IBD Update April 2019

Briefly noted:

Link (from KT Park’s twitter feed): What New Treatments for Crohn’s disease and Ulcerative Colitis Are Being Developed?

R Wittig et al. JPGN 2019; 68: 244-50. This study from Germany, using health insurance data, identified an overall pediatric inflammatory bowel disease (IBD) incidence of 17.41 per 100,000 in 2012 compared to 13.65/100,000 in 2009.  This is one of the highest incidence rates reported and agrees with other data suggesting increasing rates of IBD in pediatric populations.

B Christensen et al. Clin Gastroenterol Hepatol 2019; 17: 486-93.  This study provides data from 20 patients (CD =9, UC =11) who were treated with a combination of a calcineurin inhibitor and vedolizumab.  The calcineurin inhibitor was used as a ‘bridge’ treatment until the slower acting vedolizumab could be effective. After 52 weeks of treatment, 33% of the CD patients and 45% of the UC patients were in steroid-free clinical remission.  Three serious adverse events associated with calcineurin treatment.

G Pellet et al. Clin Gastroenterol Hepatol 2019; 17: 494-501. Retrospective study of calcineurin inhibitor induction with vedolizumab in 39 patients with refractory ulcerative colitis (36 had failed anti-TNF Rx).  11 patients (28%) required colectomy. week 14 response and remission noted in 56% and 38% respectively. Four serious adverse events were observed.

N Nalagatla et al. Clin Gastroenterol Hepatol 2019; 17: 494-501. In a retrospective study of 213 patients with steroid refractory acute severe ulcerative colitis, the authors did not find lower rates of colectomy in patients who received an accelerated infliximab dosing.  However, they were unable to control for confounding by disease severity. Patients who received an intial dose of 10 mg/kg had a lower colectomy rate than patients who received an initial dose of 5 mg/kg. Colectomy rates for accelerated vs standard infliximab dosing –in-hospital: 9% vs 8% respectively, at 3 months: 20% vs 14% respectively, at 12 months: 28% vs 27% respectively.

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Management of Acute Severe Colitis

A recent review (KG Whatley, MJ Rosen. Inflamm Bowel Dis 2019; 25: 56-66) succinctly summarizes the contemporary medical management of acute severe ulcerative colitis (ASUC).

Figure 1 provides a useful initial checklist which includes the following:

  • PUCAI score
  • Labs/Imaging: CBC/d, CMP, CRP/ESR, Stool studies (culture/C diff), AXR
  • Pre-salvage labs: TB screen, Hep B serology, VZV serology if needing anit-TNF, TPMT if contemplating thiopurine, lipids if contemplating calcineurin inhibitor
  • Endoscopy: Consider Flex Sig (unsedated) with tissue for CMV PCR if not responding to 3 days of IV steroids
  • Thromboembolism prophylaxis: Low molecular weight heparin (adults, & high-risk pediatric patients), pneumatic compression (low-risk pediatric)
  • Nutrition plan
  • Corticosteroids: methylprednisolone 1-15. mg/kg (to max of 40-60 mg daily)

Each of these recommendations is discussed. For the flex sig recommendation, the authors note that a “full colonoscopy is not recommended due to risk of perforation.” With regard to CMV, the authors acknowledge the low quality of evidence to support antiviral treatment of CMV in this setting.  In addition, the authors suggest PCP prophylaxis in those who receive triple immunosuppression or in those receiving calcineurin inhibitors.

Figure 2 provides a handy algorithm for infliximab salvage therapy in the setting of ASUC:

  • If salvage therapy with infliximab is indicated (day 3-5 of IV steroids), the authors recommend 10 mg/kg dosing.  If there is no response after 3-5 days, repeat dosing is recommended.  If there is no response after an additional 3-5 days, colectomy is recommended.
  • If there is a response to infliximab, the algorithm recommends outpatient management. At time of the 3rd dose (week 5-6), the authors obtain an IFX level.  In those with a level <15, then dosing at 4 week maintenance is recommended; whereas in those 15 and above, every 8 week maintenance is recommended.

The authors discuss some potential emerging treatments. Recommendations from the authors with regard to surgery:

  • Most patients are best served with a subtotal colectomy/end ileostomy in preparation for future ileal pouch anal anastomosis
  • “Surgery should not be delayed to enhance nutrition or taper steroids.”

My take: This article summarizes current approaches with emphasis on not waiting a long time for salvage therapies and using early therapeutic drug monitoring to assist in dosing frequency.

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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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