Bridging Pediatric and Adult Care in Spinal Muscular Atrophy

This is a 2-part Q&A. Click here to view Part 1 of this conversation.

Nearly a decade into the treatment era in spinal muscular atrophy (SMA), a rare autosomal recessive neuromuscular disorder caused by biallelic variants in the survival motor neuron 1 (SMN1) gene, clinicians are managing a population whose trajectory no longer matches the disease as it was historically described. Patients identified through newborn screening and treated presymptomatically are reaching motor milestones that were once out of reach, while patients diagnosed years earlier have often been exposed to several therapies in sequence. What that combined experience produces over time is not yet characterized in the literature.

Two consequences follow. The first is an evidence gap: with multiple disease-modifying therapies now available and no head-to-head data, clinicians and families are weighing options without the comparative evidence that would ordinarily inform the decision. The second is structural. As treated patients live longer and function better, a growing group is aging out of pediatric neuromuscular programs and into adult systems that were not built to receive them.

In the second part of a conversation with NeurologyLive^® in recognition of SMA Awareness Month, held annually throughout August, Divya Jayaraman, MD, PhD, assistant professor of neurology and pediatrics in the Division of Child Neurology at Columbia University Irving Medical Center and a member of the Muscular Dystrophy Association Care Center team, discussed both. She addressed why she does not consider SMA a solved problem, what evidence she would most like to see generated, and why the pediatric-to-adult transition remains a challenge she believes no center has fully resolved. She also identified the specialties where she sees the largest awareness gaps, including obstetrics and maternal-fetal medicine, and made the case for reengaging adults with milder disease who may never have started treatment.

In the first part of the conversation, Jayaraman discussed how her clinic structures its multidisciplinary team and how the expansion of treatment options has reshaped the clinic visit. 

NeurologyLive: What does the expansion of treatment options mean for how the field understands SMA now?

Divya Jayaraman, MD, PhD: Essentially, we’re generating a new treated natural history. Patients have had exposures often to many therapies sequentially, in combination, depending on where they were when the various treatments came out. So it’s both exciting and also challenging, because if there are maybe expected declines, say around puberty or just growth related, then teasing out what is actually expected becomes difficult. They will ask us, how do you compare this treatment versus that treatment? I have to tell them that data hasn’t been analyzed or doesn’t exist yet, and is still being generated as we speak. So, exciting things, but it makes our job more challenging, and I would say it also makes the research more important.

People think of SMA as a problem that is solved. I do not think so. I think the questions have only become more nuanced. Right now, I think what a lot of people are wondering is, how do the existing treatments compare, and might the answer even differ in different subpopulations?

What is a common gap or challenge you see in coordinating care across specialties, and how might clinicians address it?

Prospective data is needed, and a trial would be great, but even retrospective data comparing what already exists would help. That’s an evidence gap that has been identified.

The other big care gap is continuity across the lifespan. What do we do, especially at that pediatric-to-adult transition point? I don’t know that any center has figured that out entirely. Some may do a better job of it than others, but it’s a common challenge I see. It’s not just, “is there an adult neuromuscular doctor who’s comfortable taking care of these patients?” They might be, but do they have the infrastructure built around them? Do they have the other subspecialists who are comfortable with these patients and what they need, the pulmonologists, the physical therapists, and everyone else?

I would say we do have quite a few patients who are off to college and doing great things, and that’s exciting. We might not have seen that a generation ago to this degree, except for the milder, less affected types. But now we’re seeing people live longer, and that’s really wonderful. It’s more a matter of, now that we’ve created this need, how do we meet that need?

Is there anything you would tell clinicians to keep in mind about that transition period specifically?

It’s really challenging. On the pediatric side, I will say that patients are used to a certain amount of care coordination and hand-holding to a certain extent, and as they’re transitioning to adult medical care, there’s less of that in the adult medical world. I don’t think that is saying something negative. I think it’s just being factual. So to the degree that we can prepare them for that, that’s helpful. To the degree that, as kids are growing up, we prepare them to take ownership of their own medical care, that’s helpful, while knowing this is a complicated disease and we’re asking much more of them than of their peers.

Then it’s a bit of a lift for the adult caregivers who are taking over. I have colleagues whom I trained with in residency and fellowship who are adult neurologists, some of whom are setting up SMA care centers for adults. So I think there is an increasing recognition of the need for this type of coordinated care model on the adult side as well. I think it just needs some time to catch up, and some hopefully institutional buy-in, as well as hopefully payers also keeping up. It’s not going to be solved by an individual, let alone one person.

Do you have any closing remarks on why it is important to raise awareness of SMA?

I think the pediatric world is fairly aware of SMA, in the sense that our general child neurology colleagues and even pediatrician colleagues remember the days when they gave a devastating infant SMA diagnosis. There’s at least awareness that there are treatments.

In terms of getting awareness out, I feel like OB/GYNs are aware of the disease, but maybe not aware of how many treatments there are, or the time sensitivity of it. We recommend, if there’s a prenatal diagnosis made, say on amniocentesis, to consider slightly early delivery at 36 to 37 weeks, so that gives us several weeks of lead time in getting the patient treated postnatally. I know other centers are doing that as well. So awareness for OB/GYNs and maternal-fetal medicine specialists, that would be one thing.

Then for older patients, including adults, there’s this sense that there are several who are in the woodwork, who may not even be on treatment because their disease has been so mild, to consider reengaging as these new treatments come up that are hopefully less burdensome. The tablet form of risdiplam (Evrysdi; Roche) is an excellent example of that. No longer needing a liquid form, doesn’t need to be refrigerated, so that’s huge. Then the higher dose of nusinersen (Spinraza; Biogen). All of these newer treatments, I could see a lot of benefit for adults who have maybe not been as engaged.

Transcript edited for clarity. For more perspectives on the multidisciplinary care approach in SMA, click here to read our previous Q&A in this series.