Category Archives: inflammatory bowel disease

Antidepressants for Patients with IBD and Their (Beneficial) Affect on Bowel Disease Activity

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A recent population-based cohort study (MS Kristensen et al. Inflamm Bowel Dis 2019; 25: 886-93) indicates that antidepressants are likely to be beneficial for patients with inflammatory bowel disease and could lower disease activity in addition to improving mood.

This study population, n=42,890, with prospectively collected data comprised all patients in the Danish National Patient Registry from 2000-2017 with ICD diagnoses of ulcerative colitis (UC, 69.5%) or Crohn’s disease (CD, 30.5%).  Outcome measures included markers of disease relapse:

  • hospitalizations with IBD as primary diagnosis
  • surgery with IBD as primary operation code
  • step-up medications with corticosteroids or anti-TNF treatment

Key findings:

  • After adjusting for confounders, lower incidence rate of disease activity was found among antidepressant users than nonusers.
    • For CD, the incidence rate ratio was 0.75 (CI 0.68-0.82).
    • For UC, the incidence rate ratio was 0.90 (CI 0.84-0.95).
    • For CD patients without prior use of antidepressants before diagnosis of CD, there was markedly lower incidence rate ratio of 0.51 (CI 0.43-0.62).
  • 28% of the study population redeemed at least 1 prescription for an antidepressant at some point.  This is similar to a Finnish study in which antidepressant use in IBD was 28% compared to 19% in general population

The authors note that anti-depressants may affect the level of pro-inflammatory cytokines which are involved in the pathogenesis of IBD.  This study did not assess potential adverse effects of using anti-depressants.

My take: This study is intriguing and suggests that antidepressants may improve the disease course in IBD. Whether this is related to more favorable brain-gut interaction or whether this is related to drug effects on inflammatory agents is unclear.

Related blog post: Psychosocial Problems in Adolescents with IBD

Park Guell -Fantastic Park in Barcelona (need to buy a pass to get to some parts)

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.

 

Vedolizumab vs Adalimumab for Infliximab Failure in Ulcerative Colitis –Which is Better?

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A recent retrospective study (A Favale et al. Comparative Efficacy of Vedolizumab and Adalimumab in Ulcerative Colitis Patients Previously Treated With Infliximab Inflammatory Bowel Diseases, izz057, https://doi.org/10.1093/ibd/izz057 Published: 01 April 2019) suggests that vedolizumab is more effective for ulcerative colitis with secondary infliximab failure.

Here’s the abstract:

Background

Adalimumab (ADA) and vedolizumab (VDZ) have shown efficacy in moderate to severe ulcerative colitis (UC) patients who failed infliximab (IFX). Although, a comparative efficacy evaluation of ADA and VDZ in this clinical setting is currently missing.

Aim

The aim of this study is to compare the efficacy of ADA and VDZ in patients affected by UC who failed IFX.

Methods

Clinical records of UC patients from 8 Italian IBD referral centers who failed IFX and were candidates to receive either ADA or VDZ were retrospectively reviewed. The primary end point was therapeutic failure at week 52. Secondary end points included therapy discontinuation at weeks 8, 24 and 52, the discontinuation-free survival, and safety.

Results

One hundred sixty-one UC patients, 15 (9.2%) primary, 83 (51.6%) secondary IFX failures, and 63 (39.2%) IFX intolerants were included. Sixty-four (40%) patients received ADA and 97 (60%) VDZ as second line therapy. At week 52, 37.5% and 28.9% of patients on ADA and VDZ, respectively, had therapeutic failure (P = 0.302). However, the failure rate was significantly higher in the ADA group as compared with VDZ group among IFX secondary failures (48.0% ADA vs 22.4%VDZ, P = 0.035). The therapy discontinuation-free survival was significantly higher in the group of IFX secondary failures who received VDZ as compared with ADA at both the univariate (P = 0.007) and multivariate survival analysis (OR 2.79; 95% CI, 1.23–6.34; P = 0.014). No difference in the failure and biologic discontinuation-free survival was observed in the IFX primary failure and intolerant subgroups.

Conclusion

Vedolizumab might be the therapy of choice in those UC patients who showed secondary failure to IFX.

Link to video abstract (2 min):  Comparative Efficacy of Vedolizumab and Adalimumab in Ulcerative Colitis Patients Previously Treated With Infliximab

 

IBD Briefs: May 2019 (Part 2)

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KP Quinn et la. Inflamm Bowel Dis 2019; 25: 460-71.  This is a terrific review of evaluation and management of pouch disorders.

A Armuzzi et al. Inflamm Bowel Dis 2019; 25: 568-79. This prospective cohort study examined infliximab biosimilar in 810 patients (PROSIT cohort).  This included 459 patients naive to anti-TNF therapy (group a) , 196 with previous exposure (group b), and 155 who were switched while on original infliximab (group c).  At 12 months, patients without a loss of response were 71%, 64%, and 82% respectively in these three groups.

S Coward et al Gastroenterol 2019; 156: 1345-53. This study from Canada used population-based health administrative data from multiple provinces and then applied autoregressive integrated moving average regression to predict prevalence of IBD in 2030. Key point: “In 2018, 267,983 Canadians were estimated to be living with IBD, which was forecasted to increase to 402,853 by 2030.” This is approximately 1% of the population (981 per 100,000).

F Castiglione et al. Aliment Pharm Ther 2019; 49: 1026-39. This observational longitudinal study with 218 patients with Crohn’s disease who completed 2-years of anti-TNF treatment examined transmural healing via ultrasonography (≤3 mm bowel wall thickness).  “Transmural healing was associated with a higher rate of steroid-free clinical remission (95.6%), lower rates of hospitalization (8.8%) and need for surgery 0%).”  The authors conclude that transmural healing is associated with better long-term clinical outcomes than mucosal healing.

“Magic Fountain” Barcelona

 

How Quickly Does Tofacitinib Work for Ulcerative Colitis?

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The second study reference yesterday:

A recent study (S Hanauer et al. Clin Gastroenterol Hepatol 2019; 17: 139-47) shows that tofacitinib can work quickly to reduce symptoms in ulcerative colitis.

In a post-hoc analyses of data from OCTAVE induction 1 and 2 (n=905 patients, n=234 placebo), the authors determined that tofacitinib reduces symptoms within 3 days.

Key findings:

  • By day 3, there was a reduction in stool frequency (-1.06 vs. -0.27 for placebo) and a reduction in rectal bleeding subscore (-0.30 vs -0.14 for placebo)
  • 28.8% of tofacitinib-treated patients had a reduction in stool frequency subscore by >1 point compared to 17.9% for placebo.  For rectal bleeding subscore, tofacitinib-treated patients had a reduction by >1 point in 32% compared to 17.9% for placebo 20.1%.

My take: This study reinforces the impression that tofacitinib works rapidly.

Related blog posts:

La Boqueria, Barcelona

How Quickly Does Vedolizumab Work?

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Two recent studies highlight more rapid onset of action for vedolizumab and tofacitinib than previous reports.

In the first study (BG Feagan et al. Clin Gastroenterol Hepatol 2019; 17: 130-8), the authors performed a post-hoc analysis of data from phase 3, randomized controlled trials of vedolizumab vs placebo in adult patients (UC, N=374; CD, N=784).

Key findings:

  • In patients with UC, 19.1% overall and 22.3% of anti-TNF naive achieved a composite score of rectal bleeding of 0 and stool frequency of ≤1 at week 2 compared to 10% and 6.6% respectively in the placebo group. By 6 weeks, this response rate was 40.8% among anti-TNF naive patients.
  • In patients with CD, 15.0% of anti-TNF naive patients achieved a composite score of abdominal pain ≤1 and loose stool frequency ≤3 at week 2 compared to 7.9% of placebo; at 4 weeks, the vedolizumab group, the rate was 23.8% compared to 10.3% with placebo.

My take: This study shows that a substantial portion of patients respond fairly quickly to vedolizumab, especially among patients who are naive to anti-TNF therapy.  This is in contrast to the impression that vedolizumab is slow-acting and needs closer to 14 weeks to see clinical effects.

Related blog posts:

Jardines de Cecilio Rodríguez; Retiro Park, Madrid

IBD Update April 2019

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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

Getting the Most Out of Vedolizumab

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A recent cross-sectional study (B Al-Bawardy et al. Inflamm Bowel Dis 2019; 25: 580-6) correlated vedolizumab (VDZ) trough drug levels (VDT) and clinical outcomes in 171 patients (62% Crohn’s disease (CD), 31% ulcerative colitis (UC), and 7% indeterminate colitis (IC)).

Key findings:

  • Median VDT was 15.3 microgr/mL.
  • Median VDT was 17.3 microgr/mL for patients with normal CRP compared with 10.7 for patients with high CRP.  This differnece was noted significantly for CD (20.3 vs 10.4) but not for UC.
  • No relationship  between VDT and mucosal healing was noted.
  • Shorter dose intervals and lower BMO resulted in higher VTLs
  • Only 1 patient had detectable antibodies to VDZ

A second systematic review (L Peyrin-Biroulet et al. Clin Gastroenterol Hepatol 2019; 17: 838-46) analyzed data from 10 cohorts who had received vedolizumab.  Most had prior anti-TNF exposure. Key finding: the pooled incidence rates of loss of response were 47.9 per 100 person-years of follow up among patients with CD and 39.8 per 100 person-years of follow up among patinets with UC.  Dose intensification restored response to the drug in 53.8% of secondary non-responders.

My take: While VDZ dose intensification can restore response, the utility of therapeutic drug monitoring is unclear with VDZ therapy.

Related blog posts:

CHOP QI: Anemia in IBD Pathway

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A recent article in Gastroenterology & Enoscopy News, “QI Pathway Improves Anemia Management in Pediatric IBD” (also presented at NASPGHAN 2018 -abstract 7, J Breton et al), discusses anemia and provides a link to CHOP QI Pathway for Anemia

This link contains useful information regarding treatment options and links to recommendations on management.  This algorithm suggests using intravenous iron for anemia in all IBD patients with active disease as well as using intravenous iron for those with moderate to severe anemia.  The rationale for parenteral iron in those with active disease is due to two factors:

  1. to overcome the block to intestinal iron absorption induced by hepcidin in the setting of inflammation (making oral iron less effective in active IBD regardless of disease location)
  2. due to data showing  that oral iron may aggravate intestinal inflammation by altering the gut microbiome and increasing intestinal permeability

My take: The CHOP initiative provides some clear cut recommendations.for anemia in IBD.  Parenteral iron is more efficacious in improving anemia; however, the effects of parenteral iron on the microbiome and other potential risks (eg. increased sepsis) are not clear. In my view, more information about outcomes and costs are needed to determine the optimal approach.

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.

AGA Recommendations for Management of Functional Symptoms in Patients with Inflammatory Bowel Disease

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Full text: AGA Clinical Practice Update on Functional Gastrointestinal Symptoms in Patients With Inflammatory Bowel Disease: Expert Review (JF Columbel et al. Clin Gastroenterol Hepatol 2019; 17: 380-90).

My take: Overall, this article presents a concise review of a tricky problem and appropiriate management.  The algorithm, tables and figures are useful.

Best practice advice 1: A stepwise approach to rule-out ongoing inflammatory activity should be followed in IBD patients with persistent GI symptoms (measurement of fecal calprotectin, endoscopy with biopsy, cross-sectional imaging).

In the report, the authors note that endoscopy and cross-sectional imaging are not needed in all patients; mainly in patients with a suspected flare based on presentation, calprotectin, and blood work.

Best practice advice 2: In those patients with indeterminate fecal calprotectin levels and mild symptoms, clinicians may consider serial calprotectin monitoring to facilitate anticipatory management.

Best practice advice 3: Anatomic abnormalities or structural complications should be considered in patients with obstructive symptoms including abdominal distention, pain, nausea and vomiting, obstipation or constipation.

Best practice advice 4: Alternative pathophysiologic mechanisms should be considered and evaluated (small intestinal bacterial overgrowth, bile acid diarrhea, carbohydrate intolerance, chronic pancreatitis) based on predominant symptom patterns.

Best practice advice 5: A low FODMAP diet may be offered for management of functional GI symptoms in IBD with careful attention to nutritional adequacy.

Best practice advice 6: Psychological therapies (cognitive behavioural therapy, hypnotherapy, mindfulness therapy) should be considered in IBD patients with functional symptoms.

Best practice advice 7: Osmotic and stimulant laxative should be offered to IBD patients with chronic constipation.

Best practice advice 8: Hypomotility agents or bile-acid sequestrants may be used for chronic diarrhea in quiescent IBD.

Best practice advice 9: Antispasmodics, neuropathic-directed agents, and anti-depressants should be used for functional pain in IBD while use of opiates should be avoided.

Best practice advice 10: Probiotics may be considered for treatment of functional symptoms in IBD.

Best practice advice 11: Pelvic floor therapy should be offered to IBD patients with evidence of an underlying defecatory disorder.

Best practice advice 12: Until further evidence is available, fecal microbiota transplant should not be offered for treatment of functional GI symptoms in IBD.

Best practice advice 13: Physical exercise should be encourage in IBD patients with functional GI symptoms.

Best practice advice 14: Until further evidence is available, complementary and alternative therapies should not be routinely offered for functional symptoms in IBD.

Monticello

Origins of Hygiene Hypothesis

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A recent NY Times article explains the background of the ‘hygiene hypothesis’ and how it has held up remarkably well as a likely factor in the rising number of allergic and immune-mediated diseases.

Link: Your Environment is Cleaner. Your Immune System Has Never Been So Unprepared

An excerpt:

The British Journal of Homeopathy, volume 29, published in 1872, included a startlingly prescient observation: “Hay fever is said to be an aristocratic disease, and there can be no doubt that, if it is not almost wholly confined to the upper classes of society, it is rarely, if ever, met with but among the educated.”..

In November 1989, another highly influential paper was published on the subject of hay fever. The paper was short, less than two pages, in BMJ, titled “Hay Fever, Hygiene, and Household Size.”

The author looked at the prevalence of hay fever among 17,414 children born in March 1958. Of 16 variables the scientist explored, he described as “most striking” an association between the likelihood that a child would get hay fever allergy and the number of his or her siblings.

It was an inverse relationship, meaning the more siblings the child had, the less likely it was that he or she would get the allergy…The paper hypothesized that “allergic diseases were prevented by infection in early childhood, transmitted by unhygienic contact with older siblings, or acquired prenatally from a mother infected by contact with her older children…

[To avoid disease] we started washing our hands and took care to avoid certain foods that experience showed could be dangerous or deadly…Particularly in the wealthier areas of the world, we purified our water, and developed plumbing and waste treatment plants; we isolated and killed bacteria and other germs…

What does the immune system do when it’s not properly trained?

It can overreact. It becomes aggrieved by things like dust mites or pollen. It develops what we called allergies, chronic immune system attacks — inflammation — in a way that is counterproductive, irritating, even dangerous.

The percentage of children in the United States with a food allergy rose 50 percent between 1997–1999 and 2009–2011, according to the Centers for Disease Control and Prevention…

There are related trends in inflammatory bowel disease, lupus, rheumatic conditions and, in particular, celiac disease. The last results from the immune’s system overreacting to gluten..

And even doctors have been wrong….They have vastly overprescribed antibiotics. These may be a huge boon to an immune system faced with an otherwise deadly infection. But when used without good reason, the drugs can wipe out healthy microbes in our gut.

My take: With the increasing frequency of many diseases, there has to be environmental influences since our population genetic makeup does not change rapidly. Thus factors like infections, microbiome and exposure to antibiotics are likely important in the changing epidemiology.

Related blog posts: