Relooking at Medications for Constipation-Predominant Irritable Bowel Syndrome

A recent study (CJ Black et al. Gastroenterol 2018; 155: 1753-63) examined the effectiveness of secretagogues for constipation-predominant irritable bowel syndrome (IBS-C).  The authors conducted a systematic review and network meta-analysis with 15 eligible randomized controlled trials (8462 patients).

Key findings:

  • Linaclotide (290 mcg per day) was ranked first in efficacy using the end point recommended by the FDA for IBS-C trials
  • Tenapanor (50 mg twice a day) was ranked first for bloating
  • Plecanatide (6 mg per day) ranked first for safety
  • Diarrhea was significantly more common with all of the secretagogues except for lubiprostone; nausea was significantly more common with lubiprostone

The authors acknowledge the limitations in comparing medicines without direct head-to-head trials (which may never occur).  They state that linaclotide being superior to other treatments had a probability of 88%.

My take: This study indicates that linaclotide may be more likely to be effective than other IBS-C medications; all of these secretagogues have been shown to be superior to placebo.

In this same issue, pgs 1666-9 (J Ruddy), a patient describes her long journey with abdominal pain/GI symptoms.  She describes her initial experiences with physicians who were dismissive and not attentive. Ultimately, a physician listened to her and  helped her improve after explaining that she had a postinfectious IBS and provided treatment.

Related study: S Ishague et al. BMC Gastroenterol 2018; 18:71.  This randomized controlled trial which compared a multistrain probiotic (Bio-Kult, n=181) to placebo (n=179).  The probiotic group had a 69% decrease in abdominal pain compared to a 47% decrease in placebo group.

Sunrise, Death Valley

Five Ways to Lower the Risk of Colon Cancer

A recent study (PR Carr, et al. Gastroenterol 2018; 155: 1805-15) used an ongoing population-based case-control DACHS study (in Germany since 2003) to determine the effects of lifestyle factors on the risk of colorectal cancer (CRC).

Among 4092 patients with CRC and 3032 control patients without CRC, the investigators examined five factors:

  • Smoking – For smoking, one point was given for being a nonsmoker or a former smoker with <30 pack years.
  • Alcohol consumption –  For alcohol, a point was garnered if consumption was moderate according to AICR recommendations.
  • Diet –  Diet quality was assessed based on WCRF/AICR recommendations (supplement table 1 [https://doi.org/10.1053/j.gastro.2018.08.044]). 1 point was given with highest diet scores.
  • Physical activity – A point was given with favorable physical activity which was based on moderate-intensity aerobic exercise for at least 150 minutes per week or 75 minutes of vigorous activity.
  • Body fatness – Those with a BMI between 18.5 and 25 which was considered a healthy weight were awarded a point.

 Key findings:

Compared to patients with 0 or 1 healthy lifestyle factor:

  • Participants with 2 points had odds ratio of 0.85
  • Participants with 3 points had odds ratio of 0.62
  • Participants with 4 points had odds ratio of 0.53
  • Participants with 5 points had odds ratio of 0.33

My take (borrowed from authors): Overall, 45% of CRC cases could be attributed to these lifestyle factors.  This occurred despite the patient’s genetic profile

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Vedolizumab -Could it Work for Eosinophilic Gastroenteritis?

A recent study with only five patients (HP Kim et al. Clin Gastroenterol Hepatol 2018; 16: 1992-4) examined the use of vedolizumab for eosinophilic gastroenteritis.. The rationale was that α4β7 integrin may play an important role in eosinophilic localization in IBD and that blocking α4β7 may inhibit eosinophil recruitment to intestinal mucosa.  In addition, there are few proven therapies for EGE beyond steroids and dietary treatments.  The five patients in this study had been tried on numerous prior treatments and had a disease course of 6-17 years prior to vedolizumab.

Key findings:

  • Two of the five patients were able to wean/discontinue steroids, reported symptom improvement and had normal gastric and small bowel biopsies.  The median time to histologic followup was 2.2 months.
  • A third patient reported symptom improvement but declined a followup biopsy.

My take: A larger study of vedolizumab is needed for EGE.

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Calgary

Vonoprazan versus Lansoprazole for Initial Heartburn Relief

A recent study (T Oshima et al. Aliment Pharmacol Ther 2019; 49: 140-6) showed that a new potassium-competitive acid blocker (P-CAB) can more rapidly improve symptoms than lansoprazole. Thanks to Ben Gold for this reference.

This small study with 32 adult patients with endoscopically-confirmed erosive esophagitis with frequent heartburn were randomized in a double-blind study and received either lansoprazole 30 mg or vonoprazan 20 mg before breakfast.  The authors note that with PPIs, there is a slow onset of action, such that ‘half of all patients remain symptomatic even after 3 days of treatment.” In contrast, vonoprazan can increase intragastric pH to almost 7 within 4 hours.

Key finding:

  • Heartburn relief occurred quicker with vonoprazan.  Complete relief was noted in 31.3% at day 1 compared with only 12.5% in the lansoprazole group.

My take: Vonoprazan is currently approved in Japan.

Related article: Update on the Use of Vonoprazan DY Graham, MP Dore; Gastroenterol 2018; Volume 154, Issue 3, Pages 462–466

Mesquite Flat Sand Dunes, Death Valley

Vedolizumab Drug Levels –Are They Needed?

A recent retrospective study (E Dreesen et al Clin Gastroenterol Hepatol 2018; 16: 1937-46) with 179 consecutive patients (66 with ulcerative colitis, and 113 with Crohn’s disease) found that vedolizumab (VDZ) trough concentrations were correlated with response.

Key findings:

  • VDZ trough >30 mcg/mL at week 2, >24 mcg/mL at week 6, and >14 mcg/mL during maintenance were associated with effectiveness endpoints including endoscopic healing, physician global assessment and biochemical response (based on CRP).
  • Median VDZ trough levels during induction were 27.7 mcg/mL at week 2, 27.4 mcg/mL at week 6. With standard dosing, the maintenance VDZ trough was 13.5 mcg/mL at week 14
  • Higher BMI and more severe disease, based on CRP, albumin, and/or hemoglobin, were associated with lower VDZ trough levels and lower probability of mucosal healing (P<.05).

Interestingly, in the discussion the authors note that VDZ troughs above  3 mcg/mL completely saturate α4β7 intergrin.  This physiologic phenomenon is hard to reconcile with data showing better response with higher VDZ levels.  The authors note that “at present, there are not enough data in our study to support the role for TDM to guide clinical decision-making on dose escalation for vedolizumab.”

My take: This study implies that VDZ levels may help predict response but are not necessarily helpful in determining whether dose escalation is warranted.

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Riverwalk, Chattanooga

How Important Are Proton Pump Inhibitors for Intensive Care Patients?

A recent randomized, blinded study (M Krag et al. NEJM 2018; 379: 2199-2208, editorial 2263-4) describes the use of proton pump inhibitor (PPI) therapy in adults (n=3298) in the ICU at high risk for gastrointestinal bleeding. High risk features included liver disease, coagulopathy, shock, anticoagulant therapy, renal replacement treatment, and mechanical ventilation.

Key findings:

  • Stress-ulcer bleeding may be less prevalent than in the past, perhaps due to improved ICU care. GI bleeding occurred in 4.2% of placebo-treated patients compared to 2.5% of pantoprazole-treated patients
  • Overall outcomes were essentially identical. At 90 days, 510 patients (31.1%) in the pantoprazole group and 49 (30.4%) in the placebo group had died (RR 1.02).
  • Using a composite event score to weight potential good and adverse effects (eg C diff infection, myocardial infarction, bleeding, pneumonia) of PPI therapy, the authors found that this occurred in 21.9% of pantoprazole group compared with 22.6% of placebo group (22.6%).

Reduction in GI bleeding could be related in part to the more frequent use of enteral feedings.  And, the combination of enteral feeding with the use of PPI treatment may increase the risk of pneumonia.

In the associated commentary, the authors note that “prophylaxis with a PPI, if initiated, should be reserved for seriously ill patients who are at high risk for this complication.” They acknowledge a lack of a uniform definition of high risk and the “admittedly small (1.7%) difference in bleeding rates.”

 

Same-Day Bowel Preparation Works for Afternoon Colonoscopies

From Gastro-Hep News: Same-Day Bowel Preparation Ideal for Afternoon Colonoscopies

An excerpt:

Same-day bowel preparation provides better cleansing and is preferred over a split-dose regimen for patients scheduled for an afternoon colonoscopy, according to results of a randomized, controlled study presented in abstract form by Dr Isabel Manzanillo-DeVore on October 9, 2018 at the American College of Gastroenterology (ACG) 2018 Annual Scientific Meeting in Philadelphia, Pennsylvania (Oral abstract 42)…

Patients in both groups were instructed to drink only clear liquids … beginning at noon the day before the colonoscopy…. In the same-day group, patients began bowel preparation at 5:30 am the day of the procedure and were told to finish a polyethylene glycol–electrolyte solution (PEG-ES; 4 L) at least 4 hours before their appointment.

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