Reevaluating Neuroprotective Multiple Sclerosis Trial Designs Using the Visual System: Shiv Saidha, MBBCh
The professor of neurology at Johns Hopkins Medicine discussed the trial design of the phase 4 RENEW study assessing the long-term safety profile of mitoxantrone in multiple sclerosis. [WATCH TIME: 9 minutes]
WATCH TIME: 9 minutes
“If you're going to use anything as an outcome, you also need to understand very well what the outcome is that you're using."
Registry to Evaluate Novantrone Effects in Worsening Multiple Sclerosis (RENEW) was a phase 4 study that assessed the long-term safety profile of mitoxantrone in patients with secondary progressive multiple sclerosis (SPMS), progressive relapsing multiple sclerosis (PRMS), and worsening relapsing-remitting multiple sclerosis (RRMS). In the study, investigators enrolled 509 patients who received at least one infusion of mitoxantrone, an antineoplastic medicine used to treat MS, prostate cancer, and acute nonlymphocytic leukemia. During the treatment period, patients received laboratory workups and cardiac monitoring every 3 months and then annually up to 5 years.
Overall, annual follow-up data were only available for 250 of the enrolled patients, and 172 (33.8%) completed the 5-year period. Safety cardiovascular end points included left ventricular ejection fraction (LVEF), symptoms of congestive heart failure (CHF), and cardiac-related serious adverse events. In total, 27 (5.3%) patients reported LVEF reduction under 50% during the treatment phase (n = 509) and 14 (5.6%) patients reported it in the annual follow-up phase (n = 250). In additional safety findings, 10 (2.0%) patients reported signs and symptoms of CHF (treatment phase, n = 6; annual follow-up phase, n = 4). These findings are consistent with the known safety profile of mitoxantrone, and provide additional long-term safety data of the treatment in patients with MS.
Shiv Saidha, MBBCh, professor of neurology at Johns Hopkins Medicine, talked about the visual system as a model for neuroprotective trials in MS in a session at the 2024 Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum, held February 29 to March 2, in West Palm Beach, Florida. Following the session, Saidha sat down with NeurologyLive® to discuss the primary challenges of the RENEW clinical trial design as an example of using the visual system model. In addition, he talked about the use of fellow-eyes as surrogates affect outcome interpretation, as well as some of the advantages and disadvantages of acute optic neuritis versus non-optic neuritis models in neuroprotection studies.
Click here for more coverage of ACTRIMS 2024.
