Avaliação da resposta ao tratamento de imunotolerância em pacientes portadores de hemofilia A em um centro de referência no Estado do Ceará

Abstract

Congenital hemophilia A is a genetic disease characterized by factor VIII deficiency, which compromises the blood clotting process. The treatment consists of taking venous infusions of the deficient factor, however, there is the possibility that the continuous use of these infusions may cause the appearance of inhibitors against factor VIII that impairs the treatment. In order to eradicate these inhibitors, from 2011, the Ministry of Health instituted the Immunotolerance Protocol and, in September 2012, the Center for Hematology and Hemotherapy of Ceará (HEMOCE) began to provide this treatment in the state of Ceará. Therefore, the objective of this study was to evaluate the response to immunotherapy treatment in patients with hemophilia A in outpatient follow-up at the Center for Hematology and Hemotherapy of Ceará. To this end, the type of study was a retrospective cohort, in which data were collected from the medical records of all patients who completed the immunotolerance treatment from September 2012 to December 2021. Data from 20 patients diagnosed with hemophilia A were analyzed, from which the profile of each patient could be obtained, in which all (100%) had the severe form of hemophilia A. The average age at which the inhibitors were detected for the first time was 8 years (SD ± 10.9) and the mean age at which these patients started ITI was 11.25 years (SD ± 14.0). The type of FVIII most used by these patients was plasmatic, used by 13 patients (65%), while recombinant was used by only 7 patients (35%). As for the clinical-laboratory profile, on average, the previous titer, that is, the inhibitor titer before the start of ITI, was 30.83 UB/mL (SD ±59.46), the historical peak was 626.54 UB /mL (SD ±1196.05), the inhibitor titer after 6 months of ITI was 112.59 UB/mL (SD ±291.89) and the titer at the end of the ITI was, on average, 43.99 UB/mL mL (SD ±74.50). The mean time that patients spent on immunotolerance induction was 28.15 months (SD ±9.69) and throughout the ITI treatment, the amount of FVIII used per patient was, on average, 588,770 IU (SD ± 546,090.61). Of the 20 patients analyzed, 9 had therapeutic failure and 7 were using the monoclonal antibody Emicizumab. Finally, the therapeutic regimen of these 7 were evaluated and about 4 (57.1%) patients take their maintenance dose of Emicizumab on a weekly basis and 3 (42.9%) use it fortnightly. In addition, the relation between predictors of therapeutic success and clinical outcome were analyzed, among which the previous inhibitor titer <10 UB/mL showed 90% accuracy as a parameter to determine the success or failure of immunotolerance. Therefore, it was possible to perceive that the number of patients who had a successful ITI was higher than those who were refractory, despite the small numerical difference between them. Of those who failed, most use Emicizumab in HEMOCE, receiving a maintenance dose calculated according to weight and with a weekly or biweekly frequency of use. Among these patients, there were no reports of bleeding episodes after starting treatment with the monoclonal antibody. Regarding the influence of success predictors, the results showed that the previous inhibitor titer < 10UB/mL is of great importance to determine whether the patient will have a good response to treatment, since in this study its correlation with the therapeutic outcome was proven of being of great help for professionals to predict the therapeutic response of patients in ITI.