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European Committee for Treatment and Research in Multiple Sclerosis - ECTRIMS 2018
Revamped MS criteria boost pediatric diagnoses
BERLIN –
The increased accuracy largely hinged on a positive finding of oligoclonal bands in cerebrospinal fluid – a diagnostic hallmark that was not included in the earlier criteria, Georgina Arrambide, MD, said at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.
“Application to children of the new diagnostic criteria is limited,” said Dr. Arrambide, of the University Hospital Vall d’Hebron Multiple Sclerosis Centre of Catalonia, Barcelona. “And there are still some uncertainties with regard to fluid biomarkers and how they predict or confirm a diagnosis of MS in children, and also their relationship to the disease evolution.”
The updated McDonald criteria are intended to boost early, definitive MS diagnosis, leading to earlier initiation of therapy. They are intended primarily for patients aged 11 years and older who present with a typical clinically isolated syndrome and high probability of MS (Lancet Neurol. 2018;17[2]:162-73).
Dr. Arrambide and her colleagues used the revamped criteria to reassess MS diagnoses in a prospective Spanish cohort of children who experienced an acute first demyelinating event and were diagnosed with the 2010 criteria. The Kids-METOMS-MOGBCN Study enrolls children aged younger than 18 years within 1 year of a first acute demyelinating episode. It includes demographic, clinical, and imaging data, as well as data on oligoclonal bands and antibodies against aquaporin-4 and myelin oligodendrocyte glycoprotein (MoG). Of these fluid biomarkers, only oligoclonal bands are included in the new McDonald criteria.
The 55 children in Dr. Arrambide’s analysis were followed for a mean of 16 months. They included 25 (45%) girls with an overall median age of 6 years at the first acute event. Oligoclonal bands were present in 56%, and both anti-MoG and anti–aquaporin-4 antibodies in 82%.
All children had abnormal brain MRI at baseline, with about 33% having gadolinium-enhancing brain lesions. Spinal cord MRI was abnormal in 50%, with 39% having gadolinium-enhancing lesions. According to the 2010 criteria, only three had a definitive MS diagnosis at baseline. The diagnosis was acute disseminated encephalomyelitis in 51%, clinically isolated syndrome in 31%, radiologically isolated syndrome in 2%, and nonencephalopathic disseminated encephalomyelitis in the remainder.
At baseline, three of those had a definitive MS diagnosis, displaying dissemination in both space and time as required by both the 2010 and 2017 criteria. The addition of oligoclonal band positivity added one more patient over the 2010 criteria, and assessing the cohort with the complete 2017 criteria added three more definitive diagnoses. This was a significant increase in definitive MS diagnoses when compared against the earlier criteria (70% vs. 30%).
Diagnoses changed in 10 other patients during follow-up. The single patient with radiologically isolated syndrome was definitively diagnosed with MS. Of the seven with clinically isolated syndrome, six were diagnosed with MS and one with a relapsing optic neuritis. Of the 28 with a nonencephalopathic encephalitis, 2 were diagnosed with optic neuritis.
The study also confirmed the benefit of adding oligoclonal bands as a diagnostic marker in children. Of those with an MS diagnosis at last follow-up, 71% were positive for the cerebrospinal fluid finding, compared with just 4% of those with a non-MS diagnosis. However, none of those children had anti-MoG antibodies, compared with 58% of those with a non-MS diagnosis. None of the patients were positive for anti–aquaporin-4, regardless of diagnosis.
That finding does not necessarily mean that the absence of anti-MoG antibodies can rule out an MS diagnosis in children, Dr. Arrambide cautioned. Nevertheless, the finding is a useful clinical marker during a diagnostic work-up.
“The presence of oligoclonal bands and the absence of MOG-IgG are both useful biomarkers when evaluating the risk of MS in children with a first demyelinating event,” she said.
She disclosed financial relationships with several pharmaceutical companies.
SOURCE: Arrambide G et al. ECTRIMS 2018, Abstract 64
BERLIN –
The increased accuracy largely hinged on a positive finding of oligoclonal bands in cerebrospinal fluid – a diagnostic hallmark that was not included in the earlier criteria, Georgina Arrambide, MD, said at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.
“Application to children of the new diagnostic criteria is limited,” said Dr. Arrambide, of the University Hospital Vall d’Hebron Multiple Sclerosis Centre of Catalonia, Barcelona. “And there are still some uncertainties with regard to fluid biomarkers and how they predict or confirm a diagnosis of MS in children, and also their relationship to the disease evolution.”
The updated McDonald criteria are intended to boost early, definitive MS diagnosis, leading to earlier initiation of therapy. They are intended primarily for patients aged 11 years and older who present with a typical clinically isolated syndrome and high probability of MS (Lancet Neurol. 2018;17[2]:162-73).
Dr. Arrambide and her colleagues used the revamped criteria to reassess MS diagnoses in a prospective Spanish cohort of children who experienced an acute first demyelinating event and were diagnosed with the 2010 criteria. The Kids-METOMS-MOGBCN Study enrolls children aged younger than 18 years within 1 year of a first acute demyelinating episode. It includes demographic, clinical, and imaging data, as well as data on oligoclonal bands and antibodies against aquaporin-4 and myelin oligodendrocyte glycoprotein (MoG). Of these fluid biomarkers, only oligoclonal bands are included in the new McDonald criteria.
The 55 children in Dr. Arrambide’s analysis were followed for a mean of 16 months. They included 25 (45%) girls with an overall median age of 6 years at the first acute event. Oligoclonal bands were present in 56%, and both anti-MoG and anti–aquaporin-4 antibodies in 82%.
All children had abnormal brain MRI at baseline, with about 33% having gadolinium-enhancing brain lesions. Spinal cord MRI was abnormal in 50%, with 39% having gadolinium-enhancing lesions. According to the 2010 criteria, only three had a definitive MS diagnosis at baseline. The diagnosis was acute disseminated encephalomyelitis in 51%, clinically isolated syndrome in 31%, radiologically isolated syndrome in 2%, and nonencephalopathic disseminated encephalomyelitis in the remainder.
At baseline, three of those had a definitive MS diagnosis, displaying dissemination in both space and time as required by both the 2010 and 2017 criteria. The addition of oligoclonal band positivity added one more patient over the 2010 criteria, and assessing the cohort with the complete 2017 criteria added three more definitive diagnoses. This was a significant increase in definitive MS diagnoses when compared against the earlier criteria (70% vs. 30%).
Diagnoses changed in 10 other patients during follow-up. The single patient with radiologically isolated syndrome was definitively diagnosed with MS. Of the seven with clinically isolated syndrome, six were diagnosed with MS and one with a relapsing optic neuritis. Of the 28 with a nonencephalopathic encephalitis, 2 were diagnosed with optic neuritis.
The study also confirmed the benefit of adding oligoclonal bands as a diagnostic marker in children. Of those with an MS diagnosis at last follow-up, 71% were positive for the cerebrospinal fluid finding, compared with just 4% of those with a non-MS diagnosis. However, none of those children had anti-MoG antibodies, compared with 58% of those with a non-MS diagnosis. None of the patients were positive for anti–aquaporin-4, regardless of diagnosis.
That finding does not necessarily mean that the absence of anti-MoG antibodies can rule out an MS diagnosis in children, Dr. Arrambide cautioned. Nevertheless, the finding is a useful clinical marker during a diagnostic work-up.
“The presence of oligoclonal bands and the absence of MOG-IgG are both useful biomarkers when evaluating the risk of MS in children with a first demyelinating event,” she said.
She disclosed financial relationships with several pharmaceutical companies.
SOURCE: Arrambide G et al. ECTRIMS 2018, Abstract 64
BERLIN –
The increased accuracy largely hinged on a positive finding of oligoclonal bands in cerebrospinal fluid – a diagnostic hallmark that was not included in the earlier criteria, Georgina Arrambide, MD, said at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.
“Application to children of the new diagnostic criteria is limited,” said Dr. Arrambide, of the University Hospital Vall d’Hebron Multiple Sclerosis Centre of Catalonia, Barcelona. “And there are still some uncertainties with regard to fluid biomarkers and how they predict or confirm a diagnosis of MS in children, and also their relationship to the disease evolution.”
The updated McDonald criteria are intended to boost early, definitive MS diagnosis, leading to earlier initiation of therapy. They are intended primarily for patients aged 11 years and older who present with a typical clinically isolated syndrome and high probability of MS (Lancet Neurol. 2018;17[2]:162-73).
Dr. Arrambide and her colleagues used the revamped criteria to reassess MS diagnoses in a prospective Spanish cohort of children who experienced an acute first demyelinating event and were diagnosed with the 2010 criteria. The Kids-METOMS-MOGBCN Study enrolls children aged younger than 18 years within 1 year of a first acute demyelinating episode. It includes demographic, clinical, and imaging data, as well as data on oligoclonal bands and antibodies against aquaporin-4 and myelin oligodendrocyte glycoprotein (MoG). Of these fluid biomarkers, only oligoclonal bands are included in the new McDonald criteria.
The 55 children in Dr. Arrambide’s analysis were followed for a mean of 16 months. They included 25 (45%) girls with an overall median age of 6 years at the first acute event. Oligoclonal bands were present in 56%, and both anti-MoG and anti–aquaporin-4 antibodies in 82%.
All children had abnormal brain MRI at baseline, with about 33% having gadolinium-enhancing brain lesions. Spinal cord MRI was abnormal in 50%, with 39% having gadolinium-enhancing lesions. According to the 2010 criteria, only three had a definitive MS diagnosis at baseline. The diagnosis was acute disseminated encephalomyelitis in 51%, clinically isolated syndrome in 31%, radiologically isolated syndrome in 2%, and nonencephalopathic disseminated encephalomyelitis in the remainder.
At baseline, three of those had a definitive MS diagnosis, displaying dissemination in both space and time as required by both the 2010 and 2017 criteria. The addition of oligoclonal band positivity added one more patient over the 2010 criteria, and assessing the cohort with the complete 2017 criteria added three more definitive diagnoses. This was a significant increase in definitive MS diagnoses when compared against the earlier criteria (70% vs. 30%).
Diagnoses changed in 10 other patients during follow-up. The single patient with radiologically isolated syndrome was definitively diagnosed with MS. Of the seven with clinically isolated syndrome, six were diagnosed with MS and one with a relapsing optic neuritis. Of the 28 with a nonencephalopathic encephalitis, 2 were diagnosed with optic neuritis.
The study also confirmed the benefit of adding oligoclonal bands as a diagnostic marker in children. Of those with an MS diagnosis at last follow-up, 71% were positive for the cerebrospinal fluid finding, compared with just 4% of those with a non-MS diagnosis. However, none of those children had anti-MoG antibodies, compared with 58% of those with a non-MS diagnosis. None of the patients were positive for anti–aquaporin-4, regardless of diagnosis.
That finding does not necessarily mean that the absence of anti-MoG antibodies can rule out an MS diagnosis in children, Dr. Arrambide cautioned. Nevertheless, the finding is a useful clinical marker during a diagnostic work-up.
“The presence of oligoclonal bands and the absence of MOG-IgG are both useful biomarkers when evaluating the risk of MS in children with a first demyelinating event,” she said.
She disclosed financial relationships with several pharmaceutical companies.
SOURCE: Arrambide G et al. ECTRIMS 2018, Abstract 64
REPORTING FROM ECTRIMS 2018
Key clinical point: The revised McDonald criteria increased definitive multiple sclerosis diagnoses in children.
Major finding: The 2017 criteria boosted pediatric diagnostic accuracy by 40%.
Study details: The prospective cohort study comprised 55 patients.
Disclosures: Dr. Arrambide disclosed relationships with several pharmaceutical companies.
Source: Arrambide G et al. ECTRIMS 2018, Abstract 64.
No elevated cancer risk with MS therapies in COMBAT-MS data
BERLIN – The risk of cancer – and breast cancer in particular – was not elevated above background levels in a large cohort of multiple sclerosis patients taking disease-modifying therapies.
Those findings from the large Nordic cohort study COMBAT-MS stand in contrast to previous work showing an elevated cancer risk for some monoclonal antibodies.
After statistical adjustment and use of rituximab (Rituxan) as the standard, the hazard ratio (HR) for any malignancy with fingolimod (Gilenya) was 1.74 (95% confidence interval, 0.92-3.28). For natalizumab (Tysabri), the malignancy HR was 1.06 (95% CI, 0.53-2.10), said Peter Alping, a PhD student in the department of clinical neuroscience at the Karolinska Institute, Stockholm.
Only limited data exist for real-world multiple sclerosis (MS) cohorts who have been exposed to novel disease-modifying therapies, said Mr. Alping, presenting the findings at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis. Rituximab has been studied in patients with rheumatoid arthritis, but the treatment regimens differ, as do patient characteristics, he noted. However, surveillance for risk of malignancy is important in these therapies, he said, “since modern disease-modifying therapies exert a more profound effect on the immune system, and we know that the immune system is vital in fighting and preventing cancers.”
The anti-CD20 monoclonal antibody ocrelizumab was studied in the ORATORIO trial. “There, they saw an imbalance in the numbers of breast cancers between the ocrelizumab and placebo groups,” said Mr. Alping, with raw data showing four breast cancers in the ocrelizumab population. However, this would translate to 26.1 cancers per 10,000 person-years, as opposed to the zero breast cancers seen in the placebo group (N Engl J Med. 2017;376:209-20).
“To what degree is cancer risk a concern with novel [disease-modifying therapy] use in MS?” Mr. Alping asked.
To answer the question, he and his colleagues from the Karolinska Institute sought to compare the risk of cancer in MS patients who were treated with rituximab, fingolimod, and natalizumab.
To do this, they conducted a nationwide cohort study using the Swedish MS registry, looking at treatment episodes between 2011 and 2016. In Sweden, the MS registry is also linked to the overall patient registry, as well as registries for cancer and prescription drug use. In addition, patient data are linked to national census data.
Mr. Alping and his colleagues looked at data for the first instance of use for an MS patient of rituximab, natalizumab, and/or fingolimod between the years 2011 and 2016. Then, they matched patient records from the general population by age, sex, and geographic location, enrolling the matched controls at the same time point as the MS match entered the study.
Patients treated with mitoxantrone, those who emigrated, and those who died during the study period were excluded from the study.
The statistical analysis, Mr. Alping said, used an ever-treated approach and didn’t attempt to weight exposure duration or dose. However, statistical adjustments were made for patient and control demographics and medical history, for any previous history of cancer, and for MS disease characteristics.
At baseline, 1,558 patients had been treated with fingolimod, 1,761 with natalizumab, and 3,012 with rituximab. A little less than one-third of the patients (26.3%-31.6%) were male, and the mean age was 35-43 years. Most patients (66%-86%) had undergone one or two previous therapies. The mean Expanded Disability Status Scale (EDSS) score was 2.20-2.88. Few patients (0.9%-1.7%) had any history of previous cancer.
Overall, the incidence of cancer in the MS cohort ranged from 23.09 per 10,000 person-years for rituximab ever-takers to 46.28 for those who had ever taken fingolimod. Among the general population, rates of any malignancy were 29.62 per 10,000 person-years.
Looking just at breast cancer, rates in the MS cohort ranged from 2.19 to 2.92/10,000 person-years. For the general population, the rate was 12.07/10,000 person-years.
However, using a Cox regression analysis employing MS-specific covariates and using rituximab as the reference, Mr. Alping and his colleagues calculated an inverse proportion-weighted hazard ratio for any malignancy under the various treatment conditions. Using this analysis, the HR for any cancer with fingolimod was 1.74 (95% CI, 0.92-3.28). For natalizumab, the malignancy HR was 1.06 (95% CI, 0.53-2.10).
Among just women taking rituximab, 2,274 therapy starts occurred, and one breast cancer was seen in 4,050 person-years. This yielded an incidence of 2.32 cancers per 10,000 person-years (95% CI, 0.06-12.9). This contrasts with the adjusted incidence rate in the general female population of 11.06 breast cancers per 10,000 person-years.
Looking at all the therapy episodes captured in the cohort study, there were 6,660 incidences of therapy initiation, and 52 malignancies were seen over 17,283 person-years, Mr. Alping said.
“For malignant cancer of any type, we found no increased risk for rituximab, compared to fingolimod and natalizumab,” Mr. Alping said, pointing to the wide confidence intervals in all the adjusted data. The incidence of breast cancer in women who have taken rituximab, he said, is “comparable to, or possibly lower than, that of the general female population, and lower than the incidence rate reported in the ORATORIO trial for ocrelizumab.
“The overall cancer risk and risk of breast cancer might not be major concerns short term when treating MS patients with rituximab relative to other disease-modifying therapies,” he said.
The study was partially funded by the Patient-Centered Outcomes Research Institute. Mr. Alping reported no conflicts of interest. One study author reported relationships with several pharmaceutical companies.
koakes@mdedge.com
SOURCE: Alping P et al. Mult Scler. 2018;24(Suppl 2):36. Abstract 89.
BERLIN – The risk of cancer – and breast cancer in particular – was not elevated above background levels in a large cohort of multiple sclerosis patients taking disease-modifying therapies.
Those findings from the large Nordic cohort study COMBAT-MS stand in contrast to previous work showing an elevated cancer risk for some monoclonal antibodies.
After statistical adjustment and use of rituximab (Rituxan) as the standard, the hazard ratio (HR) for any malignancy with fingolimod (Gilenya) was 1.74 (95% confidence interval, 0.92-3.28). For natalizumab (Tysabri), the malignancy HR was 1.06 (95% CI, 0.53-2.10), said Peter Alping, a PhD student in the department of clinical neuroscience at the Karolinska Institute, Stockholm.
Only limited data exist for real-world multiple sclerosis (MS) cohorts who have been exposed to novel disease-modifying therapies, said Mr. Alping, presenting the findings at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis. Rituximab has been studied in patients with rheumatoid arthritis, but the treatment regimens differ, as do patient characteristics, he noted. However, surveillance for risk of malignancy is important in these therapies, he said, “since modern disease-modifying therapies exert a more profound effect on the immune system, and we know that the immune system is vital in fighting and preventing cancers.”
The anti-CD20 monoclonal antibody ocrelizumab was studied in the ORATORIO trial. “There, they saw an imbalance in the numbers of breast cancers between the ocrelizumab and placebo groups,” said Mr. Alping, with raw data showing four breast cancers in the ocrelizumab population. However, this would translate to 26.1 cancers per 10,000 person-years, as opposed to the zero breast cancers seen in the placebo group (N Engl J Med. 2017;376:209-20).
“To what degree is cancer risk a concern with novel [disease-modifying therapy] use in MS?” Mr. Alping asked.
To answer the question, he and his colleagues from the Karolinska Institute sought to compare the risk of cancer in MS patients who were treated with rituximab, fingolimod, and natalizumab.
To do this, they conducted a nationwide cohort study using the Swedish MS registry, looking at treatment episodes between 2011 and 2016. In Sweden, the MS registry is also linked to the overall patient registry, as well as registries for cancer and prescription drug use. In addition, patient data are linked to national census data.
Mr. Alping and his colleagues looked at data for the first instance of use for an MS patient of rituximab, natalizumab, and/or fingolimod between the years 2011 and 2016. Then, they matched patient records from the general population by age, sex, and geographic location, enrolling the matched controls at the same time point as the MS match entered the study.
Patients treated with mitoxantrone, those who emigrated, and those who died during the study period were excluded from the study.
The statistical analysis, Mr. Alping said, used an ever-treated approach and didn’t attempt to weight exposure duration or dose. However, statistical adjustments were made for patient and control demographics and medical history, for any previous history of cancer, and for MS disease characteristics.
At baseline, 1,558 patients had been treated with fingolimod, 1,761 with natalizumab, and 3,012 with rituximab. A little less than one-third of the patients (26.3%-31.6%) were male, and the mean age was 35-43 years. Most patients (66%-86%) had undergone one or two previous therapies. The mean Expanded Disability Status Scale (EDSS) score was 2.20-2.88. Few patients (0.9%-1.7%) had any history of previous cancer.
Overall, the incidence of cancer in the MS cohort ranged from 23.09 per 10,000 person-years for rituximab ever-takers to 46.28 for those who had ever taken fingolimod. Among the general population, rates of any malignancy were 29.62 per 10,000 person-years.
Looking just at breast cancer, rates in the MS cohort ranged from 2.19 to 2.92/10,000 person-years. For the general population, the rate was 12.07/10,000 person-years.
However, using a Cox regression analysis employing MS-specific covariates and using rituximab as the reference, Mr. Alping and his colleagues calculated an inverse proportion-weighted hazard ratio for any malignancy under the various treatment conditions. Using this analysis, the HR for any cancer with fingolimod was 1.74 (95% CI, 0.92-3.28). For natalizumab, the malignancy HR was 1.06 (95% CI, 0.53-2.10).
Among just women taking rituximab, 2,274 therapy starts occurred, and one breast cancer was seen in 4,050 person-years. This yielded an incidence of 2.32 cancers per 10,000 person-years (95% CI, 0.06-12.9). This contrasts with the adjusted incidence rate in the general female population of 11.06 breast cancers per 10,000 person-years.
Looking at all the therapy episodes captured in the cohort study, there were 6,660 incidences of therapy initiation, and 52 malignancies were seen over 17,283 person-years, Mr. Alping said.
“For malignant cancer of any type, we found no increased risk for rituximab, compared to fingolimod and natalizumab,” Mr. Alping said, pointing to the wide confidence intervals in all the adjusted data. The incidence of breast cancer in women who have taken rituximab, he said, is “comparable to, or possibly lower than, that of the general female population, and lower than the incidence rate reported in the ORATORIO trial for ocrelizumab.
“The overall cancer risk and risk of breast cancer might not be major concerns short term when treating MS patients with rituximab relative to other disease-modifying therapies,” he said.
The study was partially funded by the Patient-Centered Outcomes Research Institute. Mr. Alping reported no conflicts of interest. One study author reported relationships with several pharmaceutical companies.
koakes@mdedge.com
SOURCE: Alping P et al. Mult Scler. 2018;24(Suppl 2):36. Abstract 89.
BERLIN – The risk of cancer – and breast cancer in particular – was not elevated above background levels in a large cohort of multiple sclerosis patients taking disease-modifying therapies.
Those findings from the large Nordic cohort study COMBAT-MS stand in contrast to previous work showing an elevated cancer risk for some monoclonal antibodies.
After statistical adjustment and use of rituximab (Rituxan) as the standard, the hazard ratio (HR) for any malignancy with fingolimod (Gilenya) was 1.74 (95% confidence interval, 0.92-3.28). For natalizumab (Tysabri), the malignancy HR was 1.06 (95% CI, 0.53-2.10), said Peter Alping, a PhD student in the department of clinical neuroscience at the Karolinska Institute, Stockholm.
Only limited data exist for real-world multiple sclerosis (MS) cohorts who have been exposed to novel disease-modifying therapies, said Mr. Alping, presenting the findings at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis. Rituximab has been studied in patients with rheumatoid arthritis, but the treatment regimens differ, as do patient characteristics, he noted. However, surveillance for risk of malignancy is important in these therapies, he said, “since modern disease-modifying therapies exert a more profound effect on the immune system, and we know that the immune system is vital in fighting and preventing cancers.”
The anti-CD20 monoclonal antibody ocrelizumab was studied in the ORATORIO trial. “There, they saw an imbalance in the numbers of breast cancers between the ocrelizumab and placebo groups,” said Mr. Alping, with raw data showing four breast cancers in the ocrelizumab population. However, this would translate to 26.1 cancers per 10,000 person-years, as opposed to the zero breast cancers seen in the placebo group (N Engl J Med. 2017;376:209-20).
“To what degree is cancer risk a concern with novel [disease-modifying therapy] use in MS?” Mr. Alping asked.
To answer the question, he and his colleagues from the Karolinska Institute sought to compare the risk of cancer in MS patients who were treated with rituximab, fingolimod, and natalizumab.
To do this, they conducted a nationwide cohort study using the Swedish MS registry, looking at treatment episodes between 2011 and 2016. In Sweden, the MS registry is also linked to the overall patient registry, as well as registries for cancer and prescription drug use. In addition, patient data are linked to national census data.
Mr. Alping and his colleagues looked at data for the first instance of use for an MS patient of rituximab, natalizumab, and/or fingolimod between the years 2011 and 2016. Then, they matched patient records from the general population by age, sex, and geographic location, enrolling the matched controls at the same time point as the MS match entered the study.
Patients treated with mitoxantrone, those who emigrated, and those who died during the study period were excluded from the study.
The statistical analysis, Mr. Alping said, used an ever-treated approach and didn’t attempt to weight exposure duration or dose. However, statistical adjustments were made for patient and control demographics and medical history, for any previous history of cancer, and for MS disease characteristics.
At baseline, 1,558 patients had been treated with fingolimod, 1,761 with natalizumab, and 3,012 with rituximab. A little less than one-third of the patients (26.3%-31.6%) were male, and the mean age was 35-43 years. Most patients (66%-86%) had undergone one or two previous therapies. The mean Expanded Disability Status Scale (EDSS) score was 2.20-2.88. Few patients (0.9%-1.7%) had any history of previous cancer.
Overall, the incidence of cancer in the MS cohort ranged from 23.09 per 10,000 person-years for rituximab ever-takers to 46.28 for those who had ever taken fingolimod. Among the general population, rates of any malignancy were 29.62 per 10,000 person-years.
Looking just at breast cancer, rates in the MS cohort ranged from 2.19 to 2.92/10,000 person-years. For the general population, the rate was 12.07/10,000 person-years.
However, using a Cox regression analysis employing MS-specific covariates and using rituximab as the reference, Mr. Alping and his colleagues calculated an inverse proportion-weighted hazard ratio for any malignancy under the various treatment conditions. Using this analysis, the HR for any cancer with fingolimod was 1.74 (95% CI, 0.92-3.28). For natalizumab, the malignancy HR was 1.06 (95% CI, 0.53-2.10).
Among just women taking rituximab, 2,274 therapy starts occurred, and one breast cancer was seen in 4,050 person-years. This yielded an incidence of 2.32 cancers per 10,000 person-years (95% CI, 0.06-12.9). This contrasts with the adjusted incidence rate in the general female population of 11.06 breast cancers per 10,000 person-years.
Looking at all the therapy episodes captured in the cohort study, there were 6,660 incidences of therapy initiation, and 52 malignancies were seen over 17,283 person-years, Mr. Alping said.
“For malignant cancer of any type, we found no increased risk for rituximab, compared to fingolimod and natalizumab,” Mr. Alping said, pointing to the wide confidence intervals in all the adjusted data. The incidence of breast cancer in women who have taken rituximab, he said, is “comparable to, or possibly lower than, that of the general female population, and lower than the incidence rate reported in the ORATORIO trial for ocrelizumab.
“The overall cancer risk and risk of breast cancer might not be major concerns short term when treating MS patients with rituximab relative to other disease-modifying therapies,” he said.
The study was partially funded by the Patient-Centered Outcomes Research Institute. Mr. Alping reported no conflicts of interest. One study author reported relationships with several pharmaceutical companies.
koakes@mdedge.com
SOURCE: Alping P et al. Mult Scler. 2018;24(Suppl 2):36. Abstract 89.
REPORTING FROM ECTRIMS 2018
Key clinical point:
Major finding: The hazard ratios for fingolimod and natalizumab versus rituximab were 1.74 and 1.06, respectively, with confidence intervals crossing 1.
Study details: Case-matched observational cohort study of 6,331 DMT-taking patients with MS.
Disclosures: The study was sponsored in part by the Patient-Centered Outcomes Research Institute. Mr. Alping reported no disclosures; one study author reported financial relationships with multiple pharmaceutical companies.
Source: Alping P et al. Mult Scler. 2018;24(Suppl 2):36. Abstract 89.
Research highlights the use of neurofilament light chain as a biomarker
Several papers presented at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis in Berlin will describe new developments on the topic.
A highlighted session on the congress’s last day explores recent development in progressive MS. While much of the research on using Nf-L as a biomarker focuses on relapsing remitting MS, researchers from University Hospital, Basel, Switzerland, and Novartis used data from placebo-controlled, phase 3 trials of fingolimod (INFORMS) and siponimod (EXPAND) to learn how to use biomarkers to track brain atrophy in patients with primary and secondary progressive MS. Hear the results from lead researcher Jens Kuhle, MD, in Hall A at 10:30 a.m. (local time) on Friday, Oct. 12.
Nf-L also is being looked at as a way to suss out treatment failure. Researchers with the Swiss MS Cohort Study will present their study of Nf-L as a biomarker of suboptimal treatment response in patients with relapsing remitting MS on established disease-modifying therapy. Their findings will be presented by Özguer Yaldizli, MD, also of University Hospital, also in Hall A, at 8:30 a.m. (local time) on Friday, Oct. 12.
Follow #ECTRIMS2018 on Twitter to see live highlights and perspective from researchers and meeting attendees.
Several papers presented at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis in Berlin will describe new developments on the topic.
A highlighted session on the congress’s last day explores recent development in progressive MS. While much of the research on using Nf-L as a biomarker focuses on relapsing remitting MS, researchers from University Hospital, Basel, Switzerland, and Novartis used data from placebo-controlled, phase 3 trials of fingolimod (INFORMS) and siponimod (EXPAND) to learn how to use biomarkers to track brain atrophy in patients with primary and secondary progressive MS. Hear the results from lead researcher Jens Kuhle, MD, in Hall A at 10:30 a.m. (local time) on Friday, Oct. 12.
Nf-L also is being looked at as a way to suss out treatment failure. Researchers with the Swiss MS Cohort Study will present their study of Nf-L as a biomarker of suboptimal treatment response in patients with relapsing remitting MS on established disease-modifying therapy. Their findings will be presented by Özguer Yaldizli, MD, also of University Hospital, also in Hall A, at 8:30 a.m. (local time) on Friday, Oct. 12.
Follow #ECTRIMS2018 on Twitter to see live highlights and perspective from researchers and meeting attendees.
Several papers presented at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis in Berlin will describe new developments on the topic.
A highlighted session on the congress’s last day explores recent development in progressive MS. While much of the research on using Nf-L as a biomarker focuses on relapsing remitting MS, researchers from University Hospital, Basel, Switzerland, and Novartis used data from placebo-controlled, phase 3 trials of fingolimod (INFORMS) and siponimod (EXPAND) to learn how to use biomarkers to track brain atrophy in patients with primary and secondary progressive MS. Hear the results from lead researcher Jens Kuhle, MD, in Hall A at 10:30 a.m. (local time) on Friday, Oct. 12.
Nf-L also is being looked at as a way to suss out treatment failure. Researchers with the Swiss MS Cohort Study will present their study of Nf-L as a biomarker of suboptimal treatment response in patients with relapsing remitting MS on established disease-modifying therapy. Their findings will be presented by Özguer Yaldizli, MD, also of University Hospital, also in Hall A, at 8:30 a.m. (local time) on Friday, Oct. 12.
Follow #ECTRIMS2018 on Twitter to see live highlights and perspective from researchers and meeting attendees.
REPORTING FROM ECTRIMS 2018
Revised McDonald criteria to be explored at ECTRIMS
The revised McDonald criteria, issued less than a year ago in December 2017, should allow for earlier diagnosis and treatment of multiple sclerosis, but also could be leading to overdiagnosis and misdiagnosis.
A recent study published in JAMA Neurology found that sensitivity for the 2017 criteria was greater (68% vs. 36% for the 2010 criteria) but specificity was not (61% vs. 85%, respectively), based on a study of several hundred patients in the Netherlands with clinically isolated syndrome.
A highlighted session on Saturday, Oct. 10, at 2:30 p.m. (local time) entitled “Burning Debate: The new McDonald diagnostic criteria are controversial making them difficult to use in clinical practice” aims to shed some light. After an introduction from Emmanuelle Waubant, MD, professor of neurology at the University of California, San Francisco, the topic will be debated by Jiwon Oh, MD, of the University of Toronto and Frauke Zipp, MD, of the University of Mainz (Germany). The experts will take questions from the audience as well as via Twitter. Ask your questions using the meeting hashtag #ECTRIMS2018. Find the session in Hall B.
Five new papers on the impact of the revised criteria will be presented in Hall A on Sunday, Oct. 11, at 8:30 a.m. (local time). Among the investigators presenting are Roos M. van der Vuurst de Vries, MD, from the department of neurology at Erasmus Medical Center in Rotterdam, the Netherlands, who authored the recent JAMA Neurology paper, and Wallace Brownlee, MD, of University College London.
The revised McDonald criteria, issued less than a year ago in December 2017, should allow for earlier diagnosis and treatment of multiple sclerosis, but also could be leading to overdiagnosis and misdiagnosis.
A recent study published in JAMA Neurology found that sensitivity for the 2017 criteria was greater (68% vs. 36% for the 2010 criteria) but specificity was not (61% vs. 85%, respectively), based on a study of several hundred patients in the Netherlands with clinically isolated syndrome.
A highlighted session on Saturday, Oct. 10, at 2:30 p.m. (local time) entitled “Burning Debate: The new McDonald diagnostic criteria are controversial making them difficult to use in clinical practice” aims to shed some light. After an introduction from Emmanuelle Waubant, MD, professor of neurology at the University of California, San Francisco, the topic will be debated by Jiwon Oh, MD, of the University of Toronto and Frauke Zipp, MD, of the University of Mainz (Germany). The experts will take questions from the audience as well as via Twitter. Ask your questions using the meeting hashtag #ECTRIMS2018. Find the session in Hall B.
Five new papers on the impact of the revised criteria will be presented in Hall A on Sunday, Oct. 11, at 8:30 a.m. (local time). Among the investigators presenting are Roos M. van der Vuurst de Vries, MD, from the department of neurology at Erasmus Medical Center in Rotterdam, the Netherlands, who authored the recent JAMA Neurology paper, and Wallace Brownlee, MD, of University College London.
The revised McDonald criteria, issued less than a year ago in December 2017, should allow for earlier diagnosis and treatment of multiple sclerosis, but also could be leading to overdiagnosis and misdiagnosis.
A recent study published in JAMA Neurology found that sensitivity for the 2017 criteria was greater (68% vs. 36% for the 2010 criteria) but specificity was not (61% vs. 85%, respectively), based on a study of several hundred patients in the Netherlands with clinically isolated syndrome.
A highlighted session on Saturday, Oct. 10, at 2:30 p.m. (local time) entitled “Burning Debate: The new McDonald diagnostic criteria are controversial making them difficult to use in clinical practice” aims to shed some light. After an introduction from Emmanuelle Waubant, MD, professor of neurology at the University of California, San Francisco, the topic will be debated by Jiwon Oh, MD, of the University of Toronto and Frauke Zipp, MD, of the University of Mainz (Germany). The experts will take questions from the audience as well as via Twitter. Ask your questions using the meeting hashtag #ECTRIMS2018. Find the session in Hall B.
Five new papers on the impact of the revised criteria will be presented in Hall A on Sunday, Oct. 11, at 8:30 a.m. (local time). Among the investigators presenting are Roos M. van der Vuurst de Vries, MD, from the department of neurology at Erasmus Medical Center in Rotterdam, the Netherlands, who authored the recent JAMA Neurology paper, and Wallace Brownlee, MD, of University College London.
REPORTING FROM ECTRIMS 2018
Hot topic explores neuropathologic differences between MS individuals
One of the first sessions to begin the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis in Berlin takes a close look at how researchers are honing in on the mechanisms and cellular and molecular mediators that shape the ways in which multiple sclerosis neuropathology differs between individuals.
In the first presentation of the session “Hot Topic 1: Hot topics in MS neuropathology” at 8:00 a.m. (local time) on Oct. 10, Bruce Trapp, PhD, will present the details of the recently published study that he and his associates at the Cleveland Clinic in Ohio conducted on the brains of postmortem MS patients. They describe a new disease subtype, called myelocortical MS, that they characterized through 12 postmortem MS brains in which there was cortical neuronal loss and demyelination of spinal cord and cerebral cortex in the absence of cerebral white matter demyelination.
But what might be driving the degeneration of cerebral gray matter in MS patients, particularly in the cortex? Roberta Magliozzi, PhD, of the University of Verona (Italy), will follow Dr. Trapp’s talk with a presentation of recent neuropathologic findings describing a specific inflammatory protein profile in cerebrospinal fluid (CSF) stemming from meningeal infiltrates and circulating cells in the subarachnoid space that could account for differences in the speed of physical and cognitive disability progression between individuals with MS. Earlier research by Dr. Magliozzi and her colleagues characterized some of these CSF biomarkers. Whether the specific CSF inflammatory pattern proves to be a good surrogate for meningeal inflammation and thereby a good predictor of which MS patients may develop more severe gray matter demyelination and a higher risk of disease progression needs to be examined further.
In the final talk, Claudia Lucchinetti, MD, of the Mayo Clinic, Rochester, Minn., will describe the latest understanding of the pathology of radiologically isolated syndrome.
One of the first sessions to begin the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis in Berlin takes a close look at how researchers are honing in on the mechanisms and cellular and molecular mediators that shape the ways in which multiple sclerosis neuropathology differs between individuals.
In the first presentation of the session “Hot Topic 1: Hot topics in MS neuropathology” at 8:00 a.m. (local time) on Oct. 10, Bruce Trapp, PhD, will present the details of the recently published study that he and his associates at the Cleveland Clinic in Ohio conducted on the brains of postmortem MS patients. They describe a new disease subtype, called myelocortical MS, that they characterized through 12 postmortem MS brains in which there was cortical neuronal loss and demyelination of spinal cord and cerebral cortex in the absence of cerebral white matter demyelination.
But what might be driving the degeneration of cerebral gray matter in MS patients, particularly in the cortex? Roberta Magliozzi, PhD, of the University of Verona (Italy), will follow Dr. Trapp’s talk with a presentation of recent neuropathologic findings describing a specific inflammatory protein profile in cerebrospinal fluid (CSF) stemming from meningeal infiltrates and circulating cells in the subarachnoid space that could account for differences in the speed of physical and cognitive disability progression between individuals with MS. Earlier research by Dr. Magliozzi and her colleagues characterized some of these CSF biomarkers. Whether the specific CSF inflammatory pattern proves to be a good surrogate for meningeal inflammation and thereby a good predictor of which MS patients may develop more severe gray matter demyelination and a higher risk of disease progression needs to be examined further.
In the final talk, Claudia Lucchinetti, MD, of the Mayo Clinic, Rochester, Minn., will describe the latest understanding of the pathology of radiologically isolated syndrome.
One of the first sessions to begin the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis in Berlin takes a close look at how researchers are honing in on the mechanisms and cellular and molecular mediators that shape the ways in which multiple sclerosis neuropathology differs between individuals.
In the first presentation of the session “Hot Topic 1: Hot topics in MS neuropathology” at 8:00 a.m. (local time) on Oct. 10, Bruce Trapp, PhD, will present the details of the recently published study that he and his associates at the Cleveland Clinic in Ohio conducted on the brains of postmortem MS patients. They describe a new disease subtype, called myelocortical MS, that they characterized through 12 postmortem MS brains in which there was cortical neuronal loss and demyelination of spinal cord and cerebral cortex in the absence of cerebral white matter demyelination.
But what might be driving the degeneration of cerebral gray matter in MS patients, particularly in the cortex? Roberta Magliozzi, PhD, of the University of Verona (Italy), will follow Dr. Trapp’s talk with a presentation of recent neuropathologic findings describing a specific inflammatory protein profile in cerebrospinal fluid (CSF) stemming from meningeal infiltrates and circulating cells in the subarachnoid space that could account for differences in the speed of physical and cognitive disability progression between individuals with MS. Earlier research by Dr. Magliozzi and her colleagues characterized some of these CSF biomarkers. Whether the specific CSF inflammatory pattern proves to be a good surrogate for meningeal inflammation and thereby a good predictor of which MS patients may develop more severe gray matter demyelination and a higher risk of disease progression needs to be examined further.
In the final talk, Claudia Lucchinetti, MD, of the Mayo Clinic, Rochester, Minn., will describe the latest understanding of the pathology of radiologically isolated syndrome.
REPORTING FROM ECTRIMS 2018