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Satralizumab reduces risk of severe NMOSD relapse
(NMOSD), according to investigators. The drug also was associated with a lower likelihood of using acute relapse therapy.
These results were presented at the Joint European Committee for Treatment and Research in Multiple Sclerosis–Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS–ACTRIMS) 2020, this year known as MSVirtual2020.
NMOSD is characterized by acute relapses that are unpredictable and lead to the accumulation of disability. “Patients with NMOSD often recover poorly from relapses, therefore, the primary goal for disease management is to reduce attack frequency,” said Ingo Kleiter, MD, medical director of Marianne-Strauß-Klinik in Berg, Germany. “In the two phase 3 trials SAkuraSky and SAkuraStar, the IL-6 receptor inhibitor satralizumab was found to significantly reduce the risk of relapses versus placebo.” Satralizumab is a humanized, monoclonal, recycling antibody that targets the interleukin-6 receptor.
Dr. Kleiter and colleagues examined pooled data from the two phase 3 trials of satralizumab to determine the treatment’s effect on relapse severity in patients with NMOSD. Participants in those trials received placebo or 120 mg of satralizumab at weeks 0, 2, 4, and every 4 weeks thereafter.
For their research, the investigators analyzed data from the pooled intention-to-treat population in the double-blind periods of both studies. To evaluate the severity of protocol-defined relapses, they compared patients’ Expanded Disability Status Scale (EDSS) scores at the time of relapse with their scores before the relapse (i.e., their scores at the last scheduled study visit). Using the visual Functional Systems Score (FSS), Dr. Kleiter and colleagues performed a similar analysis on optic neuritis relapses. They categorized a protocol-defined relapse as severe if it entailed a change of two or more points on the EDSS or visual FSS. The investigators conducted Kaplan-Meier analyses to evaluate the time to first severe protocol-defined relapse. They also compared the number of patients receiving acute therapy for any relapse between treatment groups.
Safety profile confirmed
Dr. Kleiter and colleagues included 178 patients in their analyses. A total of 27 of 104 patients (26%) who received satralizumab had a protocol-defined relapse, compared with 34 of 74 patients (46%) who received placebo. The number and proportion of severe protocol-defined relapses were lower in the satralizumab group (5 of 27 events [19%]), compared with the placebo group (12 of 34 events [35%]). In addition, the number and proportion of severe protocol-defined optic neuritis relapses were lower in patients receiving satralizumab (2 of 8 events [25%]), compared with those receiving placebo (5 of 13 events [39%]). Compared with placebo, satralizumab was associated with a 79% reduction in the risk of severe protocol-defined relapse (hazard ratio, 0.21).
A lower proportion of patients receiving satralizumab was prescribed acute relapse therapy (38%), compared with patients receiving placebo (58%). The odds ratio of receiving a prescription of acute relapse therapy was 0.46 among patients receiving satralizumab.
The activity of IL-6 may cause neurologic damage in patients with NMOSD through astrocytic damage, disruption of the blood–brain barrier, and T cell polarization. “It is proposed that through inhibiting IL-6 across these multiple mechanisms, satralizumab reduces the risk and severity of NMOSD attacks,” Dr. Kleiter said.
To date, the rates of infection and serious infection for patients treated with satralizumab in the combined double-blind and open-label extension periods have been consistent with those for patients treated with satralizumab in the double-blind portion. These rates have not increased over time. Satralizumab is administered as a subcutaneous injection every 4 weeks, and treatment can be self-administered at the discretion of the managing physician. “These data provide reassurance to physicians about the overall profile of satralizumab, with respect to efficacy and safety in the longer term,” said Dr. Kleiter.
Does satralizumab differ from other new agents?
The main strength of the study is that sufficient numbers of relapses were available for analysis in the active and control groups, said Achim Berthele, MD, associate professor of neurology at the Technical University of Munich. This allowed the researchers to examine whether satralizumab led to a better outcome after each relapse, which it did. “A weakness is how the severity of relapses was quantified,” said Dr. Berthele. “The EDSS as a measure is not linear, and its functional systems are not clinically equivalent. However, the whole NMOSD community is struggling with this problem.”
The study’s implications for neurologists’ clinical practice are unclear, however. “Although the results presented are encouraging, the data are still too small to say with certainty that satralizumab does indeed improve the outcome of relapses,” said Dr. Berthele. “It is also an open question whether satralizumab differs in this respect from the other new immunotherapeutic agents.”
Investigators must collect further data on the outcome of relapses that occur during treatment with modern immunomodulatory therapy, Dr. Berthele added. Future research could examine whether the new anti-inflammatory immunotherapeutic agents also are suitable drugs for relapse therapy. Another salient question is whether clinical vigilance or relapse therapy in NMOSD has improved in general. “This is what Kleiter and colleagues show as well: The number of severe relapses under placebo was much lower than expected,” said Dr. Berthele.
Chugai/Roche funded the study. Dr. Kleiter has received compensation for consulting, speaking, or serving on advisory boards for Alexion, Biogen, Celgene, Merck, and Roche. Dr. Berthele was not involved in any of the satralizumab trials, but is an investigator and coauthor of the PREVENT trial of eculizumab.
SOURCE: Kleiter I, et al. MSVirtual2020. Abstract FC01.03.
(NMOSD), according to investigators. The drug also was associated with a lower likelihood of using acute relapse therapy.
These results were presented at the Joint European Committee for Treatment and Research in Multiple Sclerosis–Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS–ACTRIMS) 2020, this year known as MSVirtual2020.
NMOSD is characterized by acute relapses that are unpredictable and lead to the accumulation of disability. “Patients with NMOSD often recover poorly from relapses, therefore, the primary goal for disease management is to reduce attack frequency,” said Ingo Kleiter, MD, medical director of Marianne-Strauß-Klinik in Berg, Germany. “In the two phase 3 trials SAkuraSky and SAkuraStar, the IL-6 receptor inhibitor satralizumab was found to significantly reduce the risk of relapses versus placebo.” Satralizumab is a humanized, monoclonal, recycling antibody that targets the interleukin-6 receptor.
Dr. Kleiter and colleagues examined pooled data from the two phase 3 trials of satralizumab to determine the treatment’s effect on relapse severity in patients with NMOSD. Participants in those trials received placebo or 120 mg of satralizumab at weeks 0, 2, 4, and every 4 weeks thereafter.
For their research, the investigators analyzed data from the pooled intention-to-treat population in the double-blind periods of both studies. To evaluate the severity of protocol-defined relapses, they compared patients’ Expanded Disability Status Scale (EDSS) scores at the time of relapse with their scores before the relapse (i.e., their scores at the last scheduled study visit). Using the visual Functional Systems Score (FSS), Dr. Kleiter and colleagues performed a similar analysis on optic neuritis relapses. They categorized a protocol-defined relapse as severe if it entailed a change of two or more points on the EDSS or visual FSS. The investigators conducted Kaplan-Meier analyses to evaluate the time to first severe protocol-defined relapse. They also compared the number of patients receiving acute therapy for any relapse between treatment groups.
Safety profile confirmed
Dr. Kleiter and colleagues included 178 patients in their analyses. A total of 27 of 104 patients (26%) who received satralizumab had a protocol-defined relapse, compared with 34 of 74 patients (46%) who received placebo. The number and proportion of severe protocol-defined relapses were lower in the satralizumab group (5 of 27 events [19%]), compared with the placebo group (12 of 34 events [35%]). In addition, the number and proportion of severe protocol-defined optic neuritis relapses were lower in patients receiving satralizumab (2 of 8 events [25%]), compared with those receiving placebo (5 of 13 events [39%]). Compared with placebo, satralizumab was associated with a 79% reduction in the risk of severe protocol-defined relapse (hazard ratio, 0.21).
A lower proportion of patients receiving satralizumab was prescribed acute relapse therapy (38%), compared with patients receiving placebo (58%). The odds ratio of receiving a prescription of acute relapse therapy was 0.46 among patients receiving satralizumab.
The activity of IL-6 may cause neurologic damage in patients with NMOSD through astrocytic damage, disruption of the blood–brain barrier, and T cell polarization. “It is proposed that through inhibiting IL-6 across these multiple mechanisms, satralizumab reduces the risk and severity of NMOSD attacks,” Dr. Kleiter said.
To date, the rates of infection and serious infection for patients treated with satralizumab in the combined double-blind and open-label extension periods have been consistent with those for patients treated with satralizumab in the double-blind portion. These rates have not increased over time. Satralizumab is administered as a subcutaneous injection every 4 weeks, and treatment can be self-administered at the discretion of the managing physician. “These data provide reassurance to physicians about the overall profile of satralizumab, with respect to efficacy and safety in the longer term,” said Dr. Kleiter.
Does satralizumab differ from other new agents?
The main strength of the study is that sufficient numbers of relapses were available for analysis in the active and control groups, said Achim Berthele, MD, associate professor of neurology at the Technical University of Munich. This allowed the researchers to examine whether satralizumab led to a better outcome after each relapse, which it did. “A weakness is how the severity of relapses was quantified,” said Dr. Berthele. “The EDSS as a measure is not linear, and its functional systems are not clinically equivalent. However, the whole NMOSD community is struggling with this problem.”
The study’s implications for neurologists’ clinical practice are unclear, however. “Although the results presented are encouraging, the data are still too small to say with certainty that satralizumab does indeed improve the outcome of relapses,” said Dr. Berthele. “It is also an open question whether satralizumab differs in this respect from the other new immunotherapeutic agents.”
Investigators must collect further data on the outcome of relapses that occur during treatment with modern immunomodulatory therapy, Dr. Berthele added. Future research could examine whether the new anti-inflammatory immunotherapeutic agents also are suitable drugs for relapse therapy. Another salient question is whether clinical vigilance or relapse therapy in NMOSD has improved in general. “This is what Kleiter and colleagues show as well: The number of severe relapses under placebo was much lower than expected,” said Dr. Berthele.
Chugai/Roche funded the study. Dr. Kleiter has received compensation for consulting, speaking, or serving on advisory boards for Alexion, Biogen, Celgene, Merck, and Roche. Dr. Berthele was not involved in any of the satralizumab trials, but is an investigator and coauthor of the PREVENT trial of eculizumab.
SOURCE: Kleiter I, et al. MSVirtual2020. Abstract FC01.03.
(NMOSD), according to investigators. The drug also was associated with a lower likelihood of using acute relapse therapy.
These results were presented at the Joint European Committee for Treatment and Research in Multiple Sclerosis–Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS–ACTRIMS) 2020, this year known as MSVirtual2020.
NMOSD is characterized by acute relapses that are unpredictable and lead to the accumulation of disability. “Patients with NMOSD often recover poorly from relapses, therefore, the primary goal for disease management is to reduce attack frequency,” said Ingo Kleiter, MD, medical director of Marianne-Strauß-Klinik in Berg, Germany. “In the two phase 3 trials SAkuraSky and SAkuraStar, the IL-6 receptor inhibitor satralizumab was found to significantly reduce the risk of relapses versus placebo.” Satralizumab is a humanized, monoclonal, recycling antibody that targets the interleukin-6 receptor.
Dr. Kleiter and colleagues examined pooled data from the two phase 3 trials of satralizumab to determine the treatment’s effect on relapse severity in patients with NMOSD. Participants in those trials received placebo or 120 mg of satralizumab at weeks 0, 2, 4, and every 4 weeks thereafter.
For their research, the investigators analyzed data from the pooled intention-to-treat population in the double-blind periods of both studies. To evaluate the severity of protocol-defined relapses, they compared patients’ Expanded Disability Status Scale (EDSS) scores at the time of relapse with their scores before the relapse (i.e., their scores at the last scheduled study visit). Using the visual Functional Systems Score (FSS), Dr. Kleiter and colleagues performed a similar analysis on optic neuritis relapses. They categorized a protocol-defined relapse as severe if it entailed a change of two or more points on the EDSS or visual FSS. The investigators conducted Kaplan-Meier analyses to evaluate the time to first severe protocol-defined relapse. They also compared the number of patients receiving acute therapy for any relapse between treatment groups.
Safety profile confirmed
Dr. Kleiter and colleagues included 178 patients in their analyses. A total of 27 of 104 patients (26%) who received satralizumab had a protocol-defined relapse, compared with 34 of 74 patients (46%) who received placebo. The number and proportion of severe protocol-defined relapses were lower in the satralizumab group (5 of 27 events [19%]), compared with the placebo group (12 of 34 events [35%]). In addition, the number and proportion of severe protocol-defined optic neuritis relapses were lower in patients receiving satralizumab (2 of 8 events [25%]), compared with those receiving placebo (5 of 13 events [39%]). Compared with placebo, satralizumab was associated with a 79% reduction in the risk of severe protocol-defined relapse (hazard ratio, 0.21).
A lower proportion of patients receiving satralizumab was prescribed acute relapse therapy (38%), compared with patients receiving placebo (58%). The odds ratio of receiving a prescription of acute relapse therapy was 0.46 among patients receiving satralizumab.
The activity of IL-6 may cause neurologic damage in patients with NMOSD through astrocytic damage, disruption of the blood–brain barrier, and T cell polarization. “It is proposed that through inhibiting IL-6 across these multiple mechanisms, satralizumab reduces the risk and severity of NMOSD attacks,” Dr. Kleiter said.
To date, the rates of infection and serious infection for patients treated with satralizumab in the combined double-blind and open-label extension periods have been consistent with those for patients treated with satralizumab in the double-blind portion. These rates have not increased over time. Satralizumab is administered as a subcutaneous injection every 4 weeks, and treatment can be self-administered at the discretion of the managing physician. “These data provide reassurance to physicians about the overall profile of satralizumab, with respect to efficacy and safety in the longer term,” said Dr. Kleiter.
Does satralizumab differ from other new agents?
The main strength of the study is that sufficient numbers of relapses were available for analysis in the active and control groups, said Achim Berthele, MD, associate professor of neurology at the Technical University of Munich. This allowed the researchers to examine whether satralizumab led to a better outcome after each relapse, which it did. “A weakness is how the severity of relapses was quantified,” said Dr. Berthele. “The EDSS as a measure is not linear, and its functional systems are not clinically equivalent. However, the whole NMOSD community is struggling with this problem.”
The study’s implications for neurologists’ clinical practice are unclear, however. “Although the results presented are encouraging, the data are still too small to say with certainty that satralizumab does indeed improve the outcome of relapses,” said Dr. Berthele. “It is also an open question whether satralizumab differs in this respect from the other new immunotherapeutic agents.”
Investigators must collect further data on the outcome of relapses that occur during treatment with modern immunomodulatory therapy, Dr. Berthele added. Future research could examine whether the new anti-inflammatory immunotherapeutic agents also are suitable drugs for relapse therapy. Another salient question is whether clinical vigilance or relapse therapy in NMOSD has improved in general. “This is what Kleiter and colleagues show as well: The number of severe relapses under placebo was much lower than expected,” said Dr. Berthele.
Chugai/Roche funded the study. Dr. Kleiter has received compensation for consulting, speaking, or serving on advisory boards for Alexion, Biogen, Celgene, Merck, and Roche. Dr. Berthele was not involved in any of the satralizumab trials, but is an investigator and coauthor of the PREVENT trial of eculizumab.
SOURCE: Kleiter I, et al. MSVirtual2020. Abstract FC01.03.
FROM MSVirtual2020
Cardiovascular risk factors linked to brain atrophy in MS
The presence of cardiovascular risk factors in patients with multiple sclerosis (MS) is associated with a greater degree of brain atrophy even in young patients who are unlikely to have small vessel disease, a new study has shown.
The results were presented by Raffaello Bonacchi, MD, Vita-Salute San Raffaele University, Milan, Italy, at at the Joint European Committee for Treatment and Research in Multiple Sclerosis–Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS–ACTRIMS) 2020, this year known as MSVirtual2020. .
“Our results suggest that even low levels of exposure to cardiovascular risk factors are important in MS and might affect brain atrophy—and therefore long-term disability—even in young patients,” Dr. Bonacchi said.
“It is not only smoking,” he added. “Other cardiovascular risk factors also appear to be implicated. We found a synergistic effect of the different risk factors.”
These are only preliminary data and need to be confirmed in other studies,” he said, “but it does suggest that MS neurologists need to pay attention to comprehensive care—not just MS disease activity.
“They also need to be discussing lifestyle with their patients, evaluating their cardiovascular risk factors, and giving advice on stopping smoking, lowering blood pressure, cholesterol, etc.”
Brain changes
Dr. Bonacchi explained that previous studies have suggested a relationship between cardiovascular risk factors and changes on magnetic resonance imaging (MRI) and clinical outcomes in patients with MS that may be mediated by small vessel disease and/or inflammation.
“Small vessel disease is widespread in the population over 50 years of age, but in this study we wanted to look at the impact of cardiovascular risk factors in younger patients with MS who are not likely to have much small vessel disease to try and see whether there is still a relationship with brain atrophy or white/gray matter lesions,” he said.
Previous studies have not set an age limit for examining this relationship and they have also assessed the presence versus absence of cardiovascular risk factors, without attempting to grade the strength of exposure, he noted.
For the current study, the researchers examined several cardiovascular risk factors and in addition to just being present or absent. They also graded each risk factor as being stringent or not depending on a certain threshold.
For example, smoking was defined as a threshold of 5 pack-years (smoking 5 cigarettes a day for 20 years or 20 cigarettes a day for 5 years). And the more stringent definition was 10 pack-years.
For hypertension, the stringent definition was consistently high blood pressure levels and use of antihypertensive medication, with similar definitions used for cholesterol and diabetes.
This was a cross-sectional observational study in 124 patients with MS and 95 healthy controls. The researchers examined MRI scans and neurological exams and investigated whether the amount of cardiovascular risk factors a patient was exposed to was associated with degree of brain atrophy and white matter/gray matter volume. Results were adjusted for age, sex, disease duration, phenotype (relapsing-remitting versus progressive MS) and treatment.
Results showed no significant difference if patients were exposed to at least one classical risk factor versus no risk factors. But if a patient had at least two classical risk factors, significant differences were found in gray matter, white matter, and total brain volume.
Patients with MS and no risk factors had a mean brain volume of 1524 mL versus 1481 mL in those with at least two risk factors, a difference that was significant (P = 0.003). Mean gray matter volume was 856 mL in MS patients without cardiovascular risk factors and 836 mL in those with at least two risk factors (P = 0.01) Mean white matter volume was 668 mL in MS patients without cardiovascular risk factors and 845 mL in those with at least two risk factors (P = 0.03).
“This is one of the first studies to have graded degrees of risk factors and we found one stringent risk factor was associated with the same effects on brain atrophy as two less stringent risk factors,” Dr. Bonacchi reported.
Healthy controls showed no differences in any of the brain volume outcomes in those with or without cardiovascular risk factors.
“As our population was under aged 50 years, who are unlikely to have much small vessel disease, our results suggest that the influence of cardiovascular risk factors on brain atrophy in MS is not just mediated through small vessel disease and is probably also mediated by increased inflammation,” Dr. Bonacchi suggested.
Impact of CV risk factors
Commenting on the study, Dalia Rotstein, MD, assistant professor, department of neurology, University of Toronto, Ontario, Canada, session cochair, said: “This is an interesting study that captures the impact of cardiovascular risk factors on various measures of brain atrophy in MS.”
The cohort was quite young, under age 50, and the effect on brain atrophy was increased with more severe cardiovascular risk factors, she noted.
“The investigators compared these effects to a population of healthy controls and did not observe as substantial an effect in controls. However, they were likely underpowered for the analysis in the healthy controls because of a relatively small number of subjects with cardiovascular risk factors in this group,” Dr. Rotstein noted.
“More research is needed to determine whether the observed relationship is unique to MS and whether treating cardiovascular risk factors may help protect against neurodegeneration in MS,” she added.
Dr. Bonacchi has reported no relevant financial relationships. Dr. Rotstein has reported acting as a consultant for Roche, Alexion, Novartis, EMD Serono, and Sanofi Aventis.
SOURCE: Bonacchi R. et al. MSVirtual2020. Session PS04.05.
This article originally appeared on Medscape.com .
The presence of cardiovascular risk factors in patients with multiple sclerosis (MS) is associated with a greater degree of brain atrophy even in young patients who are unlikely to have small vessel disease, a new study has shown.
The results were presented by Raffaello Bonacchi, MD, Vita-Salute San Raffaele University, Milan, Italy, at at the Joint European Committee for Treatment and Research in Multiple Sclerosis–Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS–ACTRIMS) 2020, this year known as MSVirtual2020. .
“Our results suggest that even low levels of exposure to cardiovascular risk factors are important in MS and might affect brain atrophy—and therefore long-term disability—even in young patients,” Dr. Bonacchi said.
“It is not only smoking,” he added. “Other cardiovascular risk factors also appear to be implicated. We found a synergistic effect of the different risk factors.”
These are only preliminary data and need to be confirmed in other studies,” he said, “but it does suggest that MS neurologists need to pay attention to comprehensive care—not just MS disease activity.
“They also need to be discussing lifestyle with their patients, evaluating their cardiovascular risk factors, and giving advice on stopping smoking, lowering blood pressure, cholesterol, etc.”
Brain changes
Dr. Bonacchi explained that previous studies have suggested a relationship between cardiovascular risk factors and changes on magnetic resonance imaging (MRI) and clinical outcomes in patients with MS that may be mediated by small vessel disease and/or inflammation.
“Small vessel disease is widespread in the population over 50 years of age, but in this study we wanted to look at the impact of cardiovascular risk factors in younger patients with MS who are not likely to have much small vessel disease to try and see whether there is still a relationship with brain atrophy or white/gray matter lesions,” he said.
Previous studies have not set an age limit for examining this relationship and they have also assessed the presence versus absence of cardiovascular risk factors, without attempting to grade the strength of exposure, he noted.
For the current study, the researchers examined several cardiovascular risk factors and in addition to just being present or absent. They also graded each risk factor as being stringent or not depending on a certain threshold.
For example, smoking was defined as a threshold of 5 pack-years (smoking 5 cigarettes a day for 20 years or 20 cigarettes a day for 5 years). And the more stringent definition was 10 pack-years.
For hypertension, the stringent definition was consistently high blood pressure levels and use of antihypertensive medication, with similar definitions used for cholesterol and diabetes.
This was a cross-sectional observational study in 124 patients with MS and 95 healthy controls. The researchers examined MRI scans and neurological exams and investigated whether the amount of cardiovascular risk factors a patient was exposed to was associated with degree of brain atrophy and white matter/gray matter volume. Results were adjusted for age, sex, disease duration, phenotype (relapsing-remitting versus progressive MS) and treatment.
Results showed no significant difference if patients were exposed to at least one classical risk factor versus no risk factors. But if a patient had at least two classical risk factors, significant differences were found in gray matter, white matter, and total brain volume.
Patients with MS and no risk factors had a mean brain volume of 1524 mL versus 1481 mL in those with at least two risk factors, a difference that was significant (P = 0.003). Mean gray matter volume was 856 mL in MS patients without cardiovascular risk factors and 836 mL in those with at least two risk factors (P = 0.01) Mean white matter volume was 668 mL in MS patients without cardiovascular risk factors and 845 mL in those with at least two risk factors (P = 0.03).
“This is one of the first studies to have graded degrees of risk factors and we found one stringent risk factor was associated with the same effects on brain atrophy as two less stringent risk factors,” Dr. Bonacchi reported.
Healthy controls showed no differences in any of the brain volume outcomes in those with or without cardiovascular risk factors.
“As our population was under aged 50 years, who are unlikely to have much small vessel disease, our results suggest that the influence of cardiovascular risk factors on brain atrophy in MS is not just mediated through small vessel disease and is probably also mediated by increased inflammation,” Dr. Bonacchi suggested.
Impact of CV risk factors
Commenting on the study, Dalia Rotstein, MD, assistant professor, department of neurology, University of Toronto, Ontario, Canada, session cochair, said: “This is an interesting study that captures the impact of cardiovascular risk factors on various measures of brain atrophy in MS.”
The cohort was quite young, under age 50, and the effect on brain atrophy was increased with more severe cardiovascular risk factors, she noted.
“The investigators compared these effects to a population of healthy controls and did not observe as substantial an effect in controls. However, they were likely underpowered for the analysis in the healthy controls because of a relatively small number of subjects with cardiovascular risk factors in this group,” Dr. Rotstein noted.
“More research is needed to determine whether the observed relationship is unique to MS and whether treating cardiovascular risk factors may help protect against neurodegeneration in MS,” she added.
Dr. Bonacchi has reported no relevant financial relationships. Dr. Rotstein has reported acting as a consultant for Roche, Alexion, Novartis, EMD Serono, and Sanofi Aventis.
SOURCE: Bonacchi R. et al. MSVirtual2020. Session PS04.05.
This article originally appeared on Medscape.com .
The presence of cardiovascular risk factors in patients with multiple sclerosis (MS) is associated with a greater degree of brain atrophy even in young patients who are unlikely to have small vessel disease, a new study has shown.
The results were presented by Raffaello Bonacchi, MD, Vita-Salute San Raffaele University, Milan, Italy, at at the Joint European Committee for Treatment and Research in Multiple Sclerosis–Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS–ACTRIMS) 2020, this year known as MSVirtual2020. .
“Our results suggest that even low levels of exposure to cardiovascular risk factors are important in MS and might affect brain atrophy—and therefore long-term disability—even in young patients,” Dr. Bonacchi said.
“It is not only smoking,” he added. “Other cardiovascular risk factors also appear to be implicated. We found a synergistic effect of the different risk factors.”
These are only preliminary data and need to be confirmed in other studies,” he said, “but it does suggest that MS neurologists need to pay attention to comprehensive care—not just MS disease activity.
“They also need to be discussing lifestyle with their patients, evaluating their cardiovascular risk factors, and giving advice on stopping smoking, lowering blood pressure, cholesterol, etc.”
Brain changes
Dr. Bonacchi explained that previous studies have suggested a relationship between cardiovascular risk factors and changes on magnetic resonance imaging (MRI) and clinical outcomes in patients with MS that may be mediated by small vessel disease and/or inflammation.
“Small vessel disease is widespread in the population over 50 years of age, but in this study we wanted to look at the impact of cardiovascular risk factors in younger patients with MS who are not likely to have much small vessel disease to try and see whether there is still a relationship with brain atrophy or white/gray matter lesions,” he said.
Previous studies have not set an age limit for examining this relationship and they have also assessed the presence versus absence of cardiovascular risk factors, without attempting to grade the strength of exposure, he noted.
For the current study, the researchers examined several cardiovascular risk factors and in addition to just being present or absent. They also graded each risk factor as being stringent or not depending on a certain threshold.
For example, smoking was defined as a threshold of 5 pack-years (smoking 5 cigarettes a day for 20 years or 20 cigarettes a day for 5 years). And the more stringent definition was 10 pack-years.
For hypertension, the stringent definition was consistently high blood pressure levels and use of antihypertensive medication, with similar definitions used for cholesterol and diabetes.
This was a cross-sectional observational study in 124 patients with MS and 95 healthy controls. The researchers examined MRI scans and neurological exams and investigated whether the amount of cardiovascular risk factors a patient was exposed to was associated with degree of brain atrophy and white matter/gray matter volume. Results were adjusted for age, sex, disease duration, phenotype (relapsing-remitting versus progressive MS) and treatment.
Results showed no significant difference if patients were exposed to at least one classical risk factor versus no risk factors. But if a patient had at least two classical risk factors, significant differences were found in gray matter, white matter, and total brain volume.
Patients with MS and no risk factors had a mean brain volume of 1524 mL versus 1481 mL in those with at least two risk factors, a difference that was significant (P = 0.003). Mean gray matter volume was 856 mL in MS patients without cardiovascular risk factors and 836 mL in those with at least two risk factors (P = 0.01) Mean white matter volume was 668 mL in MS patients without cardiovascular risk factors and 845 mL in those with at least two risk factors (P = 0.03).
“This is one of the first studies to have graded degrees of risk factors and we found one stringent risk factor was associated with the same effects on brain atrophy as two less stringent risk factors,” Dr. Bonacchi reported.
Healthy controls showed no differences in any of the brain volume outcomes in those with or without cardiovascular risk factors.
“As our population was under aged 50 years, who are unlikely to have much small vessel disease, our results suggest that the influence of cardiovascular risk factors on brain atrophy in MS is not just mediated through small vessel disease and is probably also mediated by increased inflammation,” Dr. Bonacchi suggested.
Impact of CV risk factors
Commenting on the study, Dalia Rotstein, MD, assistant professor, department of neurology, University of Toronto, Ontario, Canada, session cochair, said: “This is an interesting study that captures the impact of cardiovascular risk factors on various measures of brain atrophy in MS.”
The cohort was quite young, under age 50, and the effect on brain atrophy was increased with more severe cardiovascular risk factors, she noted.
“The investigators compared these effects to a population of healthy controls and did not observe as substantial an effect in controls. However, they were likely underpowered for the analysis in the healthy controls because of a relatively small number of subjects with cardiovascular risk factors in this group,” Dr. Rotstein noted.
“More research is needed to determine whether the observed relationship is unique to MS and whether treating cardiovascular risk factors may help protect against neurodegeneration in MS,” she added.
Dr. Bonacchi has reported no relevant financial relationships. Dr. Rotstein has reported acting as a consultant for Roche, Alexion, Novartis, EMD Serono, and Sanofi Aventis.
SOURCE: Bonacchi R. et al. MSVirtual2020. Session PS04.05.
This article originally appeared on Medscape.com .
FROM MSVirtual2020
Lessons for patients with MS and COVID-19
Two important lessons about managing patients with multiple sclerosis (MS) and COVID-19 have emerged from a hospital clinic in Madrid that managed COVID-infected patients with MS through the peak of the pandemic: Combined polymeric chain reaction and serology testing helped avoid disease reactivation in asymptomatic carriers during the pandemic peak, although after the peak PCR alone proved just as effective; and
Virginia Meca-Lallana, MD, a neurologist and coordinator of the demyelinating diseases unit at the Hospital of the University of the Princess in Madrid, and colleagues presented their findings in two posters at the Joint European Committee for Treatment and Research in Multiple Sclerosis-Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS-ACTRIMS) 2020, this year known as MSVirtual2020.
“MS treatments don’t seem to make the prognosis of COVID-19 worse, but it is very important to evaluate other risk factors,” Dr. Meca-Lallana said in an interview. “MS treatments prevent the patients’ disability, and it is very important not to stop them if it isn’t necessary.”
The results arose from a multidisciplinary safety protocol involving neurology, microbiology, and preventive medicine that the University of Princess physicians developed to keep MS stable in patients diagnosed with SARS-CoV-2.
The researchers obtained 152 PCR nasopharyngeal swabs and 140 serology tests in 90 patients with MS over 3 months before starting a variety of MS treatments: Natalizumab (96 tests), ocrelizumab (36), rituximab (3), methylprednisolone (7), cladribine (4), and dimethyl fumarate (3). The protocol identified 7 asymptomatic carriers—7.8% of the total population—5 of whom had positive immunoglobulin M and G serology. The study also confirmed 5 patients with positive IgM+IgG serology post-infection, but no COVID-19 reactivations were detected after implementation of the protocol.
“The safety protocol reached its objective of avoiding disease reactivation and clinical activation in asymptomatic carriers,” Dr. Meca-Lallana said.
The second poster she presented reported on the real-world experience with SARS-CoV-2 in the MS unit at her hospital. The observational, prospective study included 41 cases, 38 of which were relapsing-remitting MS and the remainder progressive MS. The patients had MS for an average of 9 years.
“We need more patients to draw more robust conclusions, but in our patients, MS treatments seem safe in this situation,” Dr. Meca-Lallana said. “We did not discontinue treatments, and after our first results, we only delayed treatments in patients with any additional comorbidity or when coming to the hospital was not safe.”
A total of 39 patients were taking disease-modifying therapies (DMTs): 46.3% with oral agents, 39% with monoclonal antibodies, and 10% with injectable agents; 27 patients were previously treated with other DMTs. The median Expanded Disability Status Scale (EDSS) was 2.5, and 11 patients had clinical activity the previous year. Eighteen cases were confirmed by PCR or serology, or both, and 23 were diagnosed clinically.
Among the patients with MS and COVID-19, 17% were admitted to the hospital. Six patients had pneumonia, but none required admission to the intensive care unit, and no deaths occurred. Three patients had other comorbidities. Admitted patients tended to be older and had higher EDSS scores, although the difference was not statistically significant. MS worsened in 7 patients, and 10 patients stopped or paused DMTs because of the infection.
“Multiple sclerosis is a weakening illness,” Dr. Meca-Lallana said. “MS treatments do not seem to make the prognosis of COVID-19 worse, but it is very important to evaluate other risk factors.”
The SARS-CoV-2 infection does not seem to result in a more aggressive form of the disease in MS patients, and selective immunosuppression may improve their outcomes, she noted.
“MS treatments avoid the patient’s disability,” the investigator added, “and it is very important not to stop them if it isn’t necessary.”
Dr. Meca-Lallana had no relevant financial disclosures.
Two important lessons about managing patients with multiple sclerosis (MS) and COVID-19 have emerged from a hospital clinic in Madrid that managed COVID-infected patients with MS through the peak of the pandemic: Combined polymeric chain reaction and serology testing helped avoid disease reactivation in asymptomatic carriers during the pandemic peak, although after the peak PCR alone proved just as effective; and
Virginia Meca-Lallana, MD, a neurologist and coordinator of the demyelinating diseases unit at the Hospital of the University of the Princess in Madrid, and colleagues presented their findings in two posters at the Joint European Committee for Treatment and Research in Multiple Sclerosis-Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS-ACTRIMS) 2020, this year known as MSVirtual2020.
“MS treatments don’t seem to make the prognosis of COVID-19 worse, but it is very important to evaluate other risk factors,” Dr. Meca-Lallana said in an interview. “MS treatments prevent the patients’ disability, and it is very important not to stop them if it isn’t necessary.”
The results arose from a multidisciplinary safety protocol involving neurology, microbiology, and preventive medicine that the University of Princess physicians developed to keep MS stable in patients diagnosed with SARS-CoV-2.
The researchers obtained 152 PCR nasopharyngeal swabs and 140 serology tests in 90 patients with MS over 3 months before starting a variety of MS treatments: Natalizumab (96 tests), ocrelizumab (36), rituximab (3), methylprednisolone (7), cladribine (4), and dimethyl fumarate (3). The protocol identified 7 asymptomatic carriers—7.8% of the total population—5 of whom had positive immunoglobulin M and G serology. The study also confirmed 5 patients with positive IgM+IgG serology post-infection, but no COVID-19 reactivations were detected after implementation of the protocol.
“The safety protocol reached its objective of avoiding disease reactivation and clinical activation in asymptomatic carriers,” Dr. Meca-Lallana said.
The second poster she presented reported on the real-world experience with SARS-CoV-2 in the MS unit at her hospital. The observational, prospective study included 41 cases, 38 of which were relapsing-remitting MS and the remainder progressive MS. The patients had MS for an average of 9 years.
“We need more patients to draw more robust conclusions, but in our patients, MS treatments seem safe in this situation,” Dr. Meca-Lallana said. “We did not discontinue treatments, and after our first results, we only delayed treatments in patients with any additional comorbidity or when coming to the hospital was not safe.”
A total of 39 patients were taking disease-modifying therapies (DMTs): 46.3% with oral agents, 39% with monoclonal antibodies, and 10% with injectable agents; 27 patients were previously treated with other DMTs. The median Expanded Disability Status Scale (EDSS) was 2.5, and 11 patients had clinical activity the previous year. Eighteen cases were confirmed by PCR or serology, or both, and 23 were diagnosed clinically.
Among the patients with MS and COVID-19, 17% were admitted to the hospital. Six patients had pneumonia, but none required admission to the intensive care unit, and no deaths occurred. Three patients had other comorbidities. Admitted patients tended to be older and had higher EDSS scores, although the difference was not statistically significant. MS worsened in 7 patients, and 10 patients stopped or paused DMTs because of the infection.
“Multiple sclerosis is a weakening illness,” Dr. Meca-Lallana said. “MS treatments do not seem to make the prognosis of COVID-19 worse, but it is very important to evaluate other risk factors.”
The SARS-CoV-2 infection does not seem to result in a more aggressive form of the disease in MS patients, and selective immunosuppression may improve their outcomes, she noted.
“MS treatments avoid the patient’s disability,” the investigator added, “and it is very important not to stop them if it isn’t necessary.”
Dr. Meca-Lallana had no relevant financial disclosures.
Two important lessons about managing patients with multiple sclerosis (MS) and COVID-19 have emerged from a hospital clinic in Madrid that managed COVID-infected patients with MS through the peak of the pandemic: Combined polymeric chain reaction and serology testing helped avoid disease reactivation in asymptomatic carriers during the pandemic peak, although after the peak PCR alone proved just as effective; and
Virginia Meca-Lallana, MD, a neurologist and coordinator of the demyelinating diseases unit at the Hospital of the University of the Princess in Madrid, and colleagues presented their findings in two posters at the Joint European Committee for Treatment and Research in Multiple Sclerosis-Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS-ACTRIMS) 2020, this year known as MSVirtual2020.
“MS treatments don’t seem to make the prognosis of COVID-19 worse, but it is very important to evaluate other risk factors,” Dr. Meca-Lallana said in an interview. “MS treatments prevent the patients’ disability, and it is very important not to stop them if it isn’t necessary.”
The results arose from a multidisciplinary safety protocol involving neurology, microbiology, and preventive medicine that the University of Princess physicians developed to keep MS stable in patients diagnosed with SARS-CoV-2.
The researchers obtained 152 PCR nasopharyngeal swabs and 140 serology tests in 90 patients with MS over 3 months before starting a variety of MS treatments: Natalizumab (96 tests), ocrelizumab (36), rituximab (3), methylprednisolone (7), cladribine (4), and dimethyl fumarate (3). The protocol identified 7 asymptomatic carriers—7.8% of the total population—5 of whom had positive immunoglobulin M and G serology. The study also confirmed 5 patients with positive IgM+IgG serology post-infection, but no COVID-19 reactivations were detected after implementation of the protocol.
“The safety protocol reached its objective of avoiding disease reactivation and clinical activation in asymptomatic carriers,” Dr. Meca-Lallana said.
The second poster she presented reported on the real-world experience with SARS-CoV-2 in the MS unit at her hospital. The observational, prospective study included 41 cases, 38 of which were relapsing-remitting MS and the remainder progressive MS. The patients had MS for an average of 9 years.
“We need more patients to draw more robust conclusions, but in our patients, MS treatments seem safe in this situation,” Dr. Meca-Lallana said. “We did not discontinue treatments, and after our first results, we only delayed treatments in patients with any additional comorbidity or when coming to the hospital was not safe.”
A total of 39 patients were taking disease-modifying therapies (DMTs): 46.3% with oral agents, 39% with monoclonal antibodies, and 10% with injectable agents; 27 patients were previously treated with other DMTs. The median Expanded Disability Status Scale (EDSS) was 2.5, and 11 patients had clinical activity the previous year. Eighteen cases were confirmed by PCR or serology, or both, and 23 were diagnosed clinically.
Among the patients with MS and COVID-19, 17% were admitted to the hospital. Six patients had pneumonia, but none required admission to the intensive care unit, and no deaths occurred. Three patients had other comorbidities. Admitted patients tended to be older and had higher EDSS scores, although the difference was not statistically significant. MS worsened in 7 patients, and 10 patients stopped or paused DMTs because of the infection.
“Multiple sclerosis is a weakening illness,” Dr. Meca-Lallana said. “MS treatments do not seem to make the prognosis of COVID-19 worse, but it is very important to evaluate other risk factors.”
The SARS-CoV-2 infection does not seem to result in a more aggressive form of the disease in MS patients, and selective immunosuppression may improve their outcomes, she noted.
“MS treatments avoid the patient’s disability,” the investigator added, “and it is very important not to stop them if it isn’t necessary.”
Dr. Meca-Lallana had no relevant financial disclosures.
FROM MSVirtual2020
Exposure to DMT may delay disability accumulation in primary progressive MS
Reducing the delay to treatment initiation, as well as treating younger patients, might improve long-term disability outcomes, according to a new study.
“To optimize treatment decision-making in primary progressive MS, further profiling of the best candidates for treatment is needed,” said the researchers. The study was presented at the Joint European Committee for Treatment and Research in Multiple Sclerosis–Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS–ACTRIMS) 2020, this year known as MSVirtual2020.
Ocrelizumab remains the only treatment available for patients with primary progressive MS. In clinical trials, other drugs have failed to reduce disability progression in this population. Mattia Fonderico, a doctoral student and research assistant at the University of Florence (Italy), and colleagues reviewed data from the Italian MS Registry to examine whether DMT affects the attainment of given disability outcomes.
Patients with longer exposure were younger at baseline
Patients eligible for inclusion in the study had primary progressive MS, at least three evaluations using the Expanded Disability Status Scale (EDSS), and 3 years’ follow-up. The investigators defined the baseline for untreated patients as the first EDSS evaluation. For treated patients, the baseline was the date of DMT initiation.
Using multivariable Cox regression models, Ms. Fonderico and colleagues examined the effect of DMT on the risk of reaching EDSS scores of 6 (i.e., requirement for intermittent or unilateral constant walking assistance) and 7 (i.e., restriction to a wheelchair) as a dichotomous variable and as a time-dependent covariate. The researchers adjusted the data for age at baseline, sex, first EDSS score, symptoms at onset, annualized visit rate, and annualized relapse rate. They compared outcomes with an as-treated analysis and chose cohorts with similar baseline characteristics using propensity-score matching. In addition, Ms. Fonderico and colleagues also analyzed quartiles of DMT exposure.
The investigators included 1,214 patients (671 women) in their analysis. The population’s mean age at baseline was 48.7 years, and its mean EDSS score was 4.1. A total of 626 patients (52%) received DMT during follow-up. Approximately 57% of DMTs were platform therapies, and 43% were high-efficacy therapies.
Mean follow-up duration was 11.6 years. By the end of follow-up, 994 patients (82%) reached an EDSS score of 6, and 539 (44%) reached an EDSS score of 7. Multivariable Cox regression models indicated that DMT, analyzed as a dichotomous variable, did not affect the risk of reaching EDSS 6 (adjusted hazard ratio, 1.1) or EDSS 7 (aHR, 0.93). Longer DMT exposure, however, significantly reduced the risk of reaching EDSS 7 (aHR, 0.73).
Compared with patients with shorter exposure to DMT, patients in the highest quartile of DMT exposure were younger at baseline (mean age, 44.1 years) and initiated DMT closer to disease onset (mean time to DMT initiation was 6.8 years). The propensity score matching analysis confirmed these findings.
The investigators did not consider MRI variables, which Ms. Fonderico acknowledged was a weakness of the study. In addition, they did not analyze the effect of superimposed relapses.
A new perspective on primary progressive MS?
These results suggest that primary progressive MS behaves like relapsing-remitting MS, said Gavin Giovannoni, MD, PhD, chair of neurology at Queen Mary University of London. That is, they suggest that primary progressive MS “is modifiable by a DMT and that the earlier you treat, the better the outcome.” The results also indicate that neurologists commonly prescribe DMT off label in Italy, he added.
A weakness of the study is that it was not randomized. Furthermore, “EDSS [evaluations] tend not be done properly in routine clinical practice,” said Dr. Giovannoni. Still, the study raises an important question for future research. “Why have we missed the treatment effect in previous trials?” asked Dr. Giovannoni. Whether previous trials were too short or underpowered could be investigated, he added.
Study funding was not reported. Ms. Fonderico had no relevant disclosures. Dr. Giovannoni had no relevant disclosures.
Reducing the delay to treatment initiation, as well as treating younger patients, might improve long-term disability outcomes, according to a new study.
“To optimize treatment decision-making in primary progressive MS, further profiling of the best candidates for treatment is needed,” said the researchers. The study was presented at the Joint European Committee for Treatment and Research in Multiple Sclerosis–Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS–ACTRIMS) 2020, this year known as MSVirtual2020.
Ocrelizumab remains the only treatment available for patients with primary progressive MS. In clinical trials, other drugs have failed to reduce disability progression in this population. Mattia Fonderico, a doctoral student and research assistant at the University of Florence (Italy), and colleagues reviewed data from the Italian MS Registry to examine whether DMT affects the attainment of given disability outcomes.
Patients with longer exposure were younger at baseline
Patients eligible for inclusion in the study had primary progressive MS, at least three evaluations using the Expanded Disability Status Scale (EDSS), and 3 years’ follow-up. The investigators defined the baseline for untreated patients as the first EDSS evaluation. For treated patients, the baseline was the date of DMT initiation.
Using multivariable Cox regression models, Ms. Fonderico and colleagues examined the effect of DMT on the risk of reaching EDSS scores of 6 (i.e., requirement for intermittent or unilateral constant walking assistance) and 7 (i.e., restriction to a wheelchair) as a dichotomous variable and as a time-dependent covariate. The researchers adjusted the data for age at baseline, sex, first EDSS score, symptoms at onset, annualized visit rate, and annualized relapse rate. They compared outcomes with an as-treated analysis and chose cohorts with similar baseline characteristics using propensity-score matching. In addition, Ms. Fonderico and colleagues also analyzed quartiles of DMT exposure.
The investigators included 1,214 patients (671 women) in their analysis. The population’s mean age at baseline was 48.7 years, and its mean EDSS score was 4.1. A total of 626 patients (52%) received DMT during follow-up. Approximately 57% of DMTs were platform therapies, and 43% were high-efficacy therapies.
Mean follow-up duration was 11.6 years. By the end of follow-up, 994 patients (82%) reached an EDSS score of 6, and 539 (44%) reached an EDSS score of 7. Multivariable Cox regression models indicated that DMT, analyzed as a dichotomous variable, did not affect the risk of reaching EDSS 6 (adjusted hazard ratio, 1.1) or EDSS 7 (aHR, 0.93). Longer DMT exposure, however, significantly reduced the risk of reaching EDSS 7 (aHR, 0.73).
Compared with patients with shorter exposure to DMT, patients in the highest quartile of DMT exposure were younger at baseline (mean age, 44.1 years) and initiated DMT closer to disease onset (mean time to DMT initiation was 6.8 years). The propensity score matching analysis confirmed these findings.
The investigators did not consider MRI variables, which Ms. Fonderico acknowledged was a weakness of the study. In addition, they did not analyze the effect of superimposed relapses.
A new perspective on primary progressive MS?
These results suggest that primary progressive MS behaves like relapsing-remitting MS, said Gavin Giovannoni, MD, PhD, chair of neurology at Queen Mary University of London. That is, they suggest that primary progressive MS “is modifiable by a DMT and that the earlier you treat, the better the outcome.” The results also indicate that neurologists commonly prescribe DMT off label in Italy, he added.
A weakness of the study is that it was not randomized. Furthermore, “EDSS [evaluations] tend not be done properly in routine clinical practice,” said Dr. Giovannoni. Still, the study raises an important question for future research. “Why have we missed the treatment effect in previous trials?” asked Dr. Giovannoni. Whether previous trials were too short or underpowered could be investigated, he added.
Study funding was not reported. Ms. Fonderico had no relevant disclosures. Dr. Giovannoni had no relevant disclosures.
Reducing the delay to treatment initiation, as well as treating younger patients, might improve long-term disability outcomes, according to a new study.
“To optimize treatment decision-making in primary progressive MS, further profiling of the best candidates for treatment is needed,” said the researchers. The study was presented at the Joint European Committee for Treatment and Research in Multiple Sclerosis–Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS–ACTRIMS) 2020, this year known as MSVirtual2020.
Ocrelizumab remains the only treatment available for patients with primary progressive MS. In clinical trials, other drugs have failed to reduce disability progression in this population. Mattia Fonderico, a doctoral student and research assistant at the University of Florence (Italy), and colleagues reviewed data from the Italian MS Registry to examine whether DMT affects the attainment of given disability outcomes.
Patients with longer exposure were younger at baseline
Patients eligible for inclusion in the study had primary progressive MS, at least three evaluations using the Expanded Disability Status Scale (EDSS), and 3 years’ follow-up. The investigators defined the baseline for untreated patients as the first EDSS evaluation. For treated patients, the baseline was the date of DMT initiation.
Using multivariable Cox regression models, Ms. Fonderico and colleagues examined the effect of DMT on the risk of reaching EDSS scores of 6 (i.e., requirement for intermittent or unilateral constant walking assistance) and 7 (i.e., restriction to a wheelchair) as a dichotomous variable and as a time-dependent covariate. The researchers adjusted the data for age at baseline, sex, first EDSS score, symptoms at onset, annualized visit rate, and annualized relapse rate. They compared outcomes with an as-treated analysis and chose cohorts with similar baseline characteristics using propensity-score matching. In addition, Ms. Fonderico and colleagues also analyzed quartiles of DMT exposure.
The investigators included 1,214 patients (671 women) in their analysis. The population’s mean age at baseline was 48.7 years, and its mean EDSS score was 4.1. A total of 626 patients (52%) received DMT during follow-up. Approximately 57% of DMTs were platform therapies, and 43% were high-efficacy therapies.
Mean follow-up duration was 11.6 years. By the end of follow-up, 994 patients (82%) reached an EDSS score of 6, and 539 (44%) reached an EDSS score of 7. Multivariable Cox regression models indicated that DMT, analyzed as a dichotomous variable, did not affect the risk of reaching EDSS 6 (adjusted hazard ratio, 1.1) or EDSS 7 (aHR, 0.93). Longer DMT exposure, however, significantly reduced the risk of reaching EDSS 7 (aHR, 0.73).
Compared with patients with shorter exposure to DMT, patients in the highest quartile of DMT exposure were younger at baseline (mean age, 44.1 years) and initiated DMT closer to disease onset (mean time to DMT initiation was 6.8 years). The propensity score matching analysis confirmed these findings.
The investigators did not consider MRI variables, which Ms. Fonderico acknowledged was a weakness of the study. In addition, they did not analyze the effect of superimposed relapses.
A new perspective on primary progressive MS?
These results suggest that primary progressive MS behaves like relapsing-remitting MS, said Gavin Giovannoni, MD, PhD, chair of neurology at Queen Mary University of London. That is, they suggest that primary progressive MS “is modifiable by a DMT and that the earlier you treat, the better the outcome.” The results also indicate that neurologists commonly prescribe DMT off label in Italy, he added.
A weakness of the study is that it was not randomized. Furthermore, “EDSS [evaluations] tend not be done properly in routine clinical practice,” said Dr. Giovannoni. Still, the study raises an important question for future research. “Why have we missed the treatment effect in previous trials?” asked Dr. Giovannoni. Whether previous trials were too short or underpowered could be investigated, he added.
Study funding was not reported. Ms. Fonderico had no relevant disclosures. Dr. Giovannoni had no relevant disclosures.
FROM MSVirtual 2020
In MS, serious adverse effects are more common in rituximab versus ocrelizumab
, a new postmarketing analysis finds, and AE-related deaths were not unusual. Serious AEs, and those linked to death, were more common in the rituximab group, although the reported infection rate was higher in the ocrelizumab group.
The analysis, published Aug. 21 in the Multiple Sclerosis Journal, highlights the importance of monitoring patients for infections and encouraging them to do the same, the authors said.
“This report points out the impact of treatments in terms of unrecognized or underappreciated complications,” said Mark Gudesblatt, MD, medical director of the Comprehensive MS Care Center at South Shore Neurologic Associates in Patchogue, N.Y., who reviewed the study findings. “These medications have a significant downside.”
Lead author Natalia Gonzalez Caldito, MD, of the University of Texas Southwestern Medical Center, Dallas, and colleagues analyzed AEs for the drugs in the Food and Drug Administration’s Adverse Event Reporting System. They only included cases in which the drugs were solely used to treat MS and were indicated as the cause of the AEs.
Rituximab (Rituxan) and ocrelizumab (Ocrevus) are both monoclonal antibodies. Rituximab is not FDA approved for MS but is used off label; ocrelizumab is approved for the relapsing forms of MS and primary progressive MS.
The researchers found 623 AE reports and 1,466 total AEs for rituximab and 7,948 and 23,613, respectively, for ocrelizumab. The average ages for the groups were 48.76 versus 43.89, respectively, (P < .001), and 71% in each group were women.
Among total AEs, serious AEs were more common in the rituximab group versus the ocrelizumab group (64.8% vs. 56.3%, respectively, P < .001). Adverse events that caused death were also more common in the rituximab group versus the ocrelizumab group (5.75% vs. 2.11%, P < .001).
Infections and infestations were more common in the ocrelizumab group than the rituximab group (21.93% vs. 11.05%, respectively, P < .001). However, certain AEs were more common in the rituximab group than the ocrelizumab group: Those in the blood and lymphatic system category (2.86% vs. 0.91%, respectively, P < .001), and those in the neoplasms category (4.02% vs. 1.28%, P < .001, respectively).
Researchers found a highly strong association between rituximab and a rare side effects – ear pruritus (itching, 0.8%). They also identified signals for infusion-related reaction (4.82%), throat irritation (4.01%) and throat tightness (1.44%), malignant melanoma (0.8%), breast cancer (1.77%) and neutropenia (2.57%).
Among the ocrelizumab AEs, researchers found the strongest association with oral herpes (2.21%), and they found other signals for herpes zoster (2.89%), urinary tract infection (10.52%), nasopharyngitis (9.79%), infusion-related reaction (4.76%), throat irritation (3.08%), and notably MS relapses (4.1%).
“Additional pharmacovigilance studies are needed to explore and further characterize these findings,” the researchers wrote. “Furthermore, these observations suggest that the AE profile of other second-generation anti-CD20 [monoclonal antibodies] may also differ from those of rituximab and ocrelizumab.”
Dr. Gudesblatt praised the analysis and said the findings make sense. “Use of B-cell–depleting agents lead to accumulative immune deficiency in routine care, which leads to higher rates of infection,” he said. He added that, “in the clinical trials for ocrelizumab, patients with IgG and IgM deficiency were excluded, but there is no advisement to exclude such patients in real care. The rates of infection in those patients with MS who have preexisting immune deficiencies and who are treated with these agents are unknown.”
The prospect of AEs is especially worrisome, he said, since “this information is only short term. Who knows what effect the prolonged use of unopposed B-cell depletion will have on infections in the long run?”
Neurologist Mitchell Wallin, MD, MPH, of George Washington University, Washington, and the University of Maryland, Baltimore County, said in an interview that the analysis is rigorous and especially useful because it includes a wider array of subjects – including those who are older and sicker – than took part in earlier clinical trials. “It’s really important to look at this real-world evidence,” he said, “and basically put this in the back of your head when you follow up with your patients.”
No study funding was reported. The corresponding author reported various disclosures. Dr. Gudesblatt and Dr. Wallin reported no disclosures.
SOURCE: Gonzalez Caldito N et al. Mult Scler J. 2020 Aug 21. doi: 10.1177/1352458520949986.
, a new postmarketing analysis finds, and AE-related deaths were not unusual. Serious AEs, and those linked to death, were more common in the rituximab group, although the reported infection rate was higher in the ocrelizumab group.
The analysis, published Aug. 21 in the Multiple Sclerosis Journal, highlights the importance of monitoring patients for infections and encouraging them to do the same, the authors said.
“This report points out the impact of treatments in terms of unrecognized or underappreciated complications,” said Mark Gudesblatt, MD, medical director of the Comprehensive MS Care Center at South Shore Neurologic Associates in Patchogue, N.Y., who reviewed the study findings. “These medications have a significant downside.”
Lead author Natalia Gonzalez Caldito, MD, of the University of Texas Southwestern Medical Center, Dallas, and colleagues analyzed AEs for the drugs in the Food and Drug Administration’s Adverse Event Reporting System. They only included cases in which the drugs were solely used to treat MS and were indicated as the cause of the AEs.
Rituximab (Rituxan) and ocrelizumab (Ocrevus) are both monoclonal antibodies. Rituximab is not FDA approved for MS but is used off label; ocrelizumab is approved for the relapsing forms of MS and primary progressive MS.
The researchers found 623 AE reports and 1,466 total AEs for rituximab and 7,948 and 23,613, respectively, for ocrelizumab. The average ages for the groups were 48.76 versus 43.89, respectively, (P < .001), and 71% in each group were women.
Among total AEs, serious AEs were more common in the rituximab group versus the ocrelizumab group (64.8% vs. 56.3%, respectively, P < .001). Adverse events that caused death were also more common in the rituximab group versus the ocrelizumab group (5.75% vs. 2.11%, P < .001).
Infections and infestations were more common in the ocrelizumab group than the rituximab group (21.93% vs. 11.05%, respectively, P < .001). However, certain AEs were more common in the rituximab group than the ocrelizumab group: Those in the blood and lymphatic system category (2.86% vs. 0.91%, respectively, P < .001), and those in the neoplasms category (4.02% vs. 1.28%, P < .001, respectively).
Researchers found a highly strong association between rituximab and a rare side effects – ear pruritus (itching, 0.8%). They also identified signals for infusion-related reaction (4.82%), throat irritation (4.01%) and throat tightness (1.44%), malignant melanoma (0.8%), breast cancer (1.77%) and neutropenia (2.57%).
Among the ocrelizumab AEs, researchers found the strongest association with oral herpes (2.21%), and they found other signals for herpes zoster (2.89%), urinary tract infection (10.52%), nasopharyngitis (9.79%), infusion-related reaction (4.76%), throat irritation (3.08%), and notably MS relapses (4.1%).
“Additional pharmacovigilance studies are needed to explore and further characterize these findings,” the researchers wrote. “Furthermore, these observations suggest that the AE profile of other second-generation anti-CD20 [monoclonal antibodies] may also differ from those of rituximab and ocrelizumab.”
Dr. Gudesblatt praised the analysis and said the findings make sense. “Use of B-cell–depleting agents lead to accumulative immune deficiency in routine care, which leads to higher rates of infection,” he said. He added that, “in the clinical trials for ocrelizumab, patients with IgG and IgM deficiency were excluded, but there is no advisement to exclude such patients in real care. The rates of infection in those patients with MS who have preexisting immune deficiencies and who are treated with these agents are unknown.”
The prospect of AEs is especially worrisome, he said, since “this information is only short term. Who knows what effect the prolonged use of unopposed B-cell depletion will have on infections in the long run?”
Neurologist Mitchell Wallin, MD, MPH, of George Washington University, Washington, and the University of Maryland, Baltimore County, said in an interview that the analysis is rigorous and especially useful because it includes a wider array of subjects – including those who are older and sicker – than took part in earlier clinical trials. “It’s really important to look at this real-world evidence,” he said, “and basically put this in the back of your head when you follow up with your patients.”
No study funding was reported. The corresponding author reported various disclosures. Dr. Gudesblatt and Dr. Wallin reported no disclosures.
SOURCE: Gonzalez Caldito N et al. Mult Scler J. 2020 Aug 21. doi: 10.1177/1352458520949986.
, a new postmarketing analysis finds, and AE-related deaths were not unusual. Serious AEs, and those linked to death, were more common in the rituximab group, although the reported infection rate was higher in the ocrelizumab group.
The analysis, published Aug. 21 in the Multiple Sclerosis Journal, highlights the importance of monitoring patients for infections and encouraging them to do the same, the authors said.
“This report points out the impact of treatments in terms of unrecognized or underappreciated complications,” said Mark Gudesblatt, MD, medical director of the Comprehensive MS Care Center at South Shore Neurologic Associates in Patchogue, N.Y., who reviewed the study findings. “These medications have a significant downside.”
Lead author Natalia Gonzalez Caldito, MD, of the University of Texas Southwestern Medical Center, Dallas, and colleagues analyzed AEs for the drugs in the Food and Drug Administration’s Adverse Event Reporting System. They only included cases in which the drugs were solely used to treat MS and were indicated as the cause of the AEs.
Rituximab (Rituxan) and ocrelizumab (Ocrevus) are both monoclonal antibodies. Rituximab is not FDA approved for MS but is used off label; ocrelizumab is approved for the relapsing forms of MS and primary progressive MS.
The researchers found 623 AE reports and 1,466 total AEs for rituximab and 7,948 and 23,613, respectively, for ocrelizumab. The average ages for the groups were 48.76 versus 43.89, respectively, (P < .001), and 71% in each group were women.
Among total AEs, serious AEs were more common in the rituximab group versus the ocrelizumab group (64.8% vs. 56.3%, respectively, P < .001). Adverse events that caused death were also more common in the rituximab group versus the ocrelizumab group (5.75% vs. 2.11%, P < .001).
Infections and infestations were more common in the ocrelizumab group than the rituximab group (21.93% vs. 11.05%, respectively, P < .001). However, certain AEs were more common in the rituximab group than the ocrelizumab group: Those in the blood and lymphatic system category (2.86% vs. 0.91%, respectively, P < .001), and those in the neoplasms category (4.02% vs. 1.28%, P < .001, respectively).
Researchers found a highly strong association between rituximab and a rare side effects – ear pruritus (itching, 0.8%). They also identified signals for infusion-related reaction (4.82%), throat irritation (4.01%) and throat tightness (1.44%), malignant melanoma (0.8%), breast cancer (1.77%) and neutropenia (2.57%).
Among the ocrelizumab AEs, researchers found the strongest association with oral herpes (2.21%), and they found other signals for herpes zoster (2.89%), urinary tract infection (10.52%), nasopharyngitis (9.79%), infusion-related reaction (4.76%), throat irritation (3.08%), and notably MS relapses (4.1%).
“Additional pharmacovigilance studies are needed to explore and further characterize these findings,” the researchers wrote. “Furthermore, these observations suggest that the AE profile of other second-generation anti-CD20 [monoclonal antibodies] may also differ from those of rituximab and ocrelizumab.”
Dr. Gudesblatt praised the analysis and said the findings make sense. “Use of B-cell–depleting agents lead to accumulative immune deficiency in routine care, which leads to higher rates of infection,” he said. He added that, “in the clinical trials for ocrelizumab, patients with IgG and IgM deficiency were excluded, but there is no advisement to exclude such patients in real care. The rates of infection in those patients with MS who have preexisting immune deficiencies and who are treated with these agents are unknown.”
The prospect of AEs is especially worrisome, he said, since “this information is only short term. Who knows what effect the prolonged use of unopposed B-cell depletion will have on infections in the long run?”
Neurologist Mitchell Wallin, MD, MPH, of George Washington University, Washington, and the University of Maryland, Baltimore County, said in an interview that the analysis is rigorous and especially useful because it includes a wider array of subjects – including those who are older and sicker – than took part in earlier clinical trials. “It’s really important to look at this real-world evidence,” he said, “and basically put this in the back of your head when you follow up with your patients.”
No study funding was reported. The corresponding author reported various disclosures. Dr. Gudesblatt and Dr. Wallin reported no disclosures.
SOURCE: Gonzalez Caldito N et al. Mult Scler J. 2020 Aug 21. doi: 10.1177/1352458520949986.
FROM MULTIPLE SCLEROSIS JOURNAL
Smoking increases risk of high plasma NfL levels in patients with MS
A new study has found that At the same time, patients who have stopped smoking have notably lower risk that correlates to how long ago they quit.
“Before, all the studies that were looking at the association between smoking and MS – especially in terms of severity – were using indications like the Expanded Disability Status Scale and the Multiple Sclerosis Severity Score,” said first author Ali Manouchehrinia, PhD, assistant professor at the Karolinska Institute, Stockholm. “Now, we have NfL as a biomarker for disease activity, and we can see the effect of smoking on that biomarker.”
The ultimate goal, he added, “is to tease out the effects of MS severity and disease activity from NfL, to make sure that changes or differences in NfL levels are truly caused by MS and nothing else.”
Dr. Manouchehrinia presented his team’s findings at the virtual annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.
To determine any associations between smoking and pNfL levels, the researchers began a retrospective, population-based cohort study of 2,572 Swedish MS patients with a self-reported history of cigarette smoking. Their average age was 38.2 years, slightly more than 71% were women, and their average disease duration was 4.13 years.
Blood samples were collected at each patients’ time of diagnosis to analyze concentrations of pNfL. Three age-stratified pNfL levels were classified: above the 80th (>C80), 95th (>C95), and 99th (>C99) of 1,026 non-MS controls’ percentiles.
Of the 2,572 MS patients, 292 (11.4%) were current regular smokers and 714 (27.8%) were past regular smokers. The past smokers’ median time since quitting was 2 years. Being a current smoker was associated with much higher odds of having pNfL levels at >C99, compared with never smokers (odds ratio, 1.52; 95% confidence interval, 1.12-2.05; P = .007) and past smokers (OR, 1.42; 95% CI, 1.01-1.99; P = .043).
For past smokers who quit between 6 and 10 years ago, the risk of having pNfL levels at >C99 was considerably lower (OR, 0.53; 95% CI, 0.29-0.93; P = .032), compared with current smokers, as was the risk for past smokers who quit more than 10 years ago (OR, 0.50; 95% CI, 0.29-0.84; P = .010). The odds were also lower, though not significantly, for patients who quit 1-5 years ago (OR, 0.84; 95% CI, 0.58-1.22; P = .359).
“It looks like, after 10 years, you go back to the baseline and have the same risk as the never smokers,” Dr. Manouchehrinia said. “But the damage may have already been done. Quitting smoking is good, but it’s better to not smoke at all.”
Dr. Manouchehrinia acknowledged the study’s limitations, including the need to learn more about the role NfL levels – especially plasma NfL levels – play across MS patients, along with the complications surrounding smoking as an environmental factor. He noted that, in Sweden, many people get their nicotine from snuff rather than cigarettes. “Among our MS population, we’ve seen a recent shift toward female snuff users,” which lessens the amount they smoke and could confound the results. In fact, the study indicated that snuff users had less risk of pNfL levels at >C95, compared with nonsnuff users (OR, 0.71; 95% CI, 0.51-0.97; P = .034).
The authors reported several potential conflicts of interest, including receiving research grants and lecture honoraria and serving on advisory boards for various pharmaceutical companies.
A new study has found that At the same time, patients who have stopped smoking have notably lower risk that correlates to how long ago they quit.
“Before, all the studies that were looking at the association between smoking and MS – especially in terms of severity – were using indications like the Expanded Disability Status Scale and the Multiple Sclerosis Severity Score,” said first author Ali Manouchehrinia, PhD, assistant professor at the Karolinska Institute, Stockholm. “Now, we have NfL as a biomarker for disease activity, and we can see the effect of smoking on that biomarker.”
The ultimate goal, he added, “is to tease out the effects of MS severity and disease activity from NfL, to make sure that changes or differences in NfL levels are truly caused by MS and nothing else.”
Dr. Manouchehrinia presented his team’s findings at the virtual annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.
To determine any associations between smoking and pNfL levels, the researchers began a retrospective, population-based cohort study of 2,572 Swedish MS patients with a self-reported history of cigarette smoking. Their average age was 38.2 years, slightly more than 71% were women, and their average disease duration was 4.13 years.
Blood samples were collected at each patients’ time of diagnosis to analyze concentrations of pNfL. Three age-stratified pNfL levels were classified: above the 80th (>C80), 95th (>C95), and 99th (>C99) of 1,026 non-MS controls’ percentiles.
Of the 2,572 MS patients, 292 (11.4%) were current regular smokers and 714 (27.8%) were past regular smokers. The past smokers’ median time since quitting was 2 years. Being a current smoker was associated with much higher odds of having pNfL levels at >C99, compared with never smokers (odds ratio, 1.52; 95% confidence interval, 1.12-2.05; P = .007) and past smokers (OR, 1.42; 95% CI, 1.01-1.99; P = .043).
For past smokers who quit between 6 and 10 years ago, the risk of having pNfL levels at >C99 was considerably lower (OR, 0.53; 95% CI, 0.29-0.93; P = .032), compared with current smokers, as was the risk for past smokers who quit more than 10 years ago (OR, 0.50; 95% CI, 0.29-0.84; P = .010). The odds were also lower, though not significantly, for patients who quit 1-5 years ago (OR, 0.84; 95% CI, 0.58-1.22; P = .359).
“It looks like, after 10 years, you go back to the baseline and have the same risk as the never smokers,” Dr. Manouchehrinia said. “But the damage may have already been done. Quitting smoking is good, but it’s better to not smoke at all.”
Dr. Manouchehrinia acknowledged the study’s limitations, including the need to learn more about the role NfL levels – especially plasma NfL levels – play across MS patients, along with the complications surrounding smoking as an environmental factor. He noted that, in Sweden, many people get their nicotine from snuff rather than cigarettes. “Among our MS population, we’ve seen a recent shift toward female snuff users,” which lessens the amount they smoke and could confound the results. In fact, the study indicated that snuff users had less risk of pNfL levels at >C95, compared with nonsnuff users (OR, 0.71; 95% CI, 0.51-0.97; P = .034).
The authors reported several potential conflicts of interest, including receiving research grants and lecture honoraria and serving on advisory boards for various pharmaceutical companies.
A new study has found that At the same time, patients who have stopped smoking have notably lower risk that correlates to how long ago they quit.
“Before, all the studies that were looking at the association between smoking and MS – especially in terms of severity – were using indications like the Expanded Disability Status Scale and the Multiple Sclerosis Severity Score,” said first author Ali Manouchehrinia, PhD, assistant professor at the Karolinska Institute, Stockholm. “Now, we have NfL as a biomarker for disease activity, and we can see the effect of smoking on that biomarker.”
The ultimate goal, he added, “is to tease out the effects of MS severity and disease activity from NfL, to make sure that changes or differences in NfL levels are truly caused by MS and nothing else.”
Dr. Manouchehrinia presented his team’s findings at the virtual annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.
To determine any associations between smoking and pNfL levels, the researchers began a retrospective, population-based cohort study of 2,572 Swedish MS patients with a self-reported history of cigarette smoking. Their average age was 38.2 years, slightly more than 71% were women, and their average disease duration was 4.13 years.
Blood samples were collected at each patients’ time of diagnosis to analyze concentrations of pNfL. Three age-stratified pNfL levels were classified: above the 80th (>C80), 95th (>C95), and 99th (>C99) of 1,026 non-MS controls’ percentiles.
Of the 2,572 MS patients, 292 (11.4%) were current regular smokers and 714 (27.8%) were past regular smokers. The past smokers’ median time since quitting was 2 years. Being a current smoker was associated with much higher odds of having pNfL levels at >C99, compared with never smokers (odds ratio, 1.52; 95% confidence interval, 1.12-2.05; P = .007) and past smokers (OR, 1.42; 95% CI, 1.01-1.99; P = .043).
For past smokers who quit between 6 and 10 years ago, the risk of having pNfL levels at >C99 was considerably lower (OR, 0.53; 95% CI, 0.29-0.93; P = .032), compared with current smokers, as was the risk for past smokers who quit more than 10 years ago (OR, 0.50; 95% CI, 0.29-0.84; P = .010). The odds were also lower, though not significantly, for patients who quit 1-5 years ago (OR, 0.84; 95% CI, 0.58-1.22; P = .359).
“It looks like, after 10 years, you go back to the baseline and have the same risk as the never smokers,” Dr. Manouchehrinia said. “But the damage may have already been done. Quitting smoking is good, but it’s better to not smoke at all.”
Dr. Manouchehrinia acknowledged the study’s limitations, including the need to learn more about the role NfL levels – especially plasma NfL levels – play across MS patients, along with the complications surrounding smoking as an environmental factor. He noted that, in Sweden, many people get their nicotine from snuff rather than cigarettes. “Among our MS population, we’ve seen a recent shift toward female snuff users,” which lessens the amount they smoke and could confound the results. In fact, the study indicated that snuff users had less risk of pNfL levels at >C95, compared with nonsnuff users (OR, 0.71; 95% CI, 0.51-0.97; P = .034).
The authors reported several potential conflicts of interest, including receiving research grants and lecture honoraria and serving on advisory boards for various pharmaceutical companies.
FROM ECTRIMS 2020
Lowering rituximab dose in patients with MS proves safe and effective
“Given its favorable cost-effectiveness profile, [rituximab] remains a valuable treatment option in the current landscape of MS treatments, even at the reduced dose,” wrote Giulio Disanto, MD, PhD, of the Neurocenter of Southern Switzerland in Lugano, and coauthors. The study was published in Multiple Sclerosis Journal.
To determine the clinical and radiologic effectiveness of deescalating rituximab dosage – along with assessing any adverse outcomes – this observational, single-center study examined 59 patients with MS who had been treated with rituximab at 1,000 mg for at least 1 year before the study began. Roughly 63% (n = 37) of the patients had relapsing remitting MS (RRMS), while the rest (n = 22) had secondary progressive disease (SPD). Their median age was 51, and nearly 75% were women.
All patients underwent neurologic examinations at baseline and then every 3 months for 1 year, with new symptoms, infections, or adverse events being assessed via the Expanded Disability Status Scale (EDSS). They also underwent brain and spinal MRI at baseline and at 12 months while blood samples were taken at baseline and then every 3 months for 1 year, with previous data for both collected when available.
Study results
All 59 patients completed 12-month follow-up, and no relapses occurred in the year after lowering rituximab dosage to 500 mg. No significant differences were observed when comparing EDSS scores at the start of the 1,000-mg dose with the start of the 500-mg dose (Wilcoxon P = .131) as well as from the start of the 500-mg dose to the end of follow-up (Wilcoxon P = .284). Analyzing RRMS and SPD patients separately also led to no differences in EDSS scores from the start of the 500-mg dose to the end of follow-up (Wilcoxon P = .531; Wilcoxon P = .408).
During the 1,000-mg treatment period the number of patients who developed at least one new T2 lesion on their brain or spine was 9 and 4, respectively. During the 500-mg period, just one patient developed a new T2 brain lesion and two patients developed new T2 spine lesions. IgG and IgM levels did not change from the start of 500-mg treatment, although total dose of rituximab was inversely associated with IgG concentrations when previous treatment with 1,000 mg was factored in (coefficient, −0.439; P = 0.041).
A total of 33 patients reported at least one adverse event during the 500-mg treatment period, with only three events being classified as serious: one pancreatitis, one coronary stenting, and one neutropenia.
Validating clinical experience
“This randomized trial is an important step,” said Timothy Vollmer, MD, of the Rocky Mountain MS Center in Westminster, Colo., in an interview. “It clearly supports that you can lessen the dose, which will allow us to use this revolutionary drug for a longer period of time in patients.”
Dr. Vollmer noted that, at his center, they have been using 500 mg of rituximab over a 6-month period since 2010 without a formal clinical trial and with no notable difference in adverse outcomes on MRIs or disability scales. “This validates what we’ve been doing, which we appreciate,” he said.
“The next thing you have to do is determine whether you really have to give it every 6 months,” he added, “because the treatment effect in most patients will last, in terms of B-cell depletion, about a year or more. What we should be testing next is giving the 500 mg and waiting until patients begin to recover B cells before we give them the next cycle, to see if that helps decrease the major side effect, which is a drop in IgG levels.”
The authors acknowledged their study’s limitations, including a moderate sample size, a short follow-up period after 500-mg dosage, and an inability to confirm consistency among 1,000-mg dose administration among all patients, which “may well influence efficacy and safety measures.”
The study was supported by the Neurocenter of Southern Switzerland. One author declared numerous potential conflicts of interest, including receiving speaker fees, research fees, and travel support, and serving on advisory boards for various foundations, universities, and pharmaceutical companies.
SOURCE: Disanto G et al. Mult Scler J. 2020 Aug 25. doi: 10.1177/1352458520952036.
“Given its favorable cost-effectiveness profile, [rituximab] remains a valuable treatment option in the current landscape of MS treatments, even at the reduced dose,” wrote Giulio Disanto, MD, PhD, of the Neurocenter of Southern Switzerland in Lugano, and coauthors. The study was published in Multiple Sclerosis Journal.
To determine the clinical and radiologic effectiveness of deescalating rituximab dosage – along with assessing any adverse outcomes – this observational, single-center study examined 59 patients with MS who had been treated with rituximab at 1,000 mg for at least 1 year before the study began. Roughly 63% (n = 37) of the patients had relapsing remitting MS (RRMS), while the rest (n = 22) had secondary progressive disease (SPD). Their median age was 51, and nearly 75% were women.
All patients underwent neurologic examinations at baseline and then every 3 months for 1 year, with new symptoms, infections, or adverse events being assessed via the Expanded Disability Status Scale (EDSS). They also underwent brain and spinal MRI at baseline and at 12 months while blood samples were taken at baseline and then every 3 months for 1 year, with previous data for both collected when available.
Study results
All 59 patients completed 12-month follow-up, and no relapses occurred in the year after lowering rituximab dosage to 500 mg. No significant differences were observed when comparing EDSS scores at the start of the 1,000-mg dose with the start of the 500-mg dose (Wilcoxon P = .131) as well as from the start of the 500-mg dose to the end of follow-up (Wilcoxon P = .284). Analyzing RRMS and SPD patients separately also led to no differences in EDSS scores from the start of the 500-mg dose to the end of follow-up (Wilcoxon P = .531; Wilcoxon P = .408).
During the 1,000-mg treatment period the number of patients who developed at least one new T2 lesion on their brain or spine was 9 and 4, respectively. During the 500-mg period, just one patient developed a new T2 brain lesion and two patients developed new T2 spine lesions. IgG and IgM levels did not change from the start of 500-mg treatment, although total dose of rituximab was inversely associated with IgG concentrations when previous treatment with 1,000 mg was factored in (coefficient, −0.439; P = 0.041).
A total of 33 patients reported at least one adverse event during the 500-mg treatment period, with only three events being classified as serious: one pancreatitis, one coronary stenting, and one neutropenia.
Validating clinical experience
“This randomized trial is an important step,” said Timothy Vollmer, MD, of the Rocky Mountain MS Center in Westminster, Colo., in an interview. “It clearly supports that you can lessen the dose, which will allow us to use this revolutionary drug for a longer period of time in patients.”
Dr. Vollmer noted that, at his center, they have been using 500 mg of rituximab over a 6-month period since 2010 without a formal clinical trial and with no notable difference in adverse outcomes on MRIs or disability scales. “This validates what we’ve been doing, which we appreciate,” he said.
“The next thing you have to do is determine whether you really have to give it every 6 months,” he added, “because the treatment effect in most patients will last, in terms of B-cell depletion, about a year or more. What we should be testing next is giving the 500 mg and waiting until patients begin to recover B cells before we give them the next cycle, to see if that helps decrease the major side effect, which is a drop in IgG levels.”
The authors acknowledged their study’s limitations, including a moderate sample size, a short follow-up period after 500-mg dosage, and an inability to confirm consistency among 1,000-mg dose administration among all patients, which “may well influence efficacy and safety measures.”
The study was supported by the Neurocenter of Southern Switzerland. One author declared numerous potential conflicts of interest, including receiving speaker fees, research fees, and travel support, and serving on advisory boards for various foundations, universities, and pharmaceutical companies.
SOURCE: Disanto G et al. Mult Scler J. 2020 Aug 25. doi: 10.1177/1352458520952036.
“Given its favorable cost-effectiveness profile, [rituximab] remains a valuable treatment option in the current landscape of MS treatments, even at the reduced dose,” wrote Giulio Disanto, MD, PhD, of the Neurocenter of Southern Switzerland in Lugano, and coauthors. The study was published in Multiple Sclerosis Journal.
To determine the clinical and radiologic effectiveness of deescalating rituximab dosage – along with assessing any adverse outcomes – this observational, single-center study examined 59 patients with MS who had been treated with rituximab at 1,000 mg for at least 1 year before the study began. Roughly 63% (n = 37) of the patients had relapsing remitting MS (RRMS), while the rest (n = 22) had secondary progressive disease (SPD). Their median age was 51, and nearly 75% were women.
All patients underwent neurologic examinations at baseline and then every 3 months for 1 year, with new symptoms, infections, or adverse events being assessed via the Expanded Disability Status Scale (EDSS). They also underwent brain and spinal MRI at baseline and at 12 months while blood samples were taken at baseline and then every 3 months for 1 year, with previous data for both collected when available.
Study results
All 59 patients completed 12-month follow-up, and no relapses occurred in the year after lowering rituximab dosage to 500 mg. No significant differences were observed when comparing EDSS scores at the start of the 1,000-mg dose with the start of the 500-mg dose (Wilcoxon P = .131) as well as from the start of the 500-mg dose to the end of follow-up (Wilcoxon P = .284). Analyzing RRMS and SPD patients separately also led to no differences in EDSS scores from the start of the 500-mg dose to the end of follow-up (Wilcoxon P = .531; Wilcoxon P = .408).
During the 1,000-mg treatment period the number of patients who developed at least one new T2 lesion on their brain or spine was 9 and 4, respectively. During the 500-mg period, just one patient developed a new T2 brain lesion and two patients developed new T2 spine lesions. IgG and IgM levels did not change from the start of 500-mg treatment, although total dose of rituximab was inversely associated with IgG concentrations when previous treatment with 1,000 mg was factored in (coefficient, −0.439; P = 0.041).
A total of 33 patients reported at least one adverse event during the 500-mg treatment period, with only three events being classified as serious: one pancreatitis, one coronary stenting, and one neutropenia.
Validating clinical experience
“This randomized trial is an important step,” said Timothy Vollmer, MD, of the Rocky Mountain MS Center in Westminster, Colo., in an interview. “It clearly supports that you can lessen the dose, which will allow us to use this revolutionary drug for a longer period of time in patients.”
Dr. Vollmer noted that, at his center, they have been using 500 mg of rituximab over a 6-month period since 2010 without a formal clinical trial and with no notable difference in adverse outcomes on MRIs or disability scales. “This validates what we’ve been doing, which we appreciate,” he said.
“The next thing you have to do is determine whether you really have to give it every 6 months,” he added, “because the treatment effect in most patients will last, in terms of B-cell depletion, about a year or more. What we should be testing next is giving the 500 mg and waiting until patients begin to recover B cells before we give them the next cycle, to see if that helps decrease the major side effect, which is a drop in IgG levels.”
The authors acknowledged their study’s limitations, including a moderate sample size, a short follow-up period after 500-mg dosage, and an inability to confirm consistency among 1,000-mg dose administration among all patients, which “may well influence efficacy and safety measures.”
The study was supported by the Neurocenter of Southern Switzerland. One author declared numerous potential conflicts of interest, including receiving speaker fees, research fees, and travel support, and serving on advisory boards for various foundations, universities, and pharmaceutical companies.
SOURCE: Disanto G et al. Mult Scler J. 2020 Aug 25. doi: 10.1177/1352458520952036.
FROM MULTIPLE SCLEROSIS JOURNAL
Lower urinary tract dysfunction in patients with MS
Key clinical point: Higher Expanded Disability Status Scale (EDSS) score is associated with an unfavorable urologic course in patients with multiple sclerosis (MS), and increased postvoid residual volume (PVR) correlates with male gender, EDSS, and disease course.
Major finding: The presence of lower urinary tract symptoms (LUTS) was more frequently associated with a primary progressive disease course (P = .040), a higher level of disability (mean EDSS of 6.4, P = .011), and urinary tract infection (P = .002). PVR values were higher in patients with LUTS vs. those without (P = .011). Increased PVR correlated with male gender (P less than .001), EDSS score (P = .005), and disease course (P = .041). Higher PVR correlated with incontinence (P = .007), chronic urinary retention (P less than .001), incomplete emptying (P = .015), and diminished stream intensity (P = .040).
Study details: The findings are based on a study of 501 patients with clinically definite MS (68.9% females; mean age: 56.0 ± 12.3 years).
Disclosures: No study sponsor was identified. The authors declared no conflicts of interest.
Citation: Monti Bragadin M et al. Mult Scler Relat Disord. 2020 Jul 5. doi: 10.1016/j.msard.2020.102378.
Key clinical point: Higher Expanded Disability Status Scale (EDSS) score is associated with an unfavorable urologic course in patients with multiple sclerosis (MS), and increased postvoid residual volume (PVR) correlates with male gender, EDSS, and disease course.
Major finding: The presence of lower urinary tract symptoms (LUTS) was more frequently associated with a primary progressive disease course (P = .040), a higher level of disability (mean EDSS of 6.4, P = .011), and urinary tract infection (P = .002). PVR values were higher in patients with LUTS vs. those without (P = .011). Increased PVR correlated with male gender (P less than .001), EDSS score (P = .005), and disease course (P = .041). Higher PVR correlated with incontinence (P = .007), chronic urinary retention (P less than .001), incomplete emptying (P = .015), and diminished stream intensity (P = .040).
Study details: The findings are based on a study of 501 patients with clinically definite MS (68.9% females; mean age: 56.0 ± 12.3 years).
Disclosures: No study sponsor was identified. The authors declared no conflicts of interest.
Citation: Monti Bragadin M et al. Mult Scler Relat Disord. 2020 Jul 5. doi: 10.1016/j.msard.2020.102378.
Key clinical point: Higher Expanded Disability Status Scale (EDSS) score is associated with an unfavorable urologic course in patients with multiple sclerosis (MS), and increased postvoid residual volume (PVR) correlates with male gender, EDSS, and disease course.
Major finding: The presence of lower urinary tract symptoms (LUTS) was more frequently associated with a primary progressive disease course (P = .040), a higher level of disability (mean EDSS of 6.4, P = .011), and urinary tract infection (P = .002). PVR values were higher in patients with LUTS vs. those without (P = .011). Increased PVR correlated with male gender (P less than .001), EDSS score (P = .005), and disease course (P = .041). Higher PVR correlated with incontinence (P = .007), chronic urinary retention (P less than .001), incomplete emptying (P = .015), and diminished stream intensity (P = .040).
Study details: The findings are based on a study of 501 patients with clinically definite MS (68.9% females; mean age: 56.0 ± 12.3 years).
Disclosures: No study sponsor was identified. The authors declared no conflicts of interest.
Citation: Monti Bragadin M et al. Mult Scler Relat Disord. 2020 Jul 5. doi: 10.1016/j.msard.2020.102378.
Efficacy of disease-modifying therapies in treatment-naïve patients with MS
Key clinical point: In patients with relapsing-remitting multiple sclerosis (RRMS), initiating high-efficacy disease-modifying therapies (heDMT) lowers the risk of Expanded Disability Status Scale (EDSS) score worsening and relapses compared to initiating medium-efficacy DMT (meDMT).
Major finding: The absolute probabilities of a 6-month confirmed EDSS score worsening at 2- and 4-year follow-ups were 11.5% and 16.7% for heDMT initiators and 18.3% and 30.1% for meDMT initiators, respectively (hazard ratio [HR], 0.53; P = .006). The heDMT initiators had a lower probability of a first relapse than meDMT initiators (HR, 0.50; 95% confidence interval, 0.37-0.67).
Study details: In this Danish population-based study, 194 patients with RRMS starting initial therapy with heDMT were matched to 194 patients starting meDMT.
Disclosures: There was no targeted funding. The presenting author reported receiving support for congress participation from Roche.
Citation: Buron MD et al. Neurology. 2020 Jul 7. doi: 10.1212/WNL.0000000000010135.
Key clinical point: In patients with relapsing-remitting multiple sclerosis (RRMS), initiating high-efficacy disease-modifying therapies (heDMT) lowers the risk of Expanded Disability Status Scale (EDSS) score worsening and relapses compared to initiating medium-efficacy DMT (meDMT).
Major finding: The absolute probabilities of a 6-month confirmed EDSS score worsening at 2- and 4-year follow-ups were 11.5% and 16.7% for heDMT initiators and 18.3% and 30.1% for meDMT initiators, respectively (hazard ratio [HR], 0.53; P = .006). The heDMT initiators had a lower probability of a first relapse than meDMT initiators (HR, 0.50; 95% confidence interval, 0.37-0.67).
Study details: In this Danish population-based study, 194 patients with RRMS starting initial therapy with heDMT were matched to 194 patients starting meDMT.
Disclosures: There was no targeted funding. The presenting author reported receiving support for congress participation from Roche.
Citation: Buron MD et al. Neurology. 2020 Jul 7. doi: 10.1212/WNL.0000000000010135.
Key clinical point: In patients with relapsing-remitting multiple sclerosis (RRMS), initiating high-efficacy disease-modifying therapies (heDMT) lowers the risk of Expanded Disability Status Scale (EDSS) score worsening and relapses compared to initiating medium-efficacy DMT (meDMT).
Major finding: The absolute probabilities of a 6-month confirmed EDSS score worsening at 2- and 4-year follow-ups were 11.5% and 16.7% for heDMT initiators and 18.3% and 30.1% for meDMT initiators, respectively (hazard ratio [HR], 0.53; P = .006). The heDMT initiators had a lower probability of a first relapse than meDMT initiators (HR, 0.50; 95% confidence interval, 0.37-0.67).
Study details: In this Danish population-based study, 194 patients with RRMS starting initial therapy with heDMT were matched to 194 patients starting meDMT.
Disclosures: There was no targeted funding. The presenting author reported receiving support for congress participation from Roche.
Citation: Buron MD et al. Neurology. 2020 Jul 7. doi: 10.1212/WNL.0000000000010135.
Personalized extended interval dosing does not reduce efficacy of natalizumab in MS
Key clinical point: Switching to personalized extended interval dosing of natalizumab did not result in recurrence of disease activity in stable patients with relapsing-remitting multiple sclerosis (RRMS).
Major finding: 84% of study patients extended the dosing interval from the standard 4 weeks to a 5- to 7-week interval. No patient developed gadolinium-enhancing lesions (95% confidence interval [CI], 0-7.4%) during follow-up. No patient developed new/enlarging T2 lesions or relapses during the 1-year follow-up and 1-year extension phase.
Study details: The findings are based on a prospective, multicenter, single-arm trial of 61 patients with RRMS.
Disclosures: The study was funded by the Brain Foundation Netherlands. The presenting author had no disclosures. Some of the coauthors reported ties with pharmaceutical companies.
Citation: van Kempen ZLE et al. Neurology. 2020 Jul 20. doi: 10.1212/WNL.0000000000009995.
Key clinical point: Switching to personalized extended interval dosing of natalizumab did not result in recurrence of disease activity in stable patients with relapsing-remitting multiple sclerosis (RRMS).
Major finding: 84% of study patients extended the dosing interval from the standard 4 weeks to a 5- to 7-week interval. No patient developed gadolinium-enhancing lesions (95% confidence interval [CI], 0-7.4%) during follow-up. No patient developed new/enlarging T2 lesions or relapses during the 1-year follow-up and 1-year extension phase.
Study details: The findings are based on a prospective, multicenter, single-arm trial of 61 patients with RRMS.
Disclosures: The study was funded by the Brain Foundation Netherlands. The presenting author had no disclosures. Some of the coauthors reported ties with pharmaceutical companies.
Citation: van Kempen ZLE et al. Neurology. 2020 Jul 20. doi: 10.1212/WNL.0000000000009995.
Key clinical point: Switching to personalized extended interval dosing of natalizumab did not result in recurrence of disease activity in stable patients with relapsing-remitting multiple sclerosis (RRMS).
Major finding: 84% of study patients extended the dosing interval from the standard 4 weeks to a 5- to 7-week interval. No patient developed gadolinium-enhancing lesions (95% confidence interval [CI], 0-7.4%) during follow-up. No patient developed new/enlarging T2 lesions or relapses during the 1-year follow-up and 1-year extension phase.
Study details: The findings are based on a prospective, multicenter, single-arm trial of 61 patients with RRMS.
Disclosures: The study was funded by the Brain Foundation Netherlands. The presenting author had no disclosures. Some of the coauthors reported ties with pharmaceutical companies.
Citation: van Kempen ZLE et al. Neurology. 2020 Jul 20. doi: 10.1212/WNL.0000000000009995.