when Crohn’s disease inactive from 6 months before conception until week 20 from pregnancy, the option of discontinuing anti-TNF treatment in the third trimester, this was discussed with the gynecologist and the patient.
when Crohn’s disease active any time from 6 months before conception until week 20 from
pregnancy would be continued during the entire pregnancy.
All patient were informed regarding antiTNF measurement in blood cord and peripheral maternal blood at birth. During delivery, a blood sample was collected and sent to the laboratory of gastroenterology at the Erasmus University Medical Center Rotterdam.
Birth outcomes such as gestational age at birth, birth weight, and the presence of congenital abnormalities were noted during the first visit after delivery. After 1 year, health outcomes from infants were obtained through the telephonic questionnaire with mothers and/or by obtaining medical information from the general practitioner after the consent of both parents. The 1-year outcomes included growth, infections for which systemic antibiotic treatment was needed, hospitalization for an infection, allergies, chronic diseases, adverse reactions to vaccinations, and the presence of eczema.
Anti TNF measurement is done by ELIZA from peripheral blood.
Total mothers were treated with anti-TNF?. 170 pregnancies (82 [80%] with
Crohns disease. During conception and/or pregnancy,
46 [56%] infants were exposed to Infliximab and 36 [44%] were exposed
maternal blood At birth, cord blood samples in which anti-TNF? concentration was measured were obtained from 94 mothers; 52 used infliximab and 42 used adalimumab during pregnancy. The result Median anti-TNF? concentration in cord blood [?g/mL] infliximab (4.9 ?g/mL) and adalimumab (1.
Median anti-TNF? level in maternal blood at birth [?g/mL] infliximab (1.7 ?g/mL) and
During the third trimester, infliximab transportation over the placenta increased exponentially; however, Adalimumab transportation was limited and increased in a linear fashion. Overall, health outcomes were comparable. Adalimumab may be continued longer during pregnancy because transportation over the placenta is lower than for infliximab. This may reduce the relapse risk of the mother, without increasing fetal anti-TNF? exposure.
One-year health outcomes of infants exposed to anti-TNF? in utero Out of all live births, health
outcomes until 1 year of age were obtained from 93 infants [71%]. 50 used infliximab and 43 used adalimumab. Normal growth infliximab 49 and adalimumab 42.
Number of infections treated with antibiotics [%]: infliximab 35 [76%] and adalimumab 31 [71%] in frist week while in 12 months infliximab 10 [22%] and adalimumab 10 [23%]
Hospitalization because of infection [%] : infliximab 5 [10%]and adalimumab 3 [7%]
Allergies [%]: infliximab 3 [7%] and adalimumab 5 [11%]
Chronic diseases [%] infliximab 0 [0%]and adalimumab 1 [2%].
(Ent, Rizopoulos and Woude, 2018)
present a patient treatment with adalimumab Adalimumab-induced acute myeloid leukemia in a patient with Crohns disease.
A 32-year-old African-American man presented with a medical history of CD status after two partial bowel resections several years ago and treatment with adalimumab for approximately
1 year. He was refractory to azathioprine, which he received for 2 years, and was stopped for 7 months before adalimumab was administered.
presented in the emergency department, reporting cough, chest tightness and subjective fever
for several days. the patient state health before this symptoms appearance
. His chest X-ray showed a lingula opacity consistent with possible pneumonia. He was diagnosed
with community-acquired pneumonia. He was initiated on broad-spectrum
antibiotics. However, he was prompted to return to the emergency department because his laboratory test showed pancytopenia with evidence of blast cells in the differential count, which was concerning for acute leukemia.
His laboratory tests results were pertinent for pancytopenia with an absolute neutrophil count of 244. He was continued on spectrum antibiotics and started on empiric antiviral and antifungal coverage. His bone marrow biopsy showed 20%30% blasts with an increase in eosinophils indicative of acute myeloid leukemia. The bone marrow aspirate showed rare eosinophils with basophilic granules. These findings were highly suggestive of AML with core-binding
factor beta (CBFB) gene. These findings were confirmed by a subsequent. The patient continued to fevers despite receiving vancomycin and cefepime and, therefore, underwent a CT scan of the chest, abdomen, and pelvis. The results showed tree-in-bud nodularity and
multifocal infiltrates, most prominent in the left lung, which was concerning for
mycobacterial and fungal infections. With broad-spectrum antibiotics Despite the patients persistent fevers So, antibiotics were discontinued. bronchoscopy with bronchoalveolar lavage and biopsy were performed, showed no evidence of any infection and tumor.
start chemotherapy, followed by four cycles of consolidation chemotherapy with high-dose cytarabine. A subsequent bone marrow biopsy revealed that the patient had achieved remission. Several studies have demonstrated that TNF? has a significant role in controlling cell proliferation, differentiation, and apoptosis, especially in malignant cells. Moreover, studies have shown an increased risk of hematological malignancies among patients with Crohn’s disease compared with the general population. A core-binding factor beta gene and the protein regulates a host of genes required for hematopoiesis. Rearrangement in this gene is linked to acute myeloid leukemia TNF-? causes immune suppression by suppressing the TNF superfamily of proteins. Tare needed to strongly link this chromosomal
rearrangement to the use of anti-TNF? in Crohn’s. 17 Our case describes the development of acute myeloid leukemia in a patient with Crohn’s who had been treated with adalimumab for 1 year. (Alzahrani et al., 2019)
Loss of response to scheduled infliximab therapy for Crohns disease in adults: A systematic review.
aim to estimate the pooled rate of low of response( LOR) , as well as identify the potential predictors of LOR to infliximab therapy.
LOR to infliximab therapy was identified as are emergence of disease activity after achieving an appropriate induction response, coupled with a need for altered therapy, including addition of an immunomodulator (IMM), dose intensification, or a need to discontinue Infliximab In 2018 in China doctors in Shanghai Jiao Tong University searched for articles published between 1990 and March 2017 in PubMed, Embase, and the Cochrane Library about Loss of response to scheduled infliximab therapy for Crohns disease in adults. Inclusion criteria according (1) Adult patients were diagnosed with Crohn`s disease by standard criteria. (2) Patients were followed up for a minimum of 14 weeks. (3) Rates of Low of response were reported.
Result: Twenty-six studies consolidated drug response data were obtained from 3,187 patients. observational studies (including case-control, cohort studies) and adult patients were diagnosed with CD by standard criteria. Patients were followed up for a minimum of 14 weeks.
LOR in the adult of 16-42% in patients undergoing scheduled Infliximab therapy.
Colon involve LOR in 73 patients while non-LOR in 156 patients
Non-colon involved LOR 10 patient and non-LOR in 54 patients
combination therapy LOR in 55 patient and non- LOR in 97 patients
while non-combination therapy LOR IN 121 patients and non-LOR in 74 patients
perianal lesion LOR 50 patients and non-LOR in 92 patients
while non-perianal lesion lLOR in 42 patients and non-LOR 136 patients
result estimates the incidence of LOR among adult crohn`s patient
patients undergoing infliximab therapy is 36%. The presence of perianal lesion, younger age at Crohn`s onset and involvement of colon were relative risk factors of LOR after initiating Infliximab therapy in crohn`s disease patients. Our analysis also indicates that the use of combination IMM therapy seems to decrease the incidence of LOR (Zhang et al., 2018).
The advent of tumor necrosis factor (TNF?) antagonists represented a radical change in the management of Crohn’s disease. Anti-TNF? therapy has been shown to reduce symptoms, heal mucosal ulcers, reduce hospitalizations and surgeries and spare corticosteroids. Studies have also shown the efficacy of anti TNF? for pregnancy, adult, children, and fetuses.
Living with Crohn’s disease is not as difficult as before because it is more knowledgeable about the disease and availability of treatment.TNF? antagonists have become indispensable in the management of Crohn’s disease but, should be made more studies about serious side effect with anti-TNF? treatment.