Early Fostamatinib Use Shows High Response Rates in Immune Thrombocytopenia

Immune thrombocytopenia, or ITP, has long posed a frustrating paradox for patients and physicians alike: a disease in which the body destroys its own blood-clotting platelets, yet one whose treatments often trade efficacy for toxicity. Now, one of the largest real-world studies to date suggests that an oral targeted drug called fostamatinib may deserve a much earlier place in the treatment sequence than current practice typically allows. A nationwide Spanish cohort study, published in the journal Advances in Therapy, found that when fostamatinib was deployed as a second- or third-line therapy, more than eight in ten patients responded, and two-thirds achieved platelet counts in the normal range.

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