CCFA Conference Notes 2016 (part 4) –Pregnancy and IBD

Posted on April 29, 2016 by gutsandgrowth

Pregnancy and IBD –Dr. Doug Wolf

Dr. Wolf reviewed infertility, pregnancy issues, and PIANO registry. This topic has been covered elsewhere in this blog (IBD and Pregnancy | gutsandgrowth). Vedolizumab is a FDA category B; thus far, it is considered fairly safe. Thiopurines are category D but overall thought to be low risk.

This blog entry has abbreviated/summarized this terrific presentation. Though not intentional, some important material is likely to have been omitted; in addition, transcription errors are possible as well.

“The Couric Effect”

Posted on April 18, 2016 by gutsandgrowth

A recent commentary (Am J Gastroenterol advance online publication 29 March 2016; doi: 10.1038/ajg.2016.118) by Katie Couric provides a summary of her personal journey as an advocate for preventing colon cancer.

A good read: An Unexpected Turn: My Life as a Cancer Advocate

Here’s an excerpt:

“April is the cruelest month,” T.S. Eliot wrote in “The Waste Land,” and in 1997 it certainly was for my family. That’s when my husband Jay and I discovered he had stage IV colon cancer that had spread to his liver…and the beginning of a 9-month nightmare…

the University of Michigan found that my televised colonoscopy and educational outreach contributed to a sustained 19% increase in the number of colonoscopies performed nationwide. They called it “The Couric Effect”

Anti-TNF therapy and Pregnancy -More Data

Posted on April 8, 2016 by gutsandgrowth

G Broms et al (Clin Gastroenterol Hepatol 2016; 14: 234-41) provide more data on the ‘low risk of birth defects for infants whose mothers are treated with anti-tumor necrosis factor agents during pregnancy.”

From a Danish/Swedish cohort of 1,272,424 live births (2004-2012), the authors found the following (in comparison to healthy infants):

Birth defects were increased in chronic inflammatory bowel disease: 4.8% vs. 4.2%
43 (6.3%) of the infants born to women with IBD who received anti-TNF therapy (683) had birth defects. The OR for any defect was 1.32 (CI 0.93-1.82). The types of defects were generally similar, including VSD, ASD, hypospadias, and hydronephrosis

Limitations:

In infants of mothers with chronic diseases, it is possible that more careful screening identified some less apparent defects.
Study did not examine rates of stillborn or abortions

My take: Overall there is a slightly but not significantly increased risk in birth defects based on the use of anti-TNF therapy. Stopping anti-TNF therapy is likely to be more detrimental.

Briefly noted: P Wils et al. Clin Gastroenterol Hepatol 2016; 14: 242-50. This retrospective study of 122 patients showed that 65% had a clinical benefit within 3 months of receiving ustekinumab for Crohn’s disease refractory to anti-TNF therapy. Concomitant immunosuppressant therapy was associated with an increased likelihood of benefit (OR 5.43)

Related blog posts:

IBD and Pregnancy

Posted on April 3, 2016 by gutsandgrowth

While managing inflammatory bowel disease during pregnancy is not within the scope of my practice as a pediatric gastroenterologist, it is helpful to have some familiarity with the issues.

Here’s a full-text link to AGA Guidelines: The Toronto Consensus Statements for the Management of Inflammatory Bowel Disease in Pregnancy

From the abstract, an excerpt:

Consensus was reached on 29 of the 30 recommendations considered. Preconception counseling and access to specialist care are paramount in optimizing disease management. In general, women on 5-ASA, thiopurine, or anti–tumor necrosis factor (TNF) monotherapy for maintenance should continue therapy throughout pregnancy. Discontinuation of anti-TNF therapy or switching from combination therapy to monotherapy may be considered in very select low-risk patients. Women who have a mild to moderate disease flare while on optimized 5-ASA or thiopurine therapy should be managed with systemic corticosteroid or anti-TNF therapy, and those with a corticosteroid-resistant flare should start anti-TNF therapy. Endoscopy or urgent surgery should not be delayed during pregnancy if indicated. Decisions regarding cesarean delivery should be based on obstetric considerations and not the diagnosis of IBD alone, with the exception of women with active perianal Crohn’s disease. With the exception of methotrexate, the use of medications for IBD should not influence the decision to breast-feed and vice versa. Live vaccinations are not recommended within the first 6 months of life in the offspring of women who were on anti-TNF therapy during pregnancy.

European Experience with Biosimilars

Posted on March 12, 2016 by gutsandgrowth

While there are numerous concerns regarding the use of biosimilar products, the preliminary experience with biosimilar infliximab has been favorable.

Full text link: European Experience of Infliximab Biosimilars for IBD (Gastroenterology & Hepatology)

Key points:

Biosimilars are leading to cost reductions of 30-40%. In addition, to lowering the cost of infliximab, this is leading to reductions in costs for adalimumab and vedolizumab which are competing as 1st line therapies.
In the authors study of the first 210 patients, they did not find any difference in terms of immunogenicity or side effects. In addition, efficacy was comparable to the ‘originator’ drug.

My take: Infliximab and adalimumab have been blockbuster medications for pharmaceutical companies, in part because they provide a great clinical benefit. However, if biosimilars are truly biosimilar, the cost reductions will result in their widespread adoption.

Related blog post: Biosimilars -Position Statement GutsandGrowth This position statement: “Treatment of a child with sustained remission on a specific medication should not be switched to a biosimilar until clinical trials in IBD are available to support the safety and efficacy of such a change”

Castillo San Felipe del Morro

Microbiome Predicts Constipation plus two

Posted on March 5, 2016 by gutsandgrowth

In brief:

G Parthasarathy et al. Gastroenterol 2016; 150: 367-79. Mucosal and fecal microbiota samples were collected from 25 healthy women and 25 women with chronic constipation. Key finding: The mucosal, but not fecal, microbiota profile were 94% predictive of constipation. The associated editorial (pg 300) provides a framework for understanding these findings and show the complexity of trying understand the interations between diet, motility and microbes.

S Fukudo et al. Gastroenterol 2016; 150: 358-66. This prospective study of Ramosetron for 576 women with IBS-D. Key finding: 50.7% of treatment patients reported global improvement compared with 32.0% of control patients. Patients had less abdominal pain, less discomfort, and better stool consistency. Ramosetron, a 5-HT3 antagonist, has not been reported to cause ischemic colitis (in contrast to alosetron).

In followup to a post earlier in the week, another worrisome study on the Zika virus in pregnancy from NEJM. Here’s an excerpt:

Fetal abnormalities were detected by Doppler ultrasonography in 12 of the 42 ZIKV-positive women (29%) and in none of the 16 ZIKV-negative women. Adverse findings included fetal deaths at 36 and 38 weeks of gestation (2 fetuses), in utero growth restriction with or without microcephaly (5 fetuses), ventricular calcifications or other central nervous system (CNS) lesions (7 fetuses), and abnormal amniotic fluid volume or cerebral or umbilical artery flow (7 fetuses).

Farjado, Puerto Rico

Guidelines: Microscopic Colitis & Vascular Diseases of the Liver

Posted on February 27, 2016 by gutsandgrowth

In brief:

AGA Microscopic Colitis Guideline: GC Nguyen et al. Gastroenterol 2016; 150: 242-6. Technical review DS Pardi et al. Gastroenterol 2016; 150: 247-74. Patient guide: pg 275.

EASL Clinical Practice Guidelines: Vascular diseases of the liver. J Hepatology 2016; 64: 179-202. Topics covered include Budd-Chiari, Portal vein obstruction, Heriditary hemorrhagic telangiectasia, veno-occlusive disease of the liver, management of anticoagulation in liver disease

Breath Test Reliability for Bacterial Overgrowth

Posted on February 25, 2016 by gutsandgrowth

While breath test reliability for bacterial overgrowth has been a concern for a long time, another study (EC Lin, BT Massey. Clin Gastroenterol Hepatol 2016; 14: 203-08) takes a new approach to show that the glucose breath tests are subject to a high false-positive rate. This is often related to rapid transit time.

Here’s what they did:

In a retrospective study, they examined data from 139 patients with suspected small bowel bacterial overgrowth (SBBO) (2003-2013). Abnormal glucose breath tests were indicated by either hydrogen or methane >15 parts per million within 90 minutes after glucose ingestion. In addition, they used concurrent scintigraphy (by labeling glucose with a Tc99m compound) to determine whether this increase occurred before or after glucose bolus arrived in the cecum.

Findings:

46 (33%) had abnormal breath tests. Of these 22 (48%) had false-positive results due to colonic fermentation.
False-positives were higher (65%) in the subset of patients with prior upper gastrointestinal surgery. The nonsurgical group had a 13% false-positive rate.
This study shows that with rapid transit, significant glucose malabsorption is possible.

Because direct culture of small bowel contents is expensive, invasive and subject to contamination, physicians have relied on breath tests for diagnosis of SBBO or have empirically treated for SBBO. The discussion and related editorial (pg 209) explain that lactulose breath testing is not more reliable than glucose breath testing.

My take: For patients with prior GI surgery (who are at the highest risk for SBBO), breath testing may not be more reliable than flipping a coin. True positive results are more likely if hydrogen peak occurs within 60 minutes of glucose administration.

Related blog post:

Breath Testing for Bacterial Overgrowth | gutsandgrowth

Flamenco Beach, Culebra

Common Sense: Lifestyle Intervention in Gastroesophageal Reflux Disease

Posted on February 24, 2016 by gutsandgrowth

“Common sense is not so common” –Voltaire

A recent study (E Ness-Jensen et al. Clin Gastroenterol Hepatol 2016; 14: 175-82) reviewed the literature and identified 15 original studies which met inclusion criteria regarding lifestyle interventions in gastroesophageal reflux disease (GERD).

Key findings:

Weight loss lowered esophageal acid exposure in 2 RCTs: 5.6% –>3.7% and 8.0%–>5.5% and reduced reflux symptoms in prospective observational studies
Tobacco cessation reduced reflux symptoms in normal-weight individuals in a large prospective cohort study OR 5.67
Head-of-the-bed elevation decreased supine acid exposure from 21% to 15%.
Early evening meals decreased supine acid exposure by 5.2% point change.

My take: With the increasing incidence of obesity, these type of lifestyle modifications need to be implemented in our teenagers with GERD. For those who want to decrease use of medications, these interventions, if emphasized with conviction, are a good first step.

Clinically Useful Biomarkers for Irritable Bowel Syndrome?

Posted on February 9, 2016 by gutsandgrowth

A selected summary (Gastroenterol 2016; 150: 277-79) provides good insight into the subject of irritable bowel syndrome (IBS) biomarkers. This summary focuses on a study by Pimental M et al (PLoS One 2015; 10: e0126438).

“In this study, the authors validated 2 serum biomarkers, antibodies (Abs) to cytolethal distending toxin (CdtB) and vinculin, primarily focused on differentiating diarrhea-predominant IBS (IBS-D) from IBD. CdtB is a bacterial toxin commonly produced by Campylobacter jejuni, as well as Escherichia coli, Salmonella, and Shigella…presence of Cdtb seems to be positively associated with the likelihood of developing a postinfectious IBS phenotype…Vinculin is a host cell adhesion protein, with which anti-CdtB Abs are known to cross-react.”

The study recruited 2681 participants (18-65 years) from 180 centers; most (n=2375) had Rome III IBS-D.

Key findings:

Anti-CdtB levels were higher in IBS-D 2.53 (± 0.69) compared with Crohn’s disease 1.72 (± 0.81), ulcerative colitis 1.54 (± 0.68), celiac disease 2.23 (± 0.70), and healthy subjects 1.81 (± 0.73)
Anti-vinculin Abs were higher in IBS-D as well: 1.34 (± 0.85) compared with Crohn’s disease 1.05 (± 0.91),ulcerative colitis 0.96 (± 0.77), celiac disease 1.07 (± 0.98), and healthy subjects 0.81 (± 0.59)

“Using a cutoff point of >2.80 for anti-CdtB Abs, the sensitivity was 43.7%, specificity was 91.6%.” The positive likelihood ratio (LR) was 5.2 with this cutoff. For vinculin, a cutoff of >1.68, resulted in a sensitivity of 32.6%, specificity of 83.8%, and a positive LR of 2.0.

For comparison, the commentary notes that the Rome III criteria in one study had a sensitivity of 68.8%, specificity of 79.5%, and positive LR of 3.35.

“The current study is important for 2 reasons. First, that these 2 Abs were able to differentiate IBS-D from IBD and healthy controls, with a reasonable degree of accuracy, suggests that a substantial proportion of individuals with IBS may have an overt or subclinical postinfectious trigger, resulting in intestinal microbial disturbances…Second, the ability of these tests, if positive, to rule in IBS-D and rule out IBD is encouraging.”

But…

This study may not be representative of a typical primary care population with IBS
And,”as a rule of thumb, positive LRs of >10 are very useful in ruling in a disease…the complex, and likely multifactorial etiology of IBS may mean that a single biomarker that can diagnose IBS with the accuracy required for a test to be clinically useful is not possible.”

My take: I would like to see pediatric studies, perhaps this would help determine if a postinfectious mechanism is more common in children and adolescents.