Introduction: Nintedanib, a tyrosine kinase receptor inhibitor, may be associated with increased bleeding risk. Thus, patients with an inherited predisposition to bleeding, or those receiving therapeutic doses of anticoagulants or high-dose antiplatelet therapy, have been excluded from clinical trials of nintedanib in idiopathic pulmonary fibrosis (IPF).
Objective: Our objective was to examine real-world bleeding events in patients with IPF treated with antifibrotics, including those receiving anticoagulants and/or antiplatelet therapy.
Methods: The European MultiPartner IPF Registry (EMPIRE) enrolled 2794 patients with IPF: group A (1828: no anticoagulant or antiplatelet treatment), group B (227: anticoagulant treatment), group C (659: antiplatelet treatment), and group D (80: anticoagulant and antiplatelet treatment). Overall, 673 (24.1%) received nintedanib and 933 (33.4%) received pirfenidone. Bleeding events and their relationship to antifibrotic and anticoagulation treatment were characterized.
Results: Group A patients, versus those in groups B, C, and D, were typically younger and generally had the lowest comorbidity rates. A higher proportion of patients in groups A and C, versus group B, received nintedanib. Pirfenidone, most common in group D, was more evenly balanced across groups. In patients with reported bleeding events, seven of eight received nintedanib (groups A, C, and D). Bleeding incidence was 3.0, 0, 1.3, and 18.1 per 10,000 patient-years (groups A, B, C, and D, respectively).
Conclusion: Real-world data from EMPIRE showed that patients on anticoagulant medications received nintedanib less frequently, perhaps based on its mechanism of action. Overall, bleeding incidence was low (0.29%: nintedanib 0.25%; pirfenidone 0.04%) and irrespective of anticoagulant or antiplatelet therapy received (P = 0.072).