Emerging Treatment Options for the Management of Sickle Cell Disease - Episode 14

Factors in Selecting Disease-Modifying Therapy in SCD

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Panelists take a step back to consider when they might use certain disease-modifying therapy in the setting of sickle cell disease.


Ifeyinwa Osunkwo, MD: Who would be the right candidate for voxelotor vs crizanlizumab vs Endari? We probably should get hydroxyurea. Starting with Dr Smith, who would be the best person for voxelotor?

Wally R. Smith, MD: I’m a huge fan of drug cocktails. Each of these 3 drugs was used along with hydroxyurea in their formative trials. They showed additive effects to hydroxyurea. I have people on 3 drugs that their insurance will pay for. I have a person who’s on Endari, hydroxyurea, and voxelotor. You could have somebody on crizanlizumab, Endari, and hydroxyurea, or crizanlizumab, voxelotor, and hydroxyurea, if their insurance companies will pay for it. Of course, they won’t, but that’s my belief. I don’t know how well I do this, but I try to present all these therapies to patients and let them tell me what they want—not select for them, but let them tell me what they want.

To make the selection, they’ll usually ask me to explain 1 or 2 of the drugs that sound interesting to them. They’ll ask me to confirm adverse effects, how you take it, how often you have to take it, or the mechanism of action. I don’t necessarily buy into “If you’re anemic, take voxelotor. If you hurt a lot, take Endari, hydroxyurea, and crizanlizumab.” You can back yourself up into some corners. I’d rather start with, “You have sickle cell disease. You want everything you can do to make your life better. We have 3, 4 possibilities. Which of these appeals to you, and how much can we get paid for it?”

Ifeyinwa Osunkwo, MD: I’m going to let Dr Desai and Dr Smith affirm or rebut what Dr Smith has said. Do you have a different opinion?

Payal Desai, MD: I agree. I present the patients with all the data. Having said that, genotype matters, but not in terms of hydroxyurea. I offer hydroxyurea to anyone having pain episodes. Because we know a little less, I’m a little more cautious, and maybe more scared, about the higher hemoglobin because I’ve seen a couple of complications. I’ve had patients have improvement in their pain with voxelotor,so I don’t think the boxes fit necessarily for just hemoglobin or pain. I don’t think there’s just 1 thing, and I’m hopeful that over time we’ll discover that they do multiple things. But if people have a higher hemoglobin—over 8 g/dL is usually my cutoff—I don’t always think about voxelotor. If I offer it to them if that’s what they decide, I start slower and give only 1 to 2 pills, and I closely monitor their hemoglobin.

In terms of crizanlizumab, it affects the platelets, so if patients are on full-dose blood thinners, none of those patients was included in the pivotal trial. I’m still a little hesitant. I want more data in terms of patients on anticoagulants and a P selectin inhibitor. In terms of Endari, sometimes those are patients who haven’t even tried hydroxyurea. Sometimes they have a little milder disease and accept those therapies. They are willing to because they want to do the amino acid, the thing that feels like it’s more of a supplement. That’s not saying it works better or worse, but the commitment to take a supplement 2 times a day every day indefinitely requires a patient who wants to be on board with that type of commitment. Those are some of the other nuances on top of what everybody has already mentioned in terms of drug therapy selection.

Ifeyinwa Osunkwo, MD: All right. Dr Shah?

Nirmish Ramesh Shah, MD: I completely agree that we should be discussing these therapies with everyone, even if you don’t feel this patient needs crizanlizumab or voxelotor. We should offer all this and have patients be aware. As Dr Desai brought up, we don’t have guidelines. We have guidelines for pain, but they’re not all agreeing with one another. We don’t have guidelines at all for this yet. We’re thankful that we have these options. Without a doubt, just like hypertension and congestive heart failure, for a complex disease like sickle cell, we’re going to need multiple medications to control it. Inevitably, hydroxyurea will not be enough, and we’re going to consider what else we can do. If I want to talk about a cutoff, I use somewhere around 9 to 9.5 g/dL; the study was up to 10.5 g/dL. You can draw the line in the sand anywhere. But it comes down to making sure that the patient is onboard and part of the decision about what this drug can do for them.

It’s also important to say that patients don’t know until they know, meaning not just about the drugs. I’ve had patients start voxelotor and say, “Dr Shah, I can do so much that I didn’t think I could do.” I ask them, “How are you doing?” “I’m doing great.” “Are you short of breath?” “No.” “Can you do what you need to do?” “Yes, I can do everything.” They start voxelotor, and they’re like, “My gosh. I clean the garage and my room—my wife is so happy I’m cleaning.” All these conversations that patients don’t know until they know, and the same thing holds true with crizanlizumab. “Dr Shah, I didn’t realize I was having pain and I was dealing with it, but I feel better. I have less pain.” It’s on us to offer everything we can. Patients have gotten used to where they are, and they don’t need to. Patients need to understand there are options, and they may be a good option once they start.

Transcript edited for clarity.