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AURORA, COLO. – , according to research presented at the annual meeting of the Consortium of Multiple Sclerosis Centers.
Research from the phase 3 DAYBREAK trial had already shown the safety of ozanimod, and the Food and Drug Administration approved the drug as an oral disease-modifying therapy for relapsing forms of MS in 2020.
“In the DAYBREAK study, we already have shown that the clinical and radiological disease was quite low in these patients who received the higher dose of ozanimod, and those who switched from the lower dose of the interferon to this active treatment also had decreases in their annualized relapse rate and their MRI lesion counts,” Sarah Morrow, MD, associate professor of neurology at Western University in London, Ontario, told attendees. She presented the data on behalf of senior author Bruce Cree, MD, PhD, professor of neurology and clinical research director at the University of California, San Francisco, Multiple Sclerosis Center, and the other authors. “But what was not known was whether there’s a difference in efficacy based on age, and we know that disease activity can differ based on age in person with relapsing multiple sclerosis.”
Examining efficacy by age
Analysis of data from DAYBREAK and an open-label extension study revealed that respiratory infections were more common in patients younger than 35, and urinary tract infections, dizziness, and treatment-emergent depressive symptoms became were common in patients age 50 and older. “Serious infections did not vary by age, and there were too few serious events to identify any age-related trends by specific TEAE,” the authors reported. During the open-label extension of the study, no new adverse events emerged, “confirming the ozanimod safety profile reported in the parent trials,” SUNBEAM and RADIANCE, the authors reported.
The phase 3 parent trials compared 30 mcg once weekly of intramuscular interferon beta-1a to 0.92 mg of once-daily oral ozanimod and 0.46 mg of once-daily oral ozanimod. In the DAYBREAK open-label extension, 2,256 participants underwent a dose escalation over 1 week until all reached 0.92 mg of ozanimod, where they remained for approximately 5 years of follow-up. The researchers then analyzed TEAEs, serious adverse events, and TEAEs leading to discontinuation in four age categories: 18-25, 26-35, 36-49, and 50 and older.
Respiratory infections occurred more often in those aged 18-25 (10.9%) and 26-35 (6.1%) than in those 36-49 (5.8%) and 50 and older (3.4%). However, UTIs occurred most in those age 50 and older (9.2%), versus occurring in 6.6% of those 36-49, 4.3% of those aged 26-35, and 4.6% of those 18-25.
High cholesterol occurred significantly less often in those 18-25 (1.4%) and 26-35 (2%) than in those 36-49 (5%) and 50 and older (8%), and hypertension showed a similar pattern: 2% in the youngest group, 4.7% in those aged 26-35, 12.8% in those aged 36-49, and 16.7% in those aged 50 and older.
Other TEAEs that occurred more often in older patients included depression/depressive symptoms, dizziness, back pain, joint pain, osteoarthritis, and high gamma-glutamyl transferase (GGT) levels. Overall cardiac and vascular disorders and malignancies were also more common as participants’ age increased.
Bigger concerns?
The increase in malignancy risk by age surprised Shailee Shah, MD, assistant professor of neuroimmunology and neurology at Vanderbilt University Medical Center, Nashville, Tenn., who was not involved in the research. This increase in risk was “not expanded upon much in this abstract or compared to population estimates, as this may ultimately be one of the bigger concerns with long-term use of this drug,” Dr. Shah said.
She further noted that “older patients may be at higher risk of infections and multiple cardiovascular risk factors, and so if patients already have comorbid disease, I may be less inclined to use this agent and likely less so in older individuals.”
Dr. Shah said these drugs are often recommended to individuals in their 20s and 30s at time of diagnosis. “If a patient is given this drug and tolerates it and finds it efficacious, we might continue this indefinitely, so looking at how the risk profile of young patients on this drug changes over time will be important,” Dr. Shah said. “I am also concerned about the malignancy risk and would want this elaborated upon.”
Overall efficacy across age groups
Serious infections occurred at relatively similar rates across all age groups. Incidence of any serious adverse event was 27 per 1,000 people per year in the youngest group compared with 24 events in the 26-35 group, 35 events in the 36-49 group, and 62 events per 1,000 people per year in those 50 and older.
“Patients in the 50 and older age group had a numerically lower adjusted annualized relapse rate and less gadolinium-enhancing lesions and new or enlarging T2 lesions per scan and were generally more likely to be free of gadolinium-enhancing lesions or new or enlarging T2 lesions than the 25 and younger age group,” Dr. Morrow told attendees, “but we feel that that’s more in keeping with the natural history of disease. And, overall, ozanimod, regardless of the age group, showed decreasing disease activity in the inflammatory part of disease, showing with annualized relapse rate, gad-enhancing lesions, and T2 lesions.”
Older participants were substantially more likely to withdraw from the trial because of adverse events. While 8% of the youngest group and 7.6% of participants aged 26-35 withdrew because of adverse events, 24.5% of those aged 36-49 and 18.5% of those aged 50 and older withdrew because of adverse events.
Dr. Shah said it was reassuring that no new safety signals emerged, “but based on this data, you would be concerned that long-term risk of cardiovascular disease may result in more serious adverse events over a longer period of time and will need to be considered as we see people increasingly on this drug.”
The research was funded by Bristol-Myers Squibb. The authors reported a wide range of financial disclosures, including personal fees, research funding, advisory board, and speakers fees, for multiple pharmaceutical companies, including Bristol-Myers Squibb, and five authors are employees and/or shareholders of the company. Dr. Shah has served on advisory boards for Alexion, Genentech, and Horizon.
AURORA, COLO. – , according to research presented at the annual meeting of the Consortium of Multiple Sclerosis Centers.
Research from the phase 3 DAYBREAK trial had already shown the safety of ozanimod, and the Food and Drug Administration approved the drug as an oral disease-modifying therapy for relapsing forms of MS in 2020.
“In the DAYBREAK study, we already have shown that the clinical and radiological disease was quite low in these patients who received the higher dose of ozanimod, and those who switched from the lower dose of the interferon to this active treatment also had decreases in their annualized relapse rate and their MRI lesion counts,” Sarah Morrow, MD, associate professor of neurology at Western University in London, Ontario, told attendees. She presented the data on behalf of senior author Bruce Cree, MD, PhD, professor of neurology and clinical research director at the University of California, San Francisco, Multiple Sclerosis Center, and the other authors. “But what was not known was whether there’s a difference in efficacy based on age, and we know that disease activity can differ based on age in person with relapsing multiple sclerosis.”
Examining efficacy by age
Analysis of data from DAYBREAK and an open-label extension study revealed that respiratory infections were more common in patients younger than 35, and urinary tract infections, dizziness, and treatment-emergent depressive symptoms became were common in patients age 50 and older. “Serious infections did not vary by age, and there were too few serious events to identify any age-related trends by specific TEAE,” the authors reported. During the open-label extension of the study, no new adverse events emerged, “confirming the ozanimod safety profile reported in the parent trials,” SUNBEAM and RADIANCE, the authors reported.
The phase 3 parent trials compared 30 mcg once weekly of intramuscular interferon beta-1a to 0.92 mg of once-daily oral ozanimod and 0.46 mg of once-daily oral ozanimod. In the DAYBREAK open-label extension, 2,256 participants underwent a dose escalation over 1 week until all reached 0.92 mg of ozanimod, where they remained for approximately 5 years of follow-up. The researchers then analyzed TEAEs, serious adverse events, and TEAEs leading to discontinuation in four age categories: 18-25, 26-35, 36-49, and 50 and older.
Respiratory infections occurred more often in those aged 18-25 (10.9%) and 26-35 (6.1%) than in those 36-49 (5.8%) and 50 and older (3.4%). However, UTIs occurred most in those age 50 and older (9.2%), versus occurring in 6.6% of those 36-49, 4.3% of those aged 26-35, and 4.6% of those 18-25.
High cholesterol occurred significantly less often in those 18-25 (1.4%) and 26-35 (2%) than in those 36-49 (5%) and 50 and older (8%), and hypertension showed a similar pattern: 2% in the youngest group, 4.7% in those aged 26-35, 12.8% in those aged 36-49, and 16.7% in those aged 50 and older.
Other TEAEs that occurred more often in older patients included depression/depressive symptoms, dizziness, back pain, joint pain, osteoarthritis, and high gamma-glutamyl transferase (GGT) levels. Overall cardiac and vascular disorders and malignancies were also more common as participants’ age increased.
Bigger concerns?
The increase in malignancy risk by age surprised Shailee Shah, MD, assistant professor of neuroimmunology and neurology at Vanderbilt University Medical Center, Nashville, Tenn., who was not involved in the research. This increase in risk was “not expanded upon much in this abstract or compared to population estimates, as this may ultimately be one of the bigger concerns with long-term use of this drug,” Dr. Shah said.
She further noted that “older patients may be at higher risk of infections and multiple cardiovascular risk factors, and so if patients already have comorbid disease, I may be less inclined to use this agent and likely less so in older individuals.”
Dr. Shah said these drugs are often recommended to individuals in their 20s and 30s at time of diagnosis. “If a patient is given this drug and tolerates it and finds it efficacious, we might continue this indefinitely, so looking at how the risk profile of young patients on this drug changes over time will be important,” Dr. Shah said. “I am also concerned about the malignancy risk and would want this elaborated upon.”
Overall efficacy across age groups
Serious infections occurred at relatively similar rates across all age groups. Incidence of any serious adverse event was 27 per 1,000 people per year in the youngest group compared with 24 events in the 26-35 group, 35 events in the 36-49 group, and 62 events per 1,000 people per year in those 50 and older.
“Patients in the 50 and older age group had a numerically lower adjusted annualized relapse rate and less gadolinium-enhancing lesions and new or enlarging T2 lesions per scan and were generally more likely to be free of gadolinium-enhancing lesions or new or enlarging T2 lesions than the 25 and younger age group,” Dr. Morrow told attendees, “but we feel that that’s more in keeping with the natural history of disease. And, overall, ozanimod, regardless of the age group, showed decreasing disease activity in the inflammatory part of disease, showing with annualized relapse rate, gad-enhancing lesions, and T2 lesions.”
Older participants were substantially more likely to withdraw from the trial because of adverse events. While 8% of the youngest group and 7.6% of participants aged 26-35 withdrew because of adverse events, 24.5% of those aged 36-49 and 18.5% of those aged 50 and older withdrew because of adverse events.
Dr. Shah said it was reassuring that no new safety signals emerged, “but based on this data, you would be concerned that long-term risk of cardiovascular disease may result in more serious adverse events over a longer period of time and will need to be considered as we see people increasingly on this drug.”
The research was funded by Bristol-Myers Squibb. The authors reported a wide range of financial disclosures, including personal fees, research funding, advisory board, and speakers fees, for multiple pharmaceutical companies, including Bristol-Myers Squibb, and five authors are employees and/or shareholders of the company. Dr. Shah has served on advisory boards for Alexion, Genentech, and Horizon.
AURORA, COLO. – , according to research presented at the annual meeting of the Consortium of Multiple Sclerosis Centers.
Research from the phase 3 DAYBREAK trial had already shown the safety of ozanimod, and the Food and Drug Administration approved the drug as an oral disease-modifying therapy for relapsing forms of MS in 2020.
“In the DAYBREAK study, we already have shown that the clinical and radiological disease was quite low in these patients who received the higher dose of ozanimod, and those who switched from the lower dose of the interferon to this active treatment also had decreases in their annualized relapse rate and their MRI lesion counts,” Sarah Morrow, MD, associate professor of neurology at Western University in London, Ontario, told attendees. She presented the data on behalf of senior author Bruce Cree, MD, PhD, professor of neurology and clinical research director at the University of California, San Francisco, Multiple Sclerosis Center, and the other authors. “But what was not known was whether there’s a difference in efficacy based on age, and we know that disease activity can differ based on age in person with relapsing multiple sclerosis.”
Examining efficacy by age
Analysis of data from DAYBREAK and an open-label extension study revealed that respiratory infections were more common in patients younger than 35, and urinary tract infections, dizziness, and treatment-emergent depressive symptoms became were common in patients age 50 and older. “Serious infections did not vary by age, and there were too few serious events to identify any age-related trends by specific TEAE,” the authors reported. During the open-label extension of the study, no new adverse events emerged, “confirming the ozanimod safety profile reported in the parent trials,” SUNBEAM and RADIANCE, the authors reported.
The phase 3 parent trials compared 30 mcg once weekly of intramuscular interferon beta-1a to 0.92 mg of once-daily oral ozanimod and 0.46 mg of once-daily oral ozanimod. In the DAYBREAK open-label extension, 2,256 participants underwent a dose escalation over 1 week until all reached 0.92 mg of ozanimod, where they remained for approximately 5 years of follow-up. The researchers then analyzed TEAEs, serious adverse events, and TEAEs leading to discontinuation in four age categories: 18-25, 26-35, 36-49, and 50 and older.
Respiratory infections occurred more often in those aged 18-25 (10.9%) and 26-35 (6.1%) than in those 36-49 (5.8%) and 50 and older (3.4%). However, UTIs occurred most in those age 50 and older (9.2%), versus occurring in 6.6% of those 36-49, 4.3% of those aged 26-35, and 4.6% of those 18-25.
High cholesterol occurred significantly less often in those 18-25 (1.4%) and 26-35 (2%) than in those 36-49 (5%) and 50 and older (8%), and hypertension showed a similar pattern: 2% in the youngest group, 4.7% in those aged 26-35, 12.8% in those aged 36-49, and 16.7% in those aged 50 and older.
Other TEAEs that occurred more often in older patients included depression/depressive symptoms, dizziness, back pain, joint pain, osteoarthritis, and high gamma-glutamyl transferase (GGT) levels. Overall cardiac and vascular disorders and malignancies were also more common as participants’ age increased.
Bigger concerns?
The increase in malignancy risk by age surprised Shailee Shah, MD, assistant professor of neuroimmunology and neurology at Vanderbilt University Medical Center, Nashville, Tenn., who was not involved in the research. This increase in risk was “not expanded upon much in this abstract or compared to population estimates, as this may ultimately be one of the bigger concerns with long-term use of this drug,” Dr. Shah said.
She further noted that “older patients may be at higher risk of infections and multiple cardiovascular risk factors, and so if patients already have comorbid disease, I may be less inclined to use this agent and likely less so in older individuals.”
Dr. Shah said these drugs are often recommended to individuals in their 20s and 30s at time of diagnosis. “If a patient is given this drug and tolerates it and finds it efficacious, we might continue this indefinitely, so looking at how the risk profile of young patients on this drug changes over time will be important,” Dr. Shah said. “I am also concerned about the malignancy risk and would want this elaborated upon.”
Overall efficacy across age groups
Serious infections occurred at relatively similar rates across all age groups. Incidence of any serious adverse event was 27 per 1,000 people per year in the youngest group compared with 24 events in the 26-35 group, 35 events in the 36-49 group, and 62 events per 1,000 people per year in those 50 and older.
“Patients in the 50 and older age group had a numerically lower adjusted annualized relapse rate and less gadolinium-enhancing lesions and new or enlarging T2 lesions per scan and were generally more likely to be free of gadolinium-enhancing lesions or new or enlarging T2 lesions than the 25 and younger age group,” Dr. Morrow told attendees, “but we feel that that’s more in keeping with the natural history of disease. And, overall, ozanimod, regardless of the age group, showed decreasing disease activity in the inflammatory part of disease, showing with annualized relapse rate, gad-enhancing lesions, and T2 lesions.”
Older participants were substantially more likely to withdraw from the trial because of adverse events. While 8% of the youngest group and 7.6% of participants aged 26-35 withdrew because of adverse events, 24.5% of those aged 36-49 and 18.5% of those aged 50 and older withdrew because of adverse events.
Dr. Shah said it was reassuring that no new safety signals emerged, “but based on this data, you would be concerned that long-term risk of cardiovascular disease may result in more serious adverse events over a longer period of time and will need to be considered as we see people increasingly on this drug.”
The research was funded by Bristol-Myers Squibb. The authors reported a wide range of financial disclosures, including personal fees, research funding, advisory board, and speakers fees, for multiple pharmaceutical companies, including Bristol-Myers Squibb, and five authors are employees and/or shareholders of the company. Dr. Shah has served on advisory boards for Alexion, Genentech, and Horizon.
AT CMSC 2023