijuana did not improve any symptoms.

A higher proportion of women than men reported having migraines or headaches, anxiety, and nausea or gastrointestinal issues and thought that marijuana improved these symptoms. Gender differences persisted when the investigators adjusted the data for type of MS, age, duration of disease, and current marijuana usage.

BARCELONA—Among people with multiple sclerosis (MS), more men than women report current and past use of marijuana, according to the results of a survey presented at the 31st Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).

More men have spoken to their doctor about marijuana use than women, but fewer men thought that marijuana improves symptoms associated with MS.

“Gender differences in [marijuana] use and perceptions about use should be considered in discussions about use,” said Stacey Cofield, PhD, Associate Professor of Biostatistics at the University of Alabama at Birmingham and North American Research Committee on MS (NARCOMS) Coordinating Center Deputy Director. NARCOMS conducted the survey to investigate patients’ perceptions about the effectiveness of marijuana for treating MS symptoms.

NARCOMS is a participant-driven registry with semiannual, self-reported information about MS treatments and symptomatic therapies, financial status, insurance status, and MS disease status.

Participants in NARCOMS are invited to take part in additional research separate from the semiannual updates.

In August 2014, Dr. Cofield and colleagues invited 12,260 active participants in NARCOMS to complete an anonymous online questionnaire about current behaviors and attitudes toward marijuana use and legality. For the purpose of the survey, “marijuana” referred to smoked and ingested forms of the drug, as well as any controlled substance derived from marijuana or synthetic marijuana. Questions included whether participants had used marijuana before their MS diagnosis, whether they used or considered using marijuana to treat MS symptoms, and whether they had discussed marijuana with their doctor. In addition, participants were asked what symptoms they thought marijuana might improve in MS and whether they had any of those symptoms.

A total of 5,665 participants responded to the survey, and 78.3% of respondents were women. Men were older than women at the time of the survey, but the researchers found no difference in age at diagnosis between genders. A higher proportion of men than women described their MS status as progressive without a history of relapse.

More men than women reported having used marijuana before their MS diagnosis. When examining data for marijuana users, the researchers saw no difference between genders in the number of days of marijuana use in the previous 30 days. The median number of days of use was 20 for both genders. Similarly, the researchers found no gender difference in the proportion of respondents who thought that marijuana should be legal. Overall, 91.5% of respondents supported the drug’s legality.

A higher proportion of men than women reported having muscle spasms, cramps, and spasticity, but a lower proportion of men thought that marijuana was effective for treating these symptoms. Similarly, a higher proportion of men than women reported tremor, but the researchers found no difference between genders in the perceived improvement of tremor with marijuana treatment. Also, more men than women (9.5% vs 5.9%) thought that marijuana did not improve any symptoms.

A higher proportion of women than men reported having migraines or headaches, anxiety, and nausea or gastrointestinal issues and thought that marijuana improved these symptoms. Gender differences persisted when the investigators adjusted the data for type of MS, age, duration of disease, and current marijuana usage.

BARCELONA—Among people with multiple sclerosis (MS), more men than women report current and past use of marijuana, according to the results of a survey presented at the 31st Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).

More men have spoken to their doctor about marijuana use than women, but fewer men thought that marijuana improves symptoms associated with MS.

“Gender differences in [marijuana] use and perceptions about use should be considered in discussions about use,” said Stacey Cofield, PhD, Associate Professor of Biostatistics at the University of Alabama at Birmingham and North American Research Committee on MS (NARCOMS) Coordinating Center Deputy Director. NARCOMS conducted the survey to investigate patients’ perceptions about the effectiveness of marijuana for treating MS symptoms.

NARCOMS is a participant-driven registry with semiannual, self-reported information about MS treatments and symptomatic therapies, financial status, insurance status, and MS disease status.

Participants in NARCOMS are invited to take part in additional research separate from the semiannual updates.

In August 2014, Dr. Cofield and colleagues invited 12,260 active participants in NARCOMS to complete an anonymous online questionnaire about current behaviors and attitudes toward marijuana use and legality. For the purpose of the survey, “marijuana” referred to smoked and ingested forms of the drug, as well as any controlled substance derived from marijuana or synthetic marijuana. Questions included whether participants had used marijuana before their MS diagnosis, whether they used or considered using marijuana to treat MS symptoms, and whether they had discussed marijuana with their doctor. In addition, participants were asked what symptoms they thought marijuana might improve in MS and whether they had any of those symptoms.

A total of 5,665 participants responded to the survey, and 78.3% of respondents were women. Men were older than women at the time of the survey, but the researchers found no difference in age at diagnosis between genders. A higher proportion of men than women described their MS status as progressive without a history of relapse.

More men than women reported having used marijuana before their MS diagnosis. When examining data for marijuana users, the researchers saw no difference between genders in the number of days of marijuana use in the previous 30 days. The median number of days of use was 20 for both genders. Similarly, the researchers found no gender difference in the proportion of respondents who thought that marijuana should be legal. Overall, 91.5% of respondents supported the drug’s legality.

A higher proportion of men than women reported having muscle spasms, cramps, and spasticity, but a lower proportion of men thought that marijuana was effective for treating these symptoms. Similarly, a higher proportion of men than women reported tremor, but the researchers found no difference between genders in the perceived improvement of tremor with marijuana treatment. Also, more men than women (9.5% vs 5.9%) thought that marijuana did not improve any symptoms.

A higher proportion of women than men reported having migraines or headaches, anxiety, and nausea or gastrointestinal issues and thought that marijuana improved these symptoms. Gender differences persisted when the investigators adjusted the data for type of MS, age, duration of disease, and current marijuana usage.

BARCELONA—Anti-LINGO-1 improved full-field visual evoked potential (FF-VEP) latency of the eye affected by acute optic neuritis relative to placebo, consistent with improved remyelination, according to a study reported at the 31st Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). This latency recovery was greater in older subjects, subjects given the first dose earlier, and subjects with more severe pretreatment visual impairment.

In a primary efficacy analysis of the RENEW study, Orhan Aktas, MD, of Heinrich-Heine-Universität in Düsseldorf, Germany, and colleagues demonstrated an improvement versus placebo in optic nerve latency (-7.55 ms at week 24; -9.13 ms at week 32) consistent with remyelination in subjects with acute optic neuritis.

Research subjects ages 18 to 50 with a first unilateral acute optic neuritis episode were treated with high-dose steroids, then randomized to 100 mg/kg anti-LINGO-1 IV or placebo once every four weeks (ie, six doses) and followed to week 32. Optic nerve latency was measured using FF-VEP in the affected eye versus the baseline value for the unaffected eye. Between-treatment comparisons were evaluated by ANCOVA in the per-protocol population, defined as subjects who completed the study and did not miss more than one study dose or receive disease-modifying therapy for multiple sclerosis. Further analyses of latency recovery at week 24 (affected eye FF-VEP latency ≤10% worse than baseline of fellow eye) and efficacy stratified by prespecified baseline characteristics using the median as the cutoff were performed.

FF-VEP latency recovery in the affected eye versus baseline of the fellow eye was compared between 33 subjects who received anti-LINGO-1 and 36 treated with placebo. At week 24, 24 subjects had normal or mildly prolonged FF-VEP latency, 15 from the anti-LINGO-1 and nine from the placebo group. Assessment of subjects stratified by prespecified baseline characteristics showed that improvement in FF-VEP latency in the affected eye at week 24 with anti-LINGO-1 was greater in the following patient subgroups: age 33 or older (difference vs placebo, -14.17 ms compared with -0.89 ms in subjects younger than 33); those who received treatment less than 25 days from the onset of acute optic neuritis (-9.01 ms vs -6.68 ms for those receiving treatment more than 25 days after acute optic neuritis onset); and those who had a high-contrast visual acuity score less than 49 (-10.92 ms vs -4.14 ms for a score of 49 or more). None of the subgroup-by-treatment interactions reached statistical significance due to the small sample size.

BARCELONA—Anti-LINGO-1 improved full-field visual evoked potential (FF-VEP) latency of the eye affected by acute optic neuritis relative to placebo, consistent with improved remyelination, according to a study reported at the 31st Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). This latency recovery was greater in older subjects, subjects given the first dose earlier, and subjects with more severe pretreatment visual impairment.

In a primary efficacy analysis of the RENEW study, Orhan Aktas, MD, of Heinrich-Heine-Universität in Düsseldorf, Germany, and colleagues demonstrated an improvement versus placebo in optic nerve latency (-7.55 ms at week 24; -9.13 ms at week 32) consistent with remyelination in subjects with acute optic neuritis.

Research subjects ages 18 to 50 with a first unilateral acute optic neuritis episode were treated with high-dose steroids, then randomized to 100 mg/kg anti-LINGO-1 IV or placebo once every four weeks (ie, six doses) and followed to week 32. Optic nerve latency was measured using FF-VEP in the affected eye versus the baseline value for the unaffected eye. Between-treatment comparisons were evaluated by ANCOVA in the per-protocol population, defined as subjects who completed the study and did not miss more than one study dose or receive disease-modifying therapy for multiple sclerosis. Further analyses of latency recovery at week 24 (affected eye FF-VEP latency ≤10% worse than baseline of fellow eye) and efficacy stratified by prespecified baseline characteristics using the median as the cutoff were performed.

FF-VEP latency recovery in the affected eye versus baseline of the fellow eye was compared between 33 subjects who received anti-LINGO-1 and 36 treated with placebo. At week 24, 24 subjects had normal or mildly prolonged FF-VEP latency, 15 from the anti-LINGO-1 and nine from the placebo group. Assessment of subjects stratified by prespecified baseline characteristics showed that improvement in FF-VEP latency in the affected eye at week 24 with anti-LINGO-1 was greater in the following patient subgroups: age 33 or older (difference vs placebo, -14.17 ms compared with -0.89 ms in subjects younger than 33); those who received treatment less than 25 days from the onset of acute optic neuritis (-9.01 ms vs -6.68 ms for those receiving treatment more than 25 days after acute optic neuritis onset); and those who had a high-contrast visual acuity score less than 49 (-10.92 ms vs -4.14 ms for a score of 49 or more). None of the subgroup-by-treatment interactions reached statistical significance due to the small sample size.

BARCELONA—Anti-LINGO-1 improved full-field visual evoked potential (FF-VEP) latency of the eye affected by acute optic neuritis relative to placebo, consistent with improved remyelination, according to a study reported at the 31st Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). This latency recovery was greater in older subjects, subjects given the first dose earlier, and subjects with more severe pretreatment visual impairment.

In a primary efficacy analysis of the RENEW study, Orhan Aktas, MD, of Heinrich-Heine-Universität in Düsseldorf, Germany, and colleagues demonstrated an improvement versus placebo in optic nerve latency (-7.55 ms at week 24; -9.13 ms at week 32) consistent with remyelination in subjects with acute optic neuritis.

Research subjects ages 18 to 50 with a first unilateral acute optic neuritis episode were treated with high-dose steroids, then randomized to 100 mg/kg anti-LINGO-1 IV or placebo once every four weeks (ie, six doses) and followed to week 32. Optic nerve latency was measured using FF-VEP in the affected eye versus the baseline value for the unaffected eye. Between-treatment comparisons were evaluated by ANCOVA in the per-protocol population, defined as subjects who completed the study and did not miss more than one study dose or receive disease-modifying therapy for multiple sclerosis. Further analyses of latency recovery at week 24 (affected eye FF-VEP latency ≤10% worse than baseline of fellow eye) and efficacy stratified by prespecified baseline characteristics using the median as the cutoff were performed.

FF-VEP latency recovery in the affected eye versus baseline of the fellow eye was compared between 33 subjects who received anti-LINGO-1 and 36 treated with placebo. At week 24, 24 subjects had normal or mildly prolonged FF-VEP latency, 15 from the anti-LINGO-1 and nine from the placebo group. Assessment of subjects stratified by prespecified baseline characteristics showed that improvement in FF-VEP latency in the affected eye at week 24 with anti-LINGO-1 was greater in the following patient subgroups: age 33 or older (difference vs placebo, -14.17 ms compared with -0.89 ms in subjects younger than 33); those who received treatment less than 25 days from the onset of acute optic neuritis (-9.01 ms vs -6.68 ms for those receiving treatment more than 25 days after acute optic neuritis onset); and those who had a high-contrast visual acuity score less than 49 (-10.92 ms vs -4.14 ms for a score of 49 or more). None of the subgroup-by-treatment interactions reached statistical significance due to the small sample size.