Changes in the Use of IBD Biologic Therapy

Posted on November 1, 2016 by gutsandgrowth

A recent study (W-J Lee et al. Inflamm Bowel Dis 2016; 22: 2410-17) offers a great deal of insight into changes in the use anti-Tumor Necrosis Factor Alpha (ant-TNF) therapy from 2009-2013 in patients ≤24 years. The authors utilized databases with about 180 million people and identified 11,962 patients with inflammatory bowel disease (IBD).

Key findings:

3300 of the 11,962 (27.6%) patients were treated with anti-TNF therapy.
Top-down treatment: 1298 of 3300 (39.3%) were treated with top-down therapy which was defined as usage of anti-TNF therapy within 30 days of first IBD medication prescription. Interestingly, over the course of the study, there was a trend towards more top-down (versus step-up) therapy and shorter time to initiation of anti-TNF therapy. In 2009, 31.4% used a top-down approach compared with 49.8% in 2013.
Top-down therapy is associated with lower rates of corticosteroid use.
Infliximab dominant anti-TNF: infliximab was the anti-TNF in 89.2% of patients less than 12, 82.3% of patients 12-17, and 55.1% of patients 18-24. Adalimumab accounted for the vast majority of the other TNF users. Though, the authors note a trend towards increasing use of adalimumab in both adult and pediatric patients in a separate study (Park KT et al. Inflamm Bowel Dis 2014; 20: 1242-49)
Cotherapy: thiopurines and methotrexate were used as cotherapy in 13.5% and 7.2% of top-down group compared with 54.8% and 14.6% respectively in step-up strategy.
Drug therapy among non-TNF users: 25.4% (2199) received a thiopurine, 79.3% (6871) received a 5-aminosalicylate, and 2.3% (201) received methotrexate.
Anti-TNF therapy discontinuation: Using top-down strategy 69.2% persisted on infliximab at 12 months and 56.8% persisted at 24 months. In comparison, using step-up approach with infliximab, it was 72.7% at 12 months and 64.0% at 24 months. The numbers were quite similar with all the anti-TNF agents indicating that step-up approach had significantly lower rate of anti-TNF discontinuation. The authors speculate that one factor could be use of cotherapy or possibly other adverse reactions.

The authors explain some of the limitations of their study in its reliance on databases, particularly with regard to misclassification. However, in my opinion, these limitations do not affect any of the trends that the authors are able to document.

My take: For most of my patients, I have preferred to continue to utilize cotherapy and/or step-up therapy because I think there is likely to be a more durable anti-TNF response. The fairly small differences in anti-TNF durability have huge implications for those who lose anti-TNF responsiveness given the limited treatment options.

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Hidden Lake and Bear Mountain, Glacier National Park

GI Educational Cartoons For Children

Posted on October 29, 2016 by gutsandgrowth

Diana Lerner and the Medical College of Wisconsin have developed additional GI educational videos. Previously, they had developed cartoon videos explaining endoscopy (prev post: Terrific Educational Videos on Endoscopy). Now there are several more. All of these are in English and some in Spanish.

Topics include inflammatory bowel disease, gastroesophageal reflux, eosinophilic esophagitis, and celiac disease.

Here’s the link: Pediatric Gastroenterology Cartoons For Kids

Related blog post:

Good Educational Two Minute Video on Celiac Disease

October 2016: IBD Studies

Posted on October 28, 2016 by gutsandgrowth

Briefly noted:

E Zittan et al. Inflamm Bowel Dis 2016; 22: 2442-47. In this study with 773 patients with history of ulcerative colitis/ileal pouch-anal anastomosis, there was no significant difference in complications/leak among the 196 with preoperative anti-TNF exposure (n=26, 13.2%) compared with the control group (n=66, 11.7%). Preoperative anti-TNF exposure does not appear to worsen outcomes after surgery.

C Hartman et al. JPGN 2016; 63: 437-444. This cross-sectional survey of 68 children with IBD (57 Crohn’s disease) found frequent nutrient deficiencies based on 3 day diet records. Interestingly, children on exclusive enteral nutrition were much less likely to have inadequate intakes of energy, minerals, or micronutrients. This article provides plenty of reasons for children with IBD, particularly Crohn’s disease, to work with a nutritionist.

M Fischer et al. Inflamm Bowel Dis; 2016; 22: 2402-09. In a cohort study of 67 patients (35 with Crohn’s, 31 with ulcerative colitis, and 1 indeterminate colitis), fecal microbiota transplantation (FMT) for refractory Clostridium difficile infection was successful in 53 (79%) with a single infusion. Four of the 14 failures, subsequently responded to anti-CDI antibiotics. Of the 8 who had a 2nd FMT, 6 were successful; and 1 of 2 responded to 3rd FMT. Thus, 60 of 67 responded overall to FMT. After FMT, IBD disease activity was reported as improved in 25 (37%), no change in 20 (30%) and worse in 9 (13%). In this cohort, 1 needed colectomy and 1 needed diversion. This article indicates that FMT for CDI in IBD was associated with high cure rates and low risk of IBD flare.

A Khoruts et al. Clin Gastroenterol Hepatol 2016; 14: 1433-38. This was a study of 272 consecutive patients that underwent FMT for recurrent CDI. 15% had established IBD and 2.6% were determined to have IBD at time of FMT. 74.4% of IBD patients responded to a single FMT compared with 92.1% of patients without IBD. More than one quarter of IBD patients experienced a clinical flare after FMT.

MA Conrad et al. Inflamm Bowel Dis; 2016: 22: 2425-31. This review of early pediatric experience with vedolizumab in 21 subjects (16 with Crohn’s disease) identified a clinical response in 6/19 (31.6%) evaluable subjects at week 6 and 11/19 (57.9%) by week 22. Steroid-free remission was noted in 3/20 at 14 weeks (15%) and 4/20 (20.0%) at 22 weeks. Overall, this shows a fairly low response rate to vedolizumab in this highly selected cohort. Prospective pediatric studies of vedolizumab are needed to identify which patients are most likely to benefit.

University of Virginia Rotunda

Should We Care About Subclinical Primary Sclerosing Cholangitis with Inflammatory Bowel Disease?

Posted on October 26, 2016 by gutsandgrowth

A recent study (AK Lunder et al. Gastroenterol 2016; 151: 660-69, editorial 590-3) provides more information about the prevalence of subclinical primary sclerosing cholangitis (PSC) in the setting of long-term inflammatory bowel disease. From a cohort of 756 Norwegian patients in the “IBSEN” cohort of patients with inflammatory bowel disease, the authors analyzed 327 patients with magnetic resonance cholangiography (MRC).

Key findings:

24 (7.5%) of 327 patients who had been followed for 20 years were found to have PSC lesions. Only 7 (2.2%) were known to have PSC based on biochemical or clinical features. Subsequently, a missed case of small-duct PSC was recognized increasing the rate to 8.1%.
Subclinical PSC, interestingly, was detected more often in Crohn’s patients (9.0%) compared with ulcerative colitis (6.8%)
Extensive colitis, high prevalence of colectomy, and refractory IBD symptoms were more common in patients with suspected PSC compared with those without PSC features (P= .029, P= .002, and P= .012 respectively)

The natural history of these subclinical cases of PSC is unclear. Studies have shown that patients with PSC with normal alkaline phosphatase values have an excellent outlook. Yet, there should be some concern. PSC has been associated with 400-fold higher chance of cholangiocarcinoma and 5-fold increased risk of developing colorectal cancer. This could indicate the need for more intensive surveillance in these patients –though the exact risks in those with subclinical disease is unknown.

My take: Until we know more, I doubt looking for subclinical PSC makes sense outside research protocols.

Related blog posts:

Primary Sclerosing Cholangitis 2016

Posted on October 25, 2016 by gutsandgrowth

Though this blog has reviewed primary sclerosing cholangitis (PSC), it has been a while since I’ve posted much. As such, I thought I would place a post of a recent review (KN Lazaridis, NF LaRusso. NEJM 2016; 375; 1161-70).

Key points:

Epidemiology:

Strongly associated with inflammatory bowel disease with 70-80% of PSC patients having IBD
Median age at diagnosis 41 years with ~6-% male

Clinical manifestations:

Insidious disease in most. “About half the patients with this condition do not have symptoms but receive a diagnosis after liver-function tests are found to be abnormal.”
Diagnostic criteria include increased alkaline phosphatase for more than 6 months
In adults, a liver biopsy is not need for diagnosis
Tends to be slowly progressive
Bacterial cholangitis is reported as initial presentation in ~6% and can be recurrent and intractable
Colon cancer is more frequent in patients with PSC. “Colonoscopy is warranted in all patients who have received a new diagnosis”

Subtypes:

Classic subtype (90%) involves the entire biliary tree
~5% have only small intrahepatic bile duct involvement
~5% of adults have overlap syndrome with autoimmune hepatitis. In children, overlap syndrome is present in ~35%.
There are numerous “secondary” PSC causes including AIDS-related cholangiopathy, amyloidoiss, eosinophilic cholangiopathy, histiocytosis X, IgG4-associated cholangitis, and sarcoidosis (most extensive list -see Table 1)

Pathogenesis:

The exact reasons remain unclear. There are associations with environmental triggers but these have not been proven to be causally related. For example, patients with PSC are more likely to consume steak or hamburger compared with controls and less likely to consume similar amounts of fish.
Due to its association with IBD, there are “microbiota hypothesis” to account for the aberrant cholangiocytic response.

Treatment:

“As of this writing, no effective medical therapy exists.”
The authors detail eight potential treatments that are being studied: obeticholic acid, simtuzumab, 24-nor-ursodeoxycholic acid, an apical sodium-dependent bile acid transporter inhibitor (LUM001), a human monoclonal antibody that targets vascular adhesion protein 1 (BTT1023), oral vancomycin (NCT01802073 -pediatric trial), and fecal microbiota transplantation.
Management: includes managing varices in those with cirrhosis, following for benign and malignant biliary strictures, following for gallbladder disease (eg. polyps or masses), colon cancer surveillance (typically yearly screening), and managing metabolic bone disease.

Briefly noted: M Bramuzzo et al. JPGN 2016; 63: 259-64. Using an Italian Pediatric IBD registry, the authors noted 6.8% of 677 patients had autoimmune liver disease: 61% with PSC and 33% with overlap syndrome.

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Nonsteroidal Analgesics and Risk of Empyema

Posted on October 21, 2016 by gutsandgrowth

A recent study (M Le Bourgeois et al. J Pediatr 2016; 175: 47-53) from 15 medical centers in France showed an association between nonsteroidal anti-inflammatory drugs (NSAIDs) and the development of empyema.

Methods: a case-control design with 83 cases of children with empyema and recent acute viral infection (w/in 15 days) and 83 controls who had recent acute viral infection but no emyema. Age range: 3 months-15 years. To ascertain the underlying initial viral etiology, the investigators utilized molecular techniques and identified respiratory viruses in about half of both groups of children.

Key finding: Exposure to NSAIDs was associated with a modest increase in the rate of empyema (aOR 2.79). The risk of empyema associated with NSAIDs was diminished if the child had been prescribed an antibiotic.

My take: This study, by minimizing confounding factors, suggests that the casual use of NSAIDs during acute viral illnesses increases the chance of developing empyema.

Grinnell Glacier, Glacier Nat’l Park

World Congress 2016 Postgraduate Course

Posted on October 19, 2016 by gutsandgrowth

I’ve attached (with permission) the syllabus from the World Congress 2016 Postgraduate Course: 2016-world-congress-postgraduate-course-syllabus

One lecture that I will highlight with a few slides is from Dr. Martin Martin (pg 53-62) which emphasizes a new model for evaluating neonatal intestinal failure/congenital diarrhea by using whole exome sequencing –see slides below.

Other pointers:

Pg 82. Breastmilk associated with shorter duration of TPN dependence in short bowel syndrome
Pg 137. Look for vasculopathy (MRI/MRA) and renal disease in Alagille syndrome
Pg 152. Lactated ringer’s likely better in acute pancreatitis than normal saline.
Pg 171. If constipation at less than 1 year is untreated, >60% have issues with constipation at age 3.

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.

Total Pancreatectomy with Islet Autotransplantation for Refractory Recurrent Pancreatitis

Posted on October 18, 2016 by gutsandgrowth

A recent study (MD Bellin et al. Clin Gastroenterol Hepatol 2016; 14: 1317-23) describes the use of Total Pancreatectomy with Islet Autotransplantation (TPIAT) in 49 patients (mean age 32.8 years). This study included 6 children.

All of these patients met strict criteria for recurrent acute pancreatitis and lacked imaging or functional evidence for chronic pancreatitis. All 49 required narcotics for pain management prior to TPIAT.

The surgical technique for TPIAT is well-described in the report. Patients underwent total pancreatectomy, splenectomy, cholecystectomy and partial duodenectomy with continuity restored via doudenoduodenostomy or Roux-en-Y duodenojejunostomy. The islets were isolated and then infused intraportally.

Key findings:

At 1 year following TPIAT, 22 (46%) reported no use of narcotic pain medications.
Health-related quality of life scores improved (see Figure 3)
Diabetes is a common post-op concern. Approximately half were insulin-independent at 1 and 2 years out from surgery, with one-third remaining so at 5 years.
Histopathology was consistent with chronic pancreatitis in 37 (76%) indicating that current imaging/functional features do not reliably identify chronic pancreatitis with adequate sensitivity.

In the discussion, the authors note the selected patients, due to having normal caliber pancreatitis ducts, were not candidates for surgical drainage procedures like the Puestow procedure. They also note that the Puestow procedure can compromise later islet cell isolation.

My take: TPIAT is an important option in those with severe recurrent or persistent pancreatitis disease.

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Quiet spot on Univ Virginia Grounds

Smart Doctors Still Better Than Smartphones

Posted on October 17, 2016 by gutsandgrowth

The LA Times has reviewed a recent study: JAMA Intern Med. Published online October 10, 2016. doi:10.1001/jamainternmed.2016.6001

LA Times: Your phone may be smart, but your doctor still know more than an app

An excerpt:

In a head-to-head comparison, real human physicians outperformed a collection of 23 symptom-checker apps and websites by a margin of more than 2 to 1, according to a report published Monday in the journal JAMA Internal Medicine.

Even when the contestants got three chances to figure out what ailed a hypothetical patient, the diagnostic software lagged far behind actual doctors. Indeed, the apps and websites suggested the right diagnosis only slightly more than half of the time, the report says…

Though the humans trounced the computers across the board, there were situations in which doctors did a particularly good job of naming the correct diagnosis first. For instance, their margin in cases with common conditions was 70% to 38%. In cases with uncommon conditions, it grew to 76% to 28%.

My take: According to the study, doctors still beat computer symptom algorithms. But, there may be bias: “three of the study authors are doctors, and none are apps.” At the same time, there is a likelihood of increased collaboration between physicians and computers.

NPR: Computerized Assistant for Cancer

Thermal Injury and Subsequent Esophageal Damage

Posted on October 16, 2016 by gutsandgrowth

In this picture of a ‘candy cane appearance’ of the esophagus, the 19 year old patient subsequently admitted to drinking boiling hot tea. A complete recovery was noted.