Q: What clinical data show safe and effective long-term platelet control in patients with chronic ITP?

The only long-term data that I am impressed with have been on the studies of romiplostim and eltrombopag. The data have shown that the TPO-RAs are very safe and effective treatments. There is little, if any, increase in thrombotic events. In addition, there is little, if any, increase in the development of increased reticulin, which either stabilizes or reverses after taking patients off of these drugs. The side effects are very minimal. With eltrombopag, there have been some problems with portal vein thrombosis or an increase in liver enzymes early on, but, as the data show, TPO-RAs remain effective for years with patients who can be maintained on these treatments for a very long time. I have patients who have been on romiplostim for probably 12 years. All of the clinical data show that the TPO-RAs are effective and safe for long-term use.

The long-term studies in the medical literature in patients with chronic ITP show that TPO-RAs are safe and effective for long-term use as a class of drug. The other therapy for which there are good long-term data is splenectomy. The data with splenectomy suggest that up to 85% of patients will have some sort of initial response, but, among those responders, up to 30% will relapse within the next 10 years, with most relapses occurring within the first couple of years after splenectomy. There are also pretty good long-term data on safety issues after splenectomy. These data suggest that there is about a 3-fold increased risk of serious infection or sepsis and thromboembolism after splenectomy. The TPO-RAs and splenectomy are the treatments with the most robust long-term data. Despite the positive long-term results in chronic ITP, there is a recently published, randomized control trial with rituximab that showed that the response to rituximab is no greater than placebo after about 1.5 years, which is consistent with observational studies that showed disappointing long-term responses with rituximab.

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With the TPO-RAs, there are open-label extension studies out to 5 years. These trials set the standard because they were the first randomized trials to look at the long-term efficacy and safety of an agent in chronic ITP. Therefore, we have long-term safety data for the TPO-RAs, plus there was a Risk Evaluation and Mitigation Strategy program that was made available for patients who were not participants in the early phase 3 studies and the extension studies. Since there are a lot of data on the TPO-RAs, we have a good idea of the long-term toxicities and the complications. There are even some data about potential advantages of one treatment versus another of the available TPO-RA agents. They are mostly small series, but there are some data regarding who might be a better patient for romiplostim versus eltrombopag. We do not really have the data that we need for many of the historical agents in ITP because there are no long-term data for the other treatments. We just have some retrospective analysis of a single institution’s experiences. There are now ongoing clinical trials, but I do not know what we are going to see in these studies. If they actually go to phase 3 trials, they are going to provide long-term data. Based on the studies that were done with the TPO-RAs, the US Food and Drug Administration is going to require that information.