Tag Archives: Crohn’s disease

Podcast on Vedolizumab Efficacy for Crohn’s Disease

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According to AGA Journals blog, one may need to wait up to 10 weeks to determine whether vedolizumab is effective for Crohn’s disease. Here’s the link: Vedolizumab for Crohn’s.

Here’s an excerpt: (re: Bruce Sands’ article in the September issue of Gastroenterology)

Sands et al. report that vedolizumab, an antibody against the integrin α4β7, is no more effective than placebo in inducing clinical remission at week 6 in patients with Crohn’s disease in whom previous treatment with tumor necrosis factor antagonists had failed.

However, at week 10, a higher proportion of patients given vedolizumab were in remission (26.6%) than of those given placebo (12.1%)… Adverse events were similar between groups.

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ImproveCareNow Video

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A recent (short ~2:30) ImproveCareNow (ICN) Video explains how ImproveCareNow is a forward-thinking network and how it has the potential to lead to better outcomes for children with inflammatory bowel disease.

If you are part of ICN, this video may help explain to your patients what ICN is all about.

Pattern of Skin Reactions to Anti-TNF Agents

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A recent study indicated a high rate of skin reactions to anti-TNFα in their pediatric inflammatory bowel disease (IBD) population (Inflamm Bowel Dis 2014; 20: 1309-15).

In a two-year prospective study, 84 children with IBD (64 with Crohn’s) who were receiving infliximab infusions were screened for skin changes and had labwork (blood tests and stool calprotectiin).

Key findings:

  • 40 (47.6%) had chronic skin reactions and half of these were considered severe. However, when looking at the “severe” lesions shown in Figure 2, one might question the characterization.
  • Ear lobes and scalp were affected most frequently with psoriasis-like manifestations, followed by eyelids, perioral and pubic areas, trunk, and extremities.
  • Skin reactions were more common in those with a low degree of intestinal inflammation based on calprotectin levels: 133 mg/g in those with skin changes compared with 589 in those without.
  • Seven patients (8.3% of entire cohort) discontinued therapy due to skin reaction.
  • Most patients responded well to topical potent corticosteroids.

Take-home message: In this prospectively-followed cohort, there was a surprisingly high rate of skin reactions.  In patients receiving anti-TNFα therapy, it is a good idea to look closely at their ears and scalp.

Related blog post:

TNF Antagonists and Psoriasis | gutsandgrowth

Durability of Infliximab in Pediatric Crohn’s Disease

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Similar to a previous recent study (How Long Will Infliximab Work? | gutsandgrowth), another large retrospective review confirms that infliximab has sustained effectiveness in the majority of children with Crohn’s disease (CD) (Inflamm Bowel Dise 2014; 20: 1177-86).

This study examined a 195 patients with a median age of 13.9 years from the years 2000-2011. Key findings:

  • Based on physician global assessment and pediatric Crohn’s activity index ≤10, 81% experienced a complete response.  Only 40 patients had endoscopic reassessment.  Among the 22 of these patients considered to be in a complete response, 16 (73%) had complete mucosal healing.
  • Despite optimization (based on clinical symptoms) in 35%, complete responders experienced a loss of response at a rate of 2% to 6% per year over 5 years.
  • In this cohort, combination therapy with at least 30 weeks of immunomodulator therapy improved durability of response.  Since 2006, the authors indicate that “our preference has been to use concomitant methotrexant rather than thiopurines” in boys.
  • Infliximab was well-tolerated.  However, severe infusion reactions were noted in 5% at some time point, 8% had psoratiform skin lesions, and 24% had elevated ALT.
  • Clinical response to infliximab was associated with enhanced linear growth.

Take-home message (from the authors): “the clinical response and growth data presented argue in favor of early treatment.”

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Early Results of FMT for IBD -Any Efficacy?

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As more data emerges on fecal microbiota transplantation (FMT) for inflammatory bowel disease in well-designed trials, it is not clear if FMT will be effective.  A summary of some recent abstracts is available at this link to Gastroenterology and Endoscopy News: Fecal Transplants for IBD Show Mixed Results in Trials

One trial with 53 patients with mild to moderate UC (27 randomized to FMT, 26 to placebo) once weekly for six weeks showed similar results in both groups with 7 FMT patients and 8 placebo recipients experiencing improvement of at least 30% in their Mayo scores.  Dr. Lawrence Brandt said, “It may be that we need to look at the patient’s unique bacterial composition and determine which organisms need to be replaced and formulate FMT accordingly.”

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Why Adding Vitamin D May Not Help IBD

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Despite all of the accolades that vitamin D has received, the fact that low vitamin D is associated with worse outcomes, in a number of disease states, does not prove causality. A recent article indicates that vitamin D is likely more of a marker of disease activity than a mediator of disease activity in inflammatory bowel disease (IBD), and specifically Crohn’s disease (CD) (Inflamm Bowel Dis 2014; 20: 856-60).

Background: Binding sites for the vitamin D receptor (VDR) have been “identified in genes associated with CD, and vitamin D has been shown to enhance the production of interleukin-10 (IL-10) and induction of regulatory T-cells.”

Design:The authors prospectively collected samples of 37 CD patients; the mean age in those with active disease (n=20) was 34 years and it was 30 years in those with inactive disease. In 8 patients with active disease, vitamin D levels were measured at the time of active inflammation (day 0) and at 14 days after receiving infliximab (day 14).

  • Key finding in these 8 patients: Vitamin D (25-OH) was 23 ng/mL on day 0 and 40 ng/mL 2 weeks later.  Only 1 of these 8 patients was taking a vitamin D supplement.
  • Key finding in the entire cohort: in the active disease group mean vitamin D level was 27 ng/mL compared with 38 ng/mL in those in remission (P=0.02).

Take-home point: There is an inverse relationship between vitamin D levels and disease activity.  However, the early increases in vitamin D levels with clinical response to anti-TNF therapy suggests that a major mechanism of vitamin D deficiency is related to the burden of systemic inflammation.  Hence, repeat testing when patients are in remission may obviate the need for vitamin D supplementation in many patients.

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Beauty is More Than Skin Deep

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A recent article discusses how a British model is an inspiration.  “Bethany Townsend made a bold move posting photos of herself in a bikini with colostomy bags on full display….Millions of people have seen her picture on the Crohn’s and Colitis UK page.”

If you want, take a look; here’s the link: British bikini model 

More Data on Early-Onset Pediatric Inflammatory Bowel Disease

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In 2009, a large prospective database involving Italian Pediatric Gastroenterologists was established.  A recent study describes the classification (Paris) and phenotype of early-onset pediatric inflammatory bowel disease (EO-IBD) (Inflamm Bowel Dis 2014; 20: 597-605).

In 506 consecutive patients, 224 had Crohn’s disease (CD), 245 ulcerative colitis (UC) and 37 IBD-unclassified.

Key findings:

  • 11% were aged 0-5 years, 39% 6-11 years, 50% were 12-18 years.
  • UC was more frequently diagnosed in 0-11 years of age whereas as CD was more common in 12-18 years.
  • EO-Crohn’s showed more frequent isolated colonic disease
  • EO-UC noted 62% with pancolitis compared with 38% in 6-11 years and 31% in 12-18 year group

Take-home message: The authors conclude that “EO-IBD exhibits an extensive phenotype and benefit from aggressive treatment strategies, although surgical risk is similar to later-onset disease. A family history for IBD is not common in EO disease.”

New Biomarker for Crohn’s Disease (Plus Two)

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A recent study identifies a new biomarker for Crohn’s disease (CD) (Inflamm Bowel Dis 2014; 20: 1037-48).

The authors examined a cohort of 208 newly diagnosed pediatric CD and 43 non-IBD controls for ileal/rectal expression of FcγRIA mRNA.  In addition, in a smaller cohort of 26 newly diagnosed CD patients, 83 established CD patients and 30 non-IBD controls the authors measured peripheral blood polymorphonuclear neutrophil (PMN) CD64 index.

Key findings:

  • Ileal FcγRIA mRNA expression was significantly elevated in CD compared with non-IBD controls
  • PMN CD64 was significantly elevated in CD compared with non-IBD controls and correlated with mucosal injury as measured by the simple endoscopic score for CD.
  • Patients in clinical remission with a PMN CD64 <1 had a high rate of sustained remission (95%) whereas only 56% had sustained remission if PMN CD64 was >1.

Take-home point: This study shows in pediatrics, as in adults IBD patients, that PMN CD64 index is associated with mucosal inflammation; high levels are associated with clinical relapse.  Serum biomarkers are likely to complement stool biomarkers like fecal calprotectin.

One other point the authors make: “studies have found that 57% to 59% of CD have concurrent IBS.”  Thus, there is a need for biomarkers to distinguish whether patients with clinical symptoms are experiencing an inflammatory relapse.

Related blog post: Calprotectin: Part of diagnostic algorithm for IBD …

Two other studies in same issue:

“Alterations in the Intestinal Microbiome (Dysbiosis) as a Predictor of Relapse After Infliximab Withdrawal in Crohn’s disease” pages 978-86.  N=33 CD patients. Key finding: “CD-associated dysbiosis, characterized by a decrease in Firmicutes, correlates with the time-to-relapse after infliximab withdrawal.”

“Tissue Studies in Screened First-degree Relatives Reveal a Distinct Crohn’s Disease Phenotype” pages 1049-56. N=38 asymptomatic relatives. Key finding: based on histologic scoring 61% were normal, 26% had minor lesions, and 13% had evidence of active disease. This study indicates that screening relatives may identify a subset with early biologic disease.

What I Didn’t Know About Vitamin B12 and Crohn’s Disease

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This month I learned from a recent publication (Inflamm Bowel Dis 2014; 20: 1120-23) that Crohn’s disease without ileal resection does not seem to increase the risk of Vitamin B12 (cobalamin) deficiency.  To reach this conclusion, the authors did an extensive literature search and identified 42 relevant articles with 3732 IBD patients.

Key findings:

  • Ileal resections >30 cm were associated with B12 deficiency.
  • Resections <20 cm were not associated with B12 deficiency; whereas the findings were inconsistent when resections were 20-30 cm.

Take home message:  Crohn’s disease, regardless of disease location, did not increase the risk of B12 deficiency in the absence of ileal resections >20 cm.

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