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.