Current Series: Advances in the Treatment of Spinal Muscular Atrophy

Crystal Proud, MD: Long-term safety data have been released with regard to nusinersen and the treatment of infantile and later onset SMA [spinal muscular atrophy], and findings identified that the safety in patients with longer-term treatment up to 4 years were consistent with those previously reported. John, you touched on some of those as well. Julie, how do you counsel some of your patients when you're discussing the possible benefits and potential adverse effects of treatment with nusinersen? How do you establish some of those expectations? 
 
Julie Parsons, MD: I think that it is important to establish expectations early. That's a really good point, Crystal, in terms of what we're expecting. And what we expect in a patient who is treated is that they will maintain function. If we're treating them very early on, then hopefully their function will be enhanced. Presenting the data that we have for the trials—for the ENDEAR and the CHERISH trials—presenting the data that we have to families is important to look at. 
 
We do know that, over the extended period of 4 to 5 years since the initiation of treatment, we do continue to see stabilization and improvement in motor function. It's important to show parents that graph so they understand that this isn't something that is lost. We also know from the NURTURE study, the earlier the treatment, the better the outcomes. I think that piece is important.  
 
In terms of the adverse effects, the downside is the delivery system, which is intrathecal, which means that the babies or children have to undergo serial spinal taps, and that can be uncomfortable and not terribly attractive. On the other hand, the safety profile is incredible. We do safety monitoring prior to every dose of nusinersen, including coagulation, platelet counts, and urine protein.  
 
In the long-term data that are available and were presented recently, there was just about a 2% rate of thrombocytopenia, about a 6% rate of protein in the urine. Not all of it is actionable. The biggest issue is the about 5% or less post-LP [lumbar puncture] headache or post-LP syndromes that some of the older patients experience. Counseling about that is important. We've learned a lot about helping with LPs, so we can prevent some of the syndromes by making certain that patients are very well hydrated prior to coming in.  
 
That would make them comfortable. There are things that we've done in terms of the delivery system that have helped over time, so nusinersen has shown over this period that it's an amazingly safe drug and clearly effective in terms of treatment as well. 
 
Crystal Proud, MD: And your clinical trial evaluated nusinersen in symptomatic infants.