Sticky Paediatric IBD - Articles and Research

Update on nutritional status, body composition and growth in paediatric inflammatory bowel disease.

CONCLUSION
Nutritional status, as indicated by compromised body composition (that is, reduced lean mass), is present in children with IBD and persists over time, irrespective of treatment. Further, alterations in body composition are expressed differently between boys and girls, and in response to treatment. Reports suggest girls present with wasting which morphs into cachexia with treatment. In contrast, boys present with cachexia, with resolution of lean mass with treatment, and excess of fat mass. It must be noted that literature in this area is relatively limited, and more studies are needed, particularly addressing responses to treatment.

As with compromised nutritional status, growth deficits are reported in children with IBD. Data are promising with respect to improvements in linear growth as a result of treatment with biologics, however, it is clear that further research is necessary in this area as the majority of studies conducted are retrospective in nature and subject numbers are small. Key features associated with improvements in growth appear to be successful clinical response to treatment, patients in early stages of puberty, thereby allowing a greater window of opportunity for growth potential, and the presence of growth failure at the onset of treatment, again allowing for greater growth potential. An area that is lacking for evidence is the impact of biologics on body composition, and more data are warranted in this area.
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Full Article:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3964391/
 
Optimizing 6-mercaptopurine and azathioprine therapy in the management of inflammatory bowel disease

Abstract

The thiopurine drugs, 6-mercaptopurine (6-MP) and azathioprine, are efficacious in the arsenal of inflammatory bowel disease (IBD) therapy.

Previous reports indicate that 6-thioguanine nucleotide (6-TGN) levels correlate with therapeutic efficacy, whereas high 6-methylmercaptopurine (6-MMP) levels are associated with hepatotoxicity and myelotoxicity.

Due to their complex metabolism, there is wide individual variation in patient response therein, both in achieving therapeutic drug levels as well as in developing adverse reactions. Several strategies to optimize 6-TGN while minimizing 6-MMP levels have been adopted to administer the thiopurine class of drugs to patients who otherwise would not tolerate these drugs due to side-effects.

In this report, we will review different approaches to administer the thiopurine medications, including the administration of 6-mercaptopurine in those unsuccessfully treated with azathioprine; co-administration of thiopurine with allopurinol; co-administration of thiopurine with anti-tumor necrosis factor α; 6-TGN administration; desensitization trials; and split dosing of 6-MP.
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Full Article:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3208360/

I have posted this in the research forum and also added it to the front page here. I did so as there is interesting discussion contained within as stated in the last paragraph of the abstract above.
 
This article/radio report Malnutrition and the Microbiome talks about a child's gut microbiome, and how that can lead to malnutrition. Although they do not talk about "IBD", per se, it seems to me there might be a common solution: to provide the "right" microbiome through introduction of a "good" microbiome (i.e. Fecal Microbiota Transplant).

One of the tragedies of malnutrition in children is that the problems don't end when the hunger stops. A new study has shown that the microbial communities in the gut of children who experience malnutrition seem to be compromised over the long term, and don't recover even after therapy and a return to a normal diet.
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This paper Effect of a Probiotic Preparation (VSL#3) on Induction and Maintenance of remission in Children With Ulcerative Colitis shows that probiotics can be much better than placebo. My thought, though, is that it would be very expensive.

That study that indicated that VSL#3 was effective at inducing remission. After one year, 3 of the 14 VSL#3 patients relapsed and 11 of the 15 placebo patients relapsed. VSL#3 is a mix of a bunch of probiotics, and the paper says it doesn't know which of them is responsible for the improvement. The study had the kids stay on the probiotic for the length of the study (one year). Depending on the weight of the patient, it might cost $1,000 (45 lbs) to $4,000 (140 lbs) to pay for this probiotic in a year. But in another study, they only took the probiotic for 12 weeks, so maybe the dose could be reduced instead of the full dose 'forever'.

This is what the VSL3 web site says about how long to keep on the probiotic:
In general, VSL#3 takes up to 1 week to become established in the gut. A study conducted with VSL#3 confirms that maximum bacterial colonization of the gut occurs within 20 days. This high level of colonization remains stable throughout consumption. After daily intake is interrupted, the strains in VSL#3 will survive in the gut for up to 3 weeks.
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Miele E, Pascarella F, Giannetti E, et al. Effect of a probiotic
preparation (VSL#3) on induction and maintenance of remission
in children with ulcerative colitis. Am J Gastroenterol. 2009;104:
437–443.
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DS has been on vsl#3 DS( prescription ) for over a year.
His GI had him take a higher dose for a month .
He now takes a lower dose.
 
This has been discussed here before most kids here do not "fit" that model or the one about breastmilk or junk food as the cause .
Good theories on paper .


Fwiw my non Ibd kid had way more antibiotics
Ibd kiddo has super immune system on all levels and hardly ever needed an antibiotics but showed signs of crohn's since birth .
 
my little penguin said:
This has been discussed here before most kids here do not "fit" that model or the one about breastmilk or junk food as the cause .
Good theories on paper .
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That quote was not supposed to bring in any ideas about breast milk or junk food. The idea is that the child's early microbiome was artificially altered by antibiotics and that was undeniably related to IBD later in this large population. Not saying anything about causation, only correlation.

Fwiw my non Ibd kid had way more antibiotics
Ibd kiddo has super immune system on all levels and hardly ever needed an antibiotics but showed signs of crohn's since birth .
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That's an unexpected n=2! Not to get too personal, but interesting facts in your case would include whether the mother had a narrowed microbiome at the time of delivery (pre-delivey antibiotics?) and if the mother was able to colonize the baby (vaginal vs C section) with a robust microbiome.
 
I have mulled over many theories and whilst I had one child diagnosed I entertained some of them as a possibility. Then my other child was diagnosed and the disease mirrored exactly that of the sibling in location, type and severity and genetics loomed large on the horizon for me and it has stayed there. That is not to say that there aren’t other influences but where I once gave them equal standing I now give them scant regard.

Of the three main theories that circulate around childhood my two do not fit any of them:

1. Antibiotics. My daughter was diagnosed at 14 and my son at 17, neither had been prescribed antibiotics from the time they were born until diagnosed. I too had not had antibiotics for many, many years prior to my pregnancies.

2. Birth. Both were normal vaginal deliveries.

3. Breastfed. Both were breastfed. My daughter for 12 months and my son for 18 months.

Dusty. :)
 
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I agonized for quite awhile after dx about all the little things I could've/should've maybe done differently to prevent IBD in my son. sigh!

I heard a fantastic talk a couple years back about causes. It was along the lines that genetics prime the system (make one susceptible) and inflammation starts with an environmental trigger (whether bacterial/viral infections, antibiotics use, diet, air pollution, etc). I think one's genes determine which organ is affected by the runaway immune system too, whether gut/joints/brain/skin, etc
 
First published study that I am aware of that followed kids on remicade for 5 years. Found linear growth catch up to normal by year 3 in Tanner stage 1/2 patients who started remicade within 18 months of diagnosis. Found sustained response improved by simultaneous use of immunomodulator for >= 30 months. Study authors from Toronto, Canada


Infliximab Maintains Durable Response and Facilitates Catch-up Growth in Luminal Pediatric Crohn's Disease.

http://www.ncbi.nlm.nih.gov/pubmed/24865777

CONCLUSIONS:

These data demonstrate sustained effectiveness of infliximab in children and adolescents with luminal CD. Durability of response is increased by concomitant immunomodulation. Clinical response is associated with enhanced linear growth, particularly when therapy is initiated early.
 
Hi everyone, as I'm a newbie I'm unable to link, so please search the title in order to read the entire article. Love to all you parents and caregivers of babies with dis-ease. ♥

PS. I also posted this in the Parents of Kids with IBD thread.

Crohn’s Disease Linked To Imbalance In Gut Microbiota
By Susan Scutti | Mar 12, 2014 12:57 PM EDT

A Study of Newly Diagnosed Children

To conduct the current research, a team of scientists analyzed data from the RISK Stratification Study, which was designed to investigate the factors involved in newly diagnosed pediatric cases of Crohn's disease or other inflammatory bowel diseases. At 28 institutions across the U.S. and Canada, intestinal tissue samples were taken from 447 children with a clear diagnosis of Crohn's and 221 control participants with non-inflammatory gastrointestinal conditions. The researchers also analyzed samples from an additional group of about 800 participants in previous studies, for a total of more than 1,500 individuals.

The researchers identified a proportional increase in inflammatory bacteria and a decrease in non-inflammatory, beneficial bacteria in Crohn's patients when compared with participants without the disease. (Specifically, they found an increase of Enterobacteriaceae, Pasteurellaceae, Veillonellaceae, and Fusobacteriaceae, and a decrease of Erysipelotrichales, Bacteroidales, and Clostridiales).

This imbalance was even greater in patients whose symptoms were more severe. Plus, a comparison of patients who had taken antibiotics with those who had not indicated antibiotic use amplifies microbial imbalance.
 
Small study but sounds promising for those with children that have refractory IBD:

The use of sirolimus (rapamycin) in the management of refractory inflammatory bowel disease in children.

Abstract only…

Background
Management of refractory inflammatory bowel disease (IBD) in children is challenging and once response to conventional medical therapy deviates from the expected, options are often limited. Sirolimus is commonly used in post-transplantation management and is used sparsely as rescue therapy in refractory Crohn's disease. In the present study, we report the efficacy of sirolimus as an adjuvant immunosuppressive therapy in a retrospective case review of a selected group of IBD children who were refractory to the conventional treatments.

Methods
Medical records of children with refractory IBD unresponsive to conventional therapy and started on sirolimus between 2006 and 2012 were retrospectively reviewed. Clinical response, through Pediatric Ulcerative Colitis Activity Index (PUCAI) and Pediatric Crohn's Disease Activity Index (PCDAI), as well as intestinal inflammation, through specific histological scores, was evaluated.

Results
The records of 14 patients were analyzed. Eleven of them had ulcerative colitis (UC) and 3 Crohn's disease (CD); mean age at diagnosis was 9.1 years (standard deviation 3.8). Of UC patients, 5 (45%) achieved clinical remission and 2 (18%) showed clinical response. All CD patients went into clinical remission. Mucosal healing was achieved by 5 children (45%) with UC and 2 (67%) with CD patients. One child with ulcerative colitis was weaned off adalimumab, while 2 children with CD were weaned off prednisolone and methotrexate successfully.

Conclusion
Our data provide evidence that sirolimus seems to be effective as rescue therapy in a subgroup of children with severe IBD refractory to conventional therapies by inducing both clinical remission and mucosal healing.

http://www.ecco-jccjournal.org/article/S1873-9946(14)00266-9/abstract
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Restarting infliximab for IBD after a drug holiday:

Not a paediatric study but an interesting article…

Restarting infliximab therapy after a drug holiday is safe and effective for patients with inflammatory bowel disease (IBD), according to a new study1 in Clinical Gastroenterology and Hepatology, the official clinical practice journal of the American Gastroenterological Association.

"Our findings suggest that starting infliximab after a history of prior therapy can be very beneficial to patients," said lead study author Filip Baert, MD, PhD, from the department of gastroenterology, University Hospitals Leuven in Belgium. "Most striking, response to infliximab can be regained in a subset of patients who previously had lost response to the treatment and failed several other treatments thereafter."

Researchers conducted a retrospective single-center study to evaluate the efficacy of restarting infliximab in inflammatory bowel disease patients, both those suffering from Crohn's disease and ulcerative colitis. The average duration of infliximab holiday was 15 months.

Patients who were in remission at the time infliximab was discontinued were the best candidates, with a 78 percent response rate at one year. In patients with a previous loss of response or an infusion reaction, the strategy was effective in 45 percent of patients at one year; while less than the other group, this may be enough in cases where the patient has failed other treatment options.

This study shows that starting pharmacologic monitoring (i.e., checking levels of medicine in the blood and antibodies to infliximab) early after restarting infliximab can guide physicians to predict the long-term efficacy and safety of restarting this treatment. In clinical practice, these tests are not always readily available; however, measuring drug levels and antibodies early after restarting infliximab is very valuable and allows early optimization.

How safe is the strategy? Of the 128 patients re-treated, 7 had severe infusion reactions, generally during the second or third induction dose. Unfortunately, premedication did not protect against all infusion reactions, but simultaneous immunomodulators did. Therefore, immunomodulator therapy should be strongly considered in these patients.

Patients may initially stop infliximab therapy due to loss of response, and, despite the current recommendations, patients sometimes will discontinue therapy for various reasons, including durable remission, pregnancy, safety or financial concerns.

"Clinicians understandably have been reluctant to rechallenge patients with infliximab given the fear of immediate or delayed hypersensitivity reactions with dose interruptions. This study provides the important message that restarting infliximab after a drug holiday is feasible," added Dr. Baert.

Infliximab was the first anti-tumor necrosis factor (TNF) biologic for Crohn's disease and still is used frequently for its efficacy in both Crohn's and ulcerative colitis. Studies have shown that loss of response to infliximab is about 13 percent per patient-year of treatment.

http://www.medicalnewstoday.com/releases/282165.php
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Abstract Only:

Health-Related Quality of Life in Youth with Crohn's Disease: The Role of Disease Activity and Parenting Stress.

OBJECTIVES:
Health-related quality of life (HRQOL) is an important, but understudied construct in pediatric IBD. Family-level predictors of HRQOL have been understudied as are the mechanisms through which disease activity impacts HRQOL. The current study examines the relationship between a family-level factor (parenting stress) and HRQOL in youth with Crohn's disease. Parenting stress is examined as a mechanism through with disease activity impacts HRQOL.

METHODS:
99 adolescents with Crohn's disease and their parents were recruited across three sites. Adolescents completed the IMPACT-III (IBD-specific HRQOL). Parents completed the Pediatric Inventory for Parents, a measure of medically-related parenting stress that assesses: 1) stress due to the occurrence of medical stressors and 2) stress due to the perceived difficulty of stressors. Disease activity was obtained from medical records.

RESULTS:
Parenting stress due to the occurrence of medical stressors partially mediated the disease severity-HRQOL relationship, reducing the relationship between these variables from 49.67% to 31.58% (B = -.56, p < .0001). Boot strapping analysis confirmed that the indirect effect of disease severity on HQROL via parenting stress significantly differed from zero. Parenting stress due to the perceived difficulty of medical stressors partially mediated the disease severity-HRQOL relationship, reducing the relationship from 49.67% to 30.29% (B = -.55, p < .0001). The indirect effect was confirmed via bootstrapping procedures.

CONCLUSIONS:
As disease severity increased, parenting stress also increased, and adolescent HRQOL decreased. Parenting stress should be considered and assessed for along with medical factors as part of a comprehensive approach to improving HRQOL in adolescents with Crohn's disease.

http://www.ncbi.nlm.nih.gov/pubmed/25564807
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The course of anaemia in children and adolescents with Crohn’s disease included in a prospective registry

Abstract Only:

Aim
The aim of this study is to determine the prevalence and evolution of anaemia in prospectively followed children and adolescents diagnosed with Crohn’s disease (CD).

Methods
The BELCRO registry (inclusion May 2008–April 2010), describing current clinical treatment practice of children diagnosed with CD, provided data on age, height, body mass index (BMI), paediatric Crohn’s disease activity index (PCDAI), therapy and haemoglobin (Hb) at diagnosis 12 and 24 months follow-up. Anaemia was defined as Hb < −2 sd, while severe anaemia was defined as Hb < −4 sd. Patients were classified as child ≤13 and adolescent >13 years of age.

Result
Ninety-six were included, 13 dropped out due to insufficient Hb data (37 females/46 males; median age 13.3 years, range 2.2–17.8 years). At diagnosis, the median Hb sd was −2.66 (−8.4; 1.07) and was correlated with the PCDAI (p = 0.013). At diagnosis, 51/83 (61 %) were anaemic and all had active disease. Hb z-score significantly improved (p < 0.0001) but 26/68 (38 %) remained anaemic at 12 months and 29/76 (38 %) at 24 months of follow-up. The correlation to the PCDAI disappeared. At 24 months, children were more likely to be anaemic. There was no difference in iron dose nor duration of iron supplements between children and adolescents. Iron treatment was more readily given to patients presenting with anaemia. Hb did not differ between patients with (n = 28) or without iron supplements. Half of the patients with persisting anaemia were given iron supplements, of which, only three were given intravenously.

Conclusion
Anaemia remains an important extra-intestinal manifestation of CD in children. Physicians, lacking optimal treatment strategies, undertreat their patients.

http://link.springer.com/article/10.1007/s00384-014-2042-4
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Copied to Parent’s Forum.
 
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SICUS, MRE, CE effective for imaging small bowel in pediatric IBD

Small-intestine contrast ultrasonography, magnetic resonance enterography and capsule endoscopy were all found to be effective options for imaging the small bowel to diagnose pediatric inflammatory bowel disease, according to recent study data.

Aiming to evaluate the performance of these three methods in assessing pediatric Crohn’s disease and detecting active lesions in specific segments of the small bowel, researchers performed a prospective, masked comparison study involving 25 children with known or suspected CD. All patients underwent ileocolonoscopy, magnetic resonance enterography (MRE; 1.5-Tesla whole-body MRI, Siemens Medical Solutions), small-intestine contrast ultrasonography (SICUS; Aplio XG, Toshiba Medical Systems) and capsule endoscopy (CE; PillCam, Given Imaging) during a 1-week period from April 2012 to April 2013. They compared the results of each method with a consensus reference standard for the upper small bowel and with ileocolonoscopy for the terminal ileum.

In the jejunum, SICUS and CE both had 92% (95% CI, 61-100) sensitivity, which was higher than MRE (75%; 95% CI, 43-94) but not significantly, whereas the specificity of MRE (94%; 95% CI, 73-100) was significantly higher compared with CE (61%; 95% CI, 36-83). In the proximal and mid-ileum, MRE and CE both had 100% sensitivity (95% CI, 56-100 with MRE; 95% CI, 48-100 with CE) vs. 80% (95% CI, 43-99) with SICUS, but CE had 74% specificity (95% CI, 49-90) compared with 92% (95% CI, 73-99) for both SICUS and MRE. At the terminal ileum, SICUS and MRE both had 94% sensitivity (95% CI, 64-100 with SICUS; 95% CI, 71-100 with MRE) vs. 81% (95% CI, 54-96) with CE, whereas CE had 90% (95% CI, 55-100) specificity vs. 80% (95% CI, 51-96) with MRE and 79% (95% CI, 49-95) with SICUS.

“Our study supports the use of radiation-free and well-tolerated imaging modalities as a means of first-line investigation in children with suspected or already diagnosed CD,” the researchers concluded. “The combination of SICUS and [C-reactive protein], given its high sensitivity, specificity, low-cost, and non-invasiveness, could be suggested as a first-line diagnostic approach in suspected [small-bowel] CD. MRE and CE can be subsequently used in patients with inconclusive workups, based on the local expertise and availability.” – by Adam Leitenberger

http://www.healio.com/gastroenterology/inflammatory-bowel-disease/news/online/%7B13e1b706-0118-4a52-a1a7-086b0dce242d%7D/sicus-mre-ce-effective-for-imaging-small-bowel-in-pediatric-ibd
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Occult Blood and Perianal Exam: Value Added in Pediatric Inflammatory Bowel Disease Screening.

Abstract Only:

Objective:
Pediatric inflammatory bowel disease (IBD) often presents insidiously and standard blood tests are normal in 20% of patients. We hypothesize that fecal occult blood testing (FOBT) and the perianal examination in addition to blood tests provide important information during the screening process for IBD. The goal of this study was to measure the diagnostic value of adding FOBT and perianal examination to standard screening labs in evaluating children and adolescents for IBD.

Methods:
The medical records of consecutive patients undergoing ileocolonoscopy for IBD were reviewed. Laboratory test results, FOBT, and perianal examination prior to the decision to perform the ileocolonoscopy were recorded. Standard limits of laboratory tests were used. Multivariate logistic regression was performed on a discovery cohort and applied to an independent validation cohort.

Results:
The discovery cohort included 335 patients (85 IBD and 250 non-IBD). 61.2% had FOBT and perianal examination performed prior to the decision to perform the ileocolonoscopy. 119 patients had complete blood testing, FOBT, and perianal exam available for full analysis. The sensitivity of the lab testing was 80.5% for IBD and the sensitivity of FOBT with perianal examination was 65.9%. However, the combined sensitivity of lab testing and FOBT with perianal examination was 97.6%. The most predictive model included CRP, platelets and FOBT with perianal examination and was superior to the lab value-only model (P < 0.001) which was validated in a separate cohort.

Conclusions:
Perianal examination and FOBT improves sensitivity in screening children for IBD.

http://journals.lww.com/jpgn/Abstract/publishahead/Occult_Blood_and_Perianal_Exam___Value_Added_in.97997.aspx?utm_content=bufferc6dd4&utm_medium=social&utm_source=twitter.com&utm_campaign=buffer
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Urinary Tract Infection in Infancy Is a Risk Factor for Chronic Abdominal Pain in Childhood.

Abstract Only:

Objective:
Adverse early life events are key factors for development of functional gastrointestinal disorders (FGIDs). Urinary tract infection (UTI) is associated with chronic pelvic pain in adults, a finding that has been recapitulated in murine models, but the relation between UTI and chronic pelvic and abdominal pain has not been studied in children. We hypothesized that UTI in infancy increases the risk of FGIDs and chronic abdominal pain (CAP) in childhood.

Methods:
The present study included children, ages 4 to 18 years, with a single UTI in the first year of life and their siblings with no history of UTI. Parents completed the Questionnaire on Pediatric Gastrointestinal Symptoms–Rome III Version (QPGS-III) by telephone. Children meeting QPGS-III criteria for FGIDs but with pain less than once weekly were considered to have CAP.

Results:
A total of 57 patients with UTI and 58 sibling controls were identified. Mean age at UTI was 4.8 months, and mean time since UTI was 9.3 years. At the time of survey, mean age of patients was 9.7 years (5–16 years, 40% boys) and that of controls was 9.6 years (range 4–17 years, 57% boys). FGIDs were diagnosed in 6 of 57 (11%) patients, and 1 of 58 (2%) controls (P = 0.06). CAP was identified in 10 of 57 (18%) patients and 2 of 58 (3%) controls (P = 0.02). Predominant sex (female), infecting organism (E coli), and treatment (third-generation cephalosporin) were similar in patients with UTI with and without CAP.

Conclusions:
We show for the first time that UTI is associated with CAP in childhood. We speculate that pelvic organ sensory convergence explains our findings.

Source:
http://journals.lww.com/jpgn/pages/articleviewer.aspx?year=2015&issue=02000&article=00016&type=Abstract&utm_content=bufferc8705&utm_medium=social&utm_source=twitter.com&utm_campaign=buffer
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Thanks chickie! Hubby was driving again so I was sticking my nose in the phone and dang those screens are small!
 
'Biosimilars' for children with IBD need more research, ESPGHAN expert panel states.

Children with inflammatory bowel disease (IBD) who are doing well on specific biological medications should not be switched to recently approved "biosimilar" products, concludes an expert consensus statement of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN).
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http://www.medicalnewstoday.com/releases/296726.php
 
Researchers Discover Genetic Variants Linked to Very Early Onset IBD in Children

http://ibdnewstoday.com/2015/09/10/...tic-variants-linked-early-onset-ibd-children/

In the study, researchers assessed whether very early onset IBD patients had rare or new variants in genes known to be associated with primary immunodeficiency disorders and related pathways, which could, therefore, contribute to disease development.
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The study: Exome Sequencing Analysis Reveals Variants in Primary Immunodeficiency Genes in Patients With Very Early Onset Inflammatory Bowel Disease

http://www.gastrojournal.org/articl...t.org/pub_releases/2015-09/chop-ngf090315.php
 
For this study, the authors performed genetic analysis of 209 patients with very early onset IBD and identified five patients with rare loss-of-function missense mutations in NOX1 or DUOX2. Importantly, these mutations were associated with reduced production of reactive oxygen species (ROS) and defective host resistance to the bacterial pathogen Campylobacter jejuni.

http://www.gastro.org/news_items/20...that-cause-rare-cases-of-very-early-onset-ibd
 
Efficacy and Safety of Escalation of Adalimumab Therapy to Weekly Dosing in Pediatric Patients with Crohn's Disease

Abstract

Background: The efficacy of adalimumab in inducing and maintaining remission in children with moderately to severely active Crohn's disease was shown in the IMAgINE 1 trial (NCT00409682). As per protocol, nonresponders or patients experiencing flare(s) on every other week (EOW) maintenance dosing could escalate to weekly dosing; we aimed to determine the therapeutic benefits of weekly dose escalation in this subpopulation.

Methods: Week 52 remission and response rates were assessed in patients who escalated to weekly dosing from their previous EOW schedule, which was according to randomized treatment dose (higher dose [HD] adalimumab [≥40 kg, 40 mg EOW; <40 kg, 20 mg EOW] or lower dose [LD; ≥40 kg, 20 mg EOW; <40 kg, 10 mg EOW]). Adverse events were reported for patients remaining on EOW dosing and patients receiving weekly dosing.

Results: Escalation to weekly dosing occurred in 48/95 (50.5%) patients randomized to LD and 35/93 (37.6%) patients randomized to HD adalimumab (P = 0.076). Week 52 remission and response rates were 18.8% and 47.9% for patients receiving LD adalimumab weekly and 31.4% and 57.1% for patients receiving HD adalimumab weekly, respectively (LD versus HD, P = 0.19 for remission; P = 0.41 for response). Adverse event rates were similar for patients receiving EOW and weekly adalimumab.

Conclusions: Weekly adalimumab dosing was clinically beneficial for children with Crohn's disease who experienced nonresponse or flare on EOW dosing. No increased safety risks were observed with weekly dosing.
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Full Article:
http://journals.lww.com/ibdjournal/...nd_Safety_of_Escalation_of_Adalimumab.13.aspx
 
I lifted this from xeridea’s thread in the treatment section, thanks xeridea.

4D Pharma announced that they have initiated Phase 1 trial of Thetanix for Pediatric Crohn's Disease. Phase 1 trials are for figuring out the proper/safe dosing levels of a drug.

Here is an excerpt from the top-post for Thetanix, where it was referred to by its pre-clinical development name LBP-001:

Thetanix, comprised of Bacteroides thetaiotaomicron, an obligate anaerobe, is a major endosymbiont of the human gut. Bacteroides thetaiotaomicron is a major component of the adult intestine and has been used as a useful model for the study of human-bacterial symbiosis. Its metabolic function for humans is to degrade plant polysacharides, a very essential capability for the human gut. Additionally, it is very important during the postnatal transition between mother's milk and a diet heavily consisting of plant starches. It has been found to stimulate angiogenesis (growth of new blood vessels from pre-existing vessels) within the gut, due to a microbial signal via bacterial sensing Paneth cells. B. thetaiotaomicron benefits its host by providing sufficient absorptive ability for nutrients the microbe helps process. Another postnatal developmental process within the gut mediated by Bacteroides thetaiotaomicron is the formation of the intestinal mucosal barrier, which helps protect the host against pathogenic invasion via the regulation of the expression of species-specific protein antibiotics. The environment sensing regulatory apparatus present in B. thetaiotaomicron allows for adaptive food seeking, which stabilizes food webs, and subsequently leads to the longevity of communities.
 
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NOD2 induces autophagy to control AIEC bacteria infectiveness in intestinal epithelial cells

http://link.springer.com/article/10.1007/s00011-016-0964-8?view=classic

Abstract
Objective
The importance of autophagy in mechanisms underlying inflammation has been highlighted. Downstream effects of the bacterial sensor NOD2 include autophagy induction. Recently, a relationship between defects in autophagy and adherent/invasive Escherichia coli (AIEC) persistence has emerged. The present study aims at investigating the interplay between autophagy, NOD2 and AIEC bacteria and assessing the expression level of autophagic proteins in intestinal biopsies of pediatric patients with inflammatory bowel disease (IBD).

Methods
A human epithelial colorectal adenocarcinoma (Caco2) cell line stably over-expressing NOD2 was produced (Caco2NOD2). ATG16L1, LC3 and NOD2 levels were analysed in the Caco2 cell line and Caco2NOD2 after exposure to AIEC strains, by western blot and immunofluorescence. AIEC survival inside cells and TNFα, IL-8 and IL-1βmRNA expression were analysed by gentamicin protection assay and real time PCR. ATG16L1 and LC3 expression was analyzed in the inflamed ileum and colon of 28 patients with Crohn’s disease (CD), 14 with ulcerative colitis (UC) and 23 controls by western blot.

Results
AIEC infection increased ATG16L1 and LC3 in Caco2 cells. Exposure to AIEC strains increased LC3 and ATG16L1 in Caco2 overexpressing NOD2, more than in Caco2 wild type, while a decrease of AIEC survival rate and cytokine expression was observed in the same cell line. LC3 expression was increased in the inflamed colon of CD and UC children.

Conclusions
The NOD2-mediated autophagy induction is crucial to hold the intramucosal bacterial burden, especially towards AIEC, and to limit the resulting inflammatory response. Autophagy is active in inflamed colonic tissues of IBD pediatric patients.

*****
If anyone has access to the full text of this article, please send a message to me. Thanks a lot.
 
Descriptions of remission terms



Mucosal healing and deep remission: What does it mean?
Gerhard Rogler, Stephan Vavricka, Alain Schoepfer, and Peter L Lakatos
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Abstract
The use of specific terms under different meanings and varying definitions has always been a source of confusion in science. When we point our efforts towards an evidence based medicine for inflammatory bowel diseases (IBD) the same is true: Terms such as “mucosal healing” or “deep remission” as endpoints in clinical trials or treatment goals in daily patient care may contribute to misconceptions if meanings change over time or definitions are altered. It appears to be useful to first have a look at the development of terms and their definitions, to assess their intrinsic and context-independent problems and then to analyze the different relevance in present-day clinical studies and trials. The purpose of such an attempt would be to gain clearer insights into the true impact of the clinical findings behind the terms. It may also lead to a better defined use of those terms for future studies. The terms “mucosal healing” and “deep remission” have been introduced in recent years as new therapeutic targets in the treatment of IBD patients. Several clinical trials, cohort studies or inception cohorts provided data that the long term disease course is better, when mucosal healing is achieved. However, it is still unclear whether continued or increased therapeutic measures will aid or improve mucosal healing for patients in clinical remission. Clinical trials are under way to answer this question. Attention should be paid to clearly address what levels of IBD activity are looked at. In the present review article authors aim to summarize the current evidence available on mucosal healing and deep remission and try to highlight their value and position in the everyday decision making for gastroenterologists.

Full article:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3837253/
 
Jenn said:
Article on the microbiome.
https://www.nytimes.com/2018/04/06/opinion/sunday/germs-microbes-processed-foods.html
Click to expand...

''Christine McDonald, a scientist at the Cleveland Clinic, has discovered something very similar with the food thickener maltodextrin, which seems to both thin the mucus barrier in mice and nourish a strain of E. coli linked to Crohn’s disease, an inflammatory bowel disease. ''
Click to expand...

Paradoxically, elemental nutrition, which helps repair the mucus barrier against invasive E Coli, is made with maltodextrin (glucose syrup in Europe). I really don't have an answer to this, but what McDonald sees in vitro, is not what happens in vivo.

EN is made from maltodextrins, if you use EN you consume large amounts of maltodextrins, amounts you could never get from a normal diet. Yet EN seems to help people with crohn's disease.
 
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