IBD Briefs August 2019

A Levine et al. Gastroenterol 2019; 157: 440-50.  This study found that a Crohn’s Disease Exclusion Diet plus partial enteral nutrition induced sustained remission in a 12-week prospective randomized controlled trial with 74 children.  At week 12, “76% of 37 children given CDED plus PEN were in corticosteroid-free remission compared with 14 (45.1%) of 31 children given” EEN followed by PEN.  The associated editorial on pages 295-6 provides a useful diagram of various dietary therapy components for a large number of diets that have been given for IBD.  The editorial recommends:

“For now, simple dietetic recommendations such as consuming a well-balanced diet prepared largely from fresh ingredients and thereby avoidance of emulsifiers and additives and processed foods are appropriate for all patients.  In select patients,…a trial of dietary therapy alone with a diet such as CDED could be attempted for a short period of time, with close follow-up, and with agreement with the patient that failure to fully respond is an indication to escalate therapy.”  More dietary trials are ongoing.

Related blog posts:

NJ Samadder et al Clin Gastroenterol Hepatol 2019; 17: 1807-13. In this cohort from Utah 1996-2011 with 9505 individuals with IBD, 101 developed colorectal cancer.  Standardized incidence ratio (SIR) for CRC in patients with Crohn’s disease was 3.4, in ulcerative colitis 5.2, in patients with primary sclerosing cholangitis 14.8.  A family history of CRC increased the risk of CRC in patients with IBD to 7.9 compared to general population.  Family hx/o CRC increased the SIR by about double the CRC risk in IBD patients without a family hx/o CRC.

CR Ballengee et al. Clin Gastroenterol Hepatol 2019; 17: 1799-1806. In this study with 161 subjects from the RISK cohort, the authors found that elevated CLO3A1 levels in subjects with CD was associated with the development of stricturing disease but was not elevated in those with strictures at presentation and in those who did not develop  strictures.

AL Lightner et al IBD 2019; 25: 1152-68.  Short- and Long-term Outcomes After Ileal Pouch Anal Anastomosis in Pediatric Patients: A Systematic Review.  This review included 42 papers.

  • Rates of superficial surgical site infection, pelvic sepsis, and small bowel obstruction at <30 days were 10%, 11%, and 14% respectively.
  • Rates of pouchitis, stricture, chronic fistula, incontinence and pouch failure were 30%, 17%, 12%, 20% and 8% respectively with followup between 37-109 months.
  • Mean 24-hour stool frequency was 5.

MC Choy et al IBD 2019; 25: 1169-86.  Systematic review and meta-analysis: Optimal salvage therapy in acute severe ulcerative colitis.  Among 41 cohorts (n=2158 cases) with infliximab salvage, overall colectomy-free survival was 69.8% at 12 months.  The authors could not identify an advantage of dose-intensification in outcomes, though this was used more often in patients with increased disease severity, “which may have confounded the results.”

Hood River, OR

Tofacitinib Case Reports for Acute Severe UC and Pyoderma Gangrenosum

Two recent case reports indicate that Tofacitinib may be useful in refractory cases of acute severe ulcerative colitis (ASUC) (JA Berinstein et al. Clin Gastroenterol Hepatol 2019; 17: 988-90) and for pyoderma gangrenosum (PG) (B Kochar et al. Clin Gastroenterol Hepatol 2019; 17: 991-93)

The case report for ASUC described 4 patients who received off-label high-intensity tofacitinib.  Initially dosing was 10 mg 3 times a day for 9 doses with subsequent transition to standard dosing.  All four patients had a rapid improvement, though one patient required a colectomy 6 months later and one patient required urgent colectomy after rapid return of symptoms when tofacitinib dose was reduced.

The case report for PG involved 3 patients -two healed with tofacitinib and one improved considerably; the latter patient required dose escalation to 10 mg twice a day.  To understand the mechanism of action further, the authors performed immunohistochemical staining from skin biopsy specimens from two patients and detected “strong staining of phosphorylated JAK-1, phosphorylated JAK-2, phosphorylated JAK-3…in the epidermis.”  Tofacitinib is an oral JAK-1/JAK-3 inhibitor.  In all of these patients, inflammatory arthritis was the indication for tofacitinib.

My take: Due to tofacitinib’s rapid onset of action as well as its rapid clearance, it is a promising agent for both acute severe ulcerative colitis and pyoderma gangrenosum.  More clinical trials are needed.

Related blog posts -Tofacitinib:

Related blog posts -ASUC:

Related blog posts -PG:

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.

Image below is from an unrelated tweet.

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.

Related blog posts:

Shenandoah National Park

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.

Related blog posts:

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.

Death Valley