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No ADT-dementia link in large VA prostate cancer cohort study
In contrast to other recent studies, androgen deprivation therapy (ADT) had no link to dementia in a observational cohort study of more than 45,000 men with prostate cancer who received definitive radiotherapy, investigators have reported.
No significant associations were found between ADT and Alzheimer’s disease or vascular dementia, or between shorter or longer courses of ADT and any dementia studied, according to Rishi Deka, PhD, of Veterans Affairs San Diego Health Care System, La Jolla, Calif., and coinvestigators.
“These results may mitigate concerns regarding the long-term risks of ADT on cognitive health in the treatment of prostate cancer,” Dr. Deka and colleagues wrote in JAMA Oncology.
Two other recent studies showed strong, statistically significant associations between ADT and dementia in prostate cancer. However, those studies combined patients with local and metastatic disease, receiving ADT in the upfront or recurrent settings, while the present study looked specifically at men with nonmetastatic prostate cancer who received radiotherapy.
“Different treatment modalities and disease stages are associated with substantial selection bias that may predispose results to false associations,” noted Dr. Deka and coauthors.
Their observational cohort study comprised 45,218 men diagnosed with nonmetastatic prostate cancer at the U.S. Department of Veterans Affairs who underwent radiotherapy with or without ADT. The investigators excluded men who had a diagnosis of dementia within 1 year of the prostate cancer diagnosis or who had prior diagnoses of dementia, stroke, or cognitive impairment.
A total of 1,497 patients were diagnosed with dementia over a median of 6.8 years of follow-up: 404 with Alzheimer disease, 335 with vascular dementia, and 758 with other types or unclassified dementias.
The investigators found no significant association between use of ADT and development of any dementia, the primary outcome of the analysis (subdistribution hazard ratio [SHR], 1.04; 95% confidence interval, 0.94-1.16; P = .43).
Likewise, there was no association between ADT and vascular dementia, specifically, with an SHR of 1.20 (95% CI, 0.97-1.50; P = .10) or Alzheimer’s disease, with an SHR of 1.11 (95% CI, 0.91-1.36; P = .29).
Duration of ADT longer than 1 year was not significantly associated with dementia, nor was duration shorter than 1 year, with SHRs, of 1.08 and 1.01 respectively, the analysis shows.
The SHRs in these and other analysis reported ranged from 1.00 to 1.21. That is substantially lower than hazard ratios of 1.66 to 2.32 in one previous study linking ADT to dementia, according to the investigators, suggesting that the results of the current analysis were not due to inadequate power to detect differences.
Nevertheless, the findings may not be generalizable to some other populations, they cautioned, since it was focused demographically on veterans, and was limited to radiotherapy-treated patients.
Dr. Deka and coauthors reported no conflict of interest. Their study was funded by grants from the University of California San Diego Center for Precision Radiation Medicine.
SOURCE: Deka R et al. JAMA Oncol. 2018 Oct 11. doi: 10.1001/jamaoncol.2018.4423.
In contrast to other recent studies, androgen deprivation therapy (ADT) had no link to dementia in a observational cohort study of more than 45,000 men with prostate cancer who received definitive radiotherapy, investigators have reported.
No significant associations were found between ADT and Alzheimer’s disease or vascular dementia, or between shorter or longer courses of ADT and any dementia studied, according to Rishi Deka, PhD, of Veterans Affairs San Diego Health Care System, La Jolla, Calif., and coinvestigators.
“These results may mitigate concerns regarding the long-term risks of ADT on cognitive health in the treatment of prostate cancer,” Dr. Deka and colleagues wrote in JAMA Oncology.
Two other recent studies showed strong, statistically significant associations between ADT and dementia in prostate cancer. However, those studies combined patients with local and metastatic disease, receiving ADT in the upfront or recurrent settings, while the present study looked specifically at men with nonmetastatic prostate cancer who received radiotherapy.
“Different treatment modalities and disease stages are associated with substantial selection bias that may predispose results to false associations,” noted Dr. Deka and coauthors.
Their observational cohort study comprised 45,218 men diagnosed with nonmetastatic prostate cancer at the U.S. Department of Veterans Affairs who underwent radiotherapy with or without ADT. The investigators excluded men who had a diagnosis of dementia within 1 year of the prostate cancer diagnosis or who had prior diagnoses of dementia, stroke, or cognitive impairment.
A total of 1,497 patients were diagnosed with dementia over a median of 6.8 years of follow-up: 404 with Alzheimer disease, 335 with vascular dementia, and 758 with other types or unclassified dementias.
The investigators found no significant association between use of ADT and development of any dementia, the primary outcome of the analysis (subdistribution hazard ratio [SHR], 1.04; 95% confidence interval, 0.94-1.16; P = .43).
Likewise, there was no association between ADT and vascular dementia, specifically, with an SHR of 1.20 (95% CI, 0.97-1.50; P = .10) or Alzheimer’s disease, with an SHR of 1.11 (95% CI, 0.91-1.36; P = .29).
Duration of ADT longer than 1 year was not significantly associated with dementia, nor was duration shorter than 1 year, with SHRs, of 1.08 and 1.01 respectively, the analysis shows.
The SHRs in these and other analysis reported ranged from 1.00 to 1.21. That is substantially lower than hazard ratios of 1.66 to 2.32 in one previous study linking ADT to dementia, according to the investigators, suggesting that the results of the current analysis were not due to inadequate power to detect differences.
Nevertheless, the findings may not be generalizable to some other populations, they cautioned, since it was focused demographically on veterans, and was limited to radiotherapy-treated patients.
Dr. Deka and coauthors reported no conflict of interest. Their study was funded by grants from the University of California San Diego Center for Precision Radiation Medicine.
SOURCE: Deka R et al. JAMA Oncol. 2018 Oct 11. doi: 10.1001/jamaoncol.2018.4423.
In contrast to other recent studies, androgen deprivation therapy (ADT) had no link to dementia in a observational cohort study of more than 45,000 men with prostate cancer who received definitive radiotherapy, investigators have reported.
No significant associations were found between ADT and Alzheimer’s disease or vascular dementia, or between shorter or longer courses of ADT and any dementia studied, according to Rishi Deka, PhD, of Veterans Affairs San Diego Health Care System, La Jolla, Calif., and coinvestigators.
“These results may mitigate concerns regarding the long-term risks of ADT on cognitive health in the treatment of prostate cancer,” Dr. Deka and colleagues wrote in JAMA Oncology.
Two other recent studies showed strong, statistically significant associations between ADT and dementia in prostate cancer. However, those studies combined patients with local and metastatic disease, receiving ADT in the upfront or recurrent settings, while the present study looked specifically at men with nonmetastatic prostate cancer who received radiotherapy.
“Different treatment modalities and disease stages are associated with substantial selection bias that may predispose results to false associations,” noted Dr. Deka and coauthors.
Their observational cohort study comprised 45,218 men diagnosed with nonmetastatic prostate cancer at the U.S. Department of Veterans Affairs who underwent radiotherapy with or without ADT. The investigators excluded men who had a diagnosis of dementia within 1 year of the prostate cancer diagnosis or who had prior diagnoses of dementia, stroke, or cognitive impairment.
A total of 1,497 patients were diagnosed with dementia over a median of 6.8 years of follow-up: 404 with Alzheimer disease, 335 with vascular dementia, and 758 with other types or unclassified dementias.
The investigators found no significant association between use of ADT and development of any dementia, the primary outcome of the analysis (subdistribution hazard ratio [SHR], 1.04; 95% confidence interval, 0.94-1.16; P = .43).
Likewise, there was no association between ADT and vascular dementia, specifically, with an SHR of 1.20 (95% CI, 0.97-1.50; P = .10) or Alzheimer’s disease, with an SHR of 1.11 (95% CI, 0.91-1.36; P = .29).
Duration of ADT longer than 1 year was not significantly associated with dementia, nor was duration shorter than 1 year, with SHRs, of 1.08 and 1.01 respectively, the analysis shows.
The SHRs in these and other analysis reported ranged from 1.00 to 1.21. That is substantially lower than hazard ratios of 1.66 to 2.32 in one previous study linking ADT to dementia, according to the investigators, suggesting that the results of the current analysis were not due to inadequate power to detect differences.
Nevertheless, the findings may not be generalizable to some other populations, they cautioned, since it was focused demographically on veterans, and was limited to radiotherapy-treated patients.
Dr. Deka and coauthors reported no conflict of interest. Their study was funded by grants from the University of California San Diego Center for Precision Radiation Medicine.
SOURCE: Deka R et al. JAMA Oncol. 2018 Oct 11. doi: 10.1001/jamaoncol.2018.4423.
FROM JAMA ONCOLOGY
Key clinical point: In contrast with other recent investigations in prostate cancer, researchers found no link between androgen deprivation therapy (ADT) and development of dementia.
Major finding: No significant association was found between use of ADT and development of any dementia (subdistribution hazard ratio [SHR], 1.04; 95% CI, 0.94-1.16; P = .43).
Study details: Observational cohort study of more than 45,000 veterans with nonmetastatic prostate cancer treated with radiotherapy with or without ADT.
Disclosures: This study was funded by grants from the University of California San Diego Center for Precision Radiation Medicine. Dr. Deka and coauthors reported no conflict of interest disclosures related to the work.
Source: Deka R et al. JAMA Oncol. 2018 Oct 11. doi: 10.1001/jamaoncol.2018.4423.
Which Patients Have the Best Chance With Checkpoint Inhibitors?
Checkpoint inhibitors are so new that not enough patients have received them to allow clinicians to predict who will benefit most. But researchers from the National Cancer Institute, Center for Cancer Institute; Harvard University in Cambridge, Massachusetts; University of Pennsylvania in Philadelphia; and University of Maryland in College Park may have found a clue: A gene expression predictor.
They began by looking at neuroblastoma cases where the immune system seemed to mount “an unprompted, successful immune response” to cancer, causing spontaneous tumor regression. The researchers were able to define gene expression features that separated regressing from nonregressing disease.
The researchers then computed Immuno-PREdictive Scores (IMPRES) for each patient sample. The higher the score, the more likely was spontaneous regression. Analyzing 297 samples from several studies, they found the predictor identified nearly all patients who responded to the inhibitors and more than half of those who did not. “Importantly,” the researchers say, their predictor was accurate across many different melanoma patient datasets.
Checkpoint inhibitors are so new that not enough patients have received them to allow clinicians to predict who will benefit most. But researchers from the National Cancer Institute, Center for Cancer Institute; Harvard University in Cambridge, Massachusetts; University of Pennsylvania in Philadelphia; and University of Maryland in College Park may have found a clue: A gene expression predictor.
They began by looking at neuroblastoma cases where the immune system seemed to mount “an unprompted, successful immune response” to cancer, causing spontaneous tumor regression. The researchers were able to define gene expression features that separated regressing from nonregressing disease.
The researchers then computed Immuno-PREdictive Scores (IMPRES) for each patient sample. The higher the score, the more likely was spontaneous regression. Analyzing 297 samples from several studies, they found the predictor identified nearly all patients who responded to the inhibitors and more than half of those who did not. “Importantly,” the researchers say, their predictor was accurate across many different melanoma patient datasets.
Checkpoint inhibitors are so new that not enough patients have received them to allow clinicians to predict who will benefit most. But researchers from the National Cancer Institute, Center for Cancer Institute; Harvard University in Cambridge, Massachusetts; University of Pennsylvania in Philadelphia; and University of Maryland in College Park may have found a clue: A gene expression predictor.
They began by looking at neuroblastoma cases where the immune system seemed to mount “an unprompted, successful immune response” to cancer, causing spontaneous tumor regression. The researchers were able to define gene expression features that separated regressing from nonregressing disease.
The researchers then computed Immuno-PREdictive Scores (IMPRES) for each patient sample. The higher the score, the more likely was spontaneous regression. Analyzing 297 samples from several studies, they found the predictor identified nearly all patients who responded to the inhibitors and more than half of those who did not. “Importantly,” the researchers say, their predictor was accurate across many different melanoma patient datasets.
Nf-L levels predictive of brain atrophy, disability in progressive MS
BERLIN – Neurofilament light chain (Nf-L) levels are higher in the plasma of patients with secondary progressive multiple sclerosis (SPMS) than primary progressive multiple sclerosis (PPMS) irrespective of age, according to an analysis of blood samples from two large phase 3 trials.
“Our data suggest that Nf-L should be considered as an informative endpoint for phase 2 studies in SPMS,” said the presenting study author Ludwig Kappos, MD, at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.
Much of the research on using Nf-L as a biomarker in MS to date has looked at patients with relapsing-remitting MS and the researchers wanted to see if Nf-L might be a useful biomarker in progressive MS because drug development in this area needs long-term and large trials to show an effect of a drug on disability. Conventional magnetic resonance imaging measures show only a modest association with disease evolution in SPMS and PPMS, and, as Nf-L is specific to neuronal damage, it should reflect damage to the brain and spinal cord, Dr. Kappos explained.
The aim of the study was to compare Nf-L levels in the two progressive subtypes of MS – SPMS and PPMS – and to see if it had any predictive value in determining the degree of brain atrophy or disability. Other objectives were to measure the sensitivity for Nf-L to detect treatment effects, and to estimate how big a sample size would be needed in a phase 2 study if it was used as a primary endpoint.
Blood samples from 1,830 patients who had participated in one of two phase 3 studies of siponimod in SPMS (EXPAND) and fingolimod (Gilyena) in PPMS (INFORMS). Nf-L levels were measured retrospectively in plasma using the SIMOA Nf-L immunoassay and categorized as being low (less than 30 pg/mL), medium (30-60 pg/mL), or high (greater than 60 pg/mL). Brain volume change on MRI was calculated using the SIENA (Structural Image Evaluation, using Normalization, of Atrophy) method, and disability changes assessed were evaluated by the Expanded Disability Status Scale (EDSS) score
“One of the confounders of measuring Nf-L is age,” Dr. Kappos acknowledged, “but we see a difference between SPMS and PPMS that is robust along the spectrum of ages.” The geometric mean of Nf-L at baseline was 32.1 pg/mL in patients with SPMS (n = 1,452) and 22.0 pg/mL in those with PPMS (n = 378).
Multiple regression analysis showed that, in both SPMS and PPMS patients, higher Nf-L levels were associated with older age and higher disease activity (increased EDSS score, more gadolinium-enhancing (Gd+) lesions and higher T2 lesion load).
Greater brain loss was seen at both 12 and 24 months in patients with high versus low Nf-L levels at baseline in both the SPMS and PPMS groups. For example, comparing high versus low Nf-L in SPMS, the mean brain volume change from baseline was –0.8% vs. –0.2% (P less than .0001) at 12 months and –1.5% vs. –0.5% at 24 months (P less than .0001). Corresponding values for PPMS were –0.8% vs. –0.4% (P = .0044) and –1.9% vs. –0.8% (P less than .0001).
Nf-L levels of 30 pg/mL were associated with a 32% increased risk of disability progression in patients with SPMS (P = .0055) and a 49% increased risk of disability progression in patients with PPMS (P = .0268).
In both groups of progressive MS patients, Nf-L levels were reduced in response to treatment at both 12 and 24 months, which remained significant.
“So, what about sample size calculation for a 1-year, phase 2 study with Nf-L as a primary endpoint?” Dr. Kappos queried. Assuming a reduction in Nf-L of 20% with a test drug, such a study would be likely to need to include 188 patients, or 94 patients per single arm to have 80% statistical power. To see a 30% reduction in Nf-L, fewer total and single-arm numbers would be needed, at 74 and 37 participants, respectively.
The study was funded by Novartis Pharma AG, Basel, Switzerland. Dr. Kappos disclosed that his institution (University Hospital Basel) had received steering committee, advisory board, and consultancy fees in the last 3 years that had been used exclusively for research support at the department from Novartis and a number of other pharmaceutical manufacturers. The Research of the MS Centre in Basel has been supported by grants from Bayer, Biogen, Novartis, the Swiss MS Society, the Swiss National Research Foundation, the European Union, and Roche Research Foundations.
SOURCE: Kuhle J et al. ECTRIMS 2018. Mult Scler. 2018;24(Suppl 2):111, Abstract 286.
BERLIN – Neurofilament light chain (Nf-L) levels are higher in the plasma of patients with secondary progressive multiple sclerosis (SPMS) than primary progressive multiple sclerosis (PPMS) irrespective of age, according to an analysis of blood samples from two large phase 3 trials.
“Our data suggest that Nf-L should be considered as an informative endpoint for phase 2 studies in SPMS,” said the presenting study author Ludwig Kappos, MD, at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.
Much of the research on using Nf-L as a biomarker in MS to date has looked at patients with relapsing-remitting MS and the researchers wanted to see if Nf-L might be a useful biomarker in progressive MS because drug development in this area needs long-term and large trials to show an effect of a drug on disability. Conventional magnetic resonance imaging measures show only a modest association with disease evolution in SPMS and PPMS, and, as Nf-L is specific to neuronal damage, it should reflect damage to the brain and spinal cord, Dr. Kappos explained.
The aim of the study was to compare Nf-L levels in the two progressive subtypes of MS – SPMS and PPMS – and to see if it had any predictive value in determining the degree of brain atrophy or disability. Other objectives were to measure the sensitivity for Nf-L to detect treatment effects, and to estimate how big a sample size would be needed in a phase 2 study if it was used as a primary endpoint.
Blood samples from 1,830 patients who had participated in one of two phase 3 studies of siponimod in SPMS (EXPAND) and fingolimod (Gilyena) in PPMS (INFORMS). Nf-L levels were measured retrospectively in plasma using the SIMOA Nf-L immunoassay and categorized as being low (less than 30 pg/mL), medium (30-60 pg/mL), or high (greater than 60 pg/mL). Brain volume change on MRI was calculated using the SIENA (Structural Image Evaluation, using Normalization, of Atrophy) method, and disability changes assessed were evaluated by the Expanded Disability Status Scale (EDSS) score
“One of the confounders of measuring Nf-L is age,” Dr. Kappos acknowledged, “but we see a difference between SPMS and PPMS that is robust along the spectrum of ages.” The geometric mean of Nf-L at baseline was 32.1 pg/mL in patients with SPMS (n = 1,452) and 22.0 pg/mL in those with PPMS (n = 378).
Multiple regression analysis showed that, in both SPMS and PPMS patients, higher Nf-L levels were associated with older age and higher disease activity (increased EDSS score, more gadolinium-enhancing (Gd+) lesions and higher T2 lesion load).
Greater brain loss was seen at both 12 and 24 months in patients with high versus low Nf-L levels at baseline in both the SPMS and PPMS groups. For example, comparing high versus low Nf-L in SPMS, the mean brain volume change from baseline was –0.8% vs. –0.2% (P less than .0001) at 12 months and –1.5% vs. –0.5% at 24 months (P less than .0001). Corresponding values for PPMS were –0.8% vs. –0.4% (P = .0044) and –1.9% vs. –0.8% (P less than .0001).
Nf-L levels of 30 pg/mL were associated with a 32% increased risk of disability progression in patients with SPMS (P = .0055) and a 49% increased risk of disability progression in patients with PPMS (P = .0268).
In both groups of progressive MS patients, Nf-L levels were reduced in response to treatment at both 12 and 24 months, which remained significant.
“So, what about sample size calculation for a 1-year, phase 2 study with Nf-L as a primary endpoint?” Dr. Kappos queried. Assuming a reduction in Nf-L of 20% with a test drug, such a study would be likely to need to include 188 patients, or 94 patients per single arm to have 80% statistical power. To see a 30% reduction in Nf-L, fewer total and single-arm numbers would be needed, at 74 and 37 participants, respectively.
The study was funded by Novartis Pharma AG, Basel, Switzerland. Dr. Kappos disclosed that his institution (University Hospital Basel) had received steering committee, advisory board, and consultancy fees in the last 3 years that had been used exclusively for research support at the department from Novartis and a number of other pharmaceutical manufacturers. The Research of the MS Centre in Basel has been supported by grants from Bayer, Biogen, Novartis, the Swiss MS Society, the Swiss National Research Foundation, the European Union, and Roche Research Foundations.
SOURCE: Kuhle J et al. ECTRIMS 2018. Mult Scler. 2018;24(Suppl 2):111, Abstract 286.
BERLIN – Neurofilament light chain (Nf-L) levels are higher in the plasma of patients with secondary progressive multiple sclerosis (SPMS) than primary progressive multiple sclerosis (PPMS) irrespective of age, according to an analysis of blood samples from two large phase 3 trials.
“Our data suggest that Nf-L should be considered as an informative endpoint for phase 2 studies in SPMS,” said the presenting study author Ludwig Kappos, MD, at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.
Much of the research on using Nf-L as a biomarker in MS to date has looked at patients with relapsing-remitting MS and the researchers wanted to see if Nf-L might be a useful biomarker in progressive MS because drug development in this area needs long-term and large trials to show an effect of a drug on disability. Conventional magnetic resonance imaging measures show only a modest association with disease evolution in SPMS and PPMS, and, as Nf-L is specific to neuronal damage, it should reflect damage to the brain and spinal cord, Dr. Kappos explained.
The aim of the study was to compare Nf-L levels in the two progressive subtypes of MS – SPMS and PPMS – and to see if it had any predictive value in determining the degree of brain atrophy or disability. Other objectives were to measure the sensitivity for Nf-L to detect treatment effects, and to estimate how big a sample size would be needed in a phase 2 study if it was used as a primary endpoint.
Blood samples from 1,830 patients who had participated in one of two phase 3 studies of siponimod in SPMS (EXPAND) and fingolimod (Gilyena) in PPMS (INFORMS). Nf-L levels were measured retrospectively in plasma using the SIMOA Nf-L immunoassay and categorized as being low (less than 30 pg/mL), medium (30-60 pg/mL), or high (greater than 60 pg/mL). Brain volume change on MRI was calculated using the SIENA (Structural Image Evaluation, using Normalization, of Atrophy) method, and disability changes assessed were evaluated by the Expanded Disability Status Scale (EDSS) score
“One of the confounders of measuring Nf-L is age,” Dr. Kappos acknowledged, “but we see a difference between SPMS and PPMS that is robust along the spectrum of ages.” The geometric mean of Nf-L at baseline was 32.1 pg/mL in patients with SPMS (n = 1,452) and 22.0 pg/mL in those with PPMS (n = 378).
Multiple regression analysis showed that, in both SPMS and PPMS patients, higher Nf-L levels were associated with older age and higher disease activity (increased EDSS score, more gadolinium-enhancing (Gd+) lesions and higher T2 lesion load).
Greater brain loss was seen at both 12 and 24 months in patients with high versus low Nf-L levels at baseline in both the SPMS and PPMS groups. For example, comparing high versus low Nf-L in SPMS, the mean brain volume change from baseline was –0.8% vs. –0.2% (P less than .0001) at 12 months and –1.5% vs. –0.5% at 24 months (P less than .0001). Corresponding values for PPMS were –0.8% vs. –0.4% (P = .0044) and –1.9% vs. –0.8% (P less than .0001).
Nf-L levels of 30 pg/mL were associated with a 32% increased risk of disability progression in patients with SPMS (P = .0055) and a 49% increased risk of disability progression in patients with PPMS (P = .0268).
In both groups of progressive MS patients, Nf-L levels were reduced in response to treatment at both 12 and 24 months, which remained significant.
“So, what about sample size calculation for a 1-year, phase 2 study with Nf-L as a primary endpoint?” Dr. Kappos queried. Assuming a reduction in Nf-L of 20% with a test drug, such a study would be likely to need to include 188 patients, or 94 patients per single arm to have 80% statistical power. To see a 30% reduction in Nf-L, fewer total and single-arm numbers would be needed, at 74 and 37 participants, respectively.
The study was funded by Novartis Pharma AG, Basel, Switzerland. Dr. Kappos disclosed that his institution (University Hospital Basel) had received steering committee, advisory board, and consultancy fees in the last 3 years that had been used exclusively for research support at the department from Novartis and a number of other pharmaceutical manufacturers. The Research of the MS Centre in Basel has been supported by grants from Bayer, Biogen, Novartis, the Swiss MS Society, the Swiss National Research Foundation, the European Union, and Roche Research Foundations.
SOURCE: Kuhle J et al. ECTRIMS 2018. Mult Scler. 2018;24(Suppl 2):111, Abstract 286.
REPORTING FROM ECTRIMS 2018
Key clinical point: Neurofilament light chain level was predictive of changes in brain atrophy, disability and sensitive to treatment effect in secondary progressive multiple sclerosis.
Major finding: Comparing high versus low baseline Nf-L in SPMS, the mean brain volume change from baseline was –0.8% vs. –0.2% (P less than .0001) at 12 months. Elevated Nf-L was associated with a 32% increase risk of disability progression.
Study details: Include study type and number of subjects.
Disclosures: The study was funded by Novartis Pharma AG, Basel, Switzerland. Dr. Kappos disclosed that his institution (University Hospital Basel) had received steering committee, advisory board, and consultancy fees in the last 3 years that had been used exclusively for research support at the department from Novartis and many other pharmaceutical manufacturers.
Source: Kuhle J et al. ECTRIMS 2018. Mult Scler. 2018;24(Suppl 2):111, Abstract 286.
Tech-based cancer company raises access concerns
Oncologists are raising concerns about care access after the launch of a new company that links patients to cancer care options and clinical trials through mobile technology.
Driver, which began in September in the U.S. and China, is a global technology platform that allows patients to access treatment options across a broad network of cancer centers without leaving home. Cancer patients join the platform using a mobile app, through which Driver obtains the required consent to acquire medical records and tumor samples, and the company uses the information to recommend treatment options and clinical trials.
A separate app called Driver for Clinic enables oncologists who belong to Driver’s partner hospitals to manage their institution’s clinical trial information and quickly filter that information based on patients’ medical history to determine the patient’s eligibility for treatments.
Driver’s mission is to connect more patients to the best cancer treatments, regardless of location, said Will Polkinghorn, MD, Driver cofounder and CEO.
“Driver’s cofounders met at Harvard Medical School [in Boston] and saw firsthand the challenges of patients getting access to the latest, cutting-edge treatments available,” Dr. Polkinghorn said in an interview. “As doctors, [we] also witnessed how difficult it was for doctors to manage information in clinic and know about all the treatments that become available all around the world. Driver was created as a platform, with an app for the patient and an app for the doctor, to solve this broken marketplace.”
As part of the model, patients can review their recommended treatment options through video with an expert oncologist and select a hospital within Driver’s network for further evaluation. The company’s global network includes more than 30 leading U.S. cancer centers, including the Cleveland Clinic; multiple locations of the Mayo Clinic; the University of California, San Francisco; and Massachusetts General Hospital, Boston. The U.S. National Cancer Institute (NCI) and the Chinese National Cancer Center are founding members of Driver’s global network, according to the company.
Making more information and treatment options available is a positive for patients, said Walter Stadler, MD, chief of hematology/oncology and director of the genitourinary oncology program at the University of Chicago. However, he noted that the cost for patients to use Driver is prohibitive for many patients. Driver charges patients $3,000 up front and then a $20 monthly fee to use its service. Insurance does not subsidize the cost, nor does Driver help with travel or treatment costs, according to its website.
“It’s inequality of access,” Dr. Stadler said in an interview. “Many of us are very concerned that the clinical trials currently being conducted do not represent the general population well because they don’t represent patients with disparities … Here, we further exacerbate the problem by saying, ‘Okay, we’ll take the 5% of patients who can afford the service and expand their access, and the others, well, that’s not our problem.’ ”
Kashyap Patel, MD, secretary for the Community Oncology Alliance and CEO for the Carolina Blood and Cancer Care in Rock Hill, S.C., also sees positives and negatives about the business model. Using technology to link patients with care and clinical trials can help speed treatment and accelerate drug development, he said. But Driver’s network of large tertiary care centers in metropolitan areas poses challenges for rural cancer patients, he said.
“Access to clinical trials for patients residing in rural areas, as well as those getting their treatment in community based clinics, would not change,” Dr. Patel said in an interview. “Hence, challenges of social and demographic disparities and inequalities in clinical trial access and participation would be altered minimally. There is much greater need for such [platforms to include] community cancer clinics that would be more inclusive and encompass larger geographic areas where the majority of patients receive their care.”
Disadvantaged populations with limited access are not being overlooked by the company, according to Driver leaders. A branch of the company called Driver for All aims to increase access to optimal treatments for free through partnerships with local communities, Dr. Polkinghorn said. Driver for All has thus far partnered with Howard University Hospital in Washington to connect Howard patients to clinical trials at NCI. A partnership with Beijing Children’s Hospital and the Futang Research Center of Pediatric Development, meanwhile, is working to connect patients with rare-disease experts. Driver has funded 100% of the cost of these projects to date, according to its website.
Outside of Driver for All, Dr. Polkinghorn acknowledges that patients must bear the cost of Driver’s consumer products; however, the price should be viewed in context, he said.
“It’s important to remember that today, in order to be evaluated by 30 [plus] centers for treatment options, patients would need to fly to these centers, make appointments, and be seen by a doctor – this would require both time and resources for flights/hotels, which would cost much more than our sticker price,” he said. “So while $3,000 is a lot of money for some patients, Driver’s product is ultimately able to provide more visibility to options that simply would not be realistic today.”
James Gulley, MD, of the National Cancer Institute Center for Cancer Research, said any platform that can efficiently provide access to clinical trial options yields another source of information for patients to utilize in decision making with their health provider. Dr. Gulley, who heads the center’s genitourinary malignancies branch, declined to comment about access-to-care concerns with Driver’s model. He emphasized that patients who participate in NIH research studies are treated without charge.
“The key to finding better [cancer] treatment is to perform science-driven clinical trials,” Dr. Gulley said in an interview. “However, there are many barriers for enrollment in clinical trials. … As a government agency, NCI is open to partnering with any organization that seeks to improve access to clinical trials for cancer patients.”
NCI and Driver recently conducted a study to validate Driver’s platform; it showed that Driver’s technology successfully predicted the eligibility of patients in NCI Center for Cancer Research clinical trials. The study, presented at a recent American Society of Clinical Oncology meeting, evaluated Driver’s processing of 21 metastatic prostate cancer patients enrolled in a therapeutic NCI clinical trial within the last five years. Results showed Driver correctly predicted that 20 of the patients were “potentially eligible” for the trial in which they were enrolled, and that one was ineligible. Based on the study, a protocol is now in development for a new clinical study, which will seek to further determine the efficiency and accuracy of the clinical trial access program created by Driver, according to Dr. Gulley.
Charles Ryan, MD, director of the division of hematology, oncology, and transplantation for the University of Minnesota, Minneapolis, views Driver’s platform as a way to eliminate geographical barriers, which often keep patients from care, while at the same time enabling researchers to find the right patients for clinical trials.
“We need breakthrough technologies and opportunities for patients to be able to access the most successful and promising cancer treatments, regardless of where they live,” Dr. Ryan said in an interview. “Companies like Driver are attempting to bridge that gap by connecting patients to doctors at world class cancer institutes and direct them toward the best care for their particular condition.”
Driver’s model also allows researchers the opportunity to develop specific, unique treatment for less common cancers and remain optimistic that they can attract patients to receive such treatments as they are developed, Dr. Ryan said.
Dr. Stadler, however, worries that Driver may be giving patients the wrong perception that all it takes is a computer and medical records to determine their best treatment route.
“There’s a lot more subtlety to treatment decisions than most people would like to admit,” Dr. Stadler said. “It’s more than just a bunch of data from sophisticated laboratory tests and the written medical record. Obtaining objective information is the first step, but it’s far from the only step.”
Patients may have significant limitations in functional status that is apparent only during an in-person assessment, for example, he said. In other cases, family members may be essential in conveying information about a patient’s cognitive disabilities. Even when such information is documented, it is sometimes difficult to extract the full picture from the record alone, he said. Dr. Stadler is also bothered that the model requires physicians and hospitals to provide their skilled analyses to a for-profit company, which in turn, charges patients to review the information.
“This is our work,” he said. “I agree that patients should have the information, and I don’t mind sharing anything I have with patients, but now I’m going to share it with another business that essentially is competing with me in terms of providing guidance to patients.”
Oncologists are raising concerns about care access after the launch of a new company that links patients to cancer care options and clinical trials through mobile technology.
Driver, which began in September in the U.S. and China, is a global technology platform that allows patients to access treatment options across a broad network of cancer centers without leaving home. Cancer patients join the platform using a mobile app, through which Driver obtains the required consent to acquire medical records and tumor samples, and the company uses the information to recommend treatment options and clinical trials.
A separate app called Driver for Clinic enables oncologists who belong to Driver’s partner hospitals to manage their institution’s clinical trial information and quickly filter that information based on patients’ medical history to determine the patient’s eligibility for treatments.
Driver’s mission is to connect more patients to the best cancer treatments, regardless of location, said Will Polkinghorn, MD, Driver cofounder and CEO.
“Driver’s cofounders met at Harvard Medical School [in Boston] and saw firsthand the challenges of patients getting access to the latest, cutting-edge treatments available,” Dr. Polkinghorn said in an interview. “As doctors, [we] also witnessed how difficult it was for doctors to manage information in clinic and know about all the treatments that become available all around the world. Driver was created as a platform, with an app for the patient and an app for the doctor, to solve this broken marketplace.”
As part of the model, patients can review their recommended treatment options through video with an expert oncologist and select a hospital within Driver’s network for further evaluation. The company’s global network includes more than 30 leading U.S. cancer centers, including the Cleveland Clinic; multiple locations of the Mayo Clinic; the University of California, San Francisco; and Massachusetts General Hospital, Boston. The U.S. National Cancer Institute (NCI) and the Chinese National Cancer Center are founding members of Driver’s global network, according to the company.
Making more information and treatment options available is a positive for patients, said Walter Stadler, MD, chief of hematology/oncology and director of the genitourinary oncology program at the University of Chicago. However, he noted that the cost for patients to use Driver is prohibitive for many patients. Driver charges patients $3,000 up front and then a $20 monthly fee to use its service. Insurance does not subsidize the cost, nor does Driver help with travel or treatment costs, according to its website.
“It’s inequality of access,” Dr. Stadler said in an interview. “Many of us are very concerned that the clinical trials currently being conducted do not represent the general population well because they don’t represent patients with disparities … Here, we further exacerbate the problem by saying, ‘Okay, we’ll take the 5% of patients who can afford the service and expand their access, and the others, well, that’s not our problem.’ ”
Kashyap Patel, MD, secretary for the Community Oncology Alliance and CEO for the Carolina Blood and Cancer Care in Rock Hill, S.C., also sees positives and negatives about the business model. Using technology to link patients with care and clinical trials can help speed treatment and accelerate drug development, he said. But Driver’s network of large tertiary care centers in metropolitan areas poses challenges for rural cancer patients, he said.
“Access to clinical trials for patients residing in rural areas, as well as those getting their treatment in community based clinics, would not change,” Dr. Patel said in an interview. “Hence, challenges of social and demographic disparities and inequalities in clinical trial access and participation would be altered minimally. There is much greater need for such [platforms to include] community cancer clinics that would be more inclusive and encompass larger geographic areas where the majority of patients receive their care.”
Disadvantaged populations with limited access are not being overlooked by the company, according to Driver leaders. A branch of the company called Driver for All aims to increase access to optimal treatments for free through partnerships with local communities, Dr. Polkinghorn said. Driver for All has thus far partnered with Howard University Hospital in Washington to connect Howard patients to clinical trials at NCI. A partnership with Beijing Children’s Hospital and the Futang Research Center of Pediatric Development, meanwhile, is working to connect patients with rare-disease experts. Driver has funded 100% of the cost of these projects to date, according to its website.
Outside of Driver for All, Dr. Polkinghorn acknowledges that patients must bear the cost of Driver’s consumer products; however, the price should be viewed in context, he said.
“It’s important to remember that today, in order to be evaluated by 30 [plus] centers for treatment options, patients would need to fly to these centers, make appointments, and be seen by a doctor – this would require both time and resources for flights/hotels, which would cost much more than our sticker price,” he said. “So while $3,000 is a lot of money for some patients, Driver’s product is ultimately able to provide more visibility to options that simply would not be realistic today.”
James Gulley, MD, of the National Cancer Institute Center for Cancer Research, said any platform that can efficiently provide access to clinical trial options yields another source of information for patients to utilize in decision making with their health provider. Dr. Gulley, who heads the center’s genitourinary malignancies branch, declined to comment about access-to-care concerns with Driver’s model. He emphasized that patients who participate in NIH research studies are treated without charge.
“The key to finding better [cancer] treatment is to perform science-driven clinical trials,” Dr. Gulley said in an interview. “However, there are many barriers for enrollment in clinical trials. … As a government agency, NCI is open to partnering with any organization that seeks to improve access to clinical trials for cancer patients.”
NCI and Driver recently conducted a study to validate Driver’s platform; it showed that Driver’s technology successfully predicted the eligibility of patients in NCI Center for Cancer Research clinical trials. The study, presented at a recent American Society of Clinical Oncology meeting, evaluated Driver’s processing of 21 metastatic prostate cancer patients enrolled in a therapeutic NCI clinical trial within the last five years. Results showed Driver correctly predicted that 20 of the patients were “potentially eligible” for the trial in which they were enrolled, and that one was ineligible. Based on the study, a protocol is now in development for a new clinical study, which will seek to further determine the efficiency and accuracy of the clinical trial access program created by Driver, according to Dr. Gulley.
Charles Ryan, MD, director of the division of hematology, oncology, and transplantation for the University of Minnesota, Minneapolis, views Driver’s platform as a way to eliminate geographical barriers, which often keep patients from care, while at the same time enabling researchers to find the right patients for clinical trials.
“We need breakthrough technologies and opportunities for patients to be able to access the most successful and promising cancer treatments, regardless of where they live,” Dr. Ryan said in an interview. “Companies like Driver are attempting to bridge that gap by connecting patients to doctors at world class cancer institutes and direct them toward the best care for their particular condition.”
Driver’s model also allows researchers the opportunity to develop specific, unique treatment for less common cancers and remain optimistic that they can attract patients to receive such treatments as they are developed, Dr. Ryan said.
Dr. Stadler, however, worries that Driver may be giving patients the wrong perception that all it takes is a computer and medical records to determine their best treatment route.
“There’s a lot more subtlety to treatment decisions than most people would like to admit,” Dr. Stadler said. “It’s more than just a bunch of data from sophisticated laboratory tests and the written medical record. Obtaining objective information is the first step, but it’s far from the only step.”
Patients may have significant limitations in functional status that is apparent only during an in-person assessment, for example, he said. In other cases, family members may be essential in conveying information about a patient’s cognitive disabilities. Even when such information is documented, it is sometimes difficult to extract the full picture from the record alone, he said. Dr. Stadler is also bothered that the model requires physicians and hospitals to provide their skilled analyses to a for-profit company, which in turn, charges patients to review the information.
“This is our work,” he said. “I agree that patients should have the information, and I don’t mind sharing anything I have with patients, but now I’m going to share it with another business that essentially is competing with me in terms of providing guidance to patients.”
Oncologists are raising concerns about care access after the launch of a new company that links patients to cancer care options and clinical trials through mobile technology.
Driver, which began in September in the U.S. and China, is a global technology platform that allows patients to access treatment options across a broad network of cancer centers without leaving home. Cancer patients join the platform using a mobile app, through which Driver obtains the required consent to acquire medical records and tumor samples, and the company uses the information to recommend treatment options and clinical trials.
A separate app called Driver for Clinic enables oncologists who belong to Driver’s partner hospitals to manage their institution’s clinical trial information and quickly filter that information based on patients’ medical history to determine the patient’s eligibility for treatments.
Driver’s mission is to connect more patients to the best cancer treatments, regardless of location, said Will Polkinghorn, MD, Driver cofounder and CEO.
“Driver’s cofounders met at Harvard Medical School [in Boston] and saw firsthand the challenges of patients getting access to the latest, cutting-edge treatments available,” Dr. Polkinghorn said in an interview. “As doctors, [we] also witnessed how difficult it was for doctors to manage information in clinic and know about all the treatments that become available all around the world. Driver was created as a platform, with an app for the patient and an app for the doctor, to solve this broken marketplace.”
As part of the model, patients can review their recommended treatment options through video with an expert oncologist and select a hospital within Driver’s network for further evaluation. The company’s global network includes more than 30 leading U.S. cancer centers, including the Cleveland Clinic; multiple locations of the Mayo Clinic; the University of California, San Francisco; and Massachusetts General Hospital, Boston. The U.S. National Cancer Institute (NCI) and the Chinese National Cancer Center are founding members of Driver’s global network, according to the company.
Making more information and treatment options available is a positive for patients, said Walter Stadler, MD, chief of hematology/oncology and director of the genitourinary oncology program at the University of Chicago. However, he noted that the cost for patients to use Driver is prohibitive for many patients. Driver charges patients $3,000 up front and then a $20 monthly fee to use its service. Insurance does not subsidize the cost, nor does Driver help with travel or treatment costs, according to its website.
“It’s inequality of access,” Dr. Stadler said in an interview. “Many of us are very concerned that the clinical trials currently being conducted do not represent the general population well because they don’t represent patients with disparities … Here, we further exacerbate the problem by saying, ‘Okay, we’ll take the 5% of patients who can afford the service and expand their access, and the others, well, that’s not our problem.’ ”
Kashyap Patel, MD, secretary for the Community Oncology Alliance and CEO for the Carolina Blood and Cancer Care in Rock Hill, S.C., also sees positives and negatives about the business model. Using technology to link patients with care and clinical trials can help speed treatment and accelerate drug development, he said. But Driver’s network of large tertiary care centers in metropolitan areas poses challenges for rural cancer patients, he said.
“Access to clinical trials for patients residing in rural areas, as well as those getting their treatment in community based clinics, would not change,” Dr. Patel said in an interview. “Hence, challenges of social and demographic disparities and inequalities in clinical trial access and participation would be altered minimally. There is much greater need for such [platforms to include] community cancer clinics that would be more inclusive and encompass larger geographic areas where the majority of patients receive their care.”
Disadvantaged populations with limited access are not being overlooked by the company, according to Driver leaders. A branch of the company called Driver for All aims to increase access to optimal treatments for free through partnerships with local communities, Dr. Polkinghorn said. Driver for All has thus far partnered with Howard University Hospital in Washington to connect Howard patients to clinical trials at NCI. A partnership with Beijing Children’s Hospital and the Futang Research Center of Pediatric Development, meanwhile, is working to connect patients with rare-disease experts. Driver has funded 100% of the cost of these projects to date, according to its website.
Outside of Driver for All, Dr. Polkinghorn acknowledges that patients must bear the cost of Driver’s consumer products; however, the price should be viewed in context, he said.
“It’s important to remember that today, in order to be evaluated by 30 [plus] centers for treatment options, patients would need to fly to these centers, make appointments, and be seen by a doctor – this would require both time and resources for flights/hotels, which would cost much more than our sticker price,” he said. “So while $3,000 is a lot of money for some patients, Driver’s product is ultimately able to provide more visibility to options that simply would not be realistic today.”
James Gulley, MD, of the National Cancer Institute Center for Cancer Research, said any platform that can efficiently provide access to clinical trial options yields another source of information for patients to utilize in decision making with their health provider. Dr. Gulley, who heads the center’s genitourinary malignancies branch, declined to comment about access-to-care concerns with Driver’s model. He emphasized that patients who participate in NIH research studies are treated without charge.
“The key to finding better [cancer] treatment is to perform science-driven clinical trials,” Dr. Gulley said in an interview. “However, there are many barriers for enrollment in clinical trials. … As a government agency, NCI is open to partnering with any organization that seeks to improve access to clinical trials for cancer patients.”
NCI and Driver recently conducted a study to validate Driver’s platform; it showed that Driver’s technology successfully predicted the eligibility of patients in NCI Center for Cancer Research clinical trials. The study, presented at a recent American Society of Clinical Oncology meeting, evaluated Driver’s processing of 21 metastatic prostate cancer patients enrolled in a therapeutic NCI clinical trial within the last five years. Results showed Driver correctly predicted that 20 of the patients were “potentially eligible” for the trial in which they were enrolled, and that one was ineligible. Based on the study, a protocol is now in development for a new clinical study, which will seek to further determine the efficiency and accuracy of the clinical trial access program created by Driver, according to Dr. Gulley.
Charles Ryan, MD, director of the division of hematology, oncology, and transplantation for the University of Minnesota, Minneapolis, views Driver’s platform as a way to eliminate geographical barriers, which often keep patients from care, while at the same time enabling researchers to find the right patients for clinical trials.
“We need breakthrough technologies and opportunities for patients to be able to access the most successful and promising cancer treatments, regardless of where they live,” Dr. Ryan said in an interview. “Companies like Driver are attempting to bridge that gap by connecting patients to doctors at world class cancer institutes and direct them toward the best care for their particular condition.”
Driver’s model also allows researchers the opportunity to develop specific, unique treatment for less common cancers and remain optimistic that they can attract patients to receive such treatments as they are developed, Dr. Ryan said.
Dr. Stadler, however, worries that Driver may be giving patients the wrong perception that all it takes is a computer and medical records to determine their best treatment route.
“There’s a lot more subtlety to treatment decisions than most people would like to admit,” Dr. Stadler said. “It’s more than just a bunch of data from sophisticated laboratory tests and the written medical record. Obtaining objective information is the first step, but it’s far from the only step.”
Patients may have significant limitations in functional status that is apparent only during an in-person assessment, for example, he said. In other cases, family members may be essential in conveying information about a patient’s cognitive disabilities. Even when such information is documented, it is sometimes difficult to extract the full picture from the record alone, he said. Dr. Stadler is also bothered that the model requires physicians and hospitals to provide their skilled analyses to a for-profit company, which in turn, charges patients to review the information.
“This is our work,” he said. “I agree that patients should have the information, and I don’t mind sharing anything I have with patients, but now I’m going to share it with another business that essentially is competing with me in terms of providing guidance to patients.”
Low spinal cord volume linked to higher MS disability
BERLIN – Spinal cord volume deficits in patients with multiple sclerosis may contribute to clinical disability that appears out of proportion to lesion load on brain imaging, according to new research.
In a pool of 362 patients with mild to moderate MS-related disability but identical white matter lesion load identified by MRI, those with higher disability had significantly lower spinal cord volumes when compared against those with disability scores in the mild range (P less than .001).
Though brain MRI is a key tool used to track disease severity and progression in MS, some patients have relatively high disability but a low burden of white matter intracerebral lesions on MRI. Little is known about spinal cord volume in MS patients with pronounced dissociation between intracerebral lesion load and disability, Michaela Andelova, MD, said in an interview during a poster session at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.
Dr. Andelova, of Charles University, Prague, said that she and her colleagues hypothesized that spinal cord volume would differ between patients who had varying levels of disability, despite identical white matter lesion load.
To test this, she and her colleagues looked at records of 1,245 patients with relapsing-remitting MS. They divided them into three groups by severity of clinical disability, and also by extent of cerebral T2 hyperintense lesion load. The investigators identified a group of patients (n = 53) whose total volume of T2-weighted hyperintense lesions was less than 3 mL, but whose Expanded Disability Status Scale (EDSS) scores were at least 3.5; this was the low lesion load/high disability (LLHD) group.
Dr. Andelova and her colleagues then identified another group of patients (n = 71) who had a volume of T2-weighted hyperintensities that was greater than 9 mL, but whose EDSS score was less than 1.5. This was the high lesion load/low disability (HLLD) group.
The remaining patients (n = 1,121), who did not have these paradoxical associations, were analyzed separately.
For all patients, mean upper cervical cord area (MUCCA) was also measured. Using images acquired by a 3 T MRI scanner, MUCCA was calculated as the mean sum of spinal cord area in 21 slices centered at the C3/4 intervertebral disk, using an in-house, semiautomated method.
“Despite higher disability, LLHD patients demonstrated significantly higher normalized total brain volume, higher normalized volumes of thalamus and callosum, and smaller lateral ventricles than [the] HLLD group,” wrote Dr. Andelova and her collaborators.
However, the LLHD patients had MUCCA values that were significantly lower than the other groups: The nonparadoxical group’s mean MUCCA was 84.02 mm2, while the HLLD group had a mean MUCCA of 85.75 mm2. This difference was not statistically significant. By contrast, the LLHD group’s mean MUCCA was significantly smaller, at 80.40 mm2 (P = .023 versus nonparadoxical patients, and P = .007 versus HLLD patients).
Looking at the data another way, Dr. Andelova and her colleagues compared 362 evenly divided patients with moderate disability (EDSS 3.5-6.5) with matched patients who had mild MS-related disability (EDSS less than 3) and identical cerebral lesion loads. They found that MUCCA was significantly smaller in the moderate disability group (78.86 versus 84.44 mm2; P less than .001).
In addition to having identical lesions loads, the mild and moderate disability groups didn’t differ significantly in normalized total brain volume or regional brain volumes. The group with moderate disability did have slightly less white matter volume (P = .039), Dr. Andelova pointed out.
All differences found between groups retained statistical significance even after adjustment for such potential confounders as age, sex, and duration of disease, Dr. Andelova said.
“Reduced spinal cord volume may explain part of the clinical-radiological paradox in patients who have high disability despite low intracranial lesion load,” Dr. Andelova and her collaborators wrote. “In line with this finding, relatively preserved spinal cord volume may be associated with functional reserve and less physical disability in patients with low disability despite high cerebral lesion load.”
Further work looking more precisely at cerebral lesion distribution and quantitative MRI investigation of lesion distribution is in the works for Dr. Andelova and her collaborators. They are hoping to see some association between various distribution patterns and accelerated spinal atrophy.
The research was supported by the Czech government. Dr. Andelova and several of her collaborators reported financial relationships with pharmaceutical companies.
SOURCE: Andelova M et al. Mult Scler. 2018;24(Suppl 2):211, Abstract P477.
BERLIN – Spinal cord volume deficits in patients with multiple sclerosis may contribute to clinical disability that appears out of proportion to lesion load on brain imaging, according to new research.
In a pool of 362 patients with mild to moderate MS-related disability but identical white matter lesion load identified by MRI, those with higher disability had significantly lower spinal cord volumes when compared against those with disability scores in the mild range (P less than .001).
Though brain MRI is a key tool used to track disease severity and progression in MS, some patients have relatively high disability but a low burden of white matter intracerebral lesions on MRI. Little is known about spinal cord volume in MS patients with pronounced dissociation between intracerebral lesion load and disability, Michaela Andelova, MD, said in an interview during a poster session at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.
Dr. Andelova, of Charles University, Prague, said that she and her colleagues hypothesized that spinal cord volume would differ between patients who had varying levels of disability, despite identical white matter lesion load.
To test this, she and her colleagues looked at records of 1,245 patients with relapsing-remitting MS. They divided them into three groups by severity of clinical disability, and also by extent of cerebral T2 hyperintense lesion load. The investigators identified a group of patients (n = 53) whose total volume of T2-weighted hyperintense lesions was less than 3 mL, but whose Expanded Disability Status Scale (EDSS) scores were at least 3.5; this was the low lesion load/high disability (LLHD) group.
Dr. Andelova and her colleagues then identified another group of patients (n = 71) who had a volume of T2-weighted hyperintensities that was greater than 9 mL, but whose EDSS score was less than 1.5. This was the high lesion load/low disability (HLLD) group.
The remaining patients (n = 1,121), who did not have these paradoxical associations, were analyzed separately.
For all patients, mean upper cervical cord area (MUCCA) was also measured. Using images acquired by a 3 T MRI scanner, MUCCA was calculated as the mean sum of spinal cord area in 21 slices centered at the C3/4 intervertebral disk, using an in-house, semiautomated method.
“Despite higher disability, LLHD patients demonstrated significantly higher normalized total brain volume, higher normalized volumes of thalamus and callosum, and smaller lateral ventricles than [the] HLLD group,” wrote Dr. Andelova and her collaborators.
However, the LLHD patients had MUCCA values that were significantly lower than the other groups: The nonparadoxical group’s mean MUCCA was 84.02 mm2, while the HLLD group had a mean MUCCA of 85.75 mm2. This difference was not statistically significant. By contrast, the LLHD group’s mean MUCCA was significantly smaller, at 80.40 mm2 (P = .023 versus nonparadoxical patients, and P = .007 versus HLLD patients).
Looking at the data another way, Dr. Andelova and her colleagues compared 362 evenly divided patients with moderate disability (EDSS 3.5-6.5) with matched patients who had mild MS-related disability (EDSS less than 3) and identical cerebral lesion loads. They found that MUCCA was significantly smaller in the moderate disability group (78.86 versus 84.44 mm2; P less than .001).
In addition to having identical lesions loads, the mild and moderate disability groups didn’t differ significantly in normalized total brain volume or regional brain volumes. The group with moderate disability did have slightly less white matter volume (P = .039), Dr. Andelova pointed out.
All differences found between groups retained statistical significance even after adjustment for such potential confounders as age, sex, and duration of disease, Dr. Andelova said.
“Reduced spinal cord volume may explain part of the clinical-radiological paradox in patients who have high disability despite low intracranial lesion load,” Dr. Andelova and her collaborators wrote. “In line with this finding, relatively preserved spinal cord volume may be associated with functional reserve and less physical disability in patients with low disability despite high cerebral lesion load.”
Further work looking more precisely at cerebral lesion distribution and quantitative MRI investigation of lesion distribution is in the works for Dr. Andelova and her collaborators. They are hoping to see some association between various distribution patterns and accelerated spinal atrophy.
The research was supported by the Czech government. Dr. Andelova and several of her collaborators reported financial relationships with pharmaceutical companies.
SOURCE: Andelova M et al. Mult Scler. 2018;24(Suppl 2):211, Abstract P477.
BERLIN – Spinal cord volume deficits in patients with multiple sclerosis may contribute to clinical disability that appears out of proportion to lesion load on brain imaging, according to new research.
In a pool of 362 patients with mild to moderate MS-related disability but identical white matter lesion load identified by MRI, those with higher disability had significantly lower spinal cord volumes when compared against those with disability scores in the mild range (P less than .001).
Though brain MRI is a key tool used to track disease severity and progression in MS, some patients have relatively high disability but a low burden of white matter intracerebral lesions on MRI. Little is known about spinal cord volume in MS patients with pronounced dissociation between intracerebral lesion load and disability, Michaela Andelova, MD, said in an interview during a poster session at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.
Dr. Andelova, of Charles University, Prague, said that she and her colleagues hypothesized that spinal cord volume would differ between patients who had varying levels of disability, despite identical white matter lesion load.
To test this, she and her colleagues looked at records of 1,245 patients with relapsing-remitting MS. They divided them into three groups by severity of clinical disability, and also by extent of cerebral T2 hyperintense lesion load. The investigators identified a group of patients (n = 53) whose total volume of T2-weighted hyperintense lesions was less than 3 mL, but whose Expanded Disability Status Scale (EDSS) scores were at least 3.5; this was the low lesion load/high disability (LLHD) group.
Dr. Andelova and her colleagues then identified another group of patients (n = 71) who had a volume of T2-weighted hyperintensities that was greater than 9 mL, but whose EDSS score was less than 1.5. This was the high lesion load/low disability (HLLD) group.
The remaining patients (n = 1,121), who did not have these paradoxical associations, were analyzed separately.
For all patients, mean upper cervical cord area (MUCCA) was also measured. Using images acquired by a 3 T MRI scanner, MUCCA was calculated as the mean sum of spinal cord area in 21 slices centered at the C3/4 intervertebral disk, using an in-house, semiautomated method.
“Despite higher disability, LLHD patients demonstrated significantly higher normalized total brain volume, higher normalized volumes of thalamus and callosum, and smaller lateral ventricles than [the] HLLD group,” wrote Dr. Andelova and her collaborators.
However, the LLHD patients had MUCCA values that were significantly lower than the other groups: The nonparadoxical group’s mean MUCCA was 84.02 mm2, while the HLLD group had a mean MUCCA of 85.75 mm2. This difference was not statistically significant. By contrast, the LLHD group’s mean MUCCA was significantly smaller, at 80.40 mm2 (P = .023 versus nonparadoxical patients, and P = .007 versus HLLD patients).
Looking at the data another way, Dr. Andelova and her colleagues compared 362 evenly divided patients with moderate disability (EDSS 3.5-6.5) with matched patients who had mild MS-related disability (EDSS less than 3) and identical cerebral lesion loads. They found that MUCCA was significantly smaller in the moderate disability group (78.86 versus 84.44 mm2; P less than .001).
In addition to having identical lesions loads, the mild and moderate disability groups didn’t differ significantly in normalized total brain volume or regional brain volumes. The group with moderate disability did have slightly less white matter volume (P = .039), Dr. Andelova pointed out.
All differences found between groups retained statistical significance even after adjustment for such potential confounders as age, sex, and duration of disease, Dr. Andelova said.
“Reduced spinal cord volume may explain part of the clinical-radiological paradox in patients who have high disability despite low intracranial lesion load,” Dr. Andelova and her collaborators wrote. “In line with this finding, relatively preserved spinal cord volume may be associated with functional reserve and less physical disability in patients with low disability despite high cerebral lesion load.”
Further work looking more precisely at cerebral lesion distribution and quantitative MRI investigation of lesion distribution is in the works for Dr. Andelova and her collaborators. They are hoping to see some association between various distribution patterns and accelerated spinal atrophy.
The research was supported by the Czech government. Dr. Andelova and several of her collaborators reported financial relationships with pharmaceutical companies.
SOURCE: Andelova M et al. Mult Scler. 2018;24(Suppl 2):211, Abstract P477.
REPORTING FROM ECTRIMS 2018
Key clinical point:
Major finding: Moderate disability patients had lower spinal cord volumes than did those with mild disability but a similar intracerebral lesion load.
Study details: Retrospective study of 1,245 patients with relapsing-remitting MS.
Disclosures: The study was sponsored by a grant from the Czech government. Several authors, including Dr. Andelova, reported multiple financial relationships with pharmaceutical companies.
Source: Andelova M et al. Mult Scler. 2018;24(Suppl 2):211, Abstract P477.
Relapsing-remitting MS best treated within 6 months of onset
BERLIN – according to real-world data from the Big Multiple Sclerosis Data Network.
Receiving disease-modifying treatments (DMTs) within 6 months of diagnosis was associated with a 28% reduction in the risk of reaching an Expanded Disability Status Scale score of 3.0 or more for the first time at 12 months versus receiving treatment after 6 months (hazard ratio, 0.72; 95% confidence interval, 0.59-0.90; P = .003).
Results were not significant, looking at all the other periods tested at 6-month intervals from 1 year up to 5 years after diagnosis. HRs (95% CIs) comparing a first DMT given at 1 year, 1.5 years, 2 years, 2.5 years, 3 years, 3.5 years, 4 years, 4.5 years, and 5 years were a respective 0.90 (0.78-1.03), 0.89 (0.79-1.01), 0.99 (0.88-1.11), 0.95 (0.85-1.06), 1.01 (0.90-1.12), 0.97 (0.86-1.09), 1.09 (0.96-1.22), 1.11 (0.98-1.25), and 1.06 (0.93-1.20).
“To date, these data represent the largest RRMS cohort with the longest follow-up ever analyzed to determine the long-term effectiveness of the early start of DMTs,” said Pietro Iaffaldano, MD, at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.
“This study also provides evidence that data sharing from MS registries and databases is feasible,” noted Dr. Iaffaldano, who is assistant professor of neurology at the University of Bari (Italy). Such an approach can provide enough statistical power to detect the impact of treatment on disability outcomes in the long term, he suggested.
For the study, a cohort of 11,934 patients was obtained by screening more than 149,636 patients from five large registries and databases of MS patients – the Italian MS Registry, the Swedish MS Registry, the Danish MS Registry, OFSEP (Observatoire Français de al Sclérose en Plaques), and MSBase. Patients were included in the current analysis if they had at least 10 years of follow-up, had at least three EDSS evaluations, and at least one DMT prescription.
“It is well known that randomized, controlled trials support the early start of treatment in MS, but open-label extensions of the same trials reported inconsistent results about the long-term benefit on disability accumulation,” Dr. Iaffaldano explained. Further, recent observational studies have suggested that initiating DMTs early might not only delay the accumulation of disability but perhaps also death.
The aim of the research was thus to look at what effect the time interval from disease onset to the first administration of a DMT might have on long-term disability accumulation, as measured by the EDSS, in patients with RRMS.
The population of patients studied was mostly (71%) female, with a median age of 27 years at disease onset. The number of relapses prior to starting a DMT was two and the baseline EDSS was 2.0. In almost all (98.9%) cases, DMT was used as first-line treatment (second line in 1.1% of cases). The median follow-up was 13.2 years and cumulative DMT exposure was 10.5 years.
The work was supported by Biogen International on the basis of a sponsored research agreement with the Big Multiple Sclerosis Data Network. Dr. Iaffaldano has served on scientific advisory boards for and received funding for travel and/or speaker honoraria from Biogen and other companies that market DMTs for MS. Several study authors are employees of Biogen, and other study authors also reported financial ties to Biogen and other pharmaceutical companies.
SOURCE: Iaffaldano P et al. Mult Scler. 2018;24(Suppl 2):71-2, Abstract 204.
BERLIN – according to real-world data from the Big Multiple Sclerosis Data Network.
Receiving disease-modifying treatments (DMTs) within 6 months of diagnosis was associated with a 28% reduction in the risk of reaching an Expanded Disability Status Scale score of 3.0 or more for the first time at 12 months versus receiving treatment after 6 months (hazard ratio, 0.72; 95% confidence interval, 0.59-0.90; P = .003).
Results were not significant, looking at all the other periods tested at 6-month intervals from 1 year up to 5 years after diagnosis. HRs (95% CIs) comparing a first DMT given at 1 year, 1.5 years, 2 years, 2.5 years, 3 years, 3.5 years, 4 years, 4.5 years, and 5 years were a respective 0.90 (0.78-1.03), 0.89 (0.79-1.01), 0.99 (0.88-1.11), 0.95 (0.85-1.06), 1.01 (0.90-1.12), 0.97 (0.86-1.09), 1.09 (0.96-1.22), 1.11 (0.98-1.25), and 1.06 (0.93-1.20).
“To date, these data represent the largest RRMS cohort with the longest follow-up ever analyzed to determine the long-term effectiveness of the early start of DMTs,” said Pietro Iaffaldano, MD, at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.
“This study also provides evidence that data sharing from MS registries and databases is feasible,” noted Dr. Iaffaldano, who is assistant professor of neurology at the University of Bari (Italy). Such an approach can provide enough statistical power to detect the impact of treatment on disability outcomes in the long term, he suggested.
For the study, a cohort of 11,934 patients was obtained by screening more than 149,636 patients from five large registries and databases of MS patients – the Italian MS Registry, the Swedish MS Registry, the Danish MS Registry, OFSEP (Observatoire Français de al Sclérose en Plaques), and MSBase. Patients were included in the current analysis if they had at least 10 years of follow-up, had at least three EDSS evaluations, and at least one DMT prescription.
“It is well known that randomized, controlled trials support the early start of treatment in MS, but open-label extensions of the same trials reported inconsistent results about the long-term benefit on disability accumulation,” Dr. Iaffaldano explained. Further, recent observational studies have suggested that initiating DMTs early might not only delay the accumulation of disability but perhaps also death.
The aim of the research was thus to look at what effect the time interval from disease onset to the first administration of a DMT might have on long-term disability accumulation, as measured by the EDSS, in patients with RRMS.
The population of patients studied was mostly (71%) female, with a median age of 27 years at disease onset. The number of relapses prior to starting a DMT was two and the baseline EDSS was 2.0. In almost all (98.9%) cases, DMT was used as first-line treatment (second line in 1.1% of cases). The median follow-up was 13.2 years and cumulative DMT exposure was 10.5 years.
The work was supported by Biogen International on the basis of a sponsored research agreement with the Big Multiple Sclerosis Data Network. Dr. Iaffaldano has served on scientific advisory boards for and received funding for travel and/or speaker honoraria from Biogen and other companies that market DMTs for MS. Several study authors are employees of Biogen, and other study authors also reported financial ties to Biogen and other pharmaceutical companies.
SOURCE: Iaffaldano P et al. Mult Scler. 2018;24(Suppl 2):71-2, Abstract 204.
BERLIN – according to real-world data from the Big Multiple Sclerosis Data Network.
Receiving disease-modifying treatments (DMTs) within 6 months of diagnosis was associated with a 28% reduction in the risk of reaching an Expanded Disability Status Scale score of 3.0 or more for the first time at 12 months versus receiving treatment after 6 months (hazard ratio, 0.72; 95% confidence interval, 0.59-0.90; P = .003).
Results were not significant, looking at all the other periods tested at 6-month intervals from 1 year up to 5 years after diagnosis. HRs (95% CIs) comparing a first DMT given at 1 year, 1.5 years, 2 years, 2.5 years, 3 years, 3.5 years, 4 years, 4.5 years, and 5 years were a respective 0.90 (0.78-1.03), 0.89 (0.79-1.01), 0.99 (0.88-1.11), 0.95 (0.85-1.06), 1.01 (0.90-1.12), 0.97 (0.86-1.09), 1.09 (0.96-1.22), 1.11 (0.98-1.25), and 1.06 (0.93-1.20).
“To date, these data represent the largest RRMS cohort with the longest follow-up ever analyzed to determine the long-term effectiveness of the early start of DMTs,” said Pietro Iaffaldano, MD, at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.
“This study also provides evidence that data sharing from MS registries and databases is feasible,” noted Dr. Iaffaldano, who is assistant professor of neurology at the University of Bari (Italy). Such an approach can provide enough statistical power to detect the impact of treatment on disability outcomes in the long term, he suggested.
For the study, a cohort of 11,934 patients was obtained by screening more than 149,636 patients from five large registries and databases of MS patients – the Italian MS Registry, the Swedish MS Registry, the Danish MS Registry, OFSEP (Observatoire Français de al Sclérose en Plaques), and MSBase. Patients were included in the current analysis if they had at least 10 years of follow-up, had at least three EDSS evaluations, and at least one DMT prescription.
“It is well known that randomized, controlled trials support the early start of treatment in MS, but open-label extensions of the same trials reported inconsistent results about the long-term benefit on disability accumulation,” Dr. Iaffaldano explained. Further, recent observational studies have suggested that initiating DMTs early might not only delay the accumulation of disability but perhaps also death.
The aim of the research was thus to look at what effect the time interval from disease onset to the first administration of a DMT might have on long-term disability accumulation, as measured by the EDSS, in patients with RRMS.
The population of patients studied was mostly (71%) female, with a median age of 27 years at disease onset. The number of relapses prior to starting a DMT was two and the baseline EDSS was 2.0. In almost all (98.9%) cases, DMT was used as first-line treatment (second line in 1.1% of cases). The median follow-up was 13.2 years and cumulative DMT exposure was 10.5 years.
The work was supported by Biogen International on the basis of a sponsored research agreement with the Big Multiple Sclerosis Data Network. Dr. Iaffaldano has served on scientific advisory boards for and received funding for travel and/or speaker honoraria from Biogen and other companies that market DMTs for MS. Several study authors are employees of Biogen, and other study authors also reported financial ties to Biogen and other pharmaceutical companies.
SOURCE: Iaffaldano P et al. Mult Scler. 2018;24(Suppl 2):71-2, Abstract 204.
REPORTING FROM ECTRIMS 2018
Key clinical point: Less disease progression occurs if disease-modifying treatments (DMTs) are given early in relapsing-remitting multiple sclerosis (RRMS).
Major finding: DMTs within 6 months vs. later decreased the risk of confirmed first disability progression at 12 months by 28% (P = .003).
Study details: 11,934 patients with RRMS with at least 10 years’ follow-up, three or more Expanded Disability Status Scale evaluations, and at least one DMT prescription.
Disclosures: The work was supported by Biogen International on the basis of a sponsored research agreement with the Big Multiple Sclerosis Data Network. Dr. Iaffaldano has served on scientific advisory boards for and received funding for travel and/or speaker honoraria from Biogen and other companies that market DMTs for MS. Several study authors are employees of Biogen, and other study authors also reported financial ties to Biogen and other pharmaceutical companies.
Source: Iaffaldano P et al. Mult Scler. 2018;24(Suppl 2):71-2, Abstract 204.
Mood disorders worsen multiple sclerosis disability
BERLIN – Depression and bipolar disorder are major risk factors for worsening disability in people with multiple sclerosis, according to the results of a large Swedish registry-based study.
The presence of depression increased the risk of having a sustained Expanded Disability Status Scale (EDSS) score of 3.0 by 54% and 4.0 by 87%, and it doubled the risk of an EDSS of 6.0.
Selective serotonin reuptake inhibitor treatment also upped the risk of greater disability, with patients exposed to SSRIs having a 40% increased risk of a sustained EDSS of 3.0, a 97% chance of having a sustained EDSS of 4.0, and 2.2-fold increased risk of a sustained EDSS of 6.0.
“We know that mood disorders are highly prevalent in people with multiple sclerosis,” Stefanie Binzer, MD, said at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis. She gave her presentation at the meeting on Oct. 10, which was World Mental Health Day.
The presence of mood disorders is associated with reduced quality of life, said Dr. Binzer of the department of clinical neuroscience at the Karolinska Institute in Stockholm. Furthermore, depression is the major risk factor for suicidality in patients with MS. However, before this study the effect of having a comorbid mood disorder on MS patients’ disability levels had not been established.
The investigators analyzed data from 5,875 patients in the Swedish MS registry between 2001 and 2014. By matching these patients to records in the Swedish National Patient Registry and the Swedish National Prescribed Drug Registry, they found that 8.5% (n = 502) had an International Classification of Diseases, 10th revision (ICD-10), code for depression. Of these, 261 had received a diagnosis of depression before their diagnosis of MS.
Of 3,817 patients with MS onset between 2005 and 2014, 27.4% (n = 1,048) had collected at least one prescription for an SSRI.
“What we found was that MS patients with either an ICD code for depression or having been exposed to SSRIs had a significantly increased risk of reaching EDSS 3.0,” Dr. Binzer reported. The age at which patients reached these milestones were younger in both groups when compared with MS patients without depression, she observed.
“The difference between the groups [MS with and MS without depression] seemed to increased with EDSS,” Dr. Binzer said.
Although not statistically significant, there was a trend for patients with depression to be more likely to convert to secondary progressive MS, with a hazard ratio of 1.38 (95% confidence interval, 0.91-2.1).
“For a sensitivity analysis, we found that those who had depression prior to their first MS symptom, the median age when they reached EDSS 3.0 and 4.0 was reduced by 3 and 7 years, respectively,” Dr. Binzer said, adding that, unfortunately, there wasn’t enough power to look at the other endpoints.
In regard to bipolar disorder, 1.5% (n = 200) of 13,125 MS patients diagnosed between 1973 and 2014 were identified with this mood disorder. Its presence significantly increased the risk of MS patients reaching an EDSS score of 4.0 by 58% (95% CI, 1.1-2.28), but not EDSS 3.0 (HR = 1.34; 95% CI, 0.94-1.92) or 6.0 (HR = 1.16; 95% CI, 0.79-1.69). The latter could be due to smaller sample size, Dr. Binzer suggested.
The investigators’ analysis of the results stratified by sex, conducted because men tend to fare worse than women with MS and progress faster, showed that for both depression and bipolar disorder, men were at significantly higher risk of reaching sustained disability milestones. Indeed, compared with women, men with depression had a 61% increased risk and those with bipolar disorder a 31% increased risk of reaching an EDSS score of 6.0. They also had 51% and 32% increased risks of conversion to secondary progressive MS.
“We don’t know the mechanisms that underlie these associations,” Dr. Binzer noted. “Irrespective of the underlying mechanisms, [the study] clearly shows that it’s imperative that we recognize, early, mood disorders in MS patients, and manage them effectively in order to provide better care and hopefully reduce MS disability worsening.”
The research was funded by the Swedish Research Council and the Swedish Brain Foundation. Dr. Binzer has received speaker fees and travel grants from Biogen.
SOURCE: Binzer S et al. Mult Scler. 2018;24(Suppl 2):41. Abstract 99.
BERLIN – Depression and bipolar disorder are major risk factors for worsening disability in people with multiple sclerosis, according to the results of a large Swedish registry-based study.
The presence of depression increased the risk of having a sustained Expanded Disability Status Scale (EDSS) score of 3.0 by 54% and 4.0 by 87%, and it doubled the risk of an EDSS of 6.0.
Selective serotonin reuptake inhibitor treatment also upped the risk of greater disability, with patients exposed to SSRIs having a 40% increased risk of a sustained EDSS of 3.0, a 97% chance of having a sustained EDSS of 4.0, and 2.2-fold increased risk of a sustained EDSS of 6.0.
“We know that mood disorders are highly prevalent in people with multiple sclerosis,” Stefanie Binzer, MD, said at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis. She gave her presentation at the meeting on Oct. 10, which was World Mental Health Day.
The presence of mood disorders is associated with reduced quality of life, said Dr. Binzer of the department of clinical neuroscience at the Karolinska Institute in Stockholm. Furthermore, depression is the major risk factor for suicidality in patients with MS. However, before this study the effect of having a comorbid mood disorder on MS patients’ disability levels had not been established.
The investigators analyzed data from 5,875 patients in the Swedish MS registry between 2001 and 2014. By matching these patients to records in the Swedish National Patient Registry and the Swedish National Prescribed Drug Registry, they found that 8.5% (n = 502) had an International Classification of Diseases, 10th revision (ICD-10), code for depression. Of these, 261 had received a diagnosis of depression before their diagnosis of MS.
Of 3,817 patients with MS onset between 2005 and 2014, 27.4% (n = 1,048) had collected at least one prescription for an SSRI.
“What we found was that MS patients with either an ICD code for depression or having been exposed to SSRIs had a significantly increased risk of reaching EDSS 3.0,” Dr. Binzer reported. The age at which patients reached these milestones were younger in both groups when compared with MS patients without depression, she observed.
“The difference between the groups [MS with and MS without depression] seemed to increased with EDSS,” Dr. Binzer said.
Although not statistically significant, there was a trend for patients with depression to be more likely to convert to secondary progressive MS, with a hazard ratio of 1.38 (95% confidence interval, 0.91-2.1).
“For a sensitivity analysis, we found that those who had depression prior to their first MS symptom, the median age when they reached EDSS 3.0 and 4.0 was reduced by 3 and 7 years, respectively,” Dr. Binzer said, adding that, unfortunately, there wasn’t enough power to look at the other endpoints.
In regard to bipolar disorder, 1.5% (n = 200) of 13,125 MS patients diagnosed between 1973 and 2014 were identified with this mood disorder. Its presence significantly increased the risk of MS patients reaching an EDSS score of 4.0 by 58% (95% CI, 1.1-2.28), but not EDSS 3.0 (HR = 1.34; 95% CI, 0.94-1.92) or 6.0 (HR = 1.16; 95% CI, 0.79-1.69). The latter could be due to smaller sample size, Dr. Binzer suggested.
The investigators’ analysis of the results stratified by sex, conducted because men tend to fare worse than women with MS and progress faster, showed that for both depression and bipolar disorder, men were at significantly higher risk of reaching sustained disability milestones. Indeed, compared with women, men with depression had a 61% increased risk and those with bipolar disorder a 31% increased risk of reaching an EDSS score of 6.0. They also had 51% and 32% increased risks of conversion to secondary progressive MS.
“We don’t know the mechanisms that underlie these associations,” Dr. Binzer noted. “Irrespective of the underlying mechanisms, [the study] clearly shows that it’s imperative that we recognize, early, mood disorders in MS patients, and manage them effectively in order to provide better care and hopefully reduce MS disability worsening.”
The research was funded by the Swedish Research Council and the Swedish Brain Foundation. Dr. Binzer has received speaker fees and travel grants from Biogen.
SOURCE: Binzer S et al. Mult Scler. 2018;24(Suppl 2):41. Abstract 99.
BERLIN – Depression and bipolar disorder are major risk factors for worsening disability in people with multiple sclerosis, according to the results of a large Swedish registry-based study.
The presence of depression increased the risk of having a sustained Expanded Disability Status Scale (EDSS) score of 3.0 by 54% and 4.0 by 87%, and it doubled the risk of an EDSS of 6.0.
Selective serotonin reuptake inhibitor treatment also upped the risk of greater disability, with patients exposed to SSRIs having a 40% increased risk of a sustained EDSS of 3.0, a 97% chance of having a sustained EDSS of 4.0, and 2.2-fold increased risk of a sustained EDSS of 6.0.
“We know that mood disorders are highly prevalent in people with multiple sclerosis,” Stefanie Binzer, MD, said at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis. She gave her presentation at the meeting on Oct. 10, which was World Mental Health Day.
The presence of mood disorders is associated with reduced quality of life, said Dr. Binzer of the department of clinical neuroscience at the Karolinska Institute in Stockholm. Furthermore, depression is the major risk factor for suicidality in patients with MS. However, before this study the effect of having a comorbid mood disorder on MS patients’ disability levels had not been established.
The investigators analyzed data from 5,875 patients in the Swedish MS registry between 2001 and 2014. By matching these patients to records in the Swedish National Patient Registry and the Swedish National Prescribed Drug Registry, they found that 8.5% (n = 502) had an International Classification of Diseases, 10th revision (ICD-10), code for depression. Of these, 261 had received a diagnosis of depression before their diagnosis of MS.
Of 3,817 patients with MS onset between 2005 and 2014, 27.4% (n = 1,048) had collected at least one prescription for an SSRI.
“What we found was that MS patients with either an ICD code for depression or having been exposed to SSRIs had a significantly increased risk of reaching EDSS 3.0,” Dr. Binzer reported. The age at which patients reached these milestones were younger in both groups when compared with MS patients without depression, she observed.
“The difference between the groups [MS with and MS without depression] seemed to increased with EDSS,” Dr. Binzer said.
Although not statistically significant, there was a trend for patients with depression to be more likely to convert to secondary progressive MS, with a hazard ratio of 1.38 (95% confidence interval, 0.91-2.1).
“For a sensitivity analysis, we found that those who had depression prior to their first MS symptom, the median age when they reached EDSS 3.0 and 4.0 was reduced by 3 and 7 years, respectively,” Dr. Binzer said, adding that, unfortunately, there wasn’t enough power to look at the other endpoints.
In regard to bipolar disorder, 1.5% (n = 200) of 13,125 MS patients diagnosed between 1973 and 2014 were identified with this mood disorder. Its presence significantly increased the risk of MS patients reaching an EDSS score of 4.0 by 58% (95% CI, 1.1-2.28), but not EDSS 3.0 (HR = 1.34; 95% CI, 0.94-1.92) or 6.0 (HR = 1.16; 95% CI, 0.79-1.69). The latter could be due to smaller sample size, Dr. Binzer suggested.
The investigators’ analysis of the results stratified by sex, conducted because men tend to fare worse than women with MS and progress faster, showed that for both depression and bipolar disorder, men were at significantly higher risk of reaching sustained disability milestones. Indeed, compared with women, men with depression had a 61% increased risk and those with bipolar disorder a 31% increased risk of reaching an EDSS score of 6.0. They also had 51% and 32% increased risks of conversion to secondary progressive MS.
“We don’t know the mechanisms that underlie these associations,” Dr. Binzer noted. “Irrespective of the underlying mechanisms, [the study] clearly shows that it’s imperative that we recognize, early, mood disorders in MS patients, and manage them effectively in order to provide better care and hopefully reduce MS disability worsening.”
The research was funded by the Swedish Research Council and the Swedish Brain Foundation. Dr. Binzer has received speaker fees and travel grants from Biogen.
SOURCE: Binzer S et al. Mult Scler. 2018;24(Suppl 2):41. Abstract 99.
REPORTING FROM ECTRIMS 2018
Key clinical point:
Major finding: Depression and bipolar disorder increased the risk of reaching Expanded Disability Status Scale scores of 3.0, 4.0, and 6.0, particularly in men with MS.
Study details: Swedish registry study of nearly 6,000 individuals with confirmed MS, 8.5% of whom had depression and 1.5% of whom had bipolar disorder.
Disclosures: The research was funded by the Swedish Research Council and the Swedish Brain Foundation. Dr. Binzer has received speaker fees and travel grants from Biogen.
Source: Binzer S et al. Mult Scler. 2018;24(Suppl 2):41. Abstract 99.
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.
ESMO 2018 to highlight research on advanced breast cancer
Oncology Practice will have on-site reporters in Munich covering the European Society for Medical Oncology 2018 Congress, held October 19-23.
A total of 2,051 abstracts will be presented, covering the latest in immunotherapy, technologies of the future, biomarkers, basic and translational research, and prevention, according to an ESMO press release.
Results from four studies on advanced breast cancer will be featured in the first presidential symposium:
- LBA1 – Results of IMpassion130: Results from a global, randomized, double-blind, phase 3 study of atezolizumab + nab-paclitaxel vs. placebo + nab-paclitaxel in treatment-naive locally advanced or metastatic triple-negative breast cancer.
- LBA2 – Analyses from PALOMA-3: Overall survival with palbociclib plus fulvestrant in women with hormone receptor–positive, human epidermal growth factor receptor 2–negative advanced breast cancer.
- LBA3 – Results of the phase 3 SOLAR-1 trial: Alpelisib + fulvestrant for advanced breast cancer.
- 283O PR – Results of the phase 3 trial: Chidamide, a subtype-selective histone deacetylase inhibitor, in combination with exemestane in patients with hormone receptor–positive advanced breast cancer.
Additional late-breaking plenary sessions will cover research on alectinib vs. crizotinib for treatment-naive anaplastic lymphoma kinase positive advanced non–small cell lung cancer, avelumab + axitinib vs. sunitinib as first-line treatment of advanced renal cell carcinoma, and a poly ADP-ribose polymerase inhibitor for maintenance therapy in advanced ovarian cancer
.
Oncology Practice will have on-site reporters in Munich covering the European Society for Medical Oncology 2018 Congress, held October 19-23.
A total of 2,051 abstracts will be presented, covering the latest in immunotherapy, technologies of the future, biomarkers, basic and translational research, and prevention, according to an ESMO press release.
Results from four studies on advanced breast cancer will be featured in the first presidential symposium:
- LBA1 – Results of IMpassion130: Results from a global, randomized, double-blind, phase 3 study of atezolizumab + nab-paclitaxel vs. placebo + nab-paclitaxel in treatment-naive locally advanced or metastatic triple-negative breast cancer.
- LBA2 – Analyses from PALOMA-3: Overall survival with palbociclib plus fulvestrant in women with hormone receptor–positive, human epidermal growth factor receptor 2–negative advanced breast cancer.
- LBA3 – Results of the phase 3 SOLAR-1 trial: Alpelisib + fulvestrant for advanced breast cancer.
- 283O PR – Results of the phase 3 trial: Chidamide, a subtype-selective histone deacetylase inhibitor, in combination with exemestane in patients with hormone receptor–positive advanced breast cancer.
Additional late-breaking plenary sessions will cover research on alectinib vs. crizotinib for treatment-naive anaplastic lymphoma kinase positive advanced non–small cell lung cancer, avelumab + axitinib vs. sunitinib as first-line treatment of advanced renal cell carcinoma, and a poly ADP-ribose polymerase inhibitor for maintenance therapy in advanced ovarian cancer
.
Oncology Practice will have on-site reporters in Munich covering the European Society for Medical Oncology 2018 Congress, held October 19-23.
A total of 2,051 abstracts will be presented, covering the latest in immunotherapy, technologies of the future, biomarkers, basic and translational research, and prevention, according to an ESMO press release.
Results from four studies on advanced breast cancer will be featured in the first presidential symposium:
- LBA1 – Results of IMpassion130: Results from a global, randomized, double-blind, phase 3 study of atezolizumab + nab-paclitaxel vs. placebo + nab-paclitaxel in treatment-naive locally advanced or metastatic triple-negative breast cancer.
- LBA2 – Analyses from PALOMA-3: Overall survival with palbociclib plus fulvestrant in women with hormone receptor–positive, human epidermal growth factor receptor 2–negative advanced breast cancer.
- LBA3 – Results of the phase 3 SOLAR-1 trial: Alpelisib + fulvestrant for advanced breast cancer.
- 283O PR – Results of the phase 3 trial: Chidamide, a subtype-selective histone deacetylase inhibitor, in combination with exemestane in patients with hormone receptor–positive advanced breast cancer.
Additional late-breaking plenary sessions will cover research on alectinib vs. crizotinib for treatment-naive anaplastic lymphoma kinase positive advanced non–small cell lung cancer, avelumab + axitinib vs. sunitinib as first-line treatment of advanced renal cell carcinoma, and a poly ADP-ribose polymerase inhibitor for maintenance therapy in advanced ovarian cancer
.