Eltrombopag Is Efficacious in Patients with Refractory Chronic Idiopathic Thrombocytopenic Purpura (ITP) - Data from the EXTEND Study
Authors: Saleh Mansoor N , Bussel James B , Cheng Gregory , Meddeb Balkis , Burgess Paul M , De Obaldia Maria E , Stone Nicole L , Aivado Manuel 
Published: April 2020

Abstract
INTRODUCTION: Refractory ITP patients have an unmet medical need for new treatment options. It is unknown how novel therapeutic agents such as eltrombopag (PROMACTA®/REVOLADE®; GlaxoSmithKline), the first oral, small-molecule, non-peptide thrombopoietin receptor agonist, may help ITP patients refractory to standard therapies. Eltrombopag was shown to substantially increase platelet counts during 2 placebo-controlled trials including &gt;200 previously treated chronic ITP patients. EXTEND is an ongoing, open-label study designed to assess the long-term safety and clinical benefit of eltrombopag in patients with chronic ITP.
METHODS: A post hoc analysis of EXTEND data assessed the efficacy of eltrombopag treatment in 165 chronic ITP patients, by refractoriness to prior therapy. Patients included had to have been on study ≥6 weeks. Refractory patients were defined as those with no response to a prior therapy (corticosteroids, IVIg, anti-D, or rituximab), and non-refractory patients were those previously treated patients who had either relapsed or become intolerant to their prior therapy. Specifically, corticosteroid-refractory patients had to have either no prior response to corticosteroids, or if there had been at least 1 documented response, there was subsequently nonresponse to all corticosteroids attempted. To determine whether outcome of prior therapy impacts a patient’s response to eltrombopag, refractory ITP patients were compared to non-refractory ITP patients with regard to 3 measures of clinical benefit: 1) the proportion of patients who achieved platelet counts ≥50,000/μL and 2X baseline, 2) median weekly platelet counts on therapy through 39 weeks (9 mo.), and 3) the proportion of patients with clinically significant bleeding symptoms (WHO Grades 2–4) at each week on therapy through 39 weeks (9 mo.). Bleeding symptoms were prospectively evaluated using the WHO Bleeding Scale: Grade 0 = no bleeding, Grade 1 = mild bleeding, Grade 2 = moderate bleeding, Grade 3 = gross bleeding, and Grade 4 = debilitating blood loss.
RESULTS: Of the 165 patients included, 68 were refractory to at least 1 of the following medications: corticosteroids (no response, n = 36; no response following prior response, n = 7), IVIg (n = 20), anti-D (n = 12), or rituximab (n = 23). The median baseline platelet count was 17,000/μL in both the refractory and non-refractory patients. Overall, 75% (n = 51/68) of refractory patients achieved platelet counts ≥50,000/μL and 2X baseline, compared to 84% (n = 81/97) of non-refractory patients. A logistic regression model, adjusted for baseline splenectomy status, ITP medication use, and baseline platelet count showed no significant difference in this response between refractory and non-refractory patients (p = 0.1425). In addition, weekly median platelet counts in both refractory and non-refractory patients generally remained at or above 50,000/μL from week 1 through week 39 (9 mo.). While refractory patients had more clinically significant bleeding at baseline than non-refractory patients: 32% (n = 22/68) and 14% (n = 14/97), respectively, the proportion of patients with clinically significant bleeding in both groups was lower than baseline at any point from weeks 1 to 39. The proportion of patients with clinically significant bleeding in both groups was generally reduced 50% from baseline throughout this period.
CONCLUSION: Eltrombopag induces long lasting platelet count increases and reduces clinically significant bleeding symptoms in refractory and non-refractory chronic ITP patients. We hypothesize that eltrombopag’s novel mechanism of action, stimulation of platelet production, underlies its ability to successfully treat patients refractory to treatments which impede platelet destruction.