Z. Zelinkova

Immunogenicity negatively influences the outcome of adalimumab treatment in Crohn’s disease

Backgroundu2002 Adalimumab is an effective treatment in patients with Crohn’s disease; as it is a humanized anti‐tumour necrosis factor monoclonal antibody, immunogenicity is thought not to be of any significance.

High intra-uterine exposure to infliximab following maternal anti-TNF treatment during pregnancy

Aliment Pharmacol Ther 2011; 33: 1053–1058

Effects of Discontinuing Anti–Tumor Necrosis Factor Therapy During Pregnancy on the Course of Inflammatory Bowel Disease and Neonatal Exposure

BACKGROUND & AIMSnWe assessed the course of inflammatory bowel disease (IBD) among pregnant women who stopped taking anti-tumor necrosis factor (TNF) agents. We also analyzed levels of anti-TNF agents in cord blood samples.nnnMETHODSnWe followed 31 pregnancies in 28 women with IBD between April 2006 and April 2011 who were treated with anti-TNF agents (18 received infliximab, and 13 received adalimumab) during pregnancy. We used enzyme-linked immunosorbent assays to measure levels of anti-TNF agents in cord blood collected from 18 newborns (12 whose mothers took infliximab, and 6 whose mothers took adalimumab).nnnRESULTSnAmong the patients taking infliximab, 12 (71%) discontinued treatment before gestational week 30; all patients remained in remission. All the patients taking adalimumab discontinued treatment before gestational week 30; two patients had relapses of IBD. There were 28 live births, 1 miscarriage among patients taking infliximab (at gestational week 6), and 2 miscarriages among patients taking adalimumab (at weeks 6 and 8); there were no congenital malformations. The mean cord blood level of infliximab was 6.4 ± 1.6 μg/mL; it was significantly lower among women who received the drug 10 weeks or less before delivery (2.8 ± 1.1 μg/mL) than those who received infliximab closer to delivery (10 ± 2.3 μg/mL; P = .02). Adalimumab was detected in 5 samples of cord blood (mean concentration, 1.7 ± 0.4 μg/mL); 1 cord blood sample from a woman who discontinued the treatment at gestational week 22 had an undetectable level of the drug.nnnCONCLUSIONSnDiscontinuation of anti-TNF therapy appears to be safe for pregnant women with quiescent IBD. However, these drugs are still detected in cord blood samples.

Predictors of dose escalation of adalimumab in a prospective cohort of Crohn's disease patients.

Backgroundu2002 Adalimumab is effective for the induction and maintenance of remission in Crohn’s disease (CD)‐patients.

Long-term follow-up of autologous hematopoietic stem cell transplantation for severe refractory Crohn's disease

BACKGROUNDnAlthough new therapeutic strategies have been developed to control Crohns disease, medical treatment for refractory cases is not able to prevent extensive and/or repeat surgery. Recently, several cases have been reported of successful remission induction in Crohns disease patients by means of hematopoietic stem cell transplantation (HSCT). Here we report our long-term (4 to 6 years) outcome in three patients.nnnPATIENTSnThree patients (two male, one female) with active severe Crohns disease were planned to undergo autologous HSCT. All patients were intolerant or refractory to conventional therapies, including anti-TNFα antibodies. Patients either refused surgery or surgery was considered not to be a feasible alternative due to the extensive disease involvement of the small intestine.nnnMETHODSnPeripheral blood stem cells were mobilized using a single infusion of cyclophosphamide 4 g/m(2), followed on day 4 by subcutaneous injections with G-CSF 5 μg/kg twice daily until leukapheresis. CD34+ cells were isolated after leukapheresis by magnetic cell sorting. In two of the three patients a second round of stem cell mobilization using G-CSF only was required, either because of low yield or because of insufficient recovery after CD34 selection. Prior to transplantation, immune ablation was achieved using cyclophosphamide 50mg/kg/day (4 days), antithymocyte globulin 30 mg/kg/day (3 days) and prednisolone 500 mg (3 days). Endoscopy, barium small bowel enteroclysis and MRI enterography were performed.nnnRESULTSnAll three patients successfully completed stem cell mobilization, and two of them subsequently underwent conditioning and autologous HSCT with CD34+ cell selection. Treatment was well tolerated, with acceptable toxicity. Now, 5 and 6 years post-transplantation, these patients are in remission under treatment. The third patient went into remission after mobilization and therefore she decided not to undergo conditioning and HSCT transplantation. After a successful pregnancy she relapsed two years later. Since then, she suffers from refractory Crohns disease for which we are now reconsidering conditioning and transplantation.nnnCONCLUSIONnAutologous HSCT appears to be safe and can be an alternative strategy for Crohns disease patients with severe and therapy resistant disease.

Preconception Care Reduces Relapse of Inflammatory Bowel Disease During Pregnancy

BACKGROUND & AIMSnWomen with inflammatory bowel disease (IBD) may have incorrect beliefs about their disease and its medication in relation to pregnancy. We studied the effects of preconception care (PCC) on patients behavior during pregnancy, disease relapse during pregnancy, and birth outcomes.nnnMETHODSnIn a prospective study, we followed up all women with IBD seen at the preconception outpatient clinic at Erasmus MC-University Medical Center in Rotterdam, The Netherlands (from 2008 through 2014). We compared patients who received PCC before they became pregnant (PCC group; nxa0= 155) with patients who visited the clinic after they already were pregnant (no-PCC group; nxa0= 162). We collected data on lifestyle, medication adherence, planning of conception, disease activity, and birth outcomes. We compared adherence to medical advice, rates of disease relapse during pregnancy, and birth outcomes.nnnRESULTSnThe PCC group was on average younger than the no-PCC group (29.7 vs 31.4 y; Pxa0= .001), and a greater proportion were nulliparous (76.1% vs 51.2%; Pxa0= .0001). PCC was associated with adherence to IBD medication during pregnancy (adjusted odds ratio [aOR],5.69; 95% confidence interval [CI], 1.88-17.27), adequate folic acid intake (aOR, 5.26; 95% CI, 2.70-10.26), and smoking cessation (aOR, 4.63; 95% CI, 1.22-17.55). PCC reduced disease relapse during pregnancy independent of parity, disease duration, or disease activity before conception (aOR, 0.51; 95% CI, 0.28-0.95). The PCC group was less likely to deliver babies of low birth weight (aOR, 0.08; 95% CI, 0.01-0.48).nnnCONCLUSIONSnIn a prospective study, we found that preconception care reduces IBD relapse during pregnancy by promoting adherence to medication and smoking cessation. Preconception also reduces risk for babies of low birth weight.

Adalimumab in Crohn's disease patients: pharmacokinetics in the first 6 months of treatment

Adalimumab is an effective therapy for Crohns disease patients. However, there is limited knowledge on the pharmacokinetic properties of adalilumab in patients with Crohns disease.

Autoimmune hepatitis following treatment with infliximab for inflammatory bowel disease

Dear Sir,nnWe read with interest the report of infliximab-induced hepatitis by Doyle et al.1 Infliximab-induced liver test abnormalities are quite common in clinical practice; however, the progression to clinical overt hepatitis is far less frequent.2–6nnWe report here two women with inflammatory bowel disease that developed hepatitis with autoimmune features following treatment with infliximab.nnThe first case was a 46-year-old woman with Crohns disease who was treated with infliximab because of steroid-resistant erythema nodosum. After three infliximab infusions (5 mg/kg), raised transaminases were found, up to 25 times upper normal values. …

High therapy adherence but substantial limitations to daily activities amongst members of the Dutch inflammatory bowel disease patients' organization: a patient empowerment study

Aliment Pharmacol Theru200230, 864–872

Maternal imprinting and female predominance in familial Crohn's disease ☆

BACKGROUND AND AIMnAlthough the genetic risk factors for familial and sporadic inflammatory bowel disease (IBD) seem identical, the relative risk for contracting IBD in the familial setting is larger as that seen in the population at large, suggesting an important role of epi- and/or paragenetic factors in familial IBD. Epidemiological data indicate a female predominance in IBD, but how this relates to familial IBD has not been assessed.nnnMETHODSnFamilial IBD patients (N=608) were compared with a cohort of 415 sporadic IBD patients with regards to the patterns of sex and disease type distribution. The imprinting pattern in 87 families in which both a parent and a child had IBD was tested using Galton binominal statistics.nnnRESULTSnThe percentage of females in familial IBD population was significantly higher (61%; female/male ratio 1.5) compared with sporadic IBD (54%; female/male ratio 1.2; p=0.011). The analysis of offspring sex distribution pattern revealed significantly higher female to female transmission compared with female to male transmission rate (36 vs. 18, respectively; p=0.02). A significantly higher number of mother to child transmissions (55 vs. 32 of father to child transmissions) was observed (p=0.018). The female imprinting was specifically related to Crohns disease (31 vs. 14 mother vs. father to child transmissions, respectively; p=0.016).nnnCONCLUSIONnWe propose that a female sex-specific epigenetic inheritance pattern for Crohns disease is a major contributing factor in the family-specific risk in Crohns disease. Sex-specific manifestation of familial Crohns disease can partly explain the epidemiologically observed increased relative risk for females for contracting IBD.