When to STOP Treatment for Immune Thrombocytopenia in Patients Experiencing a Complete Response on Thrombopoietin Receptor Agonists

Thrombopoietin receptor agonists (TPO-RAs) have revolutionized the treatment of immune thrombocytopenia (ITP), and they are currently recommended as a second-line treatment for patients who have had an inadequate response to first-line corticosteroids or intravenous immunoglobulin, or those who are dependent on corticosteroids to maintain a safe platelet count.¹  TPO-RAs have become well-established in ITP treatment algorithms in the nearly 20 years following the U.S. Food and Drug Administration’s initial approval of eltrombopag and romiplostim, with investigators turning their attention from demonstrating the efficacy of these agents to optimizing their use. Although TPO-RAs have some important toxicities, they are generally quite safe and well-tolerated.²  Two important disadvantages of TPO-RA treatment remain the need for prolonged therapy and the high cost. These factors have led to interest in whether, and when, TPO-RAs may be safely discontinued.

Inspired by early retrospective data, Adrian Newland, MA, and colleagues prospectively demonstrated that 24 of 75 patients (32%) enrolled in a single-arm phase II study of romiplostim for adults with ITP experienced sustained remission (defined as a platelet count of greater than 50x10⁹/L for more than 24 weeks) without any ITP treatment.³  Similarly, a team of Italian researchers found that 25% of adult patients with newly diagnosed or persistent primary ITP had a sustained response off treatment (SROT) — defined as a platelet count of greater than 30x10⁹/L and at least a twofold increase from baseline — lasting more than 24 weeks without any ITP treatment.⁴  While promising, these uncontrolled studies included patients with newly diagnosed ITP, raising the possibility that some of these individuals may have experienced spontaneous remissions regardless.

The French STOPAGO trial addressed this concern by including only patients with persistent or chronic ITP who had a stable complete response defined as a platelet count greater than 100x10⁹/L for more than two months on eltrombopag or romiplostim started at least three months previously.⁵  Patients were tapered off of these TPO-RAs per a standard protocol, with tapering continued if their platelet count remained greater than 30x10⁹/L. For this study, SROT was defined as a platelet count greater than 30x10⁹/L and no bleeding, while sustained complete response off treatment (SCROT) was defined as a platelet count greater than 100x10⁹/L and no bleeding. At 52 weeks, 25 of the study’s 48 patients (52.1%) experienced a SROT, with 14 patients (29.2%) experiencing a SCROT. Relapses occurred most often in the first four weeks following TPO-RA discontinuation, no severe bleeding episodes were observed in patients who relapsed, and all but one patient who relapsed responded to reinitiation of TPO-RA therapy.⁵ 

In 2025, Adrien Cottu, MD, and colleagues provided an update of the STOPAGO findings.⁶  The 25 patients who experienced at least a SROT at 52 weeks were followed for an additional four years or longer. Only two additional patients showed relapse during this extended follow-up period, with no bleeding events. This left 23 patients (47.9%) in SROT and 19 patients (39.6%) in SCROT at the end of follow-up (Figure). It is hypothesized that these sustained responses could be the result of TPO-RAs having an immunomodulatory function by restoring immune tolerance to platelet autoantigens.