Immunosuppressive agents in the treatment of inhibitors in congenital haemophilia A and B - a systematic literature review

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Immunosuppressive agents in the treatment of inhibitors in congenital haemophilia A and B - a systematic literature review. / Laros-van Gorkom, Britta Antonia Petra; Falaise, Celine; Astermark, Jan.

In: European Journal of Haematology, Vol. 93, 2014, p. 26-38.

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TY - JOUR

T1 - Immunosuppressive agents in the treatment of inhibitors in congenital haemophilia A and B - a systematic literature review

AU - Laros-van Gorkom, Britta Antonia Petra

AU - Falaise, Celine

AU - Astermark, Jan

PY - 2014

Y1 - 2014

N2 - The development of inhibitory antibodies to factor VIII (FVIII) or factor IX (FIX) in patients with haemophilia is a serious complication of treatment with coagulation factor concentrates. Antibodies develop in 10-15% of haemophilia A and in up to 5% of haemophilia B patients. Several strategies have been developed over the years to facilitate the eradication of inhibitors and reduce the cost. These include plasmapheresis and/or extracorporeal protein A absorption to remove the inhibitor from the plasma, and immunosuppression and/or immune modulation to suppress the production of inhibitory antibodies. Different immunosuppressive (IS) agents have been described with varying success. To evaluate the outcome of these agents, we performed a systematic literature review using the PubMed database. The total number of articles identified was 345; 299 papers were excluded leaving 46 papers to be included in the study. No randomised studies were identified, only case reports and case series. The most frequently used agents in the 46 case reports and cohort studies identified were cyclophosphamide and rituximab. All cases exposed to cyclophosphamide, rituximab and other IS agents had a complete success rate of 40-44%, 40-63% and 33-56%, respectively. However, the definition of success was not consistent among the studies. In conclusion, our review of the literature indicates that IS agents in combination with FVIII or FIX could be an option and may be cost-effective in many patients. The risk of adverse events seems to be relatively low. To fully explore the effect of IS agents, randomised studies are warranted.

AB - The development of inhibitory antibodies to factor VIII (FVIII) or factor IX (FIX) in patients with haemophilia is a serious complication of treatment with coagulation factor concentrates. Antibodies develop in 10-15% of haemophilia A and in up to 5% of haemophilia B patients. Several strategies have been developed over the years to facilitate the eradication of inhibitors and reduce the cost. These include plasmapheresis and/or extracorporeal protein A absorption to remove the inhibitor from the plasma, and immunosuppression and/or immune modulation to suppress the production of inhibitory antibodies. Different immunosuppressive (IS) agents have been described with varying success. To evaluate the outcome of these agents, we performed a systematic literature review using the PubMed database. The total number of articles identified was 345; 299 papers were excluded leaving 46 papers to be included in the study. No randomised studies were identified, only case reports and case series. The most frequently used agents in the 46 case reports and cohort studies identified were cyclophosphamide and rituximab. All cases exposed to cyclophosphamide, rituximab and other IS agents had a complete success rate of 40-44%, 40-63% and 33-56%, respectively. However, the definition of success was not consistent among the studies. In conclusion, our review of the literature indicates that IS agents in combination with FVIII or FIX could be an option and may be cost-effective in many patients. The risk of adverse events seems to be relatively low. To fully explore the effect of IS agents, randomised studies are warranted.

KW - immunosuppression

KW - treatment

KW - inhibitors

KW - haemophilia

KW - cyclophosphamide

KW - rituximab

U2 - 10.1111/ejh.12372

DO - 10.1111/ejh.12372

M3 - Review article

VL - 93

SP - 26

EP - 38

JO - European Journal of Haematology

T2 - European Journal of Haematology

JF - European Journal of Haematology

SN - 1600-0609

ER -