Abstract
Introduction: Fostamatinib, an oral spleen tyrosine kinase inhibitor, is approved for the treatment of chronic immune thrombocytopenia (ITP) refractory to first-line therapies. As its use expands across autoimmune and hematologic indications, including autoimmune hemolytic anemia and lymphoid malignancies, long-term safety monitoring becomes increasingly important. Hypertension has emerged as a notable adverse event in clinical trials. Given the implications of elevated blood pressure on cardiovascular and renal outcomes as, globally, hypertension affects about one in three adults with the number of people living with hypertension doubled between 1990 and 2019, from 650 million to 1.3 billion and in the United States, nearly half of adults (48.1%, or 119.9 million people) have high blood pressure. We conducted a meta-analysis to quantify the risk of new-onset hypertension associated with fostamatinib, with an emphasis on hematologic and immune-mediated conditions.
Methods: We systematically reviewed and analyzed completed randomized controlled trials (RCTs) evaluating fostamatinib in adults (≥18 years) with hematologic and autoimmune diseases, focusing on chronic ITP, but also including autoimmune hemolytic anemia, systemic lupus erythematosus, rheumatoid arthritis, and IgA nephropathy. Studies were included if they reported hypertension as a treatment-emergent adverse event and used placebo or standard-of-care comparators. Non-randomized studies, observational cohorts, and non–English full-texts were excluded. Meta-analysis was performed using a random-effects model in accordance with the Cochrane Handbook. Heterogeneity was assessed using the I² statistic, and sampling error was evaluated qualitatively.
Results: Six RCTs n =1623 [1037 who took Fostamatinib] met inclusion criteria. Fostamatinib was associated with a significantly increased risk of new-onset hypertension compared to placebo or active comparators, with a pooled odds ratio (OR) of 2.45 (95% CI: 1.53–3.91; p < 0.001). No significant heterogeneity was observed (I² = 0%). All studies demonstrated consistent directionality of effect, with no single study disproportionately influencing the overall result.
Conclusion: Fostamatinib use is associated with a 2.5-fold increased risk of developing hypertension. For patients with hematologic conditions such as ITP, where chronic therapy is required, this adverse effect may contribute to increased long-term cardiovascular and renal morbidity. We recommend routine ambulatory blood pressure monitoring as per the AHA guidelines of maintaining a blood pressure goal of less than 140 systolic and/or 90 diastolic as well as a goal of less than 130 systolic and/or 80 diastolic for certain populations such as diabetes and early lifestyle or pharmacologic interventions to mitigate this risk. Future analyses will explore additional safety signals and long-term outcomes in hematologic patient populations.
