Combination Therapy Study Points to Central Role of Adequate Drug Levels

A recent study (JF Colombel et al. Clin Gastroenterol Hepatol 2019; 17: 1525-32) examines the effect of combination therapy and drug levels in achieving corticosteroid-free remission at week 26 (CSFR26).

The authors performed a post hoc analysis from 206 patients with Crohn’s disease (CD): 97 monotherapy with infliximab & 109 with combination infliximab/azathioprine

Key findings:

  • The proportions of patients achieving CSFR26 were not significantly greater among those receiving combination therapy vs monotherapy within the same serum infliximab concentrations
  • Mean trough infliximab concentrations in the combination therapy were higher than for monotherapy: 3.54 mcg/mL vs. 1.55 mcg/mL
  • Higher levels of antidrug antibodies were seen with monotherapy: 35.9% vs 8.3% of those with combination therapy.  Antidrug antibodies were detected only in those with lowest quartile of infliximab trough levels.

My take: This study indicates that combination therapy’s higher efficacy is due to  favorable pharmacokinetics rather than drug synergy.  If good infliximab trough levels can be achieved with infliximab monotherapy, this may obviate the need for combination therapy.  The uncertain factor is whether closer attention to trough levels will minimize the development of antidrug antibodies as effectively as the use of combination therapy.

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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.

Sagrada Familia, Barcelona

Red Meat for Dietary Cynics

A recent randomized study (L Albenberg et al. Gastroenterol 2019; 157: 128-36) examined whether a diet low in red or processed meats could reduce rates of Crohn’s disease (CD) flares.

Methods: Adults with CD were recruited into the FACES (Food and Crohn’s Disease Exacerbation Study) trial from 2013 to 2015. Participants were recruited from an internet-based cohort (n=15,600).  Eligible participants (consumed red meat at least once a week & in remission) were randomly assigned to high meat, n=118 (minimum of 2 servings per week) or low meat, n=96 (no more than 1 serving per month).  Outcomes were based on changes in sCDAI scores or need for treatment (new medication or surgery)

Key findings:

  • Any relapse occurred in 62% of participants in the high meat group compared to 42% in the low meat group.  This was not statistically significant.
  • At week 20, 18 participants in each arm had a stool calprotectin with the high meat group having a higher median: 74.5 mcg/g compared to 36.0 mcg/g (P=.13)
  • The high meat group did consume at least 2 servings per week in 98.5% of observed weeks compared to 18.8% of the low meat group.

Limitations:

  • Small number of diet participants
  • Study was not blinded and only a subset included more objective markers of response
  • Whether complete avoidance of red meat/processed meats would be more effective is unclear
  • In those in remission at baseline, it could take longer for the benefits of a dietary intervention to become evident

My take:  Limiting consumption of red and processed meats (particularly if meat is not lean) has been shown to have cardiovascular benefits.  While this study does not show a statistically-significant improvement in relapse rates in this cohort with Crohn’s disease, there are still strong arguments that a diet with increased fruits/vegetables and less red/processed meats would be beneficial.

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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.

Sagrada Familia, Barcelona

FDA Warning on Tofacitinib

From FDA: 7-26-19 FDA approves Boxed Warning about increased risk of blood clots and death with higher dose of arthritis and ulcerative colitis medicine tofacitinib (Xeljanz, Xeljanz XR)

An excerpt:

The U.S. Food and Drug Administration has approved new warnings about an increased risk of blood clots and of death with the 10 mg twice daily dose of tofacitinib (Xeljanz, Xeljanz XR), which is used in patients with ulcerative colitis…

Health care professionals should discontinue tofacitinib and promptly evaluate patients with symptoms of thrombosis. Counsel patients about the risks and advise them to seek medical attention immediately if they experience any unusual symptoms, including those of thrombosis listed above. Reserve tofacitinib to treat ulcerative colitis for patients who have failed or do not tolerate tumor necrosis factor (TNF) blockers. Avoid tofacitinib in patients who may have a higher risk of thrombosis. When treating ulcerative colitis, use tofacitinib at the lowest effective dose and limit the use of the 10 mg twice daily dosage to the shortest duration needed

  • 19 cases of blood clots in the lung out of 3,884 patient-years of follow-up in patients who received tofacitinib 10 mg twice daily, compared to 3 cases out of 3,982 patient-years in patients who received TNF blockers

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University of Virginia

“Sub-10-minute High-quality Diagnostic Colonoscopy”

Like the last two days, this post addresses “high quality” colonoscopy…

A recent report (M Thomson et al. JPGN 2019: 69: 6-12) describes quicker pediatric colonoscopy times than previously reported and with 100% rate of ileal intubation.

In this report, there were 181 colonoscopies.

Time of colonoscopy:

  • The authors emphasize the fact that their mean time to the terminal ileum was 9.8 minutes.  Their good technical skill is probably related in part to experience: all 6 endoscopists had more than 10 years of experience (mean 19 years) and more than a thousand prior colonoscopies each.

Ileal Intubation Rate:

  • The 100% ileal intubation rate similarly indicates good technical skill.  It may indicate that their patient population was healthier as ileal structuring (which can prevent ileal intubation) can be noted in patients with Crohn’s disease.

Low Diagnostic Yield:

  • In my view, the study reports a low diagnostic yield.  They report 33% had abnormal histology (when excluding patients with IBD followup examinations)
  • 38% of their patients had colonoscopy due to abdominal pain. They reported a yield in this group of only 11.6% though this includes 4 patients with “TI lymphoid hyperplasia.”   Is this an abnormal finding?

My take: This study shows that with good technical skill colonoscopy can be done quickly with ileal intubation times averaging 10 minutes and with ileal intubation rates close to 100%.  In my view, another quality metric is diagnostic yield and their yield is lower than has been reported in most pediatric studies.

Related references:

  • K Siau et al. JPGN 2019; 69: 18-23.  This study describes “Direct Observation of Procedural Skills” (DOPS). Among 29 trainees, 81% of DOPS were rate competent after 125-140 procedures.
  • MT Barakat et al. JPGN 2019; 69: 24-31. This study noted that the vast majority of pediatric GI centers (>90%) were performing less than 25 ERCPs annually and that >70% “believe their institution’s current arrangement for performing pediatric therapeutic endoscopy is inadequate.”

Quality Metrics in Pediatric Colonoscopy

Continuing the theme from yesterday’s post…

Because of similar research in our group, I was interested in a recent study looking at pediatric colonoscopy quality indicators: CS Pasquarella et al.. JPGN 2019; 68: 648-54. (Editorial: CG Sauer, CM Walsh. JPGN 2019; 607-08.)

The authors analyzed 391 colonoscopies.

Key findings:

  • Ileal intubation rate of 91% (which is similar to our rate)
  • Ileal intubation rate was greater in their endoscopy suite where assistance was readily available.
  • Time for procedure: 34 minutes with staff alone compared to 42 minutes with a fellow trainee participant

To this point, we have not collected data on procedure duration at our institution –though 34 minutes seemed longer than I expected.

The authors also comment on cecal intubation.  I find this statistic to be less useful in pediatrics than adult medicine.  Reaching the cecum is important in cancer screening whereas reaching the ileum is important in identifying cases of inflammatory bowel disease.  The former is the main focus in adult gastroenterology and the latter is the main focus in pediatric gastroenterology.

My take: The editorial notes that “endoscopic providers and users can only know whether high-quality care is being delivered if it is being measured.”  I do think ileal intubation is important but other measures include good prep, low complication rate, appropriate patient selection (eg. good indication), and careful followup. Our work in this area will be presented at our upcoming NASPGHAN meeting–stay tuned.

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Sagrad Familia, Barcelona

 

Colonoscopy and Isolated Abdominal Pain = Low Value Care

A recent study (HK Singh, LC Ee. JPGN 2019; 68: 214-7) reviewed a single center’s colonoscopy data (n=652) from 2011-15 with a focus on patients who underwent this procedure for abdominal pain.

Key findings:

  • Only 15 patients had isolated abdominal pain as an indication. In total 68 patients had abdominal pain as an indication but the majority had other ‘red flags’ such as rectal bleeding, family history of IBD or polyposis, weight loss, anemia, food allergy, or altered bowel habits
  • None of these 15 patients with isolated abdominal pain had organic disease
  • Among 36 patients with a measured fecal calprotectin and abdominal pain, all with elevated levels had positive histologic findings.
  • The ileal intubation rate/biopsy rate was 92.4%

I was particularly interested in this study because our group has reviewed our clinical experience in a large cohort undergoing outpatient colonoscopy (findings will be presented this fall).  Our group has a similar ileal intubation rate and a low rate of organic disease in those with isolated abdominal pain.

My take: More efforts are needed to carefully select pediatric patients undergoing endoscopy to minimize low value procedures.

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Georgia Aquarium

Depression Screening for Pediatric Patients with IBD

Recently, we had a morning conference to review depression screening for pediatric patients with IBD.  This lecture was led by Chelly Dykes, MD. Many of these slides were adapted from resources developed by the (ImproveCareNow) ICN Psychosocial Professionals group.

We have started depression screening with a subset of our patients and soon will start screening all children 13 years and older.  When this is working well, younger ages may be targeted as well.

Some of the key points:

  • Depression/anxiety are common, particularly in patients with inflammatory bowel disease
  • National rates of suicide have been increasing
  • Asking about suicide does not increase the risk of suicidality
  • We are fortunate to work closely with two psychologists, Bonney Reed-Knight and Jessica Buzenski

Some of the slides are listed below.

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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.