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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.
Secondary progressive MS: Sustained immunotherapy may improve disability outcomes
Key clinical point: Disease-modifying therapies (DMTs) are associated with improvements in disability outcomes in patients with active relapses during secondary progressive multiple sclerosis (SPMS).
Major finding: Patients who experienced superimposed relapses during SPMS and received DMTs had a greater proportion of time with a reduced Multiple Sclerosis Severity Score (MSSS) progression slope during SPMS (per 25% increase in proportion of time receiving treatment, β = −0.025; P less than .001 for low-efficacy; β = −0.022; P = .06 for medium-efficacy; and β = −0.034; P = .002 for high-efficacy therapies).
Study details: An observational cohort study of 1,621 patients with active SPMS from the international MSBase registry.
Disclosures: The study was supported by grants from the National Health and Medical Research Council. The MSBase Foundation receives funding from Bayer, bioCSL, Biogen, Merck, Novartis, Roche, and Sanofi Genzyme. The presenting author reported receiving travel compensation from Merck outside the submitted work.
Citation: Lizak N et al. JAMA Neurol. 2020 Jul 27. doi: 10.1001/jamaneurol.2020.2453.
Key clinical point: Disease-modifying therapies (DMTs) are associated with improvements in disability outcomes in patients with active relapses during secondary progressive multiple sclerosis (SPMS).
Major finding: Patients who experienced superimposed relapses during SPMS and received DMTs had a greater proportion of time with a reduced Multiple Sclerosis Severity Score (MSSS) progression slope during SPMS (per 25% increase in proportion of time receiving treatment, β = −0.025; P less than .001 for low-efficacy; β = −0.022; P = .06 for medium-efficacy; and β = −0.034; P = .002 for high-efficacy therapies).
Study details: An observational cohort study of 1,621 patients with active SPMS from the international MSBase registry.
Disclosures: The study was supported by grants from the National Health and Medical Research Council. The MSBase Foundation receives funding from Bayer, bioCSL, Biogen, Merck, Novartis, Roche, and Sanofi Genzyme. The presenting author reported receiving travel compensation from Merck outside the submitted work.
Citation: Lizak N et al. JAMA Neurol. 2020 Jul 27. doi: 10.1001/jamaneurol.2020.2453.
Key clinical point: Disease-modifying therapies (DMTs) are associated with improvements in disability outcomes in patients with active relapses during secondary progressive multiple sclerosis (SPMS).
Major finding: Patients who experienced superimposed relapses during SPMS and received DMTs had a greater proportion of time with a reduced Multiple Sclerosis Severity Score (MSSS) progression slope during SPMS (per 25% increase in proportion of time receiving treatment, β = −0.025; P less than .001 for low-efficacy; β = −0.022; P = .06 for medium-efficacy; and β = −0.034; P = .002 for high-efficacy therapies).
Study details: An observational cohort study of 1,621 patients with active SPMS from the international MSBase registry.
Disclosures: The study was supported by grants from the National Health and Medical Research Council. The MSBase Foundation receives funding from Bayer, bioCSL, Biogen, Merck, Novartis, Roche, and Sanofi Genzyme. The presenting author reported receiving travel compensation from Merck outside the submitted work.
Citation: Lizak N et al. JAMA Neurol. 2020 Jul 27. doi: 10.1001/jamaneurol.2020.2453.
TNF inhibitors linked to inflammatory CNS events
, new research suggests
The nested case-control study included more than 200 participants with diseases such as rheumatoid arthritis, psoriasis, and Crohn’s disease. Results showed that exposure to TNF inhibitors was significantly associated with increased risk for demyelinating CNS events, such as multiple sclerosis, and nondemyelinating events, such as meningitis and encephalitis.
Interestingly, disease-specific secondary analyses showed that the strongest association for inflammatory events was in patients with rheumatoid arthritis.
Lead author Amy Kunchok, MD, of Mayo Clinic, Rochester, Minn., noted that “these are highly effective therapies for patients” and that these CNS events are likely uncommon.
“Our study has observed an association, but this does not imply causality. Therefore, we are not cautioning against using these therapies in appropriate patients,” Dr. Kunchok said in an interview.
“Rather, we recommend that clinicians assessing patients with both inflammatory demyelinating and nondemyelinating CNS events consider a detailed evaluation of the medication history, particularly in patients with coexistent autoimmune diseases who may have a current or past history of biological therapies,” she said.
The findings were published in JAMA Neurology.
Poorly understood
TNF inhibitors “are common therapies for certain autoimmune diseases,” the investigators noted.
Previously, a link between exposure to these inhibitors and inflammatory CNS events “has been postulated but is poorly understood,” they wrote.
In the current study, they examined records for 106 patients who were treated at Mayo clinics in Minnesota, Arizona, or Florida from January 2003 through February 2019. All participants had been diagnosed with an autoimmune disease that the Food and Drug Administration has listed as an indication for TNF inhibitor use. This included rheumatoid arthritis (n = 48), ankylosing spondylitis (n = 4), psoriasis and psoriatic arthritis (n = 21), Crohn’s disease (n = 27), and ulcerative colitis (n = 6). Their records also showed diagnostic codes for the inflammatory demyelinating CNS events of relapsing-remitting or primary progressive MS, clinically isolated syndrome, radiologically isolated syndrome, neuromyelitis optica spectrum disorder, and transverse myelitis or for the inflammatory nondemyelinating CNS events of meningitis, meningoencephalitis, encephalitis, neurosarcoidosis, and CNS vasculitis. The investigators also included 106 age-, sex-, and autoimmune disease–matched participants 1:1 to act as the control group.
In the total study population, 64% were women and the median age at disease onset was 52 years. In addition, 60% of the patient group and 40% of the control group were exposed to TNF inhibitors.
Novel finding?
Results showed that TNF inhibitor exposure was significantly linked to increased risk for developing any inflammatory CNS event (adjusted odds ratio, 3.01; 95% CI, 1.55-5.82; P = .001). When the outcomes were stratified by class of inflammatory event, these results were similar. The aOR was 3.09 (95% CI, 1.19-8.04; P = .02) for inflammatory demyelinating CNS events and was 2.97 (95% CI, 1.15-7.65; P = .02) for inflammatory nondemyelinating events.
Dr. Kunchok noted that the association between the inhibitors and nondemyelinating events was “a novel finding from this study.”
In secondary analyses, patients with rheumatoid arthritis and exposure to TNF inhibitors had the strongest association with any inflammatory CNS event (aOR, 4.82; 95% CI, 1.62-14.36; P = .005).
A pooled cohort comprising only the participants with the other autoimmune diseases did not show a significant association between exposure to TNF inhibitors and development of CNS events (P = .09).
“Because of the lack of power, further stratification by individual autoimmune diseases was not analyzed,” the investigators reported.
Although the overall findings showed that exposure to TNF inhibitors was linked to increased risk for inflammatory events, whether this association “represents de novo or exacerbated inflammatory pathways requires further research,” the authors wrote.
Dr. Kunchok added that more research, especially population-based studies, is also needed to examine the incidence of these inflammatory CNS events in patients exposed to TNF-alpha inhibitors.
Adds to the literature
In an accompanying editorial, Jeffrey M. Gelfand, MD, department of neurology at the University of California, San Francisco, and Jinoos Yazdany, MD, Zuckerberg San Francisco General Hospital at UCSF, noted that although the study adds to the literature, the magnitude of the risk found “remains unclear.”
“Randomized clinical trials are not suited to the study of rare adverse events,” Dr. Gelfand and Dr. Yazdany wrote. They agree with Dr. Kunchok that “next steps should include population-based observational studies that control for disease severity.”
Still, the current study provides additional evidence of rare adverse events in patients receiving TNF inhibitors, they noted. So how should prescribers proceed?
“As with all treatments, the risk-benefit ratio for the individual patient’s situation must be weighed and appropriate counseling must be given to facilitate shared decision-making discussions,” wrote the editorialists.
“Given what is known about the risk of harm, avoiding TNF inhibitors is advisable in patients with known MS,” they wrote.
In addition, neurologic consultation can be helpful for clarifying diagnoses and providing advice on monitoring strategies for TNF inhibitor treatment in those with possible MS or other demyelinating conditions, noted the editorialists.
“In patients who develop new concerning neurological symptoms while receiving TNF inhibitor treatment, timely evaluation is indicated, including consideration of neuroinflammatory, infectious, and neurological diagnoses that may be unrelated to treatment,” they added.
“Broader awareness of risks that studies such as this one by Kunchok et al provide can ... encourage timelier recognition of potential TNF inhibitor–associated neuroinflammatory events and may improve outcomes for patients,” Dr. Gelfand and Dr. Yazdany concluded.
The study was funded by a grant from the National Center for Advancing Translational Sciences. Dr. Kunchok reports having received research funding from Biogen outside this study. A full list of disclosures for the other study authors is in the original article. Dr. Gelfand reports having received g rants for a clinical trial from Genentech and consulting fees from Biogen, Alexion, Theranica, Impel Neuropharma, Advanced Clinical, Biohaven, and Satsuma. Dr. Yazdany reports having received grants from Pfizer and consulting fees from AstraZeneca and Eli Lilly outside the submitted work.
A version of this article originally appeared on Medscape.com.
, new research suggests
The nested case-control study included more than 200 participants with diseases such as rheumatoid arthritis, psoriasis, and Crohn’s disease. Results showed that exposure to TNF inhibitors was significantly associated with increased risk for demyelinating CNS events, such as multiple sclerosis, and nondemyelinating events, such as meningitis and encephalitis.
Interestingly, disease-specific secondary analyses showed that the strongest association for inflammatory events was in patients with rheumatoid arthritis.
Lead author Amy Kunchok, MD, of Mayo Clinic, Rochester, Minn., noted that “these are highly effective therapies for patients” and that these CNS events are likely uncommon.
“Our study has observed an association, but this does not imply causality. Therefore, we are not cautioning against using these therapies in appropriate patients,” Dr. Kunchok said in an interview.
“Rather, we recommend that clinicians assessing patients with both inflammatory demyelinating and nondemyelinating CNS events consider a detailed evaluation of the medication history, particularly in patients with coexistent autoimmune diseases who may have a current or past history of biological therapies,” she said.
The findings were published in JAMA Neurology.
Poorly understood
TNF inhibitors “are common therapies for certain autoimmune diseases,” the investigators noted.
Previously, a link between exposure to these inhibitors and inflammatory CNS events “has been postulated but is poorly understood,” they wrote.
In the current study, they examined records for 106 patients who were treated at Mayo clinics in Minnesota, Arizona, or Florida from January 2003 through February 2019. All participants had been diagnosed with an autoimmune disease that the Food and Drug Administration has listed as an indication for TNF inhibitor use. This included rheumatoid arthritis (n = 48), ankylosing spondylitis (n = 4), psoriasis and psoriatic arthritis (n = 21), Crohn’s disease (n = 27), and ulcerative colitis (n = 6). Their records also showed diagnostic codes for the inflammatory demyelinating CNS events of relapsing-remitting or primary progressive MS, clinically isolated syndrome, radiologically isolated syndrome, neuromyelitis optica spectrum disorder, and transverse myelitis or for the inflammatory nondemyelinating CNS events of meningitis, meningoencephalitis, encephalitis, neurosarcoidosis, and CNS vasculitis. The investigators also included 106 age-, sex-, and autoimmune disease–matched participants 1:1 to act as the control group.
In the total study population, 64% were women and the median age at disease onset was 52 years. In addition, 60% of the patient group and 40% of the control group were exposed to TNF inhibitors.
Novel finding?
Results showed that TNF inhibitor exposure was significantly linked to increased risk for developing any inflammatory CNS event (adjusted odds ratio, 3.01; 95% CI, 1.55-5.82; P = .001). When the outcomes were stratified by class of inflammatory event, these results were similar. The aOR was 3.09 (95% CI, 1.19-8.04; P = .02) for inflammatory demyelinating CNS events and was 2.97 (95% CI, 1.15-7.65; P = .02) for inflammatory nondemyelinating events.
Dr. Kunchok noted that the association between the inhibitors and nondemyelinating events was “a novel finding from this study.”
In secondary analyses, patients with rheumatoid arthritis and exposure to TNF inhibitors had the strongest association with any inflammatory CNS event (aOR, 4.82; 95% CI, 1.62-14.36; P = .005).
A pooled cohort comprising only the participants with the other autoimmune diseases did not show a significant association between exposure to TNF inhibitors and development of CNS events (P = .09).
“Because of the lack of power, further stratification by individual autoimmune diseases was not analyzed,” the investigators reported.
Although the overall findings showed that exposure to TNF inhibitors was linked to increased risk for inflammatory events, whether this association “represents de novo or exacerbated inflammatory pathways requires further research,” the authors wrote.
Dr. Kunchok added that more research, especially population-based studies, is also needed to examine the incidence of these inflammatory CNS events in patients exposed to TNF-alpha inhibitors.
Adds to the literature
In an accompanying editorial, Jeffrey M. Gelfand, MD, department of neurology at the University of California, San Francisco, and Jinoos Yazdany, MD, Zuckerberg San Francisco General Hospital at UCSF, noted that although the study adds to the literature, the magnitude of the risk found “remains unclear.”
“Randomized clinical trials are not suited to the study of rare adverse events,” Dr. Gelfand and Dr. Yazdany wrote. They agree with Dr. Kunchok that “next steps should include population-based observational studies that control for disease severity.”
Still, the current study provides additional evidence of rare adverse events in patients receiving TNF inhibitors, they noted. So how should prescribers proceed?
“As with all treatments, the risk-benefit ratio for the individual patient’s situation must be weighed and appropriate counseling must be given to facilitate shared decision-making discussions,” wrote the editorialists.
“Given what is known about the risk of harm, avoiding TNF inhibitors is advisable in patients with known MS,” they wrote.
In addition, neurologic consultation can be helpful for clarifying diagnoses and providing advice on monitoring strategies for TNF inhibitor treatment in those with possible MS or other demyelinating conditions, noted the editorialists.
“In patients who develop new concerning neurological symptoms while receiving TNF inhibitor treatment, timely evaluation is indicated, including consideration of neuroinflammatory, infectious, and neurological diagnoses that may be unrelated to treatment,” they added.
“Broader awareness of risks that studies such as this one by Kunchok et al provide can ... encourage timelier recognition of potential TNF inhibitor–associated neuroinflammatory events and may improve outcomes for patients,” Dr. Gelfand and Dr. Yazdany concluded.
The study was funded by a grant from the National Center for Advancing Translational Sciences. Dr. Kunchok reports having received research funding from Biogen outside this study. A full list of disclosures for the other study authors is in the original article. Dr. Gelfand reports having received g rants for a clinical trial from Genentech and consulting fees from Biogen, Alexion, Theranica, Impel Neuropharma, Advanced Clinical, Biohaven, and Satsuma. Dr. Yazdany reports having received grants from Pfizer and consulting fees from AstraZeneca and Eli Lilly outside the submitted work.
A version of this article originally appeared on Medscape.com.
, new research suggests
The nested case-control study included more than 200 participants with diseases such as rheumatoid arthritis, psoriasis, and Crohn’s disease. Results showed that exposure to TNF inhibitors was significantly associated with increased risk for demyelinating CNS events, such as multiple sclerosis, and nondemyelinating events, such as meningitis and encephalitis.
Interestingly, disease-specific secondary analyses showed that the strongest association for inflammatory events was in patients with rheumatoid arthritis.
Lead author Amy Kunchok, MD, of Mayo Clinic, Rochester, Minn., noted that “these are highly effective therapies for patients” and that these CNS events are likely uncommon.
“Our study has observed an association, but this does not imply causality. Therefore, we are not cautioning against using these therapies in appropriate patients,” Dr. Kunchok said in an interview.
“Rather, we recommend that clinicians assessing patients with both inflammatory demyelinating and nondemyelinating CNS events consider a detailed evaluation of the medication history, particularly in patients with coexistent autoimmune diseases who may have a current or past history of biological therapies,” she said.
The findings were published in JAMA Neurology.
Poorly understood
TNF inhibitors “are common therapies for certain autoimmune diseases,” the investigators noted.
Previously, a link between exposure to these inhibitors and inflammatory CNS events “has been postulated but is poorly understood,” they wrote.
In the current study, they examined records for 106 patients who were treated at Mayo clinics in Minnesota, Arizona, or Florida from January 2003 through February 2019. All participants had been diagnosed with an autoimmune disease that the Food and Drug Administration has listed as an indication for TNF inhibitor use. This included rheumatoid arthritis (n = 48), ankylosing spondylitis (n = 4), psoriasis and psoriatic arthritis (n = 21), Crohn’s disease (n = 27), and ulcerative colitis (n = 6). Their records also showed diagnostic codes for the inflammatory demyelinating CNS events of relapsing-remitting or primary progressive MS, clinically isolated syndrome, radiologically isolated syndrome, neuromyelitis optica spectrum disorder, and transverse myelitis or for the inflammatory nondemyelinating CNS events of meningitis, meningoencephalitis, encephalitis, neurosarcoidosis, and CNS vasculitis. The investigators also included 106 age-, sex-, and autoimmune disease–matched participants 1:1 to act as the control group.
In the total study population, 64% were women and the median age at disease onset was 52 years. In addition, 60% of the patient group and 40% of the control group were exposed to TNF inhibitors.
Novel finding?
Results showed that TNF inhibitor exposure was significantly linked to increased risk for developing any inflammatory CNS event (adjusted odds ratio, 3.01; 95% CI, 1.55-5.82; P = .001). When the outcomes were stratified by class of inflammatory event, these results were similar. The aOR was 3.09 (95% CI, 1.19-8.04; P = .02) for inflammatory demyelinating CNS events and was 2.97 (95% CI, 1.15-7.65; P = .02) for inflammatory nondemyelinating events.
Dr. Kunchok noted that the association between the inhibitors and nondemyelinating events was “a novel finding from this study.”
In secondary analyses, patients with rheumatoid arthritis and exposure to TNF inhibitors had the strongest association with any inflammatory CNS event (aOR, 4.82; 95% CI, 1.62-14.36; P = .005).
A pooled cohort comprising only the participants with the other autoimmune diseases did not show a significant association between exposure to TNF inhibitors and development of CNS events (P = .09).
“Because of the lack of power, further stratification by individual autoimmune diseases was not analyzed,” the investigators reported.
Although the overall findings showed that exposure to TNF inhibitors was linked to increased risk for inflammatory events, whether this association “represents de novo or exacerbated inflammatory pathways requires further research,” the authors wrote.
Dr. Kunchok added that more research, especially population-based studies, is also needed to examine the incidence of these inflammatory CNS events in patients exposed to TNF-alpha inhibitors.
Adds to the literature
In an accompanying editorial, Jeffrey M. Gelfand, MD, department of neurology at the University of California, San Francisco, and Jinoos Yazdany, MD, Zuckerberg San Francisco General Hospital at UCSF, noted that although the study adds to the literature, the magnitude of the risk found “remains unclear.”
“Randomized clinical trials are not suited to the study of rare adverse events,” Dr. Gelfand and Dr. Yazdany wrote. They agree with Dr. Kunchok that “next steps should include population-based observational studies that control for disease severity.”
Still, the current study provides additional evidence of rare adverse events in patients receiving TNF inhibitors, they noted. So how should prescribers proceed?
“As with all treatments, the risk-benefit ratio for the individual patient’s situation must be weighed and appropriate counseling must be given to facilitate shared decision-making discussions,” wrote the editorialists.
“Given what is known about the risk of harm, avoiding TNF inhibitors is advisable in patients with known MS,” they wrote.
In addition, neurologic consultation can be helpful for clarifying diagnoses and providing advice on monitoring strategies for TNF inhibitor treatment in those with possible MS or other demyelinating conditions, noted the editorialists.
“In patients who develop new concerning neurological symptoms while receiving TNF inhibitor treatment, timely evaluation is indicated, including consideration of neuroinflammatory, infectious, and neurological diagnoses that may be unrelated to treatment,” they added.
“Broader awareness of risks that studies such as this one by Kunchok et al provide can ... encourage timelier recognition of potential TNF inhibitor–associated neuroinflammatory events and may improve outcomes for patients,” Dr. Gelfand and Dr. Yazdany concluded.
The study was funded by a grant from the National Center for Advancing Translational Sciences. Dr. Kunchok reports having received research funding from Biogen outside this study. A full list of disclosures for the other study authors is in the original article. Dr. Gelfand reports having received g rants for a clinical trial from Genentech and consulting fees from Biogen, Alexion, Theranica, Impel Neuropharma, Advanced Clinical, Biohaven, and Satsuma. Dr. Yazdany reports having received grants from Pfizer and consulting fees from AstraZeneca and Eli Lilly outside the submitted work.
A version of this article originally appeared on Medscape.com.
High-dose biotin treatment tied to increased risk of relapse in progressive MS
Key clinical point: The follow-up of patients with progressive multiple sclerosis (PMS) starting high-dose biotin (HDB) should include careful assessment of clinical and radiological activity to monitor the potential pro-inflammatory effect of biotin.
Major finding: In the crossover analysis among patients who received HDB (n=42), the number of relapses was statistically and clinically significantly higher after vs. before biotin initiation (incident rate ratio, 7.4; P less than .0001). With the propensity score matching method, relapse risk was significantly higher in the biotin vs. control group (hazard ratio [HR], 4.3; P = .01). The inverse probability of treatment weighting method with 440 control participants showed consistent results with higher risk in the biotin group (HR, 5.1; P less than .0001).
Study details: This study evaluated the association between exposure to HDB and the risk of relapse among 482 patients with PMS.
Disclosures: No study sponsor was identified. The authors declared no conflicts of interest.
Citation: Branger
Key clinical point: The follow-up of patients with progressive multiple sclerosis (PMS) starting high-dose biotin (HDB) should include careful assessment of clinical and radiological activity to monitor the potential pro-inflammatory effect of biotin.
Major finding: In the crossover analysis among patients who received HDB (n=42), the number of relapses was statistically and clinically significantly higher after vs. before biotin initiation (incident rate ratio, 7.4; P less than .0001). With the propensity score matching method, relapse risk was significantly higher in the biotin vs. control group (hazard ratio [HR], 4.3; P = .01). The inverse probability of treatment weighting method with 440 control participants showed consistent results with higher risk in the biotin group (HR, 5.1; P less than .0001).
Study details: This study evaluated the association between exposure to HDB and the risk of relapse among 482 patients with PMS.
Disclosures: No study sponsor was identified. The authors declared no conflicts of interest.
Citation: Branger
Key clinical point: The follow-up of patients with progressive multiple sclerosis (PMS) starting high-dose biotin (HDB) should include careful assessment of clinical and radiological activity to monitor the potential pro-inflammatory effect of biotin.
Major finding: In the crossover analysis among patients who received HDB (n=42), the number of relapses was statistically and clinically significantly higher after vs. before biotin initiation (incident rate ratio, 7.4; P less than .0001). With the propensity score matching method, relapse risk was significantly higher in the biotin vs. control group (hazard ratio [HR], 4.3; P = .01). The inverse probability of treatment weighting method with 440 control participants showed consistent results with higher risk in the biotin group (HR, 5.1; P less than .0001).
Study details: This study evaluated the association between exposure to HDB and the risk of relapse among 482 patients with PMS.
Disclosures: No study sponsor was identified. The authors declared no conflicts of interest.
Citation: Branger