The study, led by Tomás José González-López of Hospital Universitario de Burgos and colleagues across 22 Spanish centers, analyzed 72 adults with ITP drawn from a broader national cohort of 174 patients who had received the drug. The median age of participants was 67 years, and 55.6 percent were women, a demographic profile that reflects the typical real-world ITP population far better than the carefully selected patients enrolled in pharmaceutical registration trials. Half of the patients carried at least one comorbidity on the Charlson Comorbidity Index, and roughly a quarter had experienced bleeding in the month before starting fostamatinib, underscoring the clinical urgency that often drives treatment decisions in this disease.

ITP is an acquired immune-mediated disorder in which platelet counts fall because of a double hit: antibodies and cytotoxic T lymphocytes accelerate platelet destruction in the spleen and elsewhere, while defective megakaryocyte maturation impairs the production of replacement platelets in the bone marrow. The clinical course is highly variable. Some patients remain asymptomatic despite platelet counts well below 100 × 10⁹ per liter, while others suffer significant mucocutaneous bleeding or develop chronic, relapsing disease that demands years of therapy. Beyond the bleeding risk itself, ITP carries a substantial burden on quality of life and healthcare resources, particularly for patients who cycle through multiple treatment lines without achieving durable control.

Standard first-line therapy remains corticosteroids, sometimes supplemented by intravenous immunoglobulin when rapid platelet increases are needed. Although initial steroid responses are high, relapse after dose tapering is common, and many patients become corticosteroid-dependent with all the metabolic and infectious complications that entails. Second-line options include thrombopoietin receptor agonists such as eltrombopag and romiplostim, the anti-CD20 antibody rituximab, and splenectomy. Each has drawbacks: TPO receptor agonists require continuous administration and raise concerns about thromboembolic risk in some patients, while rituximab and splenectomy can produce durable remissions but carry delayed onset, variable long-term efficacy, and procedure- or immunosuppression-related hazards. Guidelines therefore emphasize individualized sequencing, and the search for well-tolerated earlier options has intensified.

Fostamatinib attacks the disease from a different angle. As an oral inhibitor of spleen tyrosine kinase, or SYK, it interferes with Fcγ receptor signaling in macrophages, the scavenger cells that phagocytose antibody-coated platelets. By blocking this pathway, the drug reduces antibody-dependent platelet destruction rather than simply stimulating platelet production. Its efficacy and safety were established in the pivotal phase 3 FIT trials in patients with persistent and chronic ITP who had already received multiple prior therapies, leading to regulatory approval for chronic ITP in adults refractory to other treatments. But those trials, by design, tested the drug late in the disease course, leaving a gap in evidence about how it performs when introduced earlier.

The new Spanish study was designed to fill that gap. Patients received fostamatinib at the European Medicines Agency-approved starting dose of 100 milligrams twice daily, with escalation to 150 milligrams twice daily after four weeks if platelet responses were inadequate and tolerability permitted. Fifty-six point nine percent of patients ultimately required the higher dose, typically after a median of 24 days. Forty patients, or 55.5 percent, took fostamatinib as monotherapy throughout their treatment, while the remainder used it alongside tapering corticosteroids, immunoglobulin, or other agents. The median time from ITP diagnosis to fostamatinib initiation was 17 months, and the baseline platelet count stood at just 28 × 10⁹ per liter.

The effectiveness results were striking. Overall, 83.3 percent of patients achieved a response, defined as a platelet count of at least 30 × 10⁹ per liter with at least a twofold increase from baseline, resolution of bleeding, and no rescue therapy within the preceding eight weeks. Complete response, meaning a platelet count of at least 100 × 10⁹ per liter, was reached by 65.3 percent. When fostamatinib was used as second-line therapy, 76.0 percent responded, with 56.0 percent achieving complete response; in the third-line setting, the figures rose to 87.2 percent and 70.2 percent respectively. The median time to platelet response was a brisk 10.5 days, and patients reached their peak platelet counts, a median of 140 × 10⁹ per liter, after a median of 62 days. Across the 42-month observation window, patients spent a cumulative 76.8 percent of their time in response.

Exploratory subgroup analyses hinted at interesting patterns, though the investigators caution that these were hypothesis-generating and based on small numbers. Response rates were higher among women than men, 92.5 versus 71.9 percent, and higher in chronic than in non-chronic ITP by the same margin. Patients previously treated with eltrombopag responded more often than those without such exposure, 96.3 versus 75.6 percent, while prior romiplostim exposure was associated with a lower rate. Notably, second-line use was associated with faster platelet recovery, a median of 32 days to peak count compared with 77 days for third-line use, suggesting that earlier introduction may speed benefit even when overall efficacy is similar. Twenty-seven point eight percent of patients discontinued the drug for insufficient effectiveness, and only four patients, 5.5 percent, managed to stop fostamatinib successfully after responding, indicating that the drug is best regarded as long-term maintenance therapy rather than a finite course.

Safety data were reassuring. Adverse events occurred in 44.4 percent of patients and were predominantly mild to moderate, with diarrhea, hypertension, and headache the most common complaints, generally manageable with symptomatic treatment. Only 15.3 percent of patients stopped the drug because of toxicity, and severe grade 3 to 4 events were infrequent. Three thromboembolic events occurred, two deep vein thromboses and one pulmonary embolism, but all three patients had established thrombotic risk factors unrelated to the drug, including advanced age, obesity, and immobilization. Given growing recognition that ITP itself carries an elevated thrombotic risk, the low incidence observed here, 4.2 percent, may represent a meaningful advantage for patients with cardiovascular comorbidities, a group well represented in this elderly cohort.

The findings align with a growing body of international real-world evidence, including the Spanish FOSTASUR study, the Italian GIMEMA ITP 1122 experience, and a post hoc analysis of the FIT trials that reported response rates of 94 percent and 86 percent for second- and third-line use respectively. The authors acknowledge the limitations inherent to an observational design without a control group, but the consistency across independent cohorts strengthens the case. Their conclusion is direct: fostamatinib should be considered earlier in the ITP treatment algorithm rather than reserved as a last resort, with prospective studies now needed to define the optimal timing and sequencing of a drug that, for many patients, may offer rapid, durable platelet recovery with an acceptable safety profile.

Subject of Research: Real-world effectiveness and safety of early-line fostamatinib therapy in adult immune thrombocytopenia

Article Title: Early Use of Fostamatinib in Immune Thrombocytopenia

Article References: González-López, T. J., Bermejo-Vega, N., Cardesa-Cabrera, R., Acedo, N., Luis-Navarro, J., Lakhwani, S., Bernat, S., Haces-Tirado, G. E., Galán, P., Lozano, M. L., Martínez-Carballeira, D., Hernández-Martin, R., Jimenez-Bárcenas, R., Navas-Elorza, B., Marcellini, S., Torres-Tienza, A., Perona-Blázquez, A., Benet, C., Fernandez-Jimenez, D., … García-Donás Gabaldón, G. (2026). Early Use of Fostamatinib in Immune Thrombocytopenia. Advances in Therapy. https://doi.org/10.1007/s12325-026-03769-z

Image Credits: AI Generated

DOI: 10.1007/s12325-026-03769-z

Keywords: immune thrombocytopenia, fostamatinib, SYK inhibitor, second-line therapy, third-line therapy, platelet response, real-world study, hematology, autoimmune disease, drug safety, thrombosis risk, Spain

ITP is an autoimmune bleeding disorder in which the immune system destroys platelets and suppresses their production in the bone marrow. In children, the condition often resolves on its own, but a substantial minority develop persistent or chronic disease requiring second-line therapy. TPO-RAs, which stimulate platelet production by activating the thrombopoietin receptor on megakaryocytes, are recommended second-line treatments. The class includes oral agents such as eltrombopag and avatrombopag, and the injectable peptide-mimetic romiplostim. When one agent fails, guidelines have suggested that switching within the class, particularly from an oral drug to romiplostim, may still succeed, because the agents differ in structure, metabolism, and pharmacology.

That assumption, however, had never been rigorously tested in the specific scenario that matters most: children who have failed not just one but several oral TPO-RAs. The Chinese research team, led by Shuyue Dong and Yumeng Jia with senior authors Xiaoling Cheng and Runhui Wu, was able to examine this question thanks to a unique real-world circumstance. Romiplostim reached the market late in China, which meant that children there often received it only after prolonged exposure to, and failure of, multiple oral TPO-RAs. This sequencing created a natural experiment that would be difficult to construct deliberately.

The study was a single-center, retrospective, observational analysis of patients aged 1 to 18 years with persistent or chronic ITP who received romiplostim for at least four weeks. The researchers assessed clinical characteristics, prior therapies, platelet response, bleeding outcomes, the need for rescue therapy, and adverse drug reactions. The work was approved by the Medical Ethics Committee of Beijing Children’s Hospital, and all patients provided written informed consent. The study was registered as ChiCTR2400086099 and funded by the National Key R&D Program of China and the National Natural Science Foundation of China.

Sixteen patients were analyzed in total. Thirteen of them had refractory ITP and had previously used two or more TPO-RAs before starting romiplostim. The results in this refractory group were strikingly poor. Eleven of the thirteen showed no response to romiplostim at all, and the remaining two exhibited only a transient partial response. In other words, not a single child in the refractory cohort achieved a complete or durable response once multiple oral TPO-RAs had already failed. The clinical burden in this group was substantial: twelve of the thirteen patients experienced bleeding episodes, eight required rescue therapy, and all thirteen ultimately switched to other drugs after romiplostim also proved ineffective.

The remaining three patients told a very different story, and the contrast is central to the study’s message. These children chose romiplostim not because other TPO-RAs had failed to work, but because of practical concerns such as potential drug interactions or liver dysfunction, which are recognized limitations of oral agents like eltrombopag. Only one of the three had previously used eltrombopag. In this selected group, two of the three patients achieved a complete response, while one showed no response. The findings suggest that romiplostim retains real value when it is used as a genuine alternative rather than as a last resort within an exhausted drug class.

On the safety front, the news was unambiguously positive. No adverse drug reactions were observed in any of the sixteen patients during the study period. This is consistent with the generally favorable tolerability profile that romiplostim has shown in pediatric populations, and it confirms that the drug itself is not the problem. The issue, the authors argue, is not whether romiplostim is safe or even whether it can work in children with ITP, but whether it can work in children whose disease has already demonstrated resistance to multiple members of its own class.

That resistance pattern carries important biological implications. TPO-RAs all converge on the same molecular target, the thrombopoietin receptor, also known as c-Mpl. If a child’s platelet production pathway remains unresponsive to two or more agents that activate this receptor through different chemical scaffolds, the likelihood that a third agent hitting the same target will succeed appears low. The study’s data give that reasoning empirical weight: within-class switching after multiple failures produced essentially no durable responses. This challenges the common clinical habit of cycling through TPO-RA options sequentially and suggests that the time and exposure spent on further within-class trials may come at the cost of delaying more appropriate therapies.

The authors conclude that romiplostim remains a safe and effective option for carefully selected pediatric ITP patients, but that children who have failed multiple oral TPO-RAs derive minimal benefit from switching to it. Instead, they recommend prioritizing alternative therapies that target immune dysregulation, the underlying mechanism of the disease, rather than continuing to push on the same thrombopoietin receptor pathway. Such alternatives could include immunomodulatory or immunosuppressive approaches that address the autoimmune attack driving platelet destruction, although the study itself does not evaluate specific alternative regimens.

As with any retrospective, single-center study, the findings come with limitations. The cohort was small, with only sixteen patients, and the refractory subgroup of thirteen, while internally consistent, limits statistical precision. Retrospective designs are also vulnerable to selection bias, since the decision to try romiplostim after multiple failures reflected real-world clinical judgment rather than a randomized protocol. Nevertheless, the near-universal failure of romiplostim in the multiply pretreated group is difficult to dismiss as chance, and the real-world sequencing that Chinese late-market conditions created gives the observation unusual relevance for clinicians everywhere who face the same decision. For families navigating refractory pediatric ITP, the study offers a clear if sobering message: after multiple oral TPO-RA failures, the next step should probably not be another drug from the same shelf.

Subject of Research: Romiplostim switching after multiple oral thrombopoietin receptor agonist failures in pediatric refractory immune thrombocytopenia

Article Title: Is switching to romiplostim still worthwhile after failure of multiple oral TPO-RAs in pediatric refractory ITP?

Article References: Is switching to romiplostim still worthwhile after failure of multiple oral TPO-RAs in pediatric refractory ITP?. (n.d.). https://doi.org/10.1007/s00277-026-07174-y

Image Credits: AI Generated

DOI: 10.1007/s00277-026-07174-y

Keywords: immune thrombocytopenia, romiplostim, eltrombopag, avatrombopag, TPO receptor agonists, pediatric hematology, refractory ITP, switching strategy, platelet response, drug safety, retrospective study, Beijing Children's Hospital