Use of Thrombopoietin Agonists in Immune Thrombocytopenia Purpura

Introduction: Immune/idiopathic thrombocytopenia purpura (ITP) is a condition characterized by low platelet counts. Current chronic treatment options for ITP include rituximab, a thrombopoietin (TPO) agonist, or a splenectomy. Rituximab, a CD20 monoclonal antibody that depletes B-cells to disrupt the production of harmful antibodies (Zaja et al. 2003), has historically been the primary treatment for ITP. However, early studies have shown that while effective in the short term, rituximab has a drop in efficacy after 180 days (Zaja et al. 2003). TPO agonists are a newer mechanism that mimic endogenous TPO by stimulating the maturation and proliferation of megakaryocytes to stimulate platelet production (Nugent et al. 2009).

Current TPO agonists include avatrombopag, eltrombopag, fostamatinib, and romiplostim. We explored the use of these TPO agonists practically in the hematology/oncology practice at Pennsylvania Hospital (PAH) to evaluate efficacy and responses to each therapy.

Methods: A retrospective chart review was conducted through the University of Pennsylvania Epic system investigating chronic treatment of ITP at PAH hematology/oncology department since 2012 with a diagnosis of ITP.

Results: 231 charts were analyzed. 121 patients did not require chronic treatment (1 patient was admitted for workup while the chart review occurred, and treatment is still being determined). 10 had chronic treatment via steroids, mainly prednisone, and 1 only had a family history of ITP with no ITP diagnosis. 8 charts were unable to be reviewed due to privacy concerns. This left 91 charts which were reviewed for chronic management of ITP. Of these 91 charts, 7 only presented for a second opinion on management and did not receive treatment. 15 underwent a splenectomy, but only 3 did not first receive a secondary therapy.

48 received rituximab, but only 15 (31.25%) had a sustained response. 66 patients eventually received a TPO agonist. Of these 66 patients, only 22 (33.33%) received a single therapy. The other 44 received multiple TPO agonists or rituximab and then a TPO agonist. All four TPO agonists were used, and the responses to these drugs are summarized in table 1.

Conclusions: Of the 231 patients presenting to the PAH hematology/oncology clinic, 91 required long term, non-steroidal therapy. Our findings support previous studies that show a decline in long term efficacy of rituximab with only 31.25% (15) of patients achieving a sustained response. The other 68.65% (33) required an additional therapy. Interestingly, all 3 secondary therapies (rituximab, TPO agonist, and splenectomy) were utilized by the clinicians and 72.5% (66) of patients required a TPO agonist. About one-third (22) of these 66 patients had a sustained response on a single TPO agonist on their first try. However, two-thirds (44) of the patients had to switch to another TPO agonist before finding an acceptable response. Eltrombopag and romiplostim are relatively older than fostamatinib and avatrombopag, however the newer drugs are beginning to make their way into therapy with 5 patients on ongoing therapy with fostamatinib (3) and avatrombopag (2). The downfall of the TPO agonists is that most require sustained long-term therapy with only 5 patients total achieving a sustained response without therapy. This is especially difficult for romiplostim which requires patients to come in weekly for an injection.

No relevant conflicts of interest to declare.