TY - JOUR
T1 - Treatment of acquired hemophilia A, a balancing act
T2 - results from a 27-year Dutch cohort study
AU - Schep, Sarah J.
AU - van Dijk, Wobke E. M.
AU - Beckers, Erik A. M.
AU - Meijer, Karina
AU - Coppens, Michiel
AU - Eikenboom, Jeroen
AU - Leebeek, Frank W. G.
AU - van Vulpen, Lize F. D.
AU - Fischer, Kathelijn F.
AU - Schutgens, Roger E. G.
AU - Dutch Society of Haemophilia Treaters
N1 - Funding Information:
F.L. has received unrestricted research grants from CSL Behring, Takeda and UniQure. He is consultant for Takeda, UniQure of which fees go to the institute. J.E. has received research support from CSL Behring (funds to the institute) and an honorarium for educational activity from Roche (funds to the institute). K. Meijer reports grants, travels support and speaker fees from Bayer; grants and speaker fees from Sanquin; grants from Pfizer; speaker fees from Boehringer Ingelheim, BMS and Aspen, and consulting fees from UniQure, outside the submitted work. L.V. has received a speakerʼs fee from Pfizer and has performed consultancy for Tremeau (all fees were paid to the institute). R.S. has received research support from Bayer, Baxter, CSL Behring, NovoNordisk, Pfizer and Sovi (funds to the institute). All other authors declare no conflict of interests.
Publisher Copyright:
© 2020 The Authors. American Journal of Hematology published by Wiley Periodicals LLC.
PY - 2021/1
Y1 - 2021/1
N2 - Acquired hemophilia A (AHA) is a severe auto-immune bleeding disorder. Treatment of AHA is burdensome and optimal management is still unresolved. Therefore a retrospective nationwide multi-center cohort study (1992-2018) was performed to evaluate clinical presentation and treatment efficacy and safety of AHA in the Netherlands. Multivariate logistic and Cox regression analysis was used to study independent associations between patient characteristics and clinical outcomes. A total of 143 patients (median age 73 years; 52.4% male) were included with a median follow-up of 16.8 months (IQR 3.6-41.5 months). First-line immunosuppressive treatment was mostly steroid monotherapy (67.6%), steroids/cyclophosphamide (11.9%) and steroids/rituximab (11.9%), with success rates of 35.2%, 80.0% and 66.7% respectively,P<.05. Eventually 75% of patients achieved complete remission (CR). A high anti-FVIII antibody titer, severe bleeding and steroid monotherapy were associated with lower CR rates. Infections, the most important adverse event, occurred significantly more often with steroid combination therapy compared to steroids alone (38.7% vs 10.6%;P= .001). Overall mortality was 38.2%, mostly due to infections (19.2%) compared to 7.7% fatal bleeds. Advanced age, underlying malignancy and ICU admission were predictors for mortality. This study showed that AHA is characterized by significant disease-related and treatment-related morbidity and mortality. A high anti-FVIII titer, severe bleeding and steroid monotherapy were associated with a lower CR rate. The efficacy of steroid combination therapies however, was overshadowed by higher infection rates and infections represented the most important cause of death. The challenging and delicate balance between treatment effectivity and safety requires ongoing monitoring of AHA and further identification of prognostic markers.
AB - Acquired hemophilia A (AHA) is a severe auto-immune bleeding disorder. Treatment of AHA is burdensome and optimal management is still unresolved. Therefore a retrospective nationwide multi-center cohort study (1992-2018) was performed to evaluate clinical presentation and treatment efficacy and safety of AHA in the Netherlands. Multivariate logistic and Cox regression analysis was used to study independent associations between patient characteristics and clinical outcomes. A total of 143 patients (median age 73 years; 52.4% male) were included with a median follow-up of 16.8 months (IQR 3.6-41.5 months). First-line immunosuppressive treatment was mostly steroid monotherapy (67.6%), steroids/cyclophosphamide (11.9%) and steroids/rituximab (11.9%), with success rates of 35.2%, 80.0% and 66.7% respectively,P<.05. Eventually 75% of patients achieved complete remission (CR). A high anti-FVIII antibody titer, severe bleeding and steroid monotherapy were associated with lower CR rates. Infections, the most important adverse event, occurred significantly more often with steroid combination therapy compared to steroids alone (38.7% vs 10.6%;P= .001). Overall mortality was 38.2%, mostly due to infections (19.2%) compared to 7.7% fatal bleeds. Advanced age, underlying malignancy and ICU admission were predictors for mortality. This study showed that AHA is characterized by significant disease-related and treatment-related morbidity and mortality. A high anti-FVIII titer, severe bleeding and steroid monotherapy were associated with a lower CR rate. The efficacy of steroid combination therapies however, was overshadowed by higher infection rates and infections represented the most important cause of death. The challenging and delicate balance between treatment effectivity and safety requires ongoing monitoring of AHA and further identification of prognostic markers.
KW - SURVEILLANCE
KW - EXPERIENCE
KW - INHIBITORS
U2 - 10.1002/ajh.26009
DO - 10.1002/ajh.26009
M3 - Article
C2 - 32974947
SN - 0361-8609
VL - 96
SP - 51
EP - 59
JO - American Journal of Hematology
JF - American Journal of Hematology
IS - 1
ER -