scholarly journals Prevention of Antidrug Antibody Formation to Infliximab in Crohn's Patients With Prior Failure of Thiopurines

2017 ◽  
Vol 15 (1) ◽  
pp. 69-75 ◽  
Author(s):  
Haggai Bar-Yoseph ◽  
Matti Waterman ◽  
Ronit Almog ◽  
Thomas Billiet ◽  
Séverine Vermeire ◽  
...  
2017 ◽  
Vol 376 (16) ◽  
pp. 1517-1526 ◽  
Author(s):  
Paul M Ridker ◽  
Jean-Claude Tardif ◽  
Pierre Amarenco ◽  
William Duggan ◽  
Robert J. Glynn ◽  
...  

2018 ◽  
Vol 44 (06) ◽  
pp. 531-543 ◽  
Author(s):  
Shermarke Hassan ◽  
Karin Fijnvandraat ◽  
Johanna van der Bom ◽  
Samantha Gouw

AbstractEradication of factor VIII (FVIII) specific neutralizing antibodies (also known as inhibitors) by the traditional method of immune tolerance induction (ITI) is costly and unsuccessful in one out of three patients. Furthermore, effective inhibitor prevention strategies are presently lacking. An overview is given in this narrative review of antidrug antibody prevention or eradication strategies that have been used in disorders beyond hemophilia A, with the aim of analyzing what we can learn from these strategies for hemophilia A. Prevention of antidrug antibody formation using rituximab, methotrexate, and intravenous immunoglobulins in patients with Pompe's disease seems effective but carries a high risk of adverse events. Based on studies in patients with rheumatoid arthritis and inflammatory bowel disease, it seems likely that treatment with methotrexate alone would also be able to prevent inhibitor formation in hemophilia A patients. Besides side effects, it is unclear whether immune tolerance to FVIII would persist after cessation of immunomodulatory therapy with methotrexate. A combination of cyclophosphamide and corticosteroids, used to treat antibody-mediated pure red cell aplasia, could be further investigated to eradicate inhibitors in hemophilia A patients who are refractory to ITI. In summary, insights gained from research on antidrug antibody formation in other diseases could be helpful in devising alternative treatment strategies for inhibitor development.


2016 ◽  
Vol 21 (10) ◽  
pp. 1260-1268 ◽  
Author(s):  
Emilie M.J. Brummelen ◽  
Willeke Ros ◽  
Gertjan Wolbink ◽  
Jos H. Beijnen ◽  
Jan H.M. Schellens

2021 ◽  
Vol 85 (3) ◽  
pp. AB48
Author(s):  
Jia Gao ◽  
Danika Dorelien ◽  
Abigail Cline ◽  
Bijan Safai

1990 ◽  
Vol 64 (04) ◽  
pp. 564-568 ◽  
Author(s):  
Lloyd E Lippert ◽  
Lyman Mc A Fisher ◽  
Lawrence B Schook

SummaryApproximately 14% of transfused hemophiliacs develop an anti-factor VIII inhibitory antibody which specifically neutralizes factor VIII procoagulant activity. In this study an association of the major histocompatibility complex (MHC) with inhibitor antibody formation was evaluated by restriction fragment length polymorphism (RFLP) analysis using BamHI, EcoRI, HindII, PstI, PvuII and TaqI digested genomic DNA probed with DP beta, DQ alpha, DQ beta and DR beta class II MHC gene probes. The RFLP patterns for 16 non-inhibitor and 11 inhibitor hemophiliac patients were analyzed. These 24 enzyme:probe combinations generated 231 fragments. Fifteen (15) fragments associated with the inhibitor phenotype; odds ratios ranged from 5.1 to 45 and lower bounds of 95% confidence intervals were > 1.000 for all 15 fragments. Five (5) fragments associated with non-inhibitors, with odds ratios ranging from 6.4 to 51.7. This report establishes a MHC related genetic basis for the inhibitor phenotype. No statistically significant differences in the distribution of serologically defined HLA-DR phenotypes were observed between the inhibitor and non-inhibitor groups.


1962 ◽  
Vol 41 (3) ◽  
pp. 474-480 ◽  
Author(s):  
Otto Wegelius ◽  
E. J. Jokinen

ABSTRACT In all previous investigations on experimental exophthalmos, heterologous thyrotrophic pituitary extracts have been used. These protein hormones stimulate antihormone formation in the test animals. Cortisone has been reported to effectively block antibody formation. In addition, it has been shown to potentiate TSH-induced exophthalmos in guinea-pigs. With rabbits as test animals, the hexosamine content of the orbital tissues was determined and used as an index of exophthalmos development and at the same time the antibody titres in the sera were followed. TSH injections for six weeks led to a highly significant accumulation of hexosamine in the retrobulbar connective tissue and in the extraocular muscles, i. e. an increase of up to 400% as compared with the control animals. At the same time a significant rise in antihormonal titres was detectable in the sera. Concomitant treatment with cortisone brought about an equal or higher accumulation of hexosamine but significantly lower antibody titres. The known opposite peripheral actions of TSH and cortisone can be reconciled with the synergy in producing experimental exophthalmos by attributing the synergetic action of cortisone to the blocking of antihormone formation. If less antihormones are produced, the effect of TSH is enhanced. Our experiments do not provide direct proof for this hypothesis. High hexosamine values in the orbit and low antihormone titres in the serum are, however, concomitant phenomena.


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