IPIG 2025 | Switching from C5 inhibition to proximal inhibition in PNH: selecting the right treatment approach

The talk basically was about the challenges in switching patients and the discussion is also always whether or not a patient with certain features should be switched. And it’s very hard to define those features because within the certain trials, the so-called switch trials, the definitions for example for clinically significant extravascular hemolysis were different, the baseline hemoglobin levels were different, the endpoints were somewhat different. And so the idea was to give an overview of how to approach a patient. And when asked during the session how we would do it, the question is always, is this a patient who is ideal to be switched and do we expect efficacy of the drug? And then beside the efficacy of the drug, the question also is, is this the ideal patient for the specific drug? So it’s the mantra of personalized medicine, basically, right patient, right drug at the right time. 

And so if you have a patient on a C5 inhibitor, the first question is, when should I look for signs of extravascular hemolysis? Does it make sense to look at them after three months already or should I do that six months, 12 months? What we all discussed upon and concluded is that you know it doesn’t make sense to look early on so you should have the patient at least on the C5 inhibition for six months or rather 12 months. So after 12 months you can then evaluate if there’s development of extravascular hemolysis which is indicated by reticulocytosis, indirect bilirubinuria, and a positive Coombs test which you normally don’t do in PNH patients but in this case you can do. 

And then you have to decide whether or not this is a patient who is really understanding the pathophysiology of the disease because with the switch you change not only the course of the disease but also the course of a potential side effect which is the breakthrough hemolysis and so you got to make sure that the patient understands that the breakthrough hemolysis with the proximal differs from a breakthrough hemolysis with the terminal inhibitors.

And so yeah discussing all these things there are some guidelines you should follow in terms of what to look at. Like I said, clinically relevant extravascular hemolysis and then you have to sit down with the patient and then it all depends on whether or not the patient wants an oral or you think he cannot take an oral because he has issues with taking medicine orally or you have issues in terms of that he will stick to the medication. So you rather go with a twice weekly scheme or if you have a patient who is very unreliable, however you determine that you might just add something like danicopam. So you have all these choices and it’s very hard nowadays to find exactly the right drug for the right patients because that switch normally should not lead to the next switch between proximal inhibitors. So you should choose the right drug at the first time.

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