Management of immune thrombocytopenia--something old, something new.

For most of my career, the management of immune thrombocytopenia has evolved from clinical experience rather than clinical evidence. When I was a medical student at Ohio State University in 1960, my mentors were shifting their initial treatment for immune thrombocytopenia from splenectomy to the recently available glucocorticoids.1 Over the next 40 years, although multiple other treatments were reported in case series of selected patients, glucocorticoids and splenectomy remained the most common first and second treatments, respectively, for immune thrombocytopenia. When a guideline for immune thrombocytopenia was developed by the American Society of Hematology in 1996,2 there was little clinicaltrial evidence on which to base recommendations. During the past 10 years, the management of immune thrombocytopenia and the quality of clinical evidence have changed dramatically. Rituximab has become a common second treatment, although the frequency and durability of a complete response may be less with rituximab as compared with splenectomy.3,4 The development of thrombopoietin-mimetic agents, which can increase platelet counts by increasing platelet production, began a new era in the management of immune thrombocytopenia. Two agents, romiplostim and eltrombopag, have been approved by the Food and Drug Administration and the European Medicines Agency for use in treating immune thrombocytopenia. Multiple randomized clinical trials have shown the benefit of these agents for patients in whom previous treatments have failed; recent publications include the study by Kuter and colleagues in this issue of the Journal5 and a study by Cheng and colleagues.6 The study by Kuter and colleagues is an example of the enormous enterprise required to study an uncommon disorder such as immune thrombocytopenia.5 In this randomized study, 85 investigational sites in 14 countries enrolled 234 patients to compare romiplostim with standard care in patients who had not undergone splenectomy and in whom at least one previous treatment for immune thrombocytopenia had failed. The conclusions are clear. The outcomes were better in patients receiving romiplostim than in patients receiving standard care (short of splenectomy): romiplostim was associated with a greater incidence of a sustained platelet response, less bleeding and fewer transfusions, a decreased requirement for other treatments (including splenectomy), and greater improvement in quality of life. The side effects of romiplostim therapy were minimal, but understanding the potential harms of a new treatment is more difficult than documenting its benefit; confidence about the safety of the drug requires that more patients be observed for a longer time. Because patients treated with romiplostim had better outcomes, does the work of Kuter and colleagues establish romiplostim as the new standard of care? This may have been one of the goals of the sponsor of this study (for which I consulted on romiplostim and served as an investigator in clinical trials), and this may be how it is interpreted. The standard first treatment for immune thrombocytopenia continues to be glucocorticoids2,7; they are familiar, inexpensive, and usually effective. However, durable remission is uncommon, and glucocorticoids quickly become intolerable in many patients8; therefore, a second treatment is commonly required. Romiplostim may increase platelet counts with possibly few