Eradication of factor VIII inhibitors in patients with mild and moderate hemophilia A.
In hemophilia A, up to 25% of new antifactor VIII (FVIII) inhibitory antibodies (inhibitors) occur in patients with mild or moderate disease. Once the inhibitor develops, options for management include observation, immune modulation, and immune tolerance induction (ITI). Currently, there is little data to guide a clinician's management decisions. In a case series, eight of the 26 subjects with mild or moderate hemophilia complicated by an inhibitor underwent ITI; two were successful, two were unsuccessful, and four were partially successful. In a systematic review of the literature, 12 of the 16 patients with mild or moderate hemophilia responded to rituximab for treatment to eradicate the inhibitor. To increase our understanding of treatment options for inhibitor eradication in patients with mild or moderate hemophilia A complicated by an inhibitor, a secondary analysis of clinical and treatment characteristics in a cohort of 36 patients with mild or moderate hemophilia A and inhibitor was undertaken. In multivariate analyses, rituximab alone (n = 6) and other immune-modulating treatments alone (n = 2) were significantly associated with an increased likelihood of inhibitor clearance [hazard ratio (HR) = 4.4 (95% CI = 1.06–20.03) and 10.21 (95% CI = 1.17–78.28), respectively], whereas ITI alone (n = 9) was not [HR = 1.35 (95% CI = 0.44–4.07)].
Emory University, Atlanta, Georgia 30322, USA. christine.kempton@emory.edu
Christine L
CL
Kempton
Geoff
G
Allen
Jeffrey
J
Hord
Rebecca
R
Kruse-Jarres
Rajiv K
RK
Pruthi
Christopher
C
Walsh
Guy
G
Young
J Michael
JM
Soucie
D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage / Q000627:therapeutic use*; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology; D016022:Case-Control Studies; D005169:Factor VIII / Q000235:genetics / Q000276:immunology*; D006467:Hemophilia A / Q000097:blood / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D006801:Humans; D007108:Immune Tolerance; D007155:Immunologic Factors / Q000008:administration & dosage / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D016013:Likelihood Functions; D012189:Retrospective Studies; D000069283:Rituximab; D012720:Severity of Illness Index
D058846:Antibodies, Monoclonal, Murine-Derived; D001323:Autoantibodies; D007155:Immunologic Factors; D000069283:Rituximab; D005169:Factor VIII