Krzysztof Selmaj, MD, PhD, provides his clinical expertise on strategies to monitor patients with relapsing-remitting multiple sclerosis (RRMS) taking sphinogine-1-phospate (S1P) receptor modulators.
Krzysztof Selmaj, MD, PhD: Monitoring is a very important issue because it secures the safety of our patients. Monitoring results from our knowledge on the mechanism of action of these drugs and also on the known safety issues and adverse events…. There are several aspects that should be taken into consideration for monitoring. When we talk about macular edema, the way we can monitor this is an OCT [optical coherence tomography] examination every 3 months. It should be taken every 3 months to…have enough time to stop the treatment and prevent serious consequences.
Another thing we should take regularly is the blood count. Some recommendations say about 3 months, but most say every 6 months. With this examination, we specifically check the number of lymphocytes, because most of S1P receptor–treated patients showed a decreased number of lymphocytes. The mechanism of action was dark. We should control the lymphocytes count. Specifically, we should look at whether the lymphocytes are going below 0.300 or 0.200 of cells/μL. If the number of lymphocytes goes below 0.200, then we should stop treatment and wait for recovery, which occurs in about 1 month. It depends on the different trials because half-life is different, but on average it’s 1 month. We can try to restart the treatment, but if the number is still going down, the patient should be discontinued permanently. Cell blood count is a very important parameter to monitor.
Another important parameter to monitor is of liver enzyme levels, and ALT and AST should be measured every 3 months. In a small fraction of patients—5% to 10%, depending on a given drug—the transaminases may increase. The increase can get different levels and go above the upper limit of normal…. But when it goes above 3 times the upper limit of normal, particularly 5 times above the upper limit of normal, this is a serious case of liver enzyme increase. If this continues over time, some patients might discontinue it because of an increase of transaminases. For example, in long-term observation studies with fingolimod, over an 18-year observation period, 5.5% of patients discontinued it because of increase of liver enzymes. This is an important parameter of monitoring the liver enzyme measurement.
The other requirements are measurement of blood pressure. On some occasions, there may be a slight increase in blood pressure. Especially for patients with hypertension, we should pay attention to that and adjust treatment for hypertension in these patients. An additional parameter for monitoring is skin. We should evaluate the skin for skin cancer. It’s a very rare event. It’s mostly related to the nonselective S1P receptor modulators. It wasn’t present in the selective 1. But because of the seriousness of these adverse effects, it should be taken quite regularly. We take an MRI to monitor treatment with S1P receptor modulators. It’s related also to safety, but mostly it’s related to the assessment of treatment efficacy. With an MRI you can potentially check for PML [progressive multifocal leukoencephalopathy] presence. PML is a very rare adverse effect. It was observed in patients with treatment with nonselective S1P receptor modulators. But the consequences of PML are very serious, so be very cautious about that. Also, MRI is an important parameter of monitoring.
Transcript edited for clarity.