The AGA has made several recommendations regarding biosimilars –#2 and #6 are particularly of interest to pediatric gastroenterologists. More on this topic will follow tomorrow.
Link: AGA Makes Six Recommendations to FDA on Interchangeable Biosimilars
Related blog posts:
In 2014, an influential study by Sandborn et al (Clin Gastroenterol Hepatol 2014; 12: 978-85) described the importance of mucosal healing in a strategy termed “treating to target.” The main findings (reviewed in a previous post Treating to Target) were the following:
Now, my colleagues at Emory have published a single-center experience on mucosal healing (MH) (SL Santha, PR Shankar, A Pan, B Schoen, S Kugasthasan, CG Sauer. Inflamm Bowel Dis 2017; 23: 1447-53). While this study has the typical limitations of a retrospective study, it makes several useful points. It takes a little extra effort to interpret their findings as they describe their results based only on the 104 patients with clinical remission rather than based on the total of 182 patients who had at least two colonoscopies. 78 were excluded due to ‘acute GI symptoms.’
Of the 104 patients considered to be in clinical remission, 76 had Crohn’s disease and 28 patients had ulcerative colitis.
Key findings:
The discrepancy in MH rates based on physician assessment, endoscopic scores, and histologic healing is explained. Generally, MH based on physician assessment would include normal and those with very mild mucosal disease. “For CD, this included small and rare aphthous ulcers, and for UC, this included mild Mayo 1 erythema in only one segment of bowel.”
Questions about the approach to ‘treating to target:’
As in adult patients, this study does show the need for objective markers in pediatric inflammatory bowel disease; 30% of patients who were considered to be in clinical remission had active disease with further investigation. This finding has implications for ImproveCareNow which uses physician global assessment in tracking remission rates for pediatric IBD.
In their discussion, the authors state that “changes in medical therapy can increase the MH rate to nearly 80%, which could be even higher with additional changes in those who did not demonstrate MH on a second endoscopy.” This sentence needs to be carefully interpreted. The authors were able to show MH based on physician assessment in 82 of 104 patients (79%) who were in clinical remission. This rate would be MUCH lower if the entire cohort of 182 were included, possibly no greater than 50%.
The authors conclude with “endoscopy should be considered in pediatric patients with IBD in clinical remission to identify those without MH who may require medication escalation despite the absence of clinical symptoms.”
My take: I agree with the authors that objective markers of clinical remission need to be obtained to assess the effectiveness of therapy. However, I am not convinced that endoscopy is needed in every patient who is doing well on therapy; other biomarkers and imaging may be more beneficial.
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Sign at Pisgah Fish Camp Restaurant: “On this site in 1897 nothing happened.”
In an industry-sponsored study (TD Walters et al. Inflamm Bowel Dis 2017; 23: 967-75), adalimumab (ADA) was shown to be effective agent in reversing growth failure associated with pediatric Crohn’s disease (CD).
Background: About one-third of children and adolescents with CD suffer from growth failure and delayed puberty. Several prior studies have shown that anti-TNF therapy can improve height velocity and that early treatment with anti-TNF therapy (≤3 months after diagnosis) leads to greater improvement in height obtained, if initiated before puberty or early into puberty. This study examines the effectiveness of ADA in children from the IMAgINE 1 trial.
The authors identified 73 participants with growth delays (& adequate data) along with 27 participants with no growth delays.
Key findings:
My take: In moderate to severe CD, anti-TNF agents have been demonstrated to reverse growth failure; though, this is expected to occur only in patients with clinical response. To my knowledge, no other CD medical therapies have been proven to reverse growth failure (surgical treatment can improve growth as well).
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Quiet Spot on U Chicago Campus
A recent study (S Naviglio et al. Inflamm Bowel Dis 2017; 23: 986-90) confirms that there is a low rate of ocular disease in pediatric inflammatory bowel disease (IBD); in this cohort, half had Crohn’s disease (CD) and half had ulcerative colitis.
In this single center study, 94 children with a median age of 13.4 yrs were offered ophthalmologic examination (2014-2016). None of these patients reported ocular symptoms. The authors assert that 70% had intestinal remission, though 64% had elevated fecal calprotectin levels (>100 mg/kg). Key finding: One patient (1.06%) had ocular finding of uveitis (previously diagnosed prior to study)
The authors indicate that hepatobiliary manifestations, present in 9, were the most common extraintestinal IBD manifestation (EIM). Arthropathy occurred in 8, cutaneous manifestations occurred in 6 and ‘metastatic’ CD occurred in 4.
My take: Ocular disease is an infrequent EIM in pediatric patients with IBD.
Related article: K Hata et al. Inflamm Bowel Dis 2017; 23: 1019-24. This article found that patients with EIMs were more likely to have chronic pouchitis after colectomy for ulcerative colitis. Overall, chronic pouchitis developed in 3.3%, 7.6% and 16.6% at 2, 5, and 10 years respectively. Key finding: preoperative EIM yielded a HR of 4.52.
Briefly noted: C Ma et al. Inflamm Bowel Dis 2017; 23: 833-9. This retrospective study examined the response to ustekinumab in 104 patients with Crohn’s disease. All patients had achieved a steroid-free ustekinumab induction. 92.3% had failed anti-TNFα therapy.
Key findings:
C Ma et al. Inflamm Bowel Dis 2017; 23: 833-9. This retrospective study examined the ongoing response to ustekinumab in 104 patients with Crohn’s disease. All patients had achieved a steroid-free ustekinumab induction. 92.3% had failed anti-TNFα therapy.Key findings:
Related blog post: Closer Look at Ustekinumab Data
O Truffinet et al JPGN 2017; 64: 721-25. This small study with 8 children with Crohn’s disease examined the use of tacrolimus. Six of eight showed a response to tacrolimus (target 8-15) with a clinical response at 2 months and 4 of 8 in clinical remission. Adverse effects were common, occurring in 6 of 8. These included renal dysfunction, diabetes, paresthesia and tremor.
J Adler et al. JPGN 2017; 64: e117-e124. Using ImproveCareNow registry, the authors identified perianal disease (PD) in 1399 of 6679 cases (21%). PD was more common in blacks than whites: 26% vs. 20%. Overall, this study showed a higher rate of PD than previously recognized.
J Amil-Dias et al JPGN 2017; 64: 818-35. This is an ESPGHAN IBD Porto Group guideline for surgical Crohn’s disease management in children. There are 25 graded statements. Here are a few:
Related blog post:
Musee d’Orsay
A recent study (A Assa et al. Inflamm Bowel Dis 2017; 23: 791-97) indicates that after surgery, anti-TNFα treatment is worth another try.
In this retrospective study with 53 children, 18 had “pharmacodynamic failure” with anti-TNFα medications (PK group) and 35 were controls. “Phamacocynamic failure is characterized by either a lack of improvement of CD symptoms or loss of response after initial improvement in the setting of adequate serum drug levels without ADAs” [antidrug antibodies].
Key findings:
The authors propose an explanation: “A plausible explanation for this finding is that in severely inflamed tissue with high inflammatory burden, local high levels of TNFα serves as a sink for anti-TNFα antibodies and that tissue injury and local hypoxia might further limit drug penetrance to its target.”
My take: This information is useful. Many patients who have surgery may respond to anti-TNFα therapy subsequently. The unanswered question: Could more frequent dosing of anti-TNFα therapy have averted surgery in some patients by overcoming areas of intense disease?
Another website with a few useful resources:
Note -therapeutic drug monitoring may be more useful in children due to their changing size.
Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician. This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.
Summary of recent article (Link to full study: Benchimol EI, et al. Am J Gastroenterol. 2017;doi:10.1038/ajg.2017.97) by Healio Gastroenterology: IBD incidence rapidly increasing in young Canadian children
An excerpt:
To evaluate the recent incidence, prevalence and trends in childhood-onset IBD in Canada, Benchimol and colleagues used health administrative data from five provinces to identify children aged younger than 16 years who were diagnosed with IBD between 1999 and 2010. During this period, 3,462 children were diagnosed with Crohn’s disease, 1,382 with ulcerative colitis and 279 with unclassifiable IBD, for an overall IBD incidence of 9.68 (95% CI, 9.11-10.25) per 100,000 children.
Throughout the study period, the annual percentage change in overall IBD incidence remained statistically stable, increasing by just 2.06% per year, but the incidence increased significantly among children aged younger than 5 years, rising by 7.19% per year.
Further, the annual percentage change in the prevalence of IBD increased significantly throughout the study period (4.56%), and at the end of the study period IBD prevalence was 38.25 (95% CI, 35.78-40.73) per 100,000 children.
The investigators noted their findings confirmed the predominant form of pediatric-onset IBD was Crohn’s disease, and that more boys were affected than girls.
My take: While Canada has high prevalence of IBD, I expect that there will be similar trends in epidemiology in multiple regions in young children. When one looks at the increases in IBD prevalence over the last 100 years (see previous post) and the emergence of IBD in non-Western countries, it is quite alarming.
Also, last week a blog post discussed hepatic problems associated with IBD (Liver problems with IBD): here is full article text link: Hepatic Issues and Complications Associated with IBD
Related blog posts:
A recent review (Full text: LJ Saubermann et al. JPGN 2017; 64: 639-52) discusses the hepatic issues and complications associated with inflammatory bowel disease.
Key topics:
Many of these topics have been discussed previously on this blog. A couple of pointers in this review:
PSC:
AIH:
ASC:
HAV/HBV Immunization:
Methotrexate (MTX):
My take: This article is a good starting point for liver-related issues in IBD. For concerns regarding medications, the NIH livertox website is more useful and much more comprehensive.
Related blog entries:
DILI:
PSC:
AIH:
gutsandgrowth 