User login
Alemtuzumab-induced autoimmunity: getting closer to answers
SAN DIEGO – The monoclonal antibody alemtuzumab can be an effective treatment for people living with multiple sclerosis, but there’s a catch — the agent is also associated with an increased risk for developing other autoimmune diseases, leaving clinicians with a conundrum.
“This is an efficacious treatment in multiple sclerosis” that can slow the rate of brain atrophy over the long-term, Alasdair Coles, MD, said at ACTRIMS Forum 2018, held by the Americas Committee for Treatment and Research in Multiple Sclerosis. “But 1 or 2 years after each cycle of alemtuzumab [Lemtrada], patients are at very high risk of autoimmune diseases. This is the not-too-worrying thyroid disease, but there are some very troubling and potentially highly threatening complications at lower frequency.”
Subsequent autoimmune thyroid disease can affect up to 40% of patients treated with alemtuzumab, but immune thrombocytopenia (3%) and autoimmune renal disease (0.1%) are also reported. About 1 in 10 people treated with the monoclonal antibody for MS can also develop de novo asymptomatic autoantibodies (10%).
“People ask: ‘Why doesn’t MS come back as part of this generic mechanism?’ and I don’t know the answer to that,” Dr. Coles said.
In the United States, alemtuzumab is indicated for treatment of relapsing multiple sclerosis in adults who have failed to respond adequately to two or more previous therapies. In contrast, “this has become a first-line treatment in the U.K.,” said Dr. Coles, a professor in the department of clinical neurosciences at the University of Cambridge (England).
“Unfortunately, we can offer no proven treatment to prevent this autoimmunity.”
Considering the prospects for different proposed mechanisms
Dr. Coles shared some encouraging news at ACTRIMS Forum 2018. His team and other researchers are getting closer to understanding the cellular mechanism underlying the paradoxical autoimmunity associated with alemtuzumab. Published reports in the literature from others suggest faulty immune B cells could be the culprit, pointing to a similar reconstitution of B cells after bone marrow transplantation. However, he said, “There is no difference in this reconstitution pattern between those who do and don’t get autoimmunity. So we do not think that autoimmunity after alemtuzumab is primarily a B cell problem.”
Other investigators have pointed to possible depletion of a key immune regulatory cell associated with alemtuzumab, such as alterations in CD52-positive T cells that cause depletion in T cells as part of an autoimmune cascade that involve CD52-high expressing cells and sialic acid-binding immunoglobulin-like lectin 10. “I’m not going to describe why we don’t believe any of this,” Dr. Coles said, but added, “We cannot replicate the data in type 1 diabetes or MS about the depletion of T cells.”
Along with his colleague Joanne Jones, PhD, a clinical fellow in the same department at the University of Cambridge, Dr. Coles and his team instead propose that autoimmunity after alemtuzumab therapy is associated with a homeostatic proliferation of T cells in the context of a defective thymus. “We see thymic function reduced after alemtuzumab for a few months. We don’t know if alemtuzumab is having a direct impact on the thymus or if it’s an indirect effect though a cytokine storm at the time of administering alemtuzumab.”
In addition, in contrast to B cells, both CD4-positive and CD8-positive T cells are clonally restricted after alemtuzumab treatment, Dr. Coles explained.
“These are the only changes that distinguish patients who do and do not develop autoimmunity,” he said. “Those who develop autoimmunity have reduced clonality and have impaired thymic function compared to those who don’t.”
As the theory goes, the limited clonal repertoire leads to expansion of the T cells, preferentially expanding autoreactive T cells, leading to B-cell- and antibody-mediated autoimmunity.
The bigger picture
The autoimmune phenomenon is not unique to alemtuzumab or multiple sclerosis. “This turns out to be one of a family of clinical situations where the reconstitution of the depleted lymphocyte repertoire leads to autoimmunity,” Dr. Coles said. A similar effect was seen years ago when very lymphopenic HIV patients were given antiviral therapy, he added, affecting about 10% of treated patients. About 10% of bone marrow transplant patients may experience similar autoimmune concerns.
“What we do think is true is we’ve tapped into a classical expression of autoimmunity,” Dr. Coles said. “Alemtuzumab is a fantastic opportunity to study the mechanisms underlying lymphopenia-associated autoimmunity.”
A ‘tantalizing prospect’
“It’s a tantalizing prospect that susceptible individuals might be identified in the future prior to treatment,” Dr. Coles said. One promising lead, he added, is “we also looked at IL-21. We showed that after treatment, and perhaps more interestingly, before treatment with alemtuzumab, serum IL-21 is greater in those who subsequently develop autoimmune disease. This suggests some individuals are prone to develop autoimmune disease, and could be identified potentially prior to treatment with alemtuzumab.”
More work is needed, including the development of more sensitive IL-21 assays for use in this population, Dr. Coles said. “Please do not attempt to predict the risk of autoimmunity after alemtuzumab using the current commercial assays. This is a source of some frustration for me.”
A potential route of lymphocyte repertoire reconstitution after alemtuzumab is thymic reconstitution, leading to a more diverse immune repertoire, Dr. Coles said. “The obvious corollary of this is if we can direct reconstitution through the thymic reconstitution, we should be able to prevent autoimmunity.”
Dr. Coles disclosed that he receives honoraria for travel and speaking from Sanofi Genzyme, which markets alemtuzumab.
SAN DIEGO – The monoclonal antibody alemtuzumab can be an effective treatment for people living with multiple sclerosis, but there’s a catch — the agent is also associated with an increased risk for developing other autoimmune diseases, leaving clinicians with a conundrum.
“This is an efficacious treatment in multiple sclerosis” that can slow the rate of brain atrophy over the long-term, Alasdair Coles, MD, said at ACTRIMS Forum 2018, held by the Americas Committee for Treatment and Research in Multiple Sclerosis. “But 1 or 2 years after each cycle of alemtuzumab [Lemtrada], patients are at very high risk of autoimmune diseases. This is the not-too-worrying thyroid disease, but there are some very troubling and potentially highly threatening complications at lower frequency.”
Subsequent autoimmune thyroid disease can affect up to 40% of patients treated with alemtuzumab, but immune thrombocytopenia (3%) and autoimmune renal disease (0.1%) are also reported. About 1 in 10 people treated with the monoclonal antibody for MS can also develop de novo asymptomatic autoantibodies (10%).
“People ask: ‘Why doesn’t MS come back as part of this generic mechanism?’ and I don’t know the answer to that,” Dr. Coles said.
In the United States, alemtuzumab is indicated for treatment of relapsing multiple sclerosis in adults who have failed to respond adequately to two or more previous therapies. In contrast, “this has become a first-line treatment in the U.K.,” said Dr. Coles, a professor in the department of clinical neurosciences at the University of Cambridge (England).
“Unfortunately, we can offer no proven treatment to prevent this autoimmunity.”
Considering the prospects for different proposed mechanisms
Dr. Coles shared some encouraging news at ACTRIMS Forum 2018. His team and other researchers are getting closer to understanding the cellular mechanism underlying the paradoxical autoimmunity associated with alemtuzumab. Published reports in the literature from others suggest faulty immune B cells could be the culprit, pointing to a similar reconstitution of B cells after bone marrow transplantation. However, he said, “There is no difference in this reconstitution pattern between those who do and don’t get autoimmunity. So we do not think that autoimmunity after alemtuzumab is primarily a B cell problem.”
Other investigators have pointed to possible depletion of a key immune regulatory cell associated with alemtuzumab, such as alterations in CD52-positive T cells that cause depletion in T cells as part of an autoimmune cascade that involve CD52-high expressing cells and sialic acid-binding immunoglobulin-like lectin 10. “I’m not going to describe why we don’t believe any of this,” Dr. Coles said, but added, “We cannot replicate the data in type 1 diabetes or MS about the depletion of T cells.”
Along with his colleague Joanne Jones, PhD, a clinical fellow in the same department at the University of Cambridge, Dr. Coles and his team instead propose that autoimmunity after alemtuzumab therapy is associated with a homeostatic proliferation of T cells in the context of a defective thymus. “We see thymic function reduced after alemtuzumab for a few months. We don’t know if alemtuzumab is having a direct impact on the thymus or if it’s an indirect effect though a cytokine storm at the time of administering alemtuzumab.”
In addition, in contrast to B cells, both CD4-positive and CD8-positive T cells are clonally restricted after alemtuzumab treatment, Dr. Coles explained.
“These are the only changes that distinguish patients who do and do not develop autoimmunity,” he said. “Those who develop autoimmunity have reduced clonality and have impaired thymic function compared to those who don’t.”
As the theory goes, the limited clonal repertoire leads to expansion of the T cells, preferentially expanding autoreactive T cells, leading to B-cell- and antibody-mediated autoimmunity.
The bigger picture
The autoimmune phenomenon is not unique to alemtuzumab or multiple sclerosis. “This turns out to be one of a family of clinical situations where the reconstitution of the depleted lymphocyte repertoire leads to autoimmunity,” Dr. Coles said. A similar effect was seen years ago when very lymphopenic HIV patients were given antiviral therapy, he added, affecting about 10% of treated patients. About 10% of bone marrow transplant patients may experience similar autoimmune concerns.
“What we do think is true is we’ve tapped into a classical expression of autoimmunity,” Dr. Coles said. “Alemtuzumab is a fantastic opportunity to study the mechanisms underlying lymphopenia-associated autoimmunity.”
A ‘tantalizing prospect’
“It’s a tantalizing prospect that susceptible individuals might be identified in the future prior to treatment,” Dr. Coles said. One promising lead, he added, is “we also looked at IL-21. We showed that after treatment, and perhaps more interestingly, before treatment with alemtuzumab, serum IL-21 is greater in those who subsequently develop autoimmune disease. This suggests some individuals are prone to develop autoimmune disease, and could be identified potentially prior to treatment with alemtuzumab.”
More work is needed, including the development of more sensitive IL-21 assays for use in this population, Dr. Coles said. “Please do not attempt to predict the risk of autoimmunity after alemtuzumab using the current commercial assays. This is a source of some frustration for me.”
A potential route of lymphocyte repertoire reconstitution after alemtuzumab is thymic reconstitution, leading to a more diverse immune repertoire, Dr. Coles said. “The obvious corollary of this is if we can direct reconstitution through the thymic reconstitution, we should be able to prevent autoimmunity.”
Dr. Coles disclosed that he receives honoraria for travel and speaking from Sanofi Genzyme, which markets alemtuzumab.
SAN DIEGO – The monoclonal antibody alemtuzumab can be an effective treatment for people living with multiple sclerosis, but there’s a catch — the agent is also associated with an increased risk for developing other autoimmune diseases, leaving clinicians with a conundrum.
“This is an efficacious treatment in multiple sclerosis” that can slow the rate of brain atrophy over the long-term, Alasdair Coles, MD, said at ACTRIMS Forum 2018, held by the Americas Committee for Treatment and Research in Multiple Sclerosis. “But 1 or 2 years after each cycle of alemtuzumab [Lemtrada], patients are at very high risk of autoimmune diseases. This is the not-too-worrying thyroid disease, but there are some very troubling and potentially highly threatening complications at lower frequency.”
Subsequent autoimmune thyroid disease can affect up to 40% of patients treated with alemtuzumab, but immune thrombocytopenia (3%) and autoimmune renal disease (0.1%) are also reported. About 1 in 10 people treated with the monoclonal antibody for MS can also develop de novo asymptomatic autoantibodies (10%).
“People ask: ‘Why doesn’t MS come back as part of this generic mechanism?’ and I don’t know the answer to that,” Dr. Coles said.
In the United States, alemtuzumab is indicated for treatment of relapsing multiple sclerosis in adults who have failed to respond adequately to two or more previous therapies. In contrast, “this has become a first-line treatment in the U.K.,” said Dr. Coles, a professor in the department of clinical neurosciences at the University of Cambridge (England).
“Unfortunately, we can offer no proven treatment to prevent this autoimmunity.”
Considering the prospects for different proposed mechanisms
Dr. Coles shared some encouraging news at ACTRIMS Forum 2018. His team and other researchers are getting closer to understanding the cellular mechanism underlying the paradoxical autoimmunity associated with alemtuzumab. Published reports in the literature from others suggest faulty immune B cells could be the culprit, pointing to a similar reconstitution of B cells after bone marrow transplantation. However, he said, “There is no difference in this reconstitution pattern between those who do and don’t get autoimmunity. So we do not think that autoimmunity after alemtuzumab is primarily a B cell problem.”
Other investigators have pointed to possible depletion of a key immune regulatory cell associated with alemtuzumab, such as alterations in CD52-positive T cells that cause depletion in T cells as part of an autoimmune cascade that involve CD52-high expressing cells and sialic acid-binding immunoglobulin-like lectin 10. “I’m not going to describe why we don’t believe any of this,” Dr. Coles said, but added, “We cannot replicate the data in type 1 diabetes or MS about the depletion of T cells.”
Along with his colleague Joanne Jones, PhD, a clinical fellow in the same department at the University of Cambridge, Dr. Coles and his team instead propose that autoimmunity after alemtuzumab therapy is associated with a homeostatic proliferation of T cells in the context of a defective thymus. “We see thymic function reduced after alemtuzumab for a few months. We don’t know if alemtuzumab is having a direct impact on the thymus or if it’s an indirect effect though a cytokine storm at the time of administering alemtuzumab.”
In addition, in contrast to B cells, both CD4-positive and CD8-positive T cells are clonally restricted after alemtuzumab treatment, Dr. Coles explained.
“These are the only changes that distinguish patients who do and do not develop autoimmunity,” he said. “Those who develop autoimmunity have reduced clonality and have impaired thymic function compared to those who don’t.”
As the theory goes, the limited clonal repertoire leads to expansion of the T cells, preferentially expanding autoreactive T cells, leading to B-cell- and antibody-mediated autoimmunity.
The bigger picture
The autoimmune phenomenon is not unique to alemtuzumab or multiple sclerosis. “This turns out to be one of a family of clinical situations where the reconstitution of the depleted lymphocyte repertoire leads to autoimmunity,” Dr. Coles said. A similar effect was seen years ago when very lymphopenic HIV patients were given antiviral therapy, he added, affecting about 10% of treated patients. About 10% of bone marrow transplant patients may experience similar autoimmune concerns.
“What we do think is true is we’ve tapped into a classical expression of autoimmunity,” Dr. Coles said. “Alemtuzumab is a fantastic opportunity to study the mechanisms underlying lymphopenia-associated autoimmunity.”
A ‘tantalizing prospect’
“It’s a tantalizing prospect that susceptible individuals might be identified in the future prior to treatment,” Dr. Coles said. One promising lead, he added, is “we also looked at IL-21. We showed that after treatment, and perhaps more interestingly, before treatment with alemtuzumab, serum IL-21 is greater in those who subsequently develop autoimmune disease. This suggests some individuals are prone to develop autoimmune disease, and could be identified potentially prior to treatment with alemtuzumab.”
More work is needed, including the development of more sensitive IL-21 assays for use in this population, Dr. Coles said. “Please do not attempt to predict the risk of autoimmunity after alemtuzumab using the current commercial assays. This is a source of some frustration for me.”
A potential route of lymphocyte repertoire reconstitution after alemtuzumab is thymic reconstitution, leading to a more diverse immune repertoire, Dr. Coles said. “The obvious corollary of this is if we can direct reconstitution through the thymic reconstitution, we should be able to prevent autoimmunity.”
Dr. Coles disclosed that he receives honoraria for travel and speaking from Sanofi Genzyme, which markets alemtuzumab.
EXPERT ANALYSIS FROM ACTRIMS FORUM 2018
High dose of novel compound for relapsing-remitting MS shows promise
SAN DIEGO – Early results of the novel human endogenous retrovirus-W antagonist GNbAC1 in a phase 2 trial of patients with relapsing-remitting multiple sclerosis demonstrated evidence of remyelination at week 24 among high-dose users, but it did not meet its primary endpoint of active lesions seen on MRI.
In an interview at ACTRIMS Forum 2018, held by the Americas Committee for Treatment and Research in Multiple Sclerosis, study author Robert Glanzman, MD, said that GNbAC1 is a monoclonal antibody that targets and blocks the envelope protein pHER-W ENV, a potent agonist of Toll-like receptor 4. It thereby inhibits TLR4-mediated pathogenicity, which includes activation of macrophages and microglia into proinflammatory phenotypes and direct inhibition of remyelination via TLR4.
In a study known as CHANGE-MS, 270 patients with relapsing-remitting MS were randomized to one of three doses of the GNbAC1 (6, 12, or 18 mg/kg), or placebo via monthly IV infusion over 6 months. The study was conducted at 70 centers in 13 European countries over the past 3 years. It had a 24-week, double-blind, placebo-controlled period, followed by a 24-week, dose-blind, active-only treatment period, with placebo patients randomized to the three different doses of GNbA1C. Brain MRI scans were performed at weeks 12, 16, 20, 24, and 48, to look for evidence of remyelination.
The mean age of patients was 38 years and 65% were female. The researchers observed no safety concerns and no significant effect on inflammatory measures over weeks 12-24, even though the absolute number of lesions was reduced by about 50%. Although the primary endpoint of the cumulative number of gadolinium-enhancing lesions seen on brain MRI scans every 4 weeks during weeks 12-24 was not met, post hoc analyses suggest a decrease in neuroinflammation in the 18 mg/kg GNbA1C group at week 24, compared with placebo (P = .008). “A consistent increase in MT [magnetization transfer] ratio signal was observed in normal-appearing white matter and cerebral cortex at the highest dose, suggesting remyelination,” Dr. Glanzman added. “We gained about a quarter or half of percent in normal-appearing white matter at the cerebral cortex at the high dose. Normally, MS patients lose white matter over time, both in the cortex and in gray matter. We’re actually showing evidence of remyelination, which is really exciting. If these data are replicated and confirmed at week 48, we think we really have an exciting compound.”
GeNeuro sponsored the study.
Full 48-week analyses from CHANGE-MS are expected to be unveiled at the 2018 annual meeting American Academy of Neurology.
SOURCE: Glanzman R et al. Abstract P034.
SAN DIEGO – Early results of the novel human endogenous retrovirus-W antagonist GNbAC1 in a phase 2 trial of patients with relapsing-remitting multiple sclerosis demonstrated evidence of remyelination at week 24 among high-dose users, but it did not meet its primary endpoint of active lesions seen on MRI.
In an interview at ACTRIMS Forum 2018, held by the Americas Committee for Treatment and Research in Multiple Sclerosis, study author Robert Glanzman, MD, said that GNbAC1 is a monoclonal antibody that targets and blocks the envelope protein pHER-W ENV, a potent agonist of Toll-like receptor 4. It thereby inhibits TLR4-mediated pathogenicity, which includes activation of macrophages and microglia into proinflammatory phenotypes and direct inhibition of remyelination via TLR4.
In a study known as CHANGE-MS, 270 patients with relapsing-remitting MS were randomized to one of three doses of the GNbAC1 (6, 12, or 18 mg/kg), or placebo via monthly IV infusion over 6 months. The study was conducted at 70 centers in 13 European countries over the past 3 years. It had a 24-week, double-blind, placebo-controlled period, followed by a 24-week, dose-blind, active-only treatment period, with placebo patients randomized to the three different doses of GNbA1C. Brain MRI scans were performed at weeks 12, 16, 20, 24, and 48, to look for evidence of remyelination.
The mean age of patients was 38 years and 65% were female. The researchers observed no safety concerns and no significant effect on inflammatory measures over weeks 12-24, even though the absolute number of lesions was reduced by about 50%. Although the primary endpoint of the cumulative number of gadolinium-enhancing lesions seen on brain MRI scans every 4 weeks during weeks 12-24 was not met, post hoc analyses suggest a decrease in neuroinflammation in the 18 mg/kg GNbA1C group at week 24, compared with placebo (P = .008). “A consistent increase in MT [magnetization transfer] ratio signal was observed in normal-appearing white matter and cerebral cortex at the highest dose, suggesting remyelination,” Dr. Glanzman added. “We gained about a quarter or half of percent in normal-appearing white matter at the cerebral cortex at the high dose. Normally, MS patients lose white matter over time, both in the cortex and in gray matter. We’re actually showing evidence of remyelination, which is really exciting. If these data are replicated and confirmed at week 48, we think we really have an exciting compound.”
GeNeuro sponsored the study.
Full 48-week analyses from CHANGE-MS are expected to be unveiled at the 2018 annual meeting American Academy of Neurology.
SOURCE: Glanzman R et al. Abstract P034.
SAN DIEGO – Early results of the novel human endogenous retrovirus-W antagonist GNbAC1 in a phase 2 trial of patients with relapsing-remitting multiple sclerosis demonstrated evidence of remyelination at week 24 among high-dose users, but it did not meet its primary endpoint of active lesions seen on MRI.
In an interview at ACTRIMS Forum 2018, held by the Americas Committee for Treatment and Research in Multiple Sclerosis, study author Robert Glanzman, MD, said that GNbAC1 is a monoclonal antibody that targets and blocks the envelope protein pHER-W ENV, a potent agonist of Toll-like receptor 4. It thereby inhibits TLR4-mediated pathogenicity, which includes activation of macrophages and microglia into proinflammatory phenotypes and direct inhibition of remyelination via TLR4.
In a study known as CHANGE-MS, 270 patients with relapsing-remitting MS were randomized to one of three doses of the GNbAC1 (6, 12, or 18 mg/kg), or placebo via monthly IV infusion over 6 months. The study was conducted at 70 centers in 13 European countries over the past 3 years. It had a 24-week, double-blind, placebo-controlled period, followed by a 24-week, dose-blind, active-only treatment period, with placebo patients randomized to the three different doses of GNbA1C. Brain MRI scans were performed at weeks 12, 16, 20, 24, and 48, to look for evidence of remyelination.
The mean age of patients was 38 years and 65% were female. The researchers observed no safety concerns and no significant effect on inflammatory measures over weeks 12-24, even though the absolute number of lesions was reduced by about 50%. Although the primary endpoint of the cumulative number of gadolinium-enhancing lesions seen on brain MRI scans every 4 weeks during weeks 12-24 was not met, post hoc analyses suggest a decrease in neuroinflammation in the 18 mg/kg GNbA1C group at week 24, compared with placebo (P = .008). “A consistent increase in MT [magnetization transfer] ratio signal was observed in normal-appearing white matter and cerebral cortex at the highest dose, suggesting remyelination,” Dr. Glanzman added. “We gained about a quarter or half of percent in normal-appearing white matter at the cerebral cortex at the high dose. Normally, MS patients lose white matter over time, both in the cortex and in gray matter. We’re actually showing evidence of remyelination, which is really exciting. If these data are replicated and confirmed at week 48, we think we really have an exciting compound.”
GeNeuro sponsored the study.
Full 48-week analyses from CHANGE-MS are expected to be unveiled at the 2018 annual meeting American Academy of Neurology.
SOURCE: Glanzman R et al. Abstract P034.
REPORTING FROM ACTRIMS FORUM 2018
Key clinical point:
Major finding: Although the primary endpoint was not met, post hoc analyses suggest a decrease in neuroinflammation in the 18 mg/kg GNbA1C group at week 24, compared with placebo (P = .008).
Study details: A phase 2 study of 270 patients with relapsing-remitting MS who were randomized to one of three doses of GNbAC1.
Disclosures: Dr. Glanzman is chief medical officer for GeNeuro, which sponsored the study.
Source: Glanzman R et al. Abstract P034.
Researchers find predictors of worse MS outcomes in post hoc study of three trials
SAN DIEGO – Baseline Expanded Disability Status Scale scores and number of relapses during the first year were the most consistent predictors of disability worsening or relapses over the subsequent 3 years in long-term analysis of three phase 3 fingolimod trials.
Those patients identified at higher risk for worse long-term clinical outcomes could benefit from an early review of multiple sclerosis (MS) treatment regimens to help prevent worsening disability, Pavle Repovic, MD, PhD, said in an interview.
“The idea for some time now has been to figure out what will tell whether a patient is responding to a therapy early on or not,” Dr. Repovic said at ACTRIMS Forum 2018, held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
To explore long-term clinical predictors of disability progression and relapse risk, Dr. Repovic and his colleagues analyzed three phase 3 trials assessing fingolimod (Gilenya). They evaluated parameters at baseline and during the first year of the FREEDOMS, FREEDOMS II, and TRANSFORMS studies.
Investigators in the FREEDOMS studies enrolled 1,118 people with relapsing MS and randomized them to fingolimod or placebo for 2 years. The patients who were initially treated with placebo were then re-randomized to one of two fingolimod doses for an additional 18 months. Finally, all participants underwent treatment with the same fingolimod dose during an open-label phase. Similarly, in TRANSFORMS, researchers enrolled 1,292 people with relapsing MS and randomized them to either fingolimod or interferon beta-1a for 1 year. They then re-randomized the interferon beta-1a group to one of two fingolimod doses for a 1-year extension, then assigned all participants to one dose of fingolimod for an open-label phase.
At baseline in the FREEDOMS and FREEDOMS II studies, a longer duration of MS was associated with a higher risk for clinically definite progression or relapses at 6 months (odds ratio, 1.040), as was baseline Expanded Disability Status Scale (EDSS) score (OR, 1.229).
“In the FREEDOMS trials, what we learned is that the duration of multiple sclerosis since diagnosis and the baseline disability predict worsening between 1 and 4 years,” said Dr. Repovic, a neurologist with the Multiple Sclerosis Center at the Swedish Neuroscience Institute in Seattle.
Dr. Repovic added that “there is nothing you can do about them [the baseline predictors]. Patients are as disabled as they are, and they’ve had multiple sclerosis as long as they have.”
The researchers also looked at predictors of 6-month confirmed disability progression or relapses during the first year. “The idea is that year 1 might tell you what happens next,” Dr. Repovic said. The number of confirmed relapses (OR, 2.788) and MRI lesion activity (OR, 1.638), were predictive.
“So breakthrough disease in year 1 predicts more disease down the road.”
In the TRANSFORMS trial, previous treatment for MS (OR, 1.613) and EDSS score at baseline (OR, 1.228) predicted who would do worse. The number of confirmed relapses in the first year of the study was the only predictor (OR, 1.774). There was a trend for MRI lesion activity that approached statistical significance.
The confirmed number of relapses in the first year was the common predictor among all the phase 3 studies. “So with people who relapse, we really need to watch out for them,” Dr. Repovic said.
“The challenge with this particular study is we took everybody,” Dr. Repovic added. Next he would like to look at only those participants who received fingolimod throughout the trials to see if any specific predictors emerge.
Dr. Repovic disclosed he is on the speakers bureau for Novartis, the company that sponsored the study.
SOURCE: Repovic P et al. Abstract P210.
SAN DIEGO – Baseline Expanded Disability Status Scale scores and number of relapses during the first year were the most consistent predictors of disability worsening or relapses over the subsequent 3 years in long-term analysis of three phase 3 fingolimod trials.
Those patients identified at higher risk for worse long-term clinical outcomes could benefit from an early review of multiple sclerosis (MS) treatment regimens to help prevent worsening disability, Pavle Repovic, MD, PhD, said in an interview.
“The idea for some time now has been to figure out what will tell whether a patient is responding to a therapy early on or not,” Dr. Repovic said at ACTRIMS Forum 2018, held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
To explore long-term clinical predictors of disability progression and relapse risk, Dr. Repovic and his colleagues analyzed three phase 3 trials assessing fingolimod (Gilenya). They evaluated parameters at baseline and during the first year of the FREEDOMS, FREEDOMS II, and TRANSFORMS studies.
Investigators in the FREEDOMS studies enrolled 1,118 people with relapsing MS and randomized them to fingolimod or placebo for 2 years. The patients who were initially treated with placebo were then re-randomized to one of two fingolimod doses for an additional 18 months. Finally, all participants underwent treatment with the same fingolimod dose during an open-label phase. Similarly, in TRANSFORMS, researchers enrolled 1,292 people with relapsing MS and randomized them to either fingolimod or interferon beta-1a for 1 year. They then re-randomized the interferon beta-1a group to one of two fingolimod doses for a 1-year extension, then assigned all participants to one dose of fingolimod for an open-label phase.
At baseline in the FREEDOMS and FREEDOMS II studies, a longer duration of MS was associated with a higher risk for clinically definite progression or relapses at 6 months (odds ratio, 1.040), as was baseline Expanded Disability Status Scale (EDSS) score (OR, 1.229).
“In the FREEDOMS trials, what we learned is that the duration of multiple sclerosis since diagnosis and the baseline disability predict worsening between 1 and 4 years,” said Dr. Repovic, a neurologist with the Multiple Sclerosis Center at the Swedish Neuroscience Institute in Seattle.
Dr. Repovic added that “there is nothing you can do about them [the baseline predictors]. Patients are as disabled as they are, and they’ve had multiple sclerosis as long as they have.”
The researchers also looked at predictors of 6-month confirmed disability progression or relapses during the first year. “The idea is that year 1 might tell you what happens next,” Dr. Repovic said. The number of confirmed relapses (OR, 2.788) and MRI lesion activity (OR, 1.638), were predictive.
“So breakthrough disease in year 1 predicts more disease down the road.”
In the TRANSFORMS trial, previous treatment for MS (OR, 1.613) and EDSS score at baseline (OR, 1.228) predicted who would do worse. The number of confirmed relapses in the first year of the study was the only predictor (OR, 1.774). There was a trend for MRI lesion activity that approached statistical significance.
The confirmed number of relapses in the first year was the common predictor among all the phase 3 studies. “So with people who relapse, we really need to watch out for them,” Dr. Repovic said.
“The challenge with this particular study is we took everybody,” Dr. Repovic added. Next he would like to look at only those participants who received fingolimod throughout the trials to see if any specific predictors emerge.
Dr. Repovic disclosed he is on the speakers bureau for Novartis, the company that sponsored the study.
SOURCE: Repovic P et al. Abstract P210.
SAN DIEGO – Baseline Expanded Disability Status Scale scores and number of relapses during the first year were the most consistent predictors of disability worsening or relapses over the subsequent 3 years in long-term analysis of three phase 3 fingolimod trials.
Those patients identified at higher risk for worse long-term clinical outcomes could benefit from an early review of multiple sclerosis (MS) treatment regimens to help prevent worsening disability, Pavle Repovic, MD, PhD, said in an interview.
“The idea for some time now has been to figure out what will tell whether a patient is responding to a therapy early on or not,” Dr. Repovic said at ACTRIMS Forum 2018, held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
To explore long-term clinical predictors of disability progression and relapse risk, Dr. Repovic and his colleagues analyzed three phase 3 trials assessing fingolimod (Gilenya). They evaluated parameters at baseline and during the first year of the FREEDOMS, FREEDOMS II, and TRANSFORMS studies.
Investigators in the FREEDOMS studies enrolled 1,118 people with relapsing MS and randomized them to fingolimod or placebo for 2 years. The patients who were initially treated with placebo were then re-randomized to one of two fingolimod doses for an additional 18 months. Finally, all participants underwent treatment with the same fingolimod dose during an open-label phase. Similarly, in TRANSFORMS, researchers enrolled 1,292 people with relapsing MS and randomized them to either fingolimod or interferon beta-1a for 1 year. They then re-randomized the interferon beta-1a group to one of two fingolimod doses for a 1-year extension, then assigned all participants to one dose of fingolimod for an open-label phase.
At baseline in the FREEDOMS and FREEDOMS II studies, a longer duration of MS was associated with a higher risk for clinically definite progression or relapses at 6 months (odds ratio, 1.040), as was baseline Expanded Disability Status Scale (EDSS) score (OR, 1.229).
“In the FREEDOMS trials, what we learned is that the duration of multiple sclerosis since diagnosis and the baseline disability predict worsening between 1 and 4 years,” said Dr. Repovic, a neurologist with the Multiple Sclerosis Center at the Swedish Neuroscience Institute in Seattle.
Dr. Repovic added that “there is nothing you can do about them [the baseline predictors]. Patients are as disabled as they are, and they’ve had multiple sclerosis as long as they have.”
The researchers also looked at predictors of 6-month confirmed disability progression or relapses during the first year. “The idea is that year 1 might tell you what happens next,” Dr. Repovic said. The number of confirmed relapses (OR, 2.788) and MRI lesion activity (OR, 1.638), were predictive.
“So breakthrough disease in year 1 predicts more disease down the road.”
In the TRANSFORMS trial, previous treatment for MS (OR, 1.613) and EDSS score at baseline (OR, 1.228) predicted who would do worse. The number of confirmed relapses in the first year of the study was the only predictor (OR, 1.774). There was a trend for MRI lesion activity that approached statistical significance.
The confirmed number of relapses in the first year was the common predictor among all the phase 3 studies. “So with people who relapse, we really need to watch out for them,” Dr. Repovic said.
“The challenge with this particular study is we took everybody,” Dr. Repovic added. Next he would like to look at only those participants who received fingolimod throughout the trials to see if any specific predictors emerge.
Dr. Repovic disclosed he is on the speakers bureau for Novartis, the company that sponsored the study.
SOURCE: Repovic P et al. Abstract P210.
REPORTING FROM ACTRIMS FORUM 2018
Key clinical point: Certain factors at baseline and over first year of three pooled studies were associated with worse long-term multiple sclerosis outcomes.
Major finding: The number of confirmed relapses in the first year of the FREEDOMS, FREEDOMS II, and TRANSFORMS studies predicted worse subsequent outcomes.
Study details: Pooled data from three phase 3 trials of fingolimod with 2,355 patients.
Disclosures: Dr. Repovic disclosed he is on the speakers bureau for Novartis, the company that sponsored the study.
Source: Repovic P et al. Abstract P210.
Fingolimod switch from an injectable linked to improved outcomes in relapsing MS
SAN DIEGO – People with relapsing multiple sclerosis who switched from an injectable disease-modifying therapy to fingolimod after the randomized phase of the PREFERMS trial experienced improved annualized relapse rates, exposure-adjusted percentage brain volume loss, and satisfaction, compared with study participants who did not switch.
Importantly, there were no differences between switchers who were treatment-naive or previously treated with one injectable therapy class at baseline in the phase 4, active-controlled, open-label, and multicenter PREFERMS trial, according to the researchers.
Of the 875 patients with relapsing multiple sclerosis, 254 or 58% of those initially randomized to an injectable disease-modifying therapy (iDMT) switched to fingolimod (Gilenya) during the 12-month study. Participants in the trial were permitted to switch therapy once after at least 3 months, or sooner if warranted for safety or efficacy reasons.
Compared with the end the randomization phase, patients who switched from an iDMT to fingolimod were more satisfied, defined as a Medication Satisfaction Questionnaire score of 5 or greater (odds ratio, 5.65; P less than .001) at 12 months. At the same time, their annualized relapse rate decreased (ARR ratio, 0.53; P = .0158) and their exposure-adjusted brain volume loss decreased from 0.874% to 0.463%.
The benefit of these switches was observed regardless of previous treatment status, Dr. Hunter said during a poster presentation at ACTRIMS Forum 2018, held by the Americas Committee for Treatment and Research in Multiple Sclerosis. 
At the start of the PREFERMS trial, patients were randomized 1:1 to fingolimod 0.5 mg/day or a preselected iDMT. Just more than half, 54%, were treatment-naive and 46% had previous interferon or glatiramer acetate treatment.
“Generally, because most of these people were switched, and we’re looking at people who were treatment-naive or previously treated, when you look at brain volume loss, it’s very low on fingolimod versus high while they’re on injectable therapies,” Dr. Hunter said.
Dr. Hunter and his colleagues reported similar relapse rates and brain volume loss outcomes among the 254 patients who switched to fingolimod mid-study according to baseline treatment history. The investigators noted, however, that these post hoc analyses and P values are intended for hypothesis generation only.
In the 99 treatment-naive switchers, brain volume loss was 0.54% at the end of the study, compared with 0.84% at the end of the randomization period. Among the 155 previously treated switchers, brain volume loss also decreased, from 0.90% at the end of randomization to 0.42% at study end.
Dr. Hunter disclosed that he is an investigator for Novartis, the sponsor of the study.
SOURCE: Hunter S et al. ACTRIMS Forum 2018 Abstract P019.
SAN DIEGO – People with relapsing multiple sclerosis who switched from an injectable disease-modifying therapy to fingolimod after the randomized phase of the PREFERMS trial experienced improved annualized relapse rates, exposure-adjusted percentage brain volume loss, and satisfaction, compared with study participants who did not switch.
Importantly, there were no differences between switchers who were treatment-naive or previously treated with one injectable therapy class at baseline in the phase 4, active-controlled, open-label, and multicenter PREFERMS trial, according to the researchers.
Of the 875 patients with relapsing multiple sclerosis, 254 or 58% of those initially randomized to an injectable disease-modifying therapy (iDMT) switched to fingolimod (Gilenya) during the 12-month study. Participants in the trial were permitted to switch therapy once after at least 3 months, or sooner if warranted for safety or efficacy reasons.
Compared with the end the randomization phase, patients who switched from an iDMT to fingolimod were more satisfied, defined as a Medication Satisfaction Questionnaire score of 5 or greater (odds ratio, 5.65; P less than .001) at 12 months. At the same time, their annualized relapse rate decreased (ARR ratio, 0.53; P = .0158) and their exposure-adjusted brain volume loss decreased from 0.874% to 0.463%.
The benefit of these switches was observed regardless of previous treatment status, Dr. Hunter said during a poster presentation at ACTRIMS Forum 2018, held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
At the start of the PREFERMS trial, patients were randomized 1:1 to fingolimod 0.5 mg/day or a preselected iDMT. Just more than half, 54%, were treatment-naive and 46% had previous interferon or glatiramer acetate treatment.
“Generally, because most of these people were switched, and we’re looking at people who were treatment-naive or previously treated, when you look at brain volume loss, it’s very low on fingolimod versus high while they’re on injectable therapies,” Dr. Hunter said.
Dr. Hunter and his colleagues reported similar relapse rates and brain volume loss outcomes among the 254 patients who switched to fingolimod mid-study according to baseline treatment history. The investigators noted, however, that these post hoc analyses and P values are intended for hypothesis generation only.
In the 99 treatment-naive switchers, brain volume loss was 0.54% at the end of the study, compared with 0.84% at the end of the randomization period. Among the 155 previously treated switchers, brain volume loss also decreased, from 0.90% at the end of randomization to 0.42% at study end.
Dr. Hunter disclosed that he is an investigator for Novartis, the sponsor of the study.
SOURCE: Hunter S et al. ACTRIMS Forum 2018 Abstract P019.
SAN DIEGO – People with relapsing multiple sclerosis who switched from an injectable disease-modifying therapy to fingolimod after the randomized phase of the PREFERMS trial experienced improved annualized relapse rates, exposure-adjusted percentage brain volume loss, and satisfaction, compared with study participants who did not switch.
Importantly, there were no differences between switchers who were treatment-naive or previously treated with one injectable therapy class at baseline in the phase 4, active-controlled, open-label, and multicenter PREFERMS trial, according to the researchers.
Of the 875 patients with relapsing multiple sclerosis, 254 or 58% of those initially randomized to an injectable disease-modifying therapy (iDMT) switched to fingolimod (Gilenya) during the 12-month study. Participants in the trial were permitted to switch therapy once after at least 3 months, or sooner if warranted for safety or efficacy reasons.
Compared with the end the randomization phase, patients who switched from an iDMT to fingolimod were more satisfied, defined as a Medication Satisfaction Questionnaire score of 5 or greater (odds ratio, 5.65; P less than .001) at 12 months. At the same time, their annualized relapse rate decreased (ARR ratio, 0.53; P = .0158) and their exposure-adjusted brain volume loss decreased from 0.874% to 0.463%.
The benefit of these switches was observed regardless of previous treatment status, Dr. Hunter said during a poster presentation at ACTRIMS Forum 2018, held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
At the start of the PREFERMS trial, patients were randomized 1:1 to fingolimod 0.5 mg/day or a preselected iDMT. Just more than half, 54%, were treatment-naive and 46% had previous interferon or glatiramer acetate treatment.
“Generally, because most of these people were switched, and we’re looking at people who were treatment-naive or previously treated, when you look at brain volume loss, it’s very low on fingolimod versus high while they’re on injectable therapies,” Dr. Hunter said.
Dr. Hunter and his colleagues reported similar relapse rates and brain volume loss outcomes among the 254 patients who switched to fingolimod mid-study according to baseline treatment history. The investigators noted, however, that these post hoc analyses and P values are intended for hypothesis generation only.
In the 99 treatment-naive switchers, brain volume loss was 0.54% at the end of the study, compared with 0.84% at the end of the randomization period. Among the 155 previously treated switchers, brain volume loss also decreased, from 0.90% at the end of randomization to 0.42% at study end.
Dr. Hunter disclosed that he is an investigator for Novartis, the sponsor of the study.
SOURCE: Hunter S et al. ACTRIMS Forum 2018 Abstract P019.
REPORTING FROM ACTRIMS FORUM 2018
Key clinical point:
Major finding: Patients who switched from an injectable disease-modifying therapy to fingolimod were more satisfied, defined as a Medication Satisfaction Questionnaire score of 5 or greater (odds ratio, 5.65; P less than .001).
Study details: Post hoc analyses of the extension study of the PREFERMS trial.
Disclosures: Dr. Hunter disclosed that he is an investigator for Novartis, the sponsor of the study.
Source: Hunter S et al. ACTRIMS Forum 2018 Abstract P019.
Extended-interval dosing of natalizumab linked to lower risk of PML
SAN DIEGO – A large industry-funded study of the multiple sclerosis drug natalizumab suggests that physicians can dramatically lower the likelihood of progressive multifocal leukoencephalopathy in patients at higher risk of the condition by increasing the interval between doses.
Previous research has suggested that natalizumab (Tysabri) doesn’t lose efficacy when given less frequently.
Dr. Zhovtis Ryerson presented the study findings at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
As a 2014 report explains, natalizumab is a “highly effective disease-modifying therapy for the treatment of relapsing forms of multiple sclerosis,” but the risk of progressive multifocal leukoencephalopathy (PML) “has largely contributed to it being relegated to a second-line position” (Ther Adv Chronic Dis. 2014 Mar;5[2]:62-8).
Patients previously exposed to John Cunningham (JC) virus are at higher risk of PML, a rare viral brain disease that can be severely disabling or deadly. A 2017 report estimated the combined cumulative PML probability at 2.7% (with previous immunosuppressant use) and 1.7% (no previous immunosuppressant use) over 6 years in patients with signs of exposure to the JC virus (Lancet Neurol. 2017 Nov;16[11]:925-33). According to Dr. Zhovtis Ryerson, natalizumab manufacturer Biogen reported in December 2017 that it has confirmed 756 cases of PML in natalizumab-treated patients, all except for 3 in MS patients.
Doctors are wary in the at-risk patient population. “In general,” she said, “clinicians treating patients who are JC virus positive, and therefore have a risk for PML, may not utilize the drug or may take the patient off it after 2 years, which is when the risk goes up.”
Some physicians have experimented with longer intervals between treatments of 300 mg given intravenously, administering it every 5-8 weeks instead of every 4 weeks, with an eye on not extending the interval for too long “because MS disease activity returns after 12 weeks of withholding therapy,” Dr. Zhovtis Ryerson said.
In 2016, Dr. Zhovtis Ryerson and colleagues reported in a retrospective analysis that natalizumab dosing intervals of up to 8 weeks, 5 days didn’t affect the drug’s efficacy (J Neurol Neurosurg Psychiatry. 2016 Aug;87[8]:885-9).
For the primary analyses in the new study – whether dosing history in the last 18 months of natalizumab treatment affects PML – researchers tracked 1,988 patients who took the drug via an extended interval schedule and 13,132 who took it via a standard interval. The patients were tracked in the mandated TOUCH Prescribing Program; all participants showed signs of exposure to the JC virus.
The two groups were similar at about 68% female, an average age at first infusion of about 43, and a median number of about 48 natalizumab infusions.
For patients without previous immunosuppressant use who had received 49-60 doses, the researchers estimated the incidence of PML per 1,000 patients as 1.23 in the extended-interval group and 3.96 in the standard-interval group. The numbers were slightly higher for those who received 61-72 doses. At 48 or fewer doses, there were no PML cases in patients on extended-interval dosing.
“The data showed highly significant risk reductions of up to 94%,” Dr. Zhovtis Ryerson said.
Moving forward, “in collaboration with Biogen, we have more sensitivity analysis to be done to assure that our conclusions on this are correct,” she said. “Furthermore, more evidence of efficacy of extended-interval dosing natalizumab is needed, and we hope to move forward with a prospective, randomized, controlled trial to give clinicians the highest level of evidence we can.”
The study was funded by Biogen. Dr. Zhovtis Ryerson reported personal compensation from Teva, speaker/advisory board activities for Biogen, and research support from Biogen. Seven other authors reported being Biogen employees. Other authors reported no disclosures or various disclosures, including connections to Biogen.
SOURCE: Zhovtis R et al. ACTRIMS Forum 2018 Abstract LB250.
SAN DIEGO – A large industry-funded study of the multiple sclerosis drug natalizumab suggests that physicians can dramatically lower the likelihood of progressive multifocal leukoencephalopathy in patients at higher risk of the condition by increasing the interval between doses.
Previous research has suggested that natalizumab (Tysabri) doesn’t lose efficacy when given less frequently.
Dr. Zhovtis Ryerson presented the study findings at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
As a 2014 report explains, natalizumab is a “highly effective disease-modifying therapy for the treatment of relapsing forms of multiple sclerosis,” but the risk of progressive multifocal leukoencephalopathy (PML) “has largely contributed to it being relegated to a second-line position” (Ther Adv Chronic Dis. 2014 Mar;5[2]:62-8).
Patients previously exposed to John Cunningham (JC) virus are at higher risk of PML, a rare viral brain disease that can be severely disabling or deadly. A 2017 report estimated the combined cumulative PML probability at 2.7% (with previous immunosuppressant use) and 1.7% (no previous immunosuppressant use) over 6 years in patients with signs of exposure to the JC virus (Lancet Neurol. 2017 Nov;16[11]:925-33). According to Dr. Zhovtis Ryerson, natalizumab manufacturer Biogen reported in December 2017 that it has confirmed 756 cases of PML in natalizumab-treated patients, all except for 3 in MS patients.
Doctors are wary in the at-risk patient population. “In general,” she said, “clinicians treating patients who are JC virus positive, and therefore have a risk for PML, may not utilize the drug or may take the patient off it after 2 years, which is when the risk goes up.”
Some physicians have experimented with longer intervals between treatments of 300 mg given intravenously, administering it every 5-8 weeks instead of every 4 weeks, with an eye on not extending the interval for too long “because MS disease activity returns after 12 weeks of withholding therapy,” Dr. Zhovtis Ryerson said.
In 2016, Dr. Zhovtis Ryerson and colleagues reported in a retrospective analysis that natalizumab dosing intervals of up to 8 weeks, 5 days didn’t affect the drug’s efficacy (J Neurol Neurosurg Psychiatry. 2016 Aug;87[8]:885-9).
For the primary analyses in the new study – whether dosing history in the last 18 months of natalizumab treatment affects PML – researchers tracked 1,988 patients who took the drug via an extended interval schedule and 13,132 who took it via a standard interval. The patients were tracked in the mandated TOUCH Prescribing Program; all participants showed signs of exposure to the JC virus.
The two groups were similar at about 68% female, an average age at first infusion of about 43, and a median number of about 48 natalizumab infusions.
For patients without previous immunosuppressant use who had received 49-60 doses, the researchers estimated the incidence of PML per 1,000 patients as 1.23 in the extended-interval group and 3.96 in the standard-interval group. The numbers were slightly higher for those who received 61-72 doses. At 48 or fewer doses, there were no PML cases in patients on extended-interval dosing.
“The data showed highly significant risk reductions of up to 94%,” Dr. Zhovtis Ryerson said.
Moving forward, “in collaboration with Biogen, we have more sensitivity analysis to be done to assure that our conclusions on this are correct,” she said. “Furthermore, more evidence of efficacy of extended-interval dosing natalizumab is needed, and we hope to move forward with a prospective, randomized, controlled trial to give clinicians the highest level of evidence we can.”
The study was funded by Biogen. Dr. Zhovtis Ryerson reported personal compensation from Teva, speaker/advisory board activities for Biogen, and research support from Biogen. Seven other authors reported being Biogen employees. Other authors reported no disclosures or various disclosures, including connections to Biogen.
SOURCE: Zhovtis R et al. ACTRIMS Forum 2018 Abstract LB250.
SAN DIEGO – A large industry-funded study of the multiple sclerosis drug natalizumab suggests that physicians can dramatically lower the likelihood of progressive multifocal leukoencephalopathy in patients at higher risk of the condition by increasing the interval between doses.
Previous research has suggested that natalizumab (Tysabri) doesn’t lose efficacy when given less frequently.
Dr. Zhovtis Ryerson presented the study findings at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
As a 2014 report explains, natalizumab is a “highly effective disease-modifying therapy for the treatment of relapsing forms of multiple sclerosis,” but the risk of progressive multifocal leukoencephalopathy (PML) “has largely contributed to it being relegated to a second-line position” (Ther Adv Chronic Dis. 2014 Mar;5[2]:62-8).
Patients previously exposed to John Cunningham (JC) virus are at higher risk of PML, a rare viral brain disease that can be severely disabling or deadly. A 2017 report estimated the combined cumulative PML probability at 2.7% (with previous immunosuppressant use) and 1.7% (no previous immunosuppressant use) over 6 years in patients with signs of exposure to the JC virus (Lancet Neurol. 2017 Nov;16[11]:925-33). According to Dr. Zhovtis Ryerson, natalizumab manufacturer Biogen reported in December 2017 that it has confirmed 756 cases of PML in natalizumab-treated patients, all except for 3 in MS patients.
Doctors are wary in the at-risk patient population. “In general,” she said, “clinicians treating patients who are JC virus positive, and therefore have a risk for PML, may not utilize the drug or may take the patient off it after 2 years, which is when the risk goes up.”
Some physicians have experimented with longer intervals between treatments of 300 mg given intravenously, administering it every 5-8 weeks instead of every 4 weeks, with an eye on not extending the interval for too long “because MS disease activity returns after 12 weeks of withholding therapy,” Dr. Zhovtis Ryerson said.
In 2016, Dr. Zhovtis Ryerson and colleagues reported in a retrospective analysis that natalizumab dosing intervals of up to 8 weeks, 5 days didn’t affect the drug’s efficacy (J Neurol Neurosurg Psychiatry. 2016 Aug;87[8]:885-9).
For the primary analyses in the new study – whether dosing history in the last 18 months of natalizumab treatment affects PML – researchers tracked 1,988 patients who took the drug via an extended interval schedule and 13,132 who took it via a standard interval. The patients were tracked in the mandated TOUCH Prescribing Program; all participants showed signs of exposure to the JC virus.
The two groups were similar at about 68% female, an average age at first infusion of about 43, and a median number of about 48 natalizumab infusions.
For patients without previous immunosuppressant use who had received 49-60 doses, the researchers estimated the incidence of PML per 1,000 patients as 1.23 in the extended-interval group and 3.96 in the standard-interval group. The numbers were slightly higher for those who received 61-72 doses. At 48 or fewer doses, there were no PML cases in patients on extended-interval dosing.
“The data showed highly significant risk reductions of up to 94%,” Dr. Zhovtis Ryerson said.
Moving forward, “in collaboration with Biogen, we have more sensitivity analysis to be done to assure that our conclusions on this are correct,” she said. “Furthermore, more evidence of efficacy of extended-interval dosing natalizumab is needed, and we hope to move forward with a prospective, randomized, controlled trial to give clinicians the highest level of evidence we can.”
The study was funded by Biogen. Dr. Zhovtis Ryerson reported personal compensation from Teva, speaker/advisory board activities for Biogen, and research support from Biogen. Seven other authors reported being Biogen employees. Other authors reported no disclosures or various disclosures, including connections to Biogen.
SOURCE: Zhovtis R et al. ACTRIMS Forum 2018 Abstract LB250.
REPORTING FROM ACTRIMS FORUM 2018
Key clinical point: , compared with standard-interval dosing in patients who showed signs of exposure to the JC virus.
Major finding: Estimated incidence of PML per 1,000 patients was 1.23 in an extended-interval group and 3.96 in a standard-interval group among those who had received 49-60 natalizumab doses.
Study details: 18-month analysis of multiple sclerosis patients on natalizumab who showed signs of exposure to the JC virus: 1,988 on extended-interval dosing and 13,132 on standard-interval dosing.
Disclosures: The study was funded by Biogen, and multiple study authors report being employees of Biogen or having other relationships to the company.
Source: Zhovtis R et al. ACTRIMS Forum 2018, Abstract LB250.
Is MS caused by one-two punch of pinworm and Epstein-Barr virus?
SAN DIEGO – What causes multiple sclerosis (MS)? A team of Scottish researchers offers a new theory that it’s triggered in part by a one-two punch of infection with pinworm – a common condition in the United States, especially among children – and the Epstein-Barr virus (EBV).
The theory identifies pinworm as the prime suspect to be the “missing link” that explains why EBV and MS are so tightly connected, said Patrick Kearns, MBChB, a graduate student at Harvard T.H. Chan School of Public Health in Boston.
Dr. Kearns is the lead author of two reports about the possible role of pinworm that were presented at ACTRIMS Forum 2018, which is held by the Americas Committee for Treatment and Research in Multiple Sclerosis. He spoke in an interview.
Dr. Kearns and his colleagues focused on a well-known cluster of MS cases that began to appear in the Faroe Islands – a Danish possession in the North Atlantic – during World War II. The cases began to appear after British troops occupied the islands.
“Many of the occupation soldiers were from the Scottish Highlands, where the MS prevalence is quite high: 90 cases per 100,000, comparable to the northern U.S.,” according to a National MS Society summary about MS clusters.
In a theory that spawned controversy, the late neurologist John Kurtzke, MD, speculated that the British soldiers brought a transmissible agent to the islands, which triggered MS cases.
Could the agent be EBV alone? The authors of the new studies don’t think so, although they note that EBV is “robustly linked” to MS. Indeed, a 2012 meta-analysis reported that the virus “appears to be present in 100% of MS patients,” based on studies considered to be the strongest (Mult Scler. 2013 Feb;19[2]:162-6).
The authors of the new reports note that, while EBV infection “appears necessary,” it is “clearly not sufficient” to cause the disease on its own.
“Certainly almost everyone gets EBV eventually,” Dr. Kearns said. “So mere presence of the virus is certainly not sufficient for causing the disease. But it seems still to be necessary, and timing of infection might be everything.”
So what’s the missing piece of the puzzle?
Dr. Kearns began to think it might be the lowly pinworm after helping a colleague by analyzing data from appendicitis samples in children. He noted that uninflamed samples often had pinworms in them, but the inflamed samples often didn’t, which suggested that “the rate of pinworms in normal appendices must be very high in the healthy pediatric population at any given time.”
More data confirmed this to be true, and medical literature told Dr. Kearns that pinworms were common in high latitudes – places where people often are especially prone to MS.
“Most remarkably, they are known to have very little migration and stay spatially stable in populations over long periods of time,” Dr. Kearns said, “and typically everyone in an affected population will encounter them because their eggs are transmitted in household dust.”
And, he said, “they are known to be common in soldiers who live in military accommodation.”
According to the Centers for Disease Control and Prevention, pinworm prevalence can be as high as 50% in at-risk groups – children, caregivers of infected children, and people who live in institutions. Pinworms, which are spread through ingestion, are often asymptomatic but may cause anal itching and trigger bacterial infections.
The researchers suggest that pinworm infection comes first, followed by EBV infection. This makes sense because “late EBV infection in the form of infectious mononucleosis is known to be a risk factor for MS,” Dr. Kearns said.
The one-two punch of pinworm and then EBV is a plausible theory “because EBV lives in memory B cells, which are known to be important in MS and could be specific for the previous exposure to pinworm,” Dr. Kearns said. “However, this is very speculative and some researchers will argue this is very unlikely to be the case. But I think there is a chance it could explain some of the epidemiology, so I’m keen to try and test the theory if I can.”
What’s next? Dr. Kearns wants to explore data from Scotland in search of areas of high and low MS incidence that could offer insight into environmental triggers.
He added that the development of a serological blood test to prove a history of pinworm infection would be “the most effective way to prove or disprove this theory.”
“I have approached an investigator who has a track record of doing this for other infections and have been encouraged that he thinks that it would be achievable,” he said. “But this will definitely take time and funding.”
No specific funding was reported. The study authors reported no relevant disclosures.
SOURCE: Kearns P et al. ACTRIMS Forum 2018, Abstracts LB257 and LB264.
SAN DIEGO – What causes multiple sclerosis (MS)? A team of Scottish researchers offers a new theory that it’s triggered in part by a one-two punch of infection with pinworm – a common condition in the United States, especially among children – and the Epstein-Barr virus (EBV).
The theory identifies pinworm as the prime suspect to be the “missing link” that explains why EBV and MS are so tightly connected, said Patrick Kearns, MBChB, a graduate student at Harvard T.H. Chan School of Public Health in Boston.
Dr. Kearns is the lead author of two reports about the possible role of pinworm that were presented at ACTRIMS Forum 2018, which is held by the Americas Committee for Treatment and Research in Multiple Sclerosis. He spoke in an interview.
Dr. Kearns and his colleagues focused on a well-known cluster of MS cases that began to appear in the Faroe Islands – a Danish possession in the North Atlantic – during World War II. The cases began to appear after British troops occupied the islands.
“Many of the occupation soldiers were from the Scottish Highlands, where the MS prevalence is quite high: 90 cases per 100,000, comparable to the northern U.S.,” according to a National MS Society summary about MS clusters.
In a theory that spawned controversy, the late neurologist John Kurtzke, MD, speculated that the British soldiers brought a transmissible agent to the islands, which triggered MS cases.
Could the agent be EBV alone? The authors of the new studies don’t think so, although they note that EBV is “robustly linked” to MS. Indeed, a 2012 meta-analysis reported that the virus “appears to be present in 100% of MS patients,” based on studies considered to be the strongest (Mult Scler. 2013 Feb;19[2]:162-6).
The authors of the new reports note that, while EBV infection “appears necessary,” it is “clearly not sufficient” to cause the disease on its own.
“Certainly almost everyone gets EBV eventually,” Dr. Kearns said. “So mere presence of the virus is certainly not sufficient for causing the disease. But it seems still to be necessary, and timing of infection might be everything.”
So what’s the missing piece of the puzzle?
Dr. Kearns began to think it might be the lowly pinworm after helping a colleague by analyzing data from appendicitis samples in children. He noted that uninflamed samples often had pinworms in them, but the inflamed samples often didn’t, which suggested that “the rate of pinworms in normal appendices must be very high in the healthy pediatric population at any given time.”
More data confirmed this to be true, and medical literature told Dr. Kearns that pinworms were common in high latitudes – places where people often are especially prone to MS.
“Most remarkably, they are known to have very little migration and stay spatially stable in populations over long periods of time,” Dr. Kearns said, “and typically everyone in an affected population will encounter them because their eggs are transmitted in household dust.”
And, he said, “they are known to be common in soldiers who live in military accommodation.”
According to the Centers for Disease Control and Prevention, pinworm prevalence can be as high as 50% in at-risk groups – children, caregivers of infected children, and people who live in institutions. Pinworms, which are spread through ingestion, are often asymptomatic but may cause anal itching and trigger bacterial infections.
The researchers suggest that pinworm infection comes first, followed by EBV infection. This makes sense because “late EBV infection in the form of infectious mononucleosis is known to be a risk factor for MS,” Dr. Kearns said.
The one-two punch of pinworm and then EBV is a plausible theory “because EBV lives in memory B cells, which are known to be important in MS and could be specific for the previous exposure to pinworm,” Dr. Kearns said. “However, this is very speculative and some researchers will argue this is very unlikely to be the case. But I think there is a chance it could explain some of the epidemiology, so I’m keen to try and test the theory if I can.”
What’s next? Dr. Kearns wants to explore data from Scotland in search of areas of high and low MS incidence that could offer insight into environmental triggers.
He added that the development of a serological blood test to prove a history of pinworm infection would be “the most effective way to prove or disprove this theory.”
“I have approached an investigator who has a track record of doing this for other infections and have been encouraged that he thinks that it would be achievable,” he said. “But this will definitely take time and funding.”
No specific funding was reported. The study authors reported no relevant disclosures.
SOURCE: Kearns P et al. ACTRIMS Forum 2018, Abstracts LB257 and LB264.
SAN DIEGO – What causes multiple sclerosis (MS)? A team of Scottish researchers offers a new theory that it’s triggered in part by a one-two punch of infection with pinworm – a common condition in the United States, especially among children – and the Epstein-Barr virus (EBV).
The theory identifies pinworm as the prime suspect to be the “missing link” that explains why EBV and MS are so tightly connected, said Patrick Kearns, MBChB, a graduate student at Harvard T.H. Chan School of Public Health in Boston.
Dr. Kearns is the lead author of two reports about the possible role of pinworm that were presented at ACTRIMS Forum 2018, which is held by the Americas Committee for Treatment and Research in Multiple Sclerosis. He spoke in an interview.
Dr. Kearns and his colleagues focused on a well-known cluster of MS cases that began to appear in the Faroe Islands – a Danish possession in the North Atlantic – during World War II. The cases began to appear after British troops occupied the islands.
“Many of the occupation soldiers were from the Scottish Highlands, where the MS prevalence is quite high: 90 cases per 100,000, comparable to the northern U.S.,” according to a National MS Society summary about MS clusters.
In a theory that spawned controversy, the late neurologist John Kurtzke, MD, speculated that the British soldiers brought a transmissible agent to the islands, which triggered MS cases.
Could the agent be EBV alone? The authors of the new studies don’t think so, although they note that EBV is “robustly linked” to MS. Indeed, a 2012 meta-analysis reported that the virus “appears to be present in 100% of MS patients,” based on studies considered to be the strongest (Mult Scler. 2013 Feb;19[2]:162-6).
The authors of the new reports note that, while EBV infection “appears necessary,” it is “clearly not sufficient” to cause the disease on its own.
“Certainly almost everyone gets EBV eventually,” Dr. Kearns said. “So mere presence of the virus is certainly not sufficient for causing the disease. But it seems still to be necessary, and timing of infection might be everything.”
So what’s the missing piece of the puzzle?
Dr. Kearns began to think it might be the lowly pinworm after helping a colleague by analyzing data from appendicitis samples in children. He noted that uninflamed samples often had pinworms in them, but the inflamed samples often didn’t, which suggested that “the rate of pinworms in normal appendices must be very high in the healthy pediatric population at any given time.”
More data confirmed this to be true, and medical literature told Dr. Kearns that pinworms were common in high latitudes – places where people often are especially prone to MS.
“Most remarkably, they are known to have very little migration and stay spatially stable in populations over long periods of time,” Dr. Kearns said, “and typically everyone in an affected population will encounter them because their eggs are transmitted in household dust.”
And, he said, “they are known to be common in soldiers who live in military accommodation.”
According to the Centers for Disease Control and Prevention, pinworm prevalence can be as high as 50% in at-risk groups – children, caregivers of infected children, and people who live in institutions. Pinworms, which are spread through ingestion, are often asymptomatic but may cause anal itching and trigger bacterial infections.
The researchers suggest that pinworm infection comes first, followed by EBV infection. This makes sense because “late EBV infection in the form of infectious mononucleosis is known to be a risk factor for MS,” Dr. Kearns said.
The one-two punch of pinworm and then EBV is a plausible theory “because EBV lives in memory B cells, which are known to be important in MS and could be specific for the previous exposure to pinworm,” Dr. Kearns said. “However, this is very speculative and some researchers will argue this is very unlikely to be the case. But I think there is a chance it could explain some of the epidemiology, so I’m keen to try and test the theory if I can.”
What’s next? Dr. Kearns wants to explore data from Scotland in search of areas of high and low MS incidence that could offer insight into environmental triggers.
He added that the development of a serological blood test to prove a history of pinworm infection would be “the most effective way to prove or disprove this theory.”
“I have approached an investigator who has a track record of doing this for other infections and have been encouraged that he thinks that it would be achievable,” he said. “But this will definitely take time and funding.”
No specific funding was reported. The study authors reported no relevant disclosures.
SOURCE: Kearns P et al. ACTRIMS Forum 2018, Abstracts LB257 and LB264.
REPORTING FROM ACTRIMS FORUM 2018
Study identifies characteristics that may constitute the MS prodrome
SAN DIEGO – Compared with controls, patients who developed MS were more frequently admitted to the hospital or visited a physician for problems related to the nervous system, sensory organs, musculoskeletal system, and genitourinary system in the 5 years prior to MS onset, a multicenter matched cohort study found.
“People are seeking help for different conditions that are most likely related to their MS,” one of the study authors, Elaine Kingwell, PhD, said in an interview at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. “It suggests there could be opportunity to recognize and possibly diagnose and treat MS earlier.”
In a previously published study (Lancet Neurol. 2017;16[6]:445-51) led by Helen Tremlett, PhD, and first author Jose Wijnands, PhD, the team found increased health care utilization in people with MS across all health sectors – physician, hospital, and pharmacy (prescriptions filled).
For the current study, the team set out to identify early signs and symptoms that could define the MS prodrome. “We wanted to know why people went to the hospital, why people went to their physician, what kind of drugs they were prescribed, and what kind of specialists they saw,” explained Dr. Kingwell, an epidemiologist in the department of neurology at the University of British Columbia, Vancouver.
The researchers used health administrative and MS-specific data from four Canadian provinces to conduct a multicenter matched cohort study. Individuals were required to be in the province from 5 years pre-index date, measured as either the first demyelinating event in health administrative data or MS onset as determined by the treating neurologist, until the MS cases’ third demyelinating claim or diagnosis date. The potential for a prodromal period was examined in the 5 years pre-index date, and outcomes of interest were number of physician and hospital encounters per ICD-10 chapter, number of physician encounters per physician specialty, and percentage of people with one or more filled prescription per drug class.
The researchers used rate ratios and 95% confidence intervals to compare the rates of physician and hospital encounters between MS cases and controls and the proportion test to compare the percentage of people with one or more filled prescriptions between MS cases and controls. They used random-effects meta-analyses to pool results across Canadian provinces.
The population consisted of 13,951 MS patients and 66,940 controls derived from a health administration cohort and 3,202 MS patients and 16,006 controls derived from MS clinics. Compared with controls, in the 5 years before the first demyelinating claim or symptom onset, cases had more physician and hospital encounters for the nervous system (rate ratio = 1.70-4.75), sensory organs (RR = 1.40-2.28), musculoskeletal system (RR = 1.19-1.70), and genitourinary system (RR = 1.17-1.59), Dr. Kingwell and her associates reported. 
Cases also had more encounters with psychiatrists (RR = 1.48-1.66) and urologists (RR = 1.49-1.80), and a higher proportion of filled prescriptions for hormonal preparations and drugs related to the musculoskeletal or genitourinary systems (ranging from 1.1 to 1.5 times higher; P less than .02 for all associations). “While we did not examine each individual drug, we did group drugs by their therapeutic class,” Dr. Wijnands noted in an interview after the meeting. “As for the increased number of visits to psychiatrists, it is intriguing. We don’t necessarily know all the reasons why. It opens up a lot of questions for people to follow up on.”
In contrast, MS cases had fewer pregnancy-related encounters, compared with controls (RR = 0.78-0.88).
Dr. Wijnands acknowledged certain limitations of the study, including its reliance on administrative data to measure the prodromal period. “When we described the prodrome itself, we relied on ICD codes from the physician and hospital data as well as prescriptions filled. Issues or problems for which individuals do not seek medical attention, for instance, would not be captured in our study,” she said.
The study was funded by the National MS Society. Dr. Wijnands receives salary support from the Michael Smith Foundation for Health Research /The Koehle Family Foundation, coauthor Ruth Ann Marrie, MD, PhD, holds the Waugh Family Chair in Multiple Sclerosis, and Dr. Tremlett is funded by the Canada Research Chair Program. Dr. Kingwell reported having no financial disclosures.
[email protected]
SOURCE: Kingwell E et al. ACTRIMS Forum 2018, late-breaking poster 254.
SAN DIEGO – Compared with controls, patients who developed MS were more frequently admitted to the hospital or visited a physician for problems related to the nervous system, sensory organs, musculoskeletal system, and genitourinary system in the 5 years prior to MS onset, a multicenter matched cohort study found.
“People are seeking help for different conditions that are most likely related to their MS,” one of the study authors, Elaine Kingwell, PhD, said in an interview at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. “It suggests there could be opportunity to recognize and possibly diagnose and treat MS earlier.”
In a previously published study (Lancet Neurol. 2017;16[6]:445-51) led by Helen Tremlett, PhD, and first author Jose Wijnands, PhD, the team found increased health care utilization in people with MS across all health sectors – physician, hospital, and pharmacy (prescriptions filled).
For the current study, the team set out to identify early signs and symptoms that could define the MS prodrome. “We wanted to know why people went to the hospital, why people went to their physician, what kind of drugs they were prescribed, and what kind of specialists they saw,” explained Dr. Kingwell, an epidemiologist in the department of neurology at the University of British Columbia, Vancouver.
The researchers used health administrative and MS-specific data from four Canadian provinces to conduct a multicenter matched cohort study. Individuals were required to be in the province from 5 years pre-index date, measured as either the first demyelinating event in health administrative data or MS onset as determined by the treating neurologist, until the MS cases’ third demyelinating claim or diagnosis date. The potential for a prodromal period was examined in the 5 years pre-index date, and outcomes of interest were number of physician and hospital encounters per ICD-10 chapter, number of physician encounters per physician specialty, and percentage of people with one or more filled prescription per drug class.
The researchers used rate ratios and 95% confidence intervals to compare the rates of physician and hospital encounters between MS cases and controls and the proportion test to compare the percentage of people with one or more filled prescriptions between MS cases and controls. They used random-effects meta-analyses to pool results across Canadian provinces.
The population consisted of 13,951 MS patients and 66,940 controls derived from a health administration cohort and 3,202 MS patients and 16,006 controls derived from MS clinics. Compared with controls, in the 5 years before the first demyelinating claim or symptom onset, cases had more physician and hospital encounters for the nervous system (rate ratio = 1.70-4.75), sensory organs (RR = 1.40-2.28), musculoskeletal system (RR = 1.19-1.70), and genitourinary system (RR = 1.17-1.59), Dr. Kingwell and her associates reported.
Cases also had more encounters with psychiatrists (RR = 1.48-1.66) and urologists (RR = 1.49-1.80), and a higher proportion of filled prescriptions for hormonal preparations and drugs related to the musculoskeletal or genitourinary systems (ranging from 1.1 to 1.5 times higher; P less than .02 for all associations). “While we did not examine each individual drug, we did group drugs by their therapeutic class,” Dr. Wijnands noted in an interview after the meeting. “As for the increased number of visits to psychiatrists, it is intriguing. We don’t necessarily know all the reasons why. It opens up a lot of questions for people to follow up on.”
In contrast, MS cases had fewer pregnancy-related encounters, compared with controls (RR = 0.78-0.88).
Dr. Wijnands acknowledged certain limitations of the study, including its reliance on administrative data to measure the prodromal period. “When we described the prodrome itself, we relied on ICD codes from the physician and hospital data as well as prescriptions filled. Issues or problems for which individuals do not seek medical attention, for instance, would not be captured in our study,” she said.
The study was funded by the National MS Society. Dr. Wijnands receives salary support from the Michael Smith Foundation for Health Research /The Koehle Family Foundation, coauthor Ruth Ann Marrie, MD, PhD, holds the Waugh Family Chair in Multiple Sclerosis, and Dr. Tremlett is funded by the Canada Research Chair Program. Dr. Kingwell reported having no financial disclosures.
[email protected]
SOURCE: Kingwell E et al. ACTRIMS Forum 2018, late-breaking poster 254.
SAN DIEGO – Compared with controls, patients who developed MS were more frequently admitted to the hospital or visited a physician for problems related to the nervous system, sensory organs, musculoskeletal system, and genitourinary system in the 5 years prior to MS onset, a multicenter matched cohort study found.
“People are seeking help for different conditions that are most likely related to their MS,” one of the study authors, Elaine Kingwell, PhD, said in an interview at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. “It suggests there could be opportunity to recognize and possibly diagnose and treat MS earlier.”
In a previously published study (Lancet Neurol. 2017;16[6]:445-51) led by Helen Tremlett, PhD, and first author Jose Wijnands, PhD, the team found increased health care utilization in people with MS across all health sectors – physician, hospital, and pharmacy (prescriptions filled).
For the current study, the team set out to identify early signs and symptoms that could define the MS prodrome. “We wanted to know why people went to the hospital, why people went to their physician, what kind of drugs they were prescribed, and what kind of specialists they saw,” explained Dr. Kingwell, an epidemiologist in the department of neurology at the University of British Columbia, Vancouver.
The researchers used health administrative and MS-specific data from four Canadian provinces to conduct a multicenter matched cohort study. Individuals were required to be in the province from 5 years pre-index date, measured as either the first demyelinating event in health administrative data or MS onset as determined by the treating neurologist, until the MS cases’ third demyelinating claim or diagnosis date. The potential for a prodromal period was examined in the 5 years pre-index date, and outcomes of interest were number of physician and hospital encounters per ICD-10 chapter, number of physician encounters per physician specialty, and percentage of people with one or more filled prescription per drug class.
The researchers used rate ratios and 95% confidence intervals to compare the rates of physician and hospital encounters between MS cases and controls and the proportion test to compare the percentage of people with one or more filled prescriptions between MS cases and controls. They used random-effects meta-analyses to pool results across Canadian provinces.
The population consisted of 13,951 MS patients and 66,940 controls derived from a health administration cohort and 3,202 MS patients and 16,006 controls derived from MS clinics. Compared with controls, in the 5 years before the first demyelinating claim or symptom onset, cases had more physician and hospital encounters for the nervous system (rate ratio = 1.70-4.75), sensory organs (RR = 1.40-2.28), musculoskeletal system (RR = 1.19-1.70), and genitourinary system (RR = 1.17-1.59), Dr. Kingwell and her associates reported.
Cases also had more encounters with psychiatrists (RR = 1.48-1.66) and urologists (RR = 1.49-1.80), and a higher proportion of filled prescriptions for hormonal preparations and drugs related to the musculoskeletal or genitourinary systems (ranging from 1.1 to 1.5 times higher; P less than .02 for all associations). “While we did not examine each individual drug, we did group drugs by their therapeutic class,” Dr. Wijnands noted in an interview after the meeting. “As for the increased number of visits to psychiatrists, it is intriguing. We don’t necessarily know all the reasons why. It opens up a lot of questions for people to follow up on.”
In contrast, MS cases had fewer pregnancy-related encounters, compared with controls (RR = 0.78-0.88).
Dr. Wijnands acknowledged certain limitations of the study, including its reliance on administrative data to measure the prodromal period. “When we described the prodrome itself, we relied on ICD codes from the physician and hospital data as well as prescriptions filled. Issues or problems for which individuals do not seek medical attention, for instance, would not be captured in our study,” she said.
The study was funded by the National MS Society. Dr. Wijnands receives salary support from the Michael Smith Foundation for Health Research /The Koehle Family Foundation, coauthor Ruth Ann Marrie, MD, PhD, holds the Waugh Family Chair in Multiple Sclerosis, and Dr. Tremlett is funded by the Canada Research Chair Program. Dr. Kingwell reported having no financial disclosures.
[email protected]
SOURCE: Kingwell E et al. ACTRIMS Forum 2018, late-breaking poster 254.
REPORTING FROM ACTRIMS FORUM 2018
Key clinical point: Several phenotypic characteristics may constitute the MS prodrome.
Major finding: Compared with controls, in the 5 years before the first demyelinating claim or symptom onset, MS cases had more physician and hospital encounters for the nervous system (rate ratio = 1.70-4.75), sensory organs (RR = 1.40-2.28), and musculoskeletal system (RR = 1.19-1.70).
Study details: A multicenter matched cohort study of 13,951 MS patients and 66,940 controls derived from a health administration cohort and 3,202 MS patients and 16,006 controls derived from MS clinics.
Disclosures: The study was funded by the National MS Society. Dr. Wijnands receives salary support from the Michael Smith Foundation for Health Research /The Koehle Family Foundation, coauthor Ruth Ann Marrie, MD, PhD, holds the Waugh Family Chair in Multiple Sclerosis, and Dr. Tremlett is funded by the Canada Research Chair Program. Dr. Kingwell reported having no financial disclosures.
Source: Kingwell E et al. ACTRIMS Forum 2018, late-breaking poster 254.
Physicians often bypass cognition, depression screening in MS
SAN DIEGO – A new study finds that physicians at two . Physicians who did perform screening hardly ever used validated tools and often didn’t refer appropriate patients for higher-level care.
In addition, researchers interviewed 13 leading MS specialists from coast to coast and “found that about half reported not using formal screening tools to assess cognitive impairment and depression,” said study coauthor Tamar Sapir, PhD, chief scientific officer with Prime Education, a firm based in Fort Lauderdale, Fla., that provides a variety of health-related services such as training and research.
The study findings were presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. Three of the study authors spoke in interviews.
The researchers sought to understand how frequently MS patients are screened for cognitive problems and depression.
“Cognitive impairment is experienced by approximately half of patients with multiple sclerosis, yet many are never screened or treated, which can impact their daily activities, their ability to work, and overall quality of life,” Dr. Sapir said.
Depression, meanwhile, is believed to be much more common in patients with MS than in the general population, with one recent meta-analysis of 58 studies finding that the average prevalence was 31%. Other research suggests depression is underdiagnosed and undertreated in this population (J Neurol Sci. 2017 Jan 15;372:331-41; ISRN Neurology. 2012, Article ID 427102. doi: 10.5402/2012/427102).
For the current study, researchers tracked 300 patients at two unidentified MS clinics via their charts over a 2-year period from 2014 to 2016. Their median age was 52 years, 76% were women, and 15 had experienced at least one relapse within the previous 24 months. 
“Screening for cognitive impairment and depression was documented for only 52% and 63% of MS patients, respectively, and only about a quarter of patients diagnosed with these conditions were referred to a higher level of care,” said lead author Guy J. Buckle, MD, MPH, of the Andrew C. Carlos MS Institute at Shepherd Center in Atlanta.
Among all 300 patients, just 2% and 4% were screened using a validated tool for cognitive impairment and depression, respectively.
The screening often turned up evidence of the conditions: Physicians saw signs of cognitive impairment in 69% and 78% of those screened aged under 65 years and aged 65 and older, respectively, and they detected depression in 71% and 54% of those screened in those two age groups, respectively.
Researchers also noted several disparities. “Cognitive screening was conducted more frequently in older, employed, or white patients, while the presence of cognitive impairment was documented more often in black, nonworking, and those on Medicare or Medicaid,” Dr. Buckle said. “Depression screening was performed most frequently in older or white patients, yet depression was more common in younger, nonworking patients and those on Medicare/Medicaid.”
In another part of their study, researchers surveyed 13 unidentified “national leaders” in MS research and treatment. Just seven said they used validated tools to screen for cognitive impairment and six said they used them to screen for depression.
“We hear from MS specialists that they want to be measuring for cognition but don’t know how to efficiently work it into their routine, how to approach the patient, and what tools to use,” said study coauthor Derrick S. Robertson, MD, of the University of South Florida, Tampa. “In addition, there is no one tool that is accepted in the MS treatment community.”
MS specialists who didn’t use the screening tests also pointed to factors like lack of reimbursement and lack of integration into electronic medical records. “Doubt very much that neurologists have time to use any of these tests,” one respondent said, referring to cognitive impairment screening.
What’s next? “There are several new exciting developments in clinical trials demonstrating efficacy of disease-modifying therapies in maintaining or improving cognition in patients with relapsing MS,” Dr. Robertson said. “This highlights the urgent need to overcome barriers to use of formal cognitive screening tools in clinical practice to identify patients who need a higher level of care, and perhaps even a change in treatment with the ultimate goal to improve quality of life and overall outcomes.”
Genentech funded the study through an educational grant. Dr. Sapir and three other study authors reported no relevant disclosures. Dr. Buckle and Dr. Robertson reported multiple disclosures, including principle investigator and advisory board/panel member work.
SOURCE: Buckle GJ et al. ACTRIMS Forum 2018, abstract No. P161.
SAN DIEGO – A new study finds that physicians at two . Physicians who did perform screening hardly ever used validated tools and often didn’t refer appropriate patients for higher-level care.
In addition, researchers interviewed 13 leading MS specialists from coast to coast and “found that about half reported not using formal screening tools to assess cognitive impairment and depression,” said study coauthor Tamar Sapir, PhD, chief scientific officer with Prime Education, a firm based in Fort Lauderdale, Fla., that provides a variety of health-related services such as training and research.
The study findings were presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. Three of the study authors spoke in interviews.
The researchers sought to understand how frequently MS patients are screened for cognitive problems and depression.
“Cognitive impairment is experienced by approximately half of patients with multiple sclerosis, yet many are never screened or treated, which can impact their daily activities, their ability to work, and overall quality of life,” Dr. Sapir said.
Depression, meanwhile, is believed to be much more common in patients with MS than in the general population, with one recent meta-analysis of 58 studies finding that the average prevalence was 31%. Other research suggests depression is underdiagnosed and undertreated in this population (J Neurol Sci. 2017 Jan 15;372:331-41; ISRN Neurology. 2012, Article ID 427102. doi: 10.5402/2012/427102).
For the current study, researchers tracked 300 patients at two unidentified MS clinics via their charts over a 2-year period from 2014 to 2016. Their median age was 52 years, 76% were women, and 15 had experienced at least one relapse within the previous 24 months.
“Screening for cognitive impairment and depression was documented for only 52% and 63% of MS patients, respectively, and only about a quarter of patients diagnosed with these conditions were referred to a higher level of care,” said lead author Guy J. Buckle, MD, MPH, of the Andrew C. Carlos MS Institute at Shepherd Center in Atlanta.
Among all 300 patients, just 2% and 4% were screened using a validated tool for cognitive impairment and depression, respectively.
The screening often turned up evidence of the conditions: Physicians saw signs of cognitive impairment in 69% and 78% of those screened aged under 65 years and aged 65 and older, respectively, and they detected depression in 71% and 54% of those screened in those two age groups, respectively.
Researchers also noted several disparities. “Cognitive screening was conducted more frequently in older, employed, or white patients, while the presence of cognitive impairment was documented more often in black, nonworking, and those on Medicare or Medicaid,” Dr. Buckle said. “Depression screening was performed most frequently in older or white patients, yet depression was more common in younger, nonworking patients and those on Medicare/Medicaid.”
In another part of their study, researchers surveyed 13 unidentified “national leaders” in MS research and treatment. Just seven said they used validated tools to screen for cognitive impairment and six said they used them to screen for depression.
“We hear from MS specialists that they want to be measuring for cognition but don’t know how to efficiently work it into their routine, how to approach the patient, and what tools to use,” said study coauthor Derrick S. Robertson, MD, of the University of South Florida, Tampa. “In addition, there is no one tool that is accepted in the MS treatment community.”
MS specialists who didn’t use the screening tests also pointed to factors like lack of reimbursement and lack of integration into electronic medical records. “Doubt very much that neurologists have time to use any of these tests,” one respondent said, referring to cognitive impairment screening.
What’s next? “There are several new exciting developments in clinical trials demonstrating efficacy of disease-modifying therapies in maintaining or improving cognition in patients with relapsing MS,” Dr. Robertson said. “This highlights the urgent need to overcome barriers to use of formal cognitive screening tools in clinical practice to identify patients who need a higher level of care, and perhaps even a change in treatment with the ultimate goal to improve quality of life and overall outcomes.”
Genentech funded the study through an educational grant. Dr. Sapir and three other study authors reported no relevant disclosures. Dr. Buckle and Dr. Robertson reported multiple disclosures, including principle investigator and advisory board/panel member work.
SOURCE: Buckle GJ et al. ACTRIMS Forum 2018, abstract No. P161.
SAN DIEGO – A new study finds that physicians at two . Physicians who did perform screening hardly ever used validated tools and often didn’t refer appropriate patients for higher-level care.
In addition, researchers interviewed 13 leading MS specialists from coast to coast and “found that about half reported not using formal screening tools to assess cognitive impairment and depression,” said study coauthor Tamar Sapir, PhD, chief scientific officer with Prime Education, a firm based in Fort Lauderdale, Fla., that provides a variety of health-related services such as training and research.
The study findings were presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. Three of the study authors spoke in interviews.
The researchers sought to understand how frequently MS patients are screened for cognitive problems and depression.
“Cognitive impairment is experienced by approximately half of patients with multiple sclerosis, yet many are never screened or treated, which can impact their daily activities, their ability to work, and overall quality of life,” Dr. Sapir said.
Depression, meanwhile, is believed to be much more common in patients with MS than in the general population, with one recent meta-analysis of 58 studies finding that the average prevalence was 31%. Other research suggests depression is underdiagnosed and undertreated in this population (J Neurol Sci. 2017 Jan 15;372:331-41; ISRN Neurology. 2012, Article ID 427102. doi: 10.5402/2012/427102).
For the current study, researchers tracked 300 patients at two unidentified MS clinics via their charts over a 2-year period from 2014 to 2016. Their median age was 52 years, 76% were women, and 15 had experienced at least one relapse within the previous 24 months.
“Screening for cognitive impairment and depression was documented for only 52% and 63% of MS patients, respectively, and only about a quarter of patients diagnosed with these conditions were referred to a higher level of care,” said lead author Guy J. Buckle, MD, MPH, of the Andrew C. Carlos MS Institute at Shepherd Center in Atlanta.
Among all 300 patients, just 2% and 4% were screened using a validated tool for cognitive impairment and depression, respectively.
The screening often turned up evidence of the conditions: Physicians saw signs of cognitive impairment in 69% and 78% of those screened aged under 65 years and aged 65 and older, respectively, and they detected depression in 71% and 54% of those screened in those two age groups, respectively.
Researchers also noted several disparities. “Cognitive screening was conducted more frequently in older, employed, or white patients, while the presence of cognitive impairment was documented more often in black, nonworking, and those on Medicare or Medicaid,” Dr. Buckle said. “Depression screening was performed most frequently in older or white patients, yet depression was more common in younger, nonworking patients and those on Medicare/Medicaid.”
In another part of their study, researchers surveyed 13 unidentified “national leaders” in MS research and treatment. Just seven said they used validated tools to screen for cognitive impairment and six said they used them to screen for depression.
“We hear from MS specialists that they want to be measuring for cognition but don’t know how to efficiently work it into their routine, how to approach the patient, and what tools to use,” said study coauthor Derrick S. Robertson, MD, of the University of South Florida, Tampa. “In addition, there is no one tool that is accepted in the MS treatment community.”
MS specialists who didn’t use the screening tests also pointed to factors like lack of reimbursement and lack of integration into electronic medical records. “Doubt very much that neurologists have time to use any of these tests,” one respondent said, referring to cognitive impairment screening.
What’s next? “There are several new exciting developments in clinical trials demonstrating efficacy of disease-modifying therapies in maintaining or improving cognition in patients with relapsing MS,” Dr. Robertson said. “This highlights the urgent need to overcome barriers to use of formal cognitive screening tools in clinical practice to identify patients who need a higher level of care, and perhaps even a change in treatment with the ultimate goal to improve quality of life and overall outcomes.”
Genentech funded the study through an educational grant. Dr. Sapir and three other study authors reported no relevant disclosures. Dr. Buckle and Dr. Robertson reported multiple disclosures, including principle investigator and advisory board/panel member work.
SOURCE: Buckle GJ et al. ACTRIMS Forum 2018, abstract No. P161.
REPORTING FROM ACTRIMS FORUM 2018
Key clinical point: Screening often turns up signs of trouble, but many MS patients are not screened annually for depression and cognitive impairment.
Major finding: 52% and 63% of patients with MS were screened for cognitive impairment and depression, respectively, over a 1-year period. Study details: 2-year analysis of medical records from two MS clinics in the Southeast.
Disclosures: Genentech funded the study through an educational grant. Some of the study authors reported various disclosures.
Source: Buckle GJ et al. ACTRIMS Forum 2018, abstract No. P161.
Nearly half of MS patients treated by primary docs miss out on meds
SAN DIEGO – than are those treated by neurologists, even though they have more symptoms.
Nearly 85% of those treated at MS centers by neurologists received the drugs, compared with just 51% of those treated at primary care offices, according to results of a study reported at ACTRIMS Forum 2018, held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
Dr. Halpern spoke in an interview at the ACTRIMS Forum.
The researchers analyzed data from the Sonya Slifka Longitudinal Multiple Sclerosis Study and focused on MS patients who received care at MS centers (376 patients, all treated by neurologists), neurology practices (552 patients), and primary care practices (55 patients).
In the three groups, most of the patients were female (77%-82%). To a statistically significant degree, those who were treated at primary care practices, compared with those at MS centers, were more likely to be white (98% vs. 82%), to have less than a college education (69% vs. 42%), and to have Medicaid/veteran coverage or be uninsured (22% vs. 11%).
In terms of rates of patients receiving disease-modifying therapies, there was a small difference between MS centers (84%) and neurology practices (79%); P less than .05.
However, the gap between these patients and those treated by primary care doctors was wide: Only 51% in the latter group received disease-modifying therapies, even though they reported more symptoms in areas such as vision, walking, bowel, speech, and numbness, compared with those in the other groups (P less than .05).
There was no statistically significant difference among the groups in reported symptoms of tremor, headache, pain, fatigue, cognition, swallowing, depression, mood, and anxiety.
The study doesn’t explain why the MS patients treated by primary care physicians are missing out on care, and it is not known whether the absence of treatment makes their conditions worse.
However, “it’s been well documented that the disease-modifying therapies can reduce the disease progression and the likelihood of experiencing relapses,” Dr. Halpern said. “Individuals with MS who are not being appropriately treated are more likely to experience symptoms, relapses, and faster disability.”
He speculated that primary care doctors may be falling behind on the treatment front because they lack the training and expertise to properly prescribe the MS medications, which are “difficult and complex drugs.”
Whatever the case, he said, there’s a clear need for more collaboration between MS subspecialists and primary care doctors.
The study was funded by the National MS Society. Dr. Halpern reported no relevant disclosures.
SOURCE: Halpern MT et al. ACTRIMS Forum 2018 Abstract P226.
SAN DIEGO – than are those treated by neurologists, even though they have more symptoms.
Nearly 85% of those treated at MS centers by neurologists received the drugs, compared with just 51% of those treated at primary care offices, according to results of a study reported at ACTRIMS Forum 2018, held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
Dr. Halpern spoke in an interview at the ACTRIMS Forum.
The researchers analyzed data from the Sonya Slifka Longitudinal Multiple Sclerosis Study and focused on MS patients who received care at MS centers (376 patients, all treated by neurologists), neurology practices (552 patients), and primary care practices (55 patients).
In the three groups, most of the patients were female (77%-82%). To a statistically significant degree, those who were treated at primary care practices, compared with those at MS centers, were more likely to be white (98% vs. 82%), to have less than a college education (69% vs. 42%), and to have Medicaid/veteran coverage or be uninsured (22% vs. 11%).
In terms of rates of patients receiving disease-modifying therapies, there was a small difference between MS centers (84%) and neurology practices (79%); P less than .05.
However, the gap between these patients and those treated by primary care doctors was wide: Only 51% in the latter group received disease-modifying therapies, even though they reported more symptoms in areas such as vision, walking, bowel, speech, and numbness, compared with those in the other groups (P less than .05).
There was no statistically significant difference among the groups in reported symptoms of tremor, headache, pain, fatigue, cognition, swallowing, depression, mood, and anxiety.
The study doesn’t explain why the MS patients treated by primary care physicians are missing out on care, and it is not known whether the absence of treatment makes their conditions worse.
However, “it’s been well documented that the disease-modifying therapies can reduce the disease progression and the likelihood of experiencing relapses,” Dr. Halpern said. “Individuals with MS who are not being appropriately treated are more likely to experience symptoms, relapses, and faster disability.”
He speculated that primary care doctors may be falling behind on the treatment front because they lack the training and expertise to properly prescribe the MS medications, which are “difficult and complex drugs.”
Whatever the case, he said, there’s a clear need for more collaboration between MS subspecialists and primary care doctors.
The study was funded by the National MS Society. Dr. Halpern reported no relevant disclosures.
SOURCE: Halpern MT et al. ACTRIMS Forum 2018 Abstract P226.
SAN DIEGO – than are those treated by neurologists, even though they have more symptoms.
Nearly 85% of those treated at MS centers by neurologists received the drugs, compared with just 51% of those treated at primary care offices, according to results of a study reported at ACTRIMS Forum 2018, held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
Dr. Halpern spoke in an interview at the ACTRIMS Forum.
The researchers analyzed data from the Sonya Slifka Longitudinal Multiple Sclerosis Study and focused on MS patients who received care at MS centers (376 patients, all treated by neurologists), neurology practices (552 patients), and primary care practices (55 patients).
In the three groups, most of the patients were female (77%-82%). To a statistically significant degree, those who were treated at primary care practices, compared with those at MS centers, were more likely to be white (98% vs. 82%), to have less than a college education (69% vs. 42%), and to have Medicaid/veteran coverage or be uninsured (22% vs. 11%).
In terms of rates of patients receiving disease-modifying therapies, there was a small difference between MS centers (84%) and neurology practices (79%); P less than .05.
However, the gap between these patients and those treated by primary care doctors was wide: Only 51% in the latter group received disease-modifying therapies, even though they reported more symptoms in areas such as vision, walking, bowel, speech, and numbness, compared with those in the other groups (P less than .05).
There was no statistically significant difference among the groups in reported symptoms of tremor, headache, pain, fatigue, cognition, swallowing, depression, mood, and anxiety.
The study doesn’t explain why the MS patients treated by primary care physicians are missing out on care, and it is not known whether the absence of treatment makes their conditions worse.
However, “it’s been well documented that the disease-modifying therapies can reduce the disease progression and the likelihood of experiencing relapses,” Dr. Halpern said. “Individuals with MS who are not being appropriately treated are more likely to experience symptoms, relapses, and faster disability.”
He speculated that primary care doctors may be falling behind on the treatment front because they lack the training and expertise to properly prescribe the MS medications, which are “difficult and complex drugs.”
Whatever the case, he said, there’s a clear need for more collaboration between MS subspecialists and primary care doctors.
The study was funded by the National MS Society. Dr. Halpern reported no relevant disclosures.
SOURCE: Halpern MT et al. ACTRIMS Forum 2018 Abstract P226.
REPORTING FROM ACTRIMS FORUM 2018
VIDEO: Teriflunomide and dimethyl fumarate are comparable in relapsing-remitting MS
SAN DIEGO – New industry-funded research finds that
“The fundamental conclusion is that there’s little to separate them. If you look at efficacy, safety, and MRI scanning, there were no differences between the two medications that matter. ... Both drugs can be used with equal confidence,” said Stanley Cohan, MD, PhD, medical director of Providence MS Center in Portland, Ore.
Dr. Cohan spoke in a video interview at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
The researchers analyzed retrospective data collected in the phase 4 Teri-RADAR study, which tracked two groups of 50 patients each at MS centers in the United States as they took 14 mg of teriflunomide (Aubagio) daily or 240 mg of delayed-release dimethyl fumarate (Tecfidera) twice daily.
In both groups, participants had an average age of about 49 years, about three-quarters were women, and about 93% were white. Twenty-two percent of those in the teriflunomide group had relapses in the 18 months before the index date, compared with 10% of the dimethyl fumarate group.
The study – funded by Sanofi, maker of teriflunomide – followed up with patients at a mean of 15-16 months.
Mean annualized percentage of brain volume change (PBVC) was lower in teriflunomide-treated patients, compared with those treated with dimethyl fumarate (–0.2% vs. –0.5%; P = .02). Also, fewer teriflunomide-treated patients showed signs of annualized PBVC above a mean annualized brain volume loss rate threshold of 0.4% (25.9% vs. 58.6%; P = .01).
As for adverse effects, rashes affected none of the teriflunomide group but 28% of the dimethyl fumarate group. The teriflunomide group experienced skin reactions (12%) and diarrhea (16%), while these adverse events were not reported in the dimethyl fumarate group.
The study authors reported a variety of disclosures, and several are employees of Sanofi. Dr. Cohan reported a variety of disclosures, including multiple relationships with Sanofi.
SAN DIEGO – New industry-funded research finds that
“The fundamental conclusion is that there’s little to separate them. If you look at efficacy, safety, and MRI scanning, there were no differences between the two medications that matter. ... Both drugs can be used with equal confidence,” said Stanley Cohan, MD, PhD, medical director of Providence MS Center in Portland, Ore.
Dr. Cohan spoke in a video interview at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
The researchers analyzed retrospective data collected in the phase 4 Teri-RADAR study, which tracked two groups of 50 patients each at MS centers in the United States as they took 14 mg of teriflunomide (Aubagio) daily or 240 mg of delayed-release dimethyl fumarate (Tecfidera) twice daily.
In both groups, participants had an average age of about 49 years, about three-quarters were women, and about 93% were white. Twenty-two percent of those in the teriflunomide group had relapses in the 18 months before the index date, compared with 10% of the dimethyl fumarate group.
The study – funded by Sanofi, maker of teriflunomide – followed up with patients at a mean of 15-16 months.
Mean annualized percentage of brain volume change (PBVC) was lower in teriflunomide-treated patients, compared with those treated with dimethyl fumarate (–0.2% vs. –0.5%; P = .02). Also, fewer teriflunomide-treated patients showed signs of annualized PBVC above a mean annualized brain volume loss rate threshold of 0.4% (25.9% vs. 58.6%; P = .01).
As for adverse effects, rashes affected none of the teriflunomide group but 28% of the dimethyl fumarate group. The teriflunomide group experienced skin reactions (12%) and diarrhea (16%), while these adverse events were not reported in the dimethyl fumarate group.
The study authors reported a variety of disclosures, and several are employees of Sanofi. Dr. Cohan reported a variety of disclosures, including multiple relationships with Sanofi.
SAN DIEGO – New industry-funded research finds that
“The fundamental conclusion is that there’s little to separate them. If you look at efficacy, safety, and MRI scanning, there were no differences between the two medications that matter. ... Both drugs can be used with equal confidence,” said Stanley Cohan, MD, PhD, medical director of Providence MS Center in Portland, Ore.
Dr. Cohan spoke in a video interview at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
The researchers analyzed retrospective data collected in the phase 4 Teri-RADAR study, which tracked two groups of 50 patients each at MS centers in the United States as they took 14 mg of teriflunomide (Aubagio) daily or 240 mg of delayed-release dimethyl fumarate (Tecfidera) twice daily.
In both groups, participants had an average age of about 49 years, about three-quarters were women, and about 93% were white. Twenty-two percent of those in the teriflunomide group had relapses in the 18 months before the index date, compared with 10% of the dimethyl fumarate group.
The study – funded by Sanofi, maker of teriflunomide – followed up with patients at a mean of 15-16 months.
Mean annualized percentage of brain volume change (PBVC) was lower in teriflunomide-treated patients, compared with those treated with dimethyl fumarate (–0.2% vs. –0.5%; P = .02). Also, fewer teriflunomide-treated patients showed signs of annualized PBVC above a mean annualized brain volume loss rate threshold of 0.4% (25.9% vs. 58.6%; P = .01).
As for adverse effects, rashes affected none of the teriflunomide group but 28% of the dimethyl fumarate group. The teriflunomide group experienced skin reactions (12%) and diarrhea (16%), while these adverse events were not reported in the dimethyl fumarate group.
The study authors reported a variety of disclosures, and several are employees of Sanofi. Dr. Cohan reported a variety of disclosures, including multiple relationships with Sanofi.
REPORTING FROM ACTRIMS Forum 2018
