Q: Are there biological and clinical predictive factors for treatment response that can be used to determine individualized therapy in patients with chronic ITP?

Clinical factors for treatment response can include whether a patient has comorbidities, whether it is secondary or primary ITP, whether he or she is going to need surgery, whether he or she presents with bleeding, lifestyle itself, and whether he or she requires anticoagulation therapy or aspirin therapy. As for age as a clinical factor, older age groups are more likely to be chronic and are at a higher risk of bleeding over the age of 60 or 65 years. Also, certainly for patients who are at risk of or who have had liver disease, I tend to stay away from eltrombopag. I am not impressed that we can really look at a patient’s immune profile yet to decide whether this therapy may be better than that therapy for this patient. There are interesting concepts about that, but I am just not convinced yet that we can look at a patient’s biological markers and say, ͞”Oh I know what treatment we should be picking here.”

There are no biological markers, even though there are things that are suggested that may modify platelet clearance rates, such as antibodies directed against the 1b9 complex; the asialo receptors resulting clearance independent of Fc receptors, and so on. Animal models suggest it, but there is no real extensive trial that really has assessed it. It is also not easy to look at antibodies, and cytokine profiles are worthless in terms of biological markers. It is all retrospective looks at outcomes as opposed to a prospective study. I think a lot of this would fail in a prospective study. There are good clinical things that a physician should think about (eg, age, comorbidities, secondary versus primary ITP, diabetes, hypertension) that are really more important than trying to find out whether interleukin 17 or Th1 or Th2 phenotype is going to define therapy.

We have some pretty crude tools that we use right now, such as the platelet count, bleeding history, age, gender, and duration of disease, to inform treatment decisions. What we do not do yet routinely is use any sort of biomarker to inform treatment decisions beyond the platelet count, but I think that that is a goal for the future. There are a lot of other biomarkers that have been explored that could potentially inform treatment. There is some decent evidence that the presence of antibodies against the GPIBIX-V complex predicts refractoriness to certain treatments. There is a nice paper that was just published in Blood that suggests that patients with ITP who have fewer endothelial progenitor cells and dysfunctional endothelial progenitor cells are more likely to be refractory to corticosteroids. All of those sorts of data are compelling, but they’ve never been validated in well-done, appropriately powered clinical trials, and I think that, as we’ll talk about in a question that’s coming up, that’s a new frontier in ITP that I expect to be explored over the next 10 years or so.