Fostamatinib treatment for patients with antiphospholipid syndrome and low platelet count: A case series

Antiphospholipid syndrome (APS) is an autoimmune thrombophilic disorder characterized by thromboembolic events and/or pregnancy complications in the presence of persistently positive antiphospholipid antibodies (aPL-Ab). The standard clinical management includes anticoagulation with vitamin K antagonists or heparin and anti-platelet therapy. Thrombocytopenia (TP) is the most common haematological manifestation of APS, occurring in approximately 20%–50% of patients. While severe TP (platelets 100 Gpt/L in ≥66% of measurements), while three (43%) achieved partial remission (>50 Gpt/L in ≥66% of measurements). Time to achievement of the first clinically relevant response ranged from 4 to 56 days (median 14 days, SEM 9.49, range 4–56). The first patient has been treated for more than 32 weeks without a clear clinical response. Concomitant therapy was temporarily required in seven of nine patients, including corticosteroids, TPO-RA, hydroxychloroquine, cyclophosphamide and belimumab, highlighting the importance of bridging therapy during fostamatinib initiation. The precise contribution of concomitant medications to the overall treatment outcome cannot be reliably determined. It cannot be excluded that the observed therapeutic effects were at least partly attributable to the combined use of these agents rather than to the investigational treatment alone. Three patients had systemic lupus erythematosus (SLE) as a relevant comorbidity; two of them were non-responders to fostamatinib. Anti-thrombotic therapy included low-dose aspirin in patients with arterial thromboembolism or in prophylactic intention, or systemic anticoagulation in cases of venous thrombotic events. In most cases, low molecular weight heparin was preferred due to insufficient platelet counts for the safe use of oral anticoagulants. Three patients were transitioned to oral agents upon platelet stabilization. In summary, our case series suggests that fostamatinib may be a safe and effective option in APS patients with severe TP. In contrast to other available therapies—such as glucocorticoids, IVIG or rituximab—whose efficacy is often transient or associated with relevant adverse effects, fostamatinib achieved sustained platelet responses without new thromboembolic events during treatment, although this finding is limited by the small patient cohort and the retrospective nature of the analysis. This observation aligns with clinical trial and real-world data in ITP, where fostamatinib demonstrated low thrombotic risk, and supports its potential suitability for APS patients, in whom prothrombotic complications are a major concern. This therapeutic approach may enable stable platelet recovery, allowing safer implementation of necessary anticoagulation. However, as this conclusion is based on a retrospective case series without a control group, causal relationships cannot be established, and further clinical studies are required to prospectively assess safety and efficacy in this patient population. As such, these findings should be regarded as hypothesis-generating, highlighting the need for systematic prospective evaluation of fostamatinib in APS-associated TP. EB and KT-G assembled, analysed, interpreted the data and wrote the paper; EB, RSA, SM, J-AG, CN, MB and KT-G contributed clinical data; and all authors approved the final version of the manuscript. Open Access funding enabled and organized by Projekt DEAL. EB received honoraria or is an advisor or consultant for Novartis; received personal funding from the Federal Ministry of Research, Technology and Space, Germany (‘Career Advancement in Multidimensional Tumor Targeting’); and received support for attending meetings and/or travel from AbbVie, Swedish Orphan Biovitrium GmbH and Alexion. RSA has acted as a paid consultant to CSL Behring, Amgen, Bayer, BFSH, Grifols, LFB Pharma, Medlearning, Octapharma, onkowissen, STREAMED UP (Pfizer, Grifols), Sobi, Sanofi, and Takeda Pharma; received funding from Takeda, Sobi, Octapharma, Grifols and Novartis; and meeting/congress support from Takeda, Sobi, Pfizer and Bayer. SM has received personal fees for lectures or consultancy from Bayer, Biotest, Pfizer and Swedish Orphan Biovitrium GmbH. J-AG served on scientific advisory boards for Jazz Pharmaceuticals and Novartis; received honoraria for lectures from Grifols and Sobi; and received support for attending meetings and/or travel from Amgen. CN received support for attending meetings and/or travel from SOBI and Pfizer. MB served on scientific advisory boards for Jazz Pharmaceuticals; received honoraria for lectures from Astellas, Gilead and Jazz Pharmaceuticals; and received support for attending meetings and/or travel from MSD. KT-G received honoraria or is an advisor or consultant for Amgen, BMS, Grifols, Novartis, Sanofi, SOBI, Stemline and Takeda. Data sharing not applicable to this article as no datasets were generated or analysed during the current study.