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Study examines incidence of cancer in patients taking rituximab, fingolimod, and natalizumab.
BERLIN—The risk of cancer, and breast cancer in particular, was not elevated above background levels in a large cohort of patients with multiple sclerosis (MS) taking disease-modifying therapies, according to research presented at ECTRIMS 2018.
Those findings from the 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 as the standard, the hazard ratio (HR) for any malignancy with fingolimod was 1.74 (95% confidence interval [CI], 0.92–3.28). For natalizumab, 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 in Stockholm.
Surveillance for Risk of Malignancy
Limited data exist for real-world MS cohorts exposed to novel disease-modifying therapies, said Mr. Alping. Rituximab has been studied in patients with rheumatoid arthritis, but the treatment regimens and patient characteristics differ in patients with MS, he noted. However, surveillance for risk of malignancy is important “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,” he said.
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. There were four breast cancers in the ocrelizumab population, which would translate to 26.1 cancers per 10,000 person-years, as opposed to the zero breast cancers in the placebo group. “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 at the Karolinska Institute sought to compare the risk of cancer in patients with MS who were treated with rituximab, fingolimod, and natalizumab.
They conducted a nationwide cohort study using the Swedish MS registry. The researchers examined treatment episodes between 2011 and 2016. In Sweden, the MS registry is linked to the overall patient registry, as well as to registries for cancer and prescription drug use. In addition, patient data are linked to national census data.
Mr. Alping and his colleagues identified the first instance of use for an MS patient of rituximab, natalizumab, or fingolimod between 2011 and 2016. Then they matched patient records from the general population by age, sex, and geographic location to enroll 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 used an ever-treated approach and did not attempt to weight exposure duration or dose. However, statistical adjustments were made for patient and control demographics and medical history, history of cancer, and MS disease characteristics.
Comparing Incidence Rates
At baseline, 1,558 patients had been treated with fingolimod, 1,761 with natalizumab, and 3,012 with rituximab. Less than one-third of the patients (26.3%–31.6%) were male, and the mean age was 35–43. Most patients (66%–86%) had received one or two previous therapies. The mean Expanded Disability Status Scale (EDSS) score was 2.20–2.88. Less than 2% of patients (0.9%–1.7%) had a history of 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.
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.
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 HR for any malignancy under the various treatment conditions.
Among 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.
No Increased Risk When Compared With the General Population
“For malignant cancer of any type, we found no increased risk for rituximab, compared with fingolimod and natalizumab,” Mr. Alping said, noting the wide confidence intervals in the adjusted data. The incidence of breast cancer in women who have taken rituximab 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,” he said. “The overall cancer risk and risk of breast cancer might not be major concerns in the short term when treating MS patients with rituximab, relative to other disease-modifying therapies,” Mr. Alping concluded.
The study was partially funded by the Patient-Centered Outcomes Research Institute.
—Kari Oakes
Study examines incidence of cancer in patients taking rituximab, fingolimod, and natalizumab.
Study examines incidence of cancer in patients taking rituximab, fingolimod, and natalizumab.
BERLIN—The risk of cancer, and breast cancer in particular, was not elevated above background levels in a large cohort of patients with multiple sclerosis (MS) taking disease-modifying therapies, according to research presented at ECTRIMS 2018.
Those findings from the 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 as the standard, the hazard ratio (HR) for any malignancy with fingolimod was 1.74 (95% confidence interval [CI], 0.92–3.28). For natalizumab, 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 in Stockholm.
Surveillance for Risk of Malignancy
Limited data exist for real-world MS cohorts exposed to novel disease-modifying therapies, said Mr. Alping. Rituximab has been studied in patients with rheumatoid arthritis, but the treatment regimens and patient characteristics differ in patients with MS, he noted. However, surveillance for risk of malignancy is important “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,” he said.
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. There were four breast cancers in the ocrelizumab population, which would translate to 26.1 cancers per 10,000 person-years, as opposed to the zero breast cancers in the placebo group. “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 at the Karolinska Institute sought to compare the risk of cancer in patients with MS who were treated with rituximab, fingolimod, and natalizumab.
They conducted a nationwide cohort study using the Swedish MS registry. The researchers examined treatment episodes between 2011 and 2016. In Sweden, the MS registry is linked to the overall patient registry, as well as to registries for cancer and prescription drug use. In addition, patient data are linked to national census data.
Mr. Alping and his colleagues identified the first instance of use for an MS patient of rituximab, natalizumab, or fingolimod between 2011 and 2016. Then they matched patient records from the general population by age, sex, and geographic location to enroll 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 used an ever-treated approach and did not attempt to weight exposure duration or dose. However, statistical adjustments were made for patient and control demographics and medical history, history of cancer, and MS disease characteristics.
Comparing Incidence Rates
At baseline, 1,558 patients had been treated with fingolimod, 1,761 with natalizumab, and 3,012 with rituximab. Less than one-third of the patients (26.3%–31.6%) were male, and the mean age was 35–43. Most patients (66%–86%) had received one or two previous therapies. The mean Expanded Disability Status Scale (EDSS) score was 2.20–2.88. Less than 2% of patients (0.9%–1.7%) had a history of 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.
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.
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 HR for any malignancy under the various treatment conditions.
Among 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.
No Increased Risk When Compared With the General Population
“For malignant cancer of any type, we found no increased risk for rituximab, compared with fingolimod and natalizumab,” Mr. Alping said, noting the wide confidence intervals in the adjusted data. The incidence of breast cancer in women who have taken rituximab 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,” he said. “The overall cancer risk and risk of breast cancer might not be major concerns in the short term when treating MS patients with rituximab, relative to other disease-modifying therapies,” Mr. Alping concluded.
The study was partially funded by the Patient-Centered Outcomes Research Institute.
—Kari Oakes
BERLIN—The risk of cancer, and breast cancer in particular, was not elevated above background levels in a large cohort of patients with multiple sclerosis (MS) taking disease-modifying therapies, according to research presented at ECTRIMS 2018.
Those findings from the 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 as the standard, the hazard ratio (HR) for any malignancy with fingolimod was 1.74 (95% confidence interval [CI], 0.92–3.28). For natalizumab, 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 in Stockholm.
Surveillance for Risk of Malignancy
Limited data exist for real-world MS cohorts exposed to novel disease-modifying therapies, said Mr. Alping. Rituximab has been studied in patients with rheumatoid arthritis, but the treatment regimens and patient characteristics differ in patients with MS, he noted. However, surveillance for risk of malignancy is important “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,” he said.
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. There were four breast cancers in the ocrelizumab population, which would translate to 26.1 cancers per 10,000 person-years, as opposed to the zero breast cancers in the placebo group. “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 at the Karolinska Institute sought to compare the risk of cancer in patients with MS who were treated with rituximab, fingolimod, and natalizumab.
They conducted a nationwide cohort study using the Swedish MS registry. The researchers examined treatment episodes between 2011 and 2016. In Sweden, the MS registry is linked to the overall patient registry, as well as to registries for cancer and prescription drug use. In addition, patient data are linked to national census data.
Mr. Alping and his colleagues identified the first instance of use for an MS patient of rituximab, natalizumab, or fingolimod between 2011 and 2016. Then they matched patient records from the general population by age, sex, and geographic location to enroll 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 used an ever-treated approach and did not attempt to weight exposure duration or dose. However, statistical adjustments were made for patient and control demographics and medical history, history of cancer, and MS disease characteristics.
Comparing Incidence Rates
At baseline, 1,558 patients had been treated with fingolimod, 1,761 with natalizumab, and 3,012 with rituximab. Less than one-third of the patients (26.3%–31.6%) were male, and the mean age was 35–43. Most patients (66%–86%) had received one or two previous therapies. The mean Expanded Disability Status Scale (EDSS) score was 2.20–2.88. Less than 2% of patients (0.9%–1.7%) had a history of 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.
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.
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 HR for any malignancy under the various treatment conditions.
Among 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.
No Increased Risk When Compared With the General Population
“For malignant cancer of any type, we found no increased risk for rituximab, compared with fingolimod and natalizumab,” Mr. Alping said, noting the wide confidence intervals in the adjusted data. The incidence of breast cancer in women who have taken rituximab 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,” he said. “The overall cancer risk and risk of breast cancer might not be major concerns in the short term when treating MS patients with rituximab, relative to other disease-modifying therapies,” Mr. Alping concluded.
The study was partially funded by the Patient-Centered Outcomes Research Institute.
—Kari Oakes