Thrombopoietin level predicts response to treatment with eltrombopag and romiplostim in immune thrombocytopenia

• Published in: American journal of hematology 2018-12, Vol.93 (12), p.1501-1508
• Main Authors: Al‐Samkari, Hanny, Kuter, David J.
• Format: Article
• Language: English
• Subjects: Benzoates - therapeutic use; Female; Hematology; Humans; Hydrazines - therapeutic use; Idiopathic thrombocytopenic purpura; Logistic Models; Male; Patients; Predictive Value of Tests; Prednisone; Purpura, Thrombocytopenic, Idiopathic - drug therapy; Pyrazoles - therapeutic use; Receptors, Fc - therapeutic use; Receptors, Thrombopoietin - agonists; Recombinant Fusion Proteins - therapeutic use; Regression analysis; Retrospective Studies; Thrombocytopenia; Thrombopoietin; Thrombopoietin - blood; Thrombopoietin - therapeutic use
• ISSN: 0361-8609; 1096-8652
• DOI: 10.1002/ajh.25275

Thrombopoietin receptor agonists (TPO‐RAs) are used to treat immune thrombocytopenia (ITP), but predicting clinical response to TPO‐RAs before initiation is not possible. To determine whether endogenous TPO levels predict treatment response to TPO‐RAs we performed a retrospective analysis of ITP patients with known baseline TPO levels who received TPO‐RAs. Data was collected for ITP patients with a baseline TPO level treated with eltrombopag or romiplostim. Multiple logistic regression was used to model the probability of 3 classes of treatment response (overall, moderate, and superior) based on TPO level; receiver operating characteristic (ROC) analysis was performed to identify optimal TPO thresholds for response; correlations between TPO level and various response characteristics were analyzed. A total of 67 patients (37 receiving eltrombopag and 46 receiving romiplostim) were included. Logistic regression models demonstrated a significant predictive relation between TPO level and probability of all classes of response; per 10 pg/mL TPO increase, odds ratio for overall response to eltrombopag was 0.524 (95% CI 0.327, 0.837) and romiplostim was 0.905 (95% CI, 0.844, 0.970). TPO level was inversely correlated with all classes of response; for overall response, r = −0.719 (P < .001) for eltrombopag and r = −0.584 (P < .001) for romiplostim. ROC analysis identified TPO thresholds of ≤136 pg/mL (eltrombopag) and ≤209 pg/mL (romiplostim) as optimally discriminating between responders and nonresponders. Most non‐responders had high TPO levels but did respond after addition of low‐dose prednisone. In conclusion, TPO levels predict response to eltrombopag and romiplostim in ITP patients, with lower levels predicting improved probability and magnitude of response.