Ann D. Flynn

Lack of placental transfer of certolizumab pegol during pregnancy: results from CRIB, a prospective, postmarketing, pharmacokinetic study

Objectives There is a need for effective and safe treatment during pregnancy in women with chronic inflammatory diseases. This study evaluated placental transfer of certolizumab pegol (CZP), an Fc-free anti-tumour necrosis factor drug, from CZP-treated pregnant women to their infants. Methods CRIB was a pharmacokinetic (PK) study of women ≥30 weeks pregnant receiving commercial CZP for a locally approved indication (last dose ≤35 days prior to delivery). Blood samples were collected from mothers, umbilical cords and infants at delivery, and infants again at weeks 4 and 8 post-delivery. CZP plasma concentrations were measured with a highly sensitive and CZP-specific electrochemiluminescence immunoassay (lower limit of quantification 0.032 μg/mL). Results Sixteen women entered and completed the study. Maternal CZP plasma levels at delivery were within the expected therapeutic range (median [range] 24.4 [5.0–49.4] μg/mL). Of the 16 infants, 2 were excluded from the per-protocol set: 1 due to missing data at birth and 1 due to implausible PK data. Of the remaining 14 infants, 13 had no quantifiable CZP levels at birth (<0.032 μg/mL), and 1 had a minimal CZP level of 0.042 μg/mL (infant/mother plasma ratio 0.0009); no infants had quantifiable CZP levels at weeks 4 and 8. Of 16 umbilical cord samples, 1 was excluded due to missing data; 3/15 had quantifiable CZP levels (maximum 0.048 μg/mL). Conclusions There was no to minimal placental transfer of CZP from mothers to infants, suggesting lack of in utero foetal exposure during the third trimester. These results support continuation of CZP treatment during pregnancy, when considered necessary. Trial registration number NCT02019602; Results.

Spontaneous regression of colonic lymphoma following infliximab and azathioprine withdrawal in patients with Crohn's disease.

with UC and rare chromosomal abnormalities. Patient 1: A girl with micrognathia, ocular hypertelorism, auricular abnormality, and mental and motor retardation has a karyotype of 46,XX,der(21),t(9;21)(q32;q22.3). She was diagnosed with UC at the age of 6 years. At diagnosis, her pediatric UC activity index was 65 (severe), and disease extent represented pancolitis. She did not respond to steroid treatment and received oral tacrolimus as induction therapy. Despite changing to azathioprine for maintenance therapy, she had 2 exacerbations within 1 year. She underwent colectomy at the age of 7 years. Patient 2: A girl with polyhydramnios, facial dysmorphism, “coat-hanger” appearance of the ribs, bell-shaped thorax, diastasis recti, and mental and motor retardation had paternal uniparental disomy of chromosome 14. She was diagnosed with UC at the age of 2 years 7 months. At diagnosis, her pediatric UC activity index was 65 (severe), and disease extent represented pancolitis. She was steroid dependent and was given azathioprine for maintenance therapy 9 months after the diagnosis. Unfortunately, at the age of 3 years 7 months, she died of acute respiratory distress caused by respiratory syncytial virus during a period of remission. An association between UC and TS has been described. Price reported that the prevalence UC was 1.48% in a series of 135 patients with TS; distinctive findings developed at a young age, and colitis often was severe. Similarly, these 2 patients had early onsets and refractory disease. Recently, genome-wide and candidate gene association studies have identified 47 susceptibility loci for UC. Interestingly, patient 1 has abnormalities of chromosome 9q32 and 21q22 that were included among these 47 loci. To our knowledge, this is the first report of UC associated with either of the rare chromosome abnormalities in our patients.

OP0017 Lack of placental transfer of certolizumab pegol during pregnancy: results from crib, a prospective, postmarketing, multicenter, pharmacokinetic study

Background There is a need for effective and safe treatment during pregnancy in women affected by chronic active inflammatory diseases, such as rheumatoid arthritis. Adequate disease control is crucial to ensure the best fetal and maternal health, and reduce adverse pregnancy outcomes.1,2 Anti-TNFs are an effective therapeutic option, but because most cross the placenta, they are often stopped during pregnancy.3,4 Certolizumab pegol (CZP), due to its Fc-free molecular structure, has no active placental transfer compared to other anti-TNFs.5,6 Objectives To accurately measure the potential level of placental transfer of CZP from mothers to infants using a highly sensitive, CZP-specific assay. Methods CRIB (NCT02019602) was a pharmacokinetic (PK) study of pregnant women (≥30 weeks [wks] gestation) receiving commercial CZP (maintenance dose) for an approved indication; last dose was within 35 days prior to delivery. Blood samples were collected from the mothers, umbilical cords, and infants at delivery, and infants again at Wks 4 and 8 post-delivery. CZP concentration was measured with a sensitive, CZP-specific electrochemiluminescence immunoassay validated in plasma (LLOQ=0.032 μg/mL; 10-fold lower than assay used in prior CZP PK studies6,7). Results 21 CZP-treated pregnant women were screened; 16 entered the study (Table). Maternal CZP plasma levels at delivery were within the expected therapeutic range (median [range]: 24.4 [5.0–49.4] μg/mL). Of the 16 infants delivered, 2 samples were excluded: 1 due to missing data, 1 due to implausible PK data. 13/14 infants had no quantifiable CZP levels at birth (<0.032 μg/mL); 1 infant had a minimal CZP level of 0.042 μg/mL (infant/mother plasma ratio: 0.09%); no infants had quantifiable levels at Wks 4 and 8 (Figure). 3/15 umbilical cord samples had quantifiable CZP levels (maximum: 0.048 μg/mL); 1 umbilical cord collapsed and was excluded. No anti-CZP antibodies were detected in mothers, umbilical cords, or infants. The infants of CZP-exposed mothers had a safety profile consistent with that of unexposed similar-age infants. Conclusions Using a highly sensitive assay, CZP levels were below LLOQ in 13/14 infant blood samples at birth, and all samples at Wks 4 and 8. This indicates no to negligible placental transfer of CZP from mothers to infants, suggesting lack of in utero fetus exposure during the second and third trimesters. These results support continuation of CZP treatment during pregnancy. References de Man Y. Arthritis Rheum 2009;60:3196–206. Morales M. Hepatogastroenterology 2000;47:1595–8. Ng S. Expert Rev Clin Immunol 2013;9:161–73. Østensen M. Curr Opin Pharmacol 2013;13:470–5. Porter C. J Reprod Immunol 2016;116:7–12. Mahadevan U. Clin Gastroenterol Hepatol 2013;11:286–92. Lacroix B. Gastroenterol 2010

Reproductive Planning and Contraception for Women with Inflammatory Bowel Diseases.

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Update on the Diagnosis and Management of Colon Ischemia

138:S163–4. Acknowledgements This study was funded by UCB Pharma. We are indebted to the mothers and their infants for their altruistic participation. Editorial services were provided by Costello Medical Consulting. Disclosure of Interest X. Mariette Grant/research support from: Biogen, Pfizer, UCB Pharma, Consultant for: Bristol-Myers Squibb, GlaxoSmithKline, LFB, Pfizer, UCB Pharma, A. Flynn Grant/research support from: UCB Pharma, F. Förger Grant/research support from: UCB Pharma, Speakers bureau: Mepha, Roche, UCB Pharma, A. Moltό Grant/research support from: MSD, AbbVie, Pfizer, UCB Pharma, Consultant for: MSD, AbbVie, Pfizer, UCB Pharma, R.-M. Flipo Consultant for: UCB Pharma, A. van Tubergen Grant/research support from: Pfizer, AbbVie, UCB Pharma, Janssen-Cilag, Celgene, Novartis, MSD, Consultant for: AbbVie, Novartis, Janssen-Cilag, Pfizer, Speakers bureau: MSD, Janssen-Cilag, Pfizer, L. Shaughnessy Employee of: UCB Pharma, J. Simpson Employee of: UCB Pharma, M. Teil Employee of: UCB Pharma, E. Helmer Employee of: UCB Pharma, M. Wang Employee of: UCB Pharma, E. Chakravarty Grant/research support from: UCB Pharma

Inflammatory bowel disease education: I can hear the extension for community healthcare outcomes

Abstract:Women with chronic medical conditions, such as inflammatory bowel diseases, are at increased risk for adverse pregnancy outcomes. Pregnancy outcomes for these conditions are best during stable disease remission. Unfortunately, women with inflammatory bowel disease are equally as likely as the general population to have unintended pregnancies. Patients look to their gastroenterologist for contraceptive counseling; however, the current standards for disease management do not prioritize this topic. Guidelines based on available evidence and expert opinion, such as the Centers for Disease Control U.S. Medical Eligibility Criteria for Contraceptive Use, exist to help practitioners provide safe and effective contraception to women with chronic medical conditions. If health care providers were to educate themselves and screen women with inflammatory bowel disease for risk of unintended pregnancy, there would be a reduction in the number of unintended pregnancies and subsequent adverse neonatal and maternal outcomes.

Chromoendoscopy for Dysplasia Surveillance in Inflammatory Bowel Disease

Opinion statementColonic ischemia is the most common ischemic disorder of the gastrointestinal tract. The condition occurs more commonly in women, and risk increases with advancing age. Presenting symptoms include abdominal pain, bowel urgency, and passage of bloody diarrhea; however, nearly one half of patients do not present with this classic triad of symptoms. Abdominal pain without bloody diarrhea or non-bloody diarrhea should raise concern for an isolated right colon pattern of ischemia. An isolated right colon distribution is associated with more severe outcomes, including need for surgical intervention and increased mortality. Patients that present with symptoms concerning for ischemia should undergo computed tomography (CT) scan of the abdomen and pelvis with oral and IV contrast and laboratory testing. Colonoscopy should be performed in patients without evidence of peritonitis. Medical history should be obtained to identify possible etiologies of ischemia. Thrombophilia workup should be considered in young patients and those with recurrent ischemia, but is not required universally. In cases of isolated right colon ischemia, evaluation of the mesenteric vasculature is particularly important, for exclusion of concurrent acute mesenteric ischemia. Treatment of ischemic colitis is supportive in less severe cases, with intravenous fluids and bowel rest. Broad-spectrum antibiotics should be initiated, and surgical consultation should be obtained in cases of severe disease, pancolonic ischemia, and isolated right colonic ischemia. Surgery should be performed for peritonitis, hemodynamic instability, or failure of non-operative management. This article will review colonic ischemia diagnosis, evaluation, and treatment.

Fecal microbiota transplantation for the treatment of recurrent and severe Clostridium difficile infection in solid organ transplant recipients: A multicenter experience.

Article first published online 4 May 2015.

Mo1820 - The Association of Joint Extra-Intestinal Manifestations in Patients with Inflammatory Bowel Disease on Quality of Life: A Prospective Multi-Center Study

Long-standing ulcerative colitis (UC) and extensive Crohns colitis confer increased risk for development of colorectal cancer. Screening and surveillance colonoscopy programs aim to identify, resect, or detect dysplasia or colorectal cancer. Dysplastic lesions can be removed by endoscopic resection and patients with unresectable lesions can be referred for colectomy at an earlier stage, with the goal of reducing overall morbidity and mortality from colorectal cancer. Surveillance colonoscopy for patients with inflammatory bowel disease (IBD) is endorsed by multiple specialty societies. High-definition endoscopy systems provide improved image resolution, and application of dilute indigo carmine or methylene blue for chromoendoscopy can provide increased contrast. International specialty society guidelines differ in their recommendations regarding use of chromoendoscopy for dysplasia surveillance, with some guidelines advocating a risk-stratified surveillance strategy. In this review, we discuss chromoendoscopy technique, training, implementation, yield as compared with standard-definition and high-definition white light colonoscopy, and positioning of this technique in clinical practice.

Tu1875 - Fecal Microbiota Transplantation for the Treatment of Clostridium Difficile Infection is Efficacious and Safe in Solid Organ Transplant Recipients

Fecal microbiota transplant (FMT) is recommended for Clostridium difficile infection (CDI) treatment; however, use in solid organ transplantation (SOT) patients has theoretical safety concerns. This multicenter, retrospective study evaluated FMT safety, effectiveness, and risk factors for failure in SOT patients. Primary cure and overall cure were defined as resolution of diarrhea or negative C difficile stool test after a single FMT or after subsequent FMT(s) ± anti‐CDI antibiotics, respectively. Ninety‐four SOT patients underwent FMT, 78% for recurrent CDI and 22% for severe or fulminant CDI. FMT‐related adverse events (AE) occurred in 22.3% of cases, mainly comprising self‐limiting conditions including nausea, abdominal pain, and FMT‐related diarrhea. Severe AEs occurred in 3.2% of cases, with no FMT‐related bacteremia. After FMT, 25% of patients with underlying inflammatory bowel disease had worsening disease activity, while 14% of cytomegalovirus‐seropositive patients had reactivation. At 3 months, primary cure was 58.7%, while overall cure was 91.3%. Predictors of failing a single FMT included inpatient status, severe and fulminant CDI, presence of pseudomembranous colitis, and use of non‐CDI antibiotics at the time of FMT. These data suggest FMT is safe in SOT patients. However, repeated FMT(s) or additional antibiotics may be needed to optimize rates of cure with FMT.