Management of Pediatric Ulcerative Colitis -ESGHAN/ECCO Recommendations

Two complementary articles provide extensive guidance on the management of ulcerative colitis and acute severe colitis:

  • D Turner et al. JPGN 2018; 67: 257-91
  • D Turner et al. JPGN 2018; 67: 292-310

Between the two articles there are more than 60 practice recommendations, more than 120 practice points, and more than 700 references.  As such, these articles are probably better for a journal review meeting rather than a brief blog post.

Figure 1 (2nd article, page 299) provides a handy algorithm for management of acute severe colitis:

  • On day 1-2, the algorithm recommends stool studies, starting methylprednisolone, and withholding 5-ASA.
  • On day 3, if PUCAI <45, suggests continuing steroid and transitioning to oral therapy when PUCAI <35.  On day 3, if PUCAI ≥45, the authors suggest screening for second line therapy, involve surgery (to discuss colectomy if there is nonresponse to medical treatment), and looking for CMV infection (eg. sigmoidoscopy).
  • On day 5, if PUCAI >65, recommendation is to start 2nd line Rx (eg. infliximab, tacrolimus, or cyclosporine). If PUCAI 35-65, continue corticosteroids for additional 2-5 days. The authors note that infliximab is preferred 2nd line Rx unless planning to transition to vedolizumab.
  • The authors recommend weaning corticosteroids when 2nd line Rx is started
  • The authors recommend addition of an immunomodulator for at least 6 months in responders to infliximab in effort to lower the risk of colectomy.
  • The authors state “urgent colectomy is recommended following failure of 1 second-line therapy.”

Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications/diets (along with potential adverse effects) should be confirmed by prescribing physician/nutritionist.  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.

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Is it really necessary to check for Cytomegalovirus in Children with Inflammatory Bowel Disease?

A recent retrospective study (W El-Matary et al. JPGN 2018; 67: 221-24) examined the practice of looking for Cytomegalovirus (CMV) in children with a flareup of their inflammatory bowel disease (IBD) which is currently recommended by expert consensus (JPGN 2018; 67: 292-310 –recommendation #3).

Key findings:

  • “Four of 61 patients encounters (6.6%) with UC/IBD-U, two with corticosteroid refractory disease, had positive biopsies for CMV by PCR but negative H&E and IHC.  They responded to escalated medical therapy, without needing anti-viral therapy.”
  • All children who had colectomy during the study did not have CMV detected in colonic mucosa.

The authors note that the rationale for looking for CMV is derived mainly from adult populations.  Since age is a known risk factor for CMV reactivation, the risk of CMV causing refractory IBD in children is less.

My take (borrowed in part from authors): “The low frequency of CMV in our study challenges current guidelines that recommend assessment for CMV in all pediatric patients with acute severe UC refractory to corticosteroids.”  This issue would be another that would benefit by collecting the experience of a large cohort (eg. ICN).

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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.

Serology Titers Associated with Clinical Expression of Ulcerative Colitis in Children

Briefly noted: A recent study (EA Spencer et al.Inflamm Bowel Dis 2018; 24: 1335-42) examined phenotype and serology in 399 children with newly diagnosed ulcerative colitis (PROTECT study).

Key findings:

  • 65% had positive serology for pANCA; 62% in those <12 and 66% in those ≥12 years
  • 19% had positive serology for anti-CBir1; 32% in those <12 and 14% in those ≥12 years
  • High titer (≥ 100)) pANCA positivity was associated with more extensive disease but not with PUCAI values or Mayo endoscopic subscores.

My take: The serology titers for IBD, in my view, have academic interest but do not routinely enhance patient care.

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VICTORY Consortium Showing Good Results for Vedolizumab

A presentation at the 13th Congress of the European Crohn’s and Colitis Organization (ECCO, Feb 2018) indicated that Vedolizumab had similar effectiveness as anti-TNF agents for both ulcerative colitis and Crohn’s disease. This data has been presented at a recent meeting in our office, some of the GI news magazines, and also ImproveCareNow listserv.

From Takeda website: Entyvio® (vedolizumab) Shows Higher Rates of Mucosal Healing Versus TNFα-Antagonist Therapy in Ulcerative Colitis and Crohn’s Disease Patients in Comparative Effectiveness Real-World Data Analysis

These analyses observed that patients with UC treated with Entyvio compared to TNFα-antagonist therapy had statistically significant higher 12-month cumulative rates of mucosal healing (50% vs 42%, hazard ratio [HR] 1.73, 95% confidence interval [CI] 1.10‑2.73) and clinical remission (54% vs 37%; HR 1.54, 95% CI 1.08‑2.18), and numerically higher steroid-free clinical remission rates (49% vs 38%; HR 1.43, 95% CI 0.79‑2.60). In CD, results reported statistically significant higher 12-month cumulative rates of mucosal healing (50% vs 41%; HR 1.67, 95% CI 1.13‑2.47), and numerically higher rates of clinical remission (38% vs 34%; HR 1.27, 95% CI 0.91‑1.78) and steroid-free clinical remission (26% vs 18%; HR 1.75, 95% CI 0.90‑3.43) compared to TNFα-antagonist therapy. These analyses were conducted by the VICTORY (Vedolizumab Health OuTComes in InflammatORY Bowel Diseases) Consortium.

My take: While the data compare anti-TNFs to vedolizumab in a “real-world setting,” the reported outcomes for anti-TNFs are lower than in other studies.  Vedolizumab had the best results in those with colonic disease.  Patients with Crohn’s disease with isolated small bowel disease had lower response rates.

Related study: AK Waljee et al Inflamm Bowel Dis 2018; 24: 1185-95. Using phase 3 clinical trial data with 594 subjects, the authors note that the majority of patients who will respond to vedolizumab can be identified by week 6 using a laboratory algorithm based on hemoglobin, albumin, vedolizumab level and CRP. Fformula: Hgb*Albumin*VDZ level/CRP*Weight. A cutoff of 185.96 predicted success with an AuROC of 0.75.   Higher hemoglobin, higher albumin, and higher vedolizumab level, and lower CRP are associate with higher response rates.

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Opiates, Inflammatory Bowel Disease and Mortality

A recent retrospective study (NE Burr et al. Clin Gastroenterol Hepatol 2018; 16: 534-41) with 3517 patient’s with Crohn’s disease (CD) and 5349 with ulcerative colitis (UC) examined the frequency of opioid prescriptions and the relationship to fatal outcomes.

Key findings:

  • Compared to 1990-93, the period of 2010-13 saw a sharp rise in the use of opiods in England: 10% compared to 30%.
  • Prescription of strong opioids (>3 prescriptions per calendar year) was associated with premature mortality: Hazard ratio 2.18 for CD and 3.3 for UC.

This study is in agreement with other data showing increasing use of opiate prescriptions worldwide for chronic noncancer pain (although there has been a drop in the past year).  As with other studies of patients with inflammatory bowel disease, this study shows an association between opioid use and mortality.

My take: Needing an opioid may be a marker for more severe disease. Whether the opioid use directly contributes to mortality remains unclear.

 

Time Will Tell: Granulomatous Upper GI Inflammation

A recent retrospective study (K Queliza et al. JPGN 2018; 66: 620-23) describes seven patients with granulomatous disease in the upper GI tract who were diagnosed with ulcerative colitis.

This study examined patients at a single center between 2007-2016 with ages ranging from 2 years to 17 years.  Median time of followup is not provided.  Two patients required colectomy.  All patients had non-casseating granulomas identified in either the stomach or duodenum (or both) along with moderate to severe pancolitis.  All of the patients had extensive investigations, generally cross-sectional imaging (MRE or CT) or capsule endoscopy

Key point::

  • “The final classification of IBD was based on expert opinion from gastroenterologists, radiologists, and pathologists upon thorough review of the medical records.”

My take: This study highlights the confusion of the essentially binary classification of IBD into either Crohn’s disease or ulcerative colitis, when in fact there are hundreds of genetic mutations which give rise to inflammatory bowel disease.  Given that granulomas are a hallmark of Crohn’s disease and there are no pathognomic features of ulcerative colitis, only time will tell if these patients have an ulcerative colitis phenotype.  I wonder how many centers would take exception to this classification and describe these patients as ‘indeterminate’ colitis/IBDU (IBD unclassified).

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