Navigating the adverse effects, and potential benefits, for the neurological condition's treatments.
Stephen Krieger (pictured), MD, associate professor for the Mount Sinai Hospital, spoke recently with MD Magazine about the booming rate of disease-modifying therapy (DMT) options for multiple sclerosis (MS), and navigating the effects seen in clinical trials that could come to light with patients — if not properly addressed.
What are the benefits and risks of disease-modifying therapy?
Krieger: With any disease-modifying therapy, you have to take into account the safety profile and try to figure how to take the data from the clinical trials and apply it into our actual practice with real patients who may have other comorbidities, or complex medical histories and situations to treat. I think with ocrelizumab, we have to think about potential risks for infection, a possibility that our most feared opportunistic infection — progressive multifocal leukoencephalopathy (PML) — can appear with this agent. Then we have to think about things like opportunistic cancers, malignancies.
There’s a small signal for breast cancer seen in the clinical trial for ocrelizumab, and I think that’s something we need to think about in the background, talk to our patients about, and see how that data looks over the coming years.
Other medicines we have also require screening for infections. At this point, I’ll tell my trainees that we really have to think about a panel of infectious risks when we are looking at changing or starting an MS disease-modifying therapy. We look at a history of hepatitis exposure, which is important for our B-cell depleting medicines. We look for a history of tuberculosis exposure. We think about the immunity to chicken pox as being important — we don’t want patients on certain medicines for relapsing MS that could suppress the immune system to be naïve to chicken pox.
Finally, the big one is to look for a history of JC virus exposure, and that’s become a really crucial test for us in trying to maximize the benefit-risk ratio of natalizumab, and it may ultimately pertain to minimalizing the risk of PML with other medicines.
Where are there positives in daclizumab’s reported effects?
Krieger: Daclizumab is another monoclonal antibody that was approved this past year for relapsing MS. It was studied in a head-to-head trial against an injectable interferon, so we have data for superiority here, for our agent versus one of our longstanding injectable agents.
Daclizumab is given once a month by self-injection, so from a dose-frequency perspective that’s favorable as well. It does, however, have a set of possible side effects, particularly relating to liver function, which has to be checked monthly before each subsequent dose. So it’s a commitment to both get the bloodwork done and do the injection.
There’s a possibility for cutaneous or skin reactions, which at least from the clinical trial were occasionally severe. I haven’t seen a broad enough sense of what it’s been like in clinical practice yet to comment on it in standard practice. But those are the things the trial data, and from the way the approval was written, show the monitoring we need to do and that everyone needs to know about daclizumab.