Real World Practices of Thrombopoietin Receptor Agonist Use and Discontinuation in Pediatric Patients with Immune Thrombocytopenia (ITP): A Single Center Retrospective Review

Introduction

Thrombopoietin Receptor Agonists (TPO-RAs) are becoming widely used as second-line treatment in patients with immune thrombocytopenia (ITP). These can be weaned/discontinued in adults. There is a paucity of literature on weaning and discontinuation practices in pediatric ITP.

Methods

We performed a retrospective review of pediatric patients aged 0-18 years with ITP treated with TPO-RAs at our institution over an eight-year period (2015-2022). Weaning and discontinuation practices were compared between patients based on timing of TPO-RA initiation: <3 months from diagnosis (group A), ≥3 to <12 months from diagnosis (group B), <12 months from diagnosis (group AB) or ≥12 months from diagnosis (group C).

Results

There were 11, 12 and 32 patients in group A, B, and C respectively (table 1). As of last follow up, 10 patients successfully weaned and discontinued their TPO-RA. Eighteen patients were weaning their TPO-RA monotherapy and 15 continued a TPO-RA at maximal dose or required the addition of another agent, such as an immunosuppressant, to permit TPO-RA weaning. Five patients discontinued their TPO-RA due to poor response. Seven patients had stopped the TPO-RA due to an alternate reason (family preference, side effects, etc.). There was no difference in any of these outcomes based on timing of TPO-RA initiation.

In patients whose platelet count responded to TPO-RAs, the dose was weaned at the provider’s discretion. The dose was generally not weaned for a platelet count <50k.

Among only patients in which the TPO-RA monotherapy was weaned, patients in group AB had a shorter duration of TPO-RA treatment than patients in group C (IQR 12.1-48.9 months vs 37.5-88.0 months; p=0.019). While not statistically significant, after the start of the TPO-RA dose weaning, patients in group A weaned their TPO-RA at a faster rate (IQR 4.7-20.5% of maximal dose per month) compared to patients in groups B and C (IQR 1.8-5.1% of maximal dose per month and 1.5-5.5% of maximal dose per month).

The 10 patients who fully weaned their TPO-RA had a shorter duration of TPO-RA use compared to the 18 patients who partially weaned their TPO-RA monotherapy (IQR 11.5-38.6 months vs 27.6-82.1 months; p=0.018). Once the wean of TPO-RA dose was started, patients who fully weaned their TPO-RA did so at a faster rate than patients who partially weaned (IQR 5.6-29.6% of maximal dose per month vs 1.0-3.4% of maximal dose per month; p=0.017; figure 1).

Seven patients who fully weaned their TPO-RA had follow up CBCs between one and three months after discontinuation. Of these, five patients had platelet counts >100k, while the other two had platelet counts >40k that continued to rise to >80k within a year of discontinuation without further treatment. Of the remaining three patients, two had CBCs more than three months post TPO-RA discontinuation with platelet counts >100k without additional treatment and one had no follow up CBC after TPO-RA discontinuation. Two patients with follow-up had transient ITP exacerbations with platelet counts <10k at 14 and 31 months after TPO-RA discontinuation that were treated with anti-D/steroids and IVIG respectively with subsequent sustained improvement in platelet counts that did not require any further intervention.

There was no difference in the number of rescue medications (IVIG, anti-D, steroids) required between patient groups based on timing of TPO-RA initiation or type of agent used. Patients who were treated with both romiplostim and eltrombopag required adjunctive therapies (such as immunosuppressants) more than patients treated with either agent alone (p=0.022).

Conclusion

TPO-RAs were weaned and successfully discontinued in 10 of 55 (18.2%) pediatric patients with ITP in our small cohort with a low rate of subsequent ITP exacerbation. There was no difference in TPO-RA discontinuation rate in patients with a good platelet response based on timing of TPO-RA initiation. Patients who started a TPO-RA within 12 months of their ITP diagnosis had a shorter duration of TPO-RA use than patients who started a TPO-RA more than 12 months after diagnosis. Patients who started a TPO-RA within three months of diagnosis were able to wean their TPO-RA dose at a faster rate than patients who started a TPO-RA more than three months after diagnosis. TPO-RA dose was weaned at a faster rate in patients who fully weaned their TPO-RA compared to patients who were partially weaned. This data should be validated in a larger study.