Tag Archives: Crohn’s disease

Curcumin Was NOT Effective For Post-operative Crohn’s Disease, Goldman Sachs Take on Masks

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NBC/NY Link: Goldman Sachs Says National Mask Mandate Could Slash Infections, Save Economy From 5% Hit

Briefly noted: G Bommelear et al. Clin Gastroenterol Hepatol; 2020; 18: 1553-60. Oral Curcumin No More Effective Than Placebo in Preventing Recurrence of Crohn’s Disease After Surgery in a Randomized Controlled Trial

Methods:

  • Double-blind randomized controlled trial at 8 referral centers in France, from October 2014 through January 2018, with 62 consecutive patients with CD undergoing bowel resection.
  • Patients received azathioprine (2.5 mg/kg) and were randomly assigned to groups given oral curcumin (3 g/day; n = 31) or an identical placebo (n = 31) for 6 months, and were then evaluated by colonoscopy.
  • The primary endpoint: postoperative recurrence of CD in each group (Rutgeerts’ index score ≥i2) at month 6

Key findings:

  • Postoperative recurrence at 6 months: (Rutgeerts’ index score ≥i2): 58% receiving curcumin vs 68% receiving placebo (P = .60).
  • Severe recurrence: 55% receiving Curcumin 55%vs 26% receiving placebo –had a severe recurrence of CD (Rutgeerts’ index score ≥i3) (P = .034).
  • Clinical recurrence of CD (CD activity index score >150) at 6 months: 30% with curcumin compared with 45%  receiving placebo (P = .80)

My take: Curcumin was ineffective in preventing recurrent post-operative Crohn’s disease

Related blog posts:

 

Can Microscopic Colitis Lead to Crohn’s Disease or Ulcerative Colitis?

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A recent prospective cohort “ESPRESSO” study (H Khalili et al. Gastroenterol 2020; 158: 1574-83) from 1990-2017 examined the risk of incident inflammatory bowel disease (IBD) in subjects with microscopic colitis, n=13,957 (& each matched with 5 controls). ESPRESSO = Epidemiology Strengthened by histoPathology Reports in Sweden.

Key findings:

  • In the microscopic colitis group, there were 323 incident cases of ulcerative colitis (UC) and 108 cases of Crohn’s disease (CD)
  • Mean times to diagnosis were 3.2 years for UC and 3.3 years for CD
  • Microscopic colitis was associated with an aHR of 12.6 for CD and 17.3 fo rUC
  • The absolute excess risk compared to matched control over a 10-year period were 2.6% for UC and 0.9% for CD

My take: Individuals with microscopic colitis are at increased risk of developing UC and CD.

Related blog post/related article:

 

IBD Briefs June 2020

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SA Draiweesh et al. Safety of Combination Biologic and Antirejection Therapy Post-Liver Transplantation in Patients with Inflammatory Bowel Disease. Inflamm Bowel Dis 2020; 26: 949-59. In this case series of 19 patients, 14 who had liver transplantation for PSC, there was no increased risk of serious infections among patients receiving biologic therapy in combination with antirejection medications.

A Malian et al. Pedictors [sic] of Perianal Fistula Relapse in Crohn’s Disease. Inflamm Bowel Dis 2020; 26: 926-31. In this retrospective study with 137 patients, fistula relapse rates were not different in patients receiving infliximab or adalimumab (P = 0.66). In patients treated by anti-TNF at inclusion, discontinuation of anti-TNF therapy (odds ratio 3.49, P = 0.04), colonic location (OR 6.25, P = 0.01), and stricturing phenotype (odds ratio 4.39, P = 0.01) were independently associated with fistula relapse in multivariate analysis.

M-H Wang et al. Unique Phenotypic Characteristics and Clinical Course in Patients With Ulcerative Colitis and Primary Sclerosing Cholangitis: A Multicenter US Experience. Inflamm Bowel Dis 2020; 26: 774-81. Among 522 patients with UC, 56 (10.7%) had PSC. Compared with UC alone, patients with UC-PSC were younger (younger than 20 years) at diagnosis (odds ratios [OR], 2.35; adjusted P = 0.02) and had milder UC severity (adjusted P = 0.05), despite having pancolonic involvement (OR, 7.01; adjusted P < 0.001).  In the biologics era (calendar year 2005 to 2015), patients with UC-PSC less commonly received anti-TNF therapy compared with patients with UC (OR, 0.38; adjusted P = 0.009), but their response rates were similar.

B Barberio et al. Matrix Metalloproteinase 3 Predicts Therapeutic Response in Inflammatory Bowel Disease Patients Treated with Infliximab. Inflamm Bowel Dis 2020; 26: 756-62. Retrospectively, 73 IBD patients who had received IFX for at least 1 year were enrolled: 35 patients were responders and 38 were nonresponders at 52 weeks…The MMP3 levels were similar at baseline (19.83 vs 17.92 ng/mL), but at postinduction, patients who failed to respond at 1 year had significantly higher levels than patients who responded (26.09 vs 8.68 ng/mL, P < 0.001); the difference was confirmed at week 52 (29.56 vs 11.48 ng/mL, P < 0.001)…The MMP3 serum determination may represent an early marker of response to infliximab.

 

“No Solid Conclusions” for Alternative/Complementary Therapies for Inflammatory Bowel Disease

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In this clinical review (N Chande et al Inflamm Bowel Dis 2020; 26: 843-51) assess evidence from Cochrane reviews of four popular nontraditional treatments for inflammatory bowel disease (IBD):

  • Fecal Microbiota Transplantation (FMT)
  • Nutritional Therapies including Enteral Nutrition (EN)
  • Naltrexone for Crohn’s Disease (CD)
  • Cannabis for IBD

So what does the literature have to say about these treatments:

  • FMT: FMT for mild to moderate ulcerative colitis (UC) increased the proportion of patients achieving clinical remission. “However, the number of included studies was small and the quality of evidence was low.”  Other problems included uncertainty regarding serious adverse events and short duration of followup.
  • “As a result, no solid conclusions [the authors did not indicate this as a pun] can be drawn at this time.”
  • Nutritional Therapies: For remission in CD, “EN may be more effective than corticosteroids in children, although the opposite was true in adults.”
  • “Exclusion diets did not promote clinical remission or reduce clinical relapse in UC”
  • “The overall certainty of evidence in these studies were generally very low, largely due to sparse data.”
  • Naltrexone for Crohn’s Disease (CD): “The paucity of data makes it impossible to draw any firm conclusions about the effectiveness and safety” of low dose naltrexone.
  • Cannabis for IBD: “The risk of adverse events was significantly higher in cannabis-treated patients”…though these events were generally mild (eg. sleepiness, confusion, nausea).
  • “The results of these studies suggest that cannabis is not effective for the treatment of IBD”  This conclusion is limited by the small number of patients in prior studies.  Cannabis may be helpful as an adjunct for some symptoms though this “warrants further study.”

Related blog posts:

 

 

Ionizing Radiation Exposure in Adults with Inflammatory Bowel Disease

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From The Onion:

In the largest reported cohort to date, GC Nguyen et al (Inflamm Bowel Dis 2020; 26: 898-906) describe the ionization radiation exposure (IRE) in individuals (≥18 years) with inflammatory bowel disease (IBD).

Methods: N=72,933 with IBD,1994-2016. During 1st 5 yrs after diagnosis, IRE was estimated in a retrospective matched cohort in Ontario.

Key findings:

  • IBD patients were exposed to nearly 6-fold IRE due to abdominal imaging compared to controls: 18.6 mSv vs 2.9 mSv
  • Patients with CD had higher IRE than UC: 26 mSv vs 12 mSv (P<0.001).  CD patients were more likely to have >50 mSv exposure (15.6% vs 6.2%) and >100 mSv 5.0% vs 2.1%
  • Women were less likely to have high IRE compared to males
  • Residents in the poorest neighborhoods were 27% more likely to have IRE >100 mSv.  Socioeconomic status was an independent factor after accounting for comorbidities. The authors speculate that this could be related to increased use of emergency rooms where they may be more likely to receive a CT.
  • The use of CT scan began to decline after 2007…likely explained by the rise of MRE studies.

While strict guidelines on IRE are lacking, the International Commission on Radiological Protection has suggested that occupational exposure (eg. nuclear workers) should be limited to <100 mSv over 5 years and not more than 50 mSv in a single year.

My take: We need to continue efforts to reduce IRE due to concerns about subsequent secondary malignancies. This likely means avoiding CT for non-emergencies and working with our ED colleagues to think carefully about lifetime IRE in IBD patients.

Related blog posts:

Additional references:

  • -AJR 2001; 176: 289-96. Estimated risks of radiation-induced fatal cancer from pediatric CT
  • -Br J Radiol 2012; 85: 523-28.  Justification of CTs -some not needed
  • -AJR 2010; 194: 868-73.  Lower CT radiation doses in pediatric patients.  ‘Image gently’
  • -Arch Intern Med 2009; 169: 2078-86.

From LA Times:

 

Expert Guidance on Inflammatory Bowel Disease (Part 3)

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A recent issue of Clinical Gastroenterology and Hepatology focused solely on the clinical features and management of inflammatory bowel disease. Even for those with expertise in IBD, there is a lot of useful information and concise reviews of what is known.

Here are some of my notes from this issue (part 3):

RP Hirten et al. Clinical Gastroenterol Hepatol: 2020; 18: 1336-45. A User’s Guide to De-escalating Immunomodulator and Biologic Therapy in Inflammatory Bowel Disease

This article emphasizes the need for assessment of bowel disease activity before attempting de-escalation and provides a list of risk factors for flare-up off therapy.

Some of the Risk factors for Disease Flare with De-escalation:

  • Disease activity/abnormal biomarkers (CRP, WBC, Hemoglobin, Calprotectin)
  • Perianal disease
  • Penetrating disease
  • Extensive disease involvement
  • Abnormal bowel wall thickening on MRE
  • Young age at diagnosis
  • Short treatment duration
  • Prior surgeries

Key points:

  • In individuals on combination therapy, dropping immunomodulator therapy (but not biologic therapy) did NOT increase the short term risk of a flare up in a recent Cochrane review.  However, this did impact anti-TNF kinetics and lowers anti-TNF troughs.
  • With regard to stopping biologics, among patients in deep remission, the authors advise counseling patients (CD and UC) that stopping biologic agents results in a “40-50% relapse over the following 2 years that will further increase over time.”
  • Careful followup is recommended if a patient elects to stop biologic therapy. “CD and UC are progressive relapsing conditions…and approximately 80% of subjects” require re-initiation of biologic therapy with 7 years.”
  • “Repeat colonoscopy or imaging should be performed if a significant change in symptoms occurs or abnormal biomarkers are detected.”
  • In patients who resume infliximab, the authors advocate for an initial induction of 0, 4, and 8 weeks.  The presence of antidrug antibodies at week 2 “precludes drug administration and alternative agent should be started.”

Related blog posts:

M Kaur et al Clinical Gastroenterol Hepatol 2020; 18: 1346-55. Inpatient Management of Inflammatory Bowel Disease-Related Complications

This article reviews the approach to acute severe ulcerative colitis which has been discussed recently on this blog post and offers management recommendations for complications related to Crohn’s disease including abscesses, strictures/bowel obstruction.  With regard to abscess management, the authors note that medical therapy is more likely to be effective in those with a first-time abscess, spontaneous origin, right lower quadrant location, and smaller abscess size (<3 cm).  Stricture with upstream dilatation of bowel, multi-loculated abscesses and steroid use are features that make therapy less likely to be successful.

Related blog posts -ASUC:

Abscess-related blog posts:

EL Barnes et al Clinical Gastroenterol Hepatol 2020; 18: 1356-66. Perioperative and Postoperative Management of Patients With Crohn’s Disease and Ulcerative Colitis

This article reviews risk factors for disease recurrence after surgery, presurgical management (eg. minimize steroids, improve nutrition, do not delay surgery based on preoperative biologic exposure), postoperative strategies and management of pouchitis.

  • In those at high risk for postoperative disease recurrence, the authors advocate anti-TNF therapy plus an immunomodulator with colonoscopy at 6-12 months. In those at low risk, many are placed on no medications and have a colonoscopy at 6 months postoperatively.
  • The section on pouchitis lists alternatives to metronidazole and ciprofloxacin if these lose efficacy.  This includes amoxicillin-clavulanate, sulfamethoxazole-trimethoprim, doxycycline and vancomycin.
  • Related blog post: What’s Going on With Pouchitis?

S Singh et al Clinical Gastroenterol Hepatol 2020; 18: 1367-80. Management of Inflammatory Bowel Diseases in Special Populations: Obese, Old, or Obstetric

A Levine et al Clinical Gastroenterol Hepatol 2020; 18: 1381-92. Dietary Guidance From the International Organization for the Study of Inflammatory Bowel Diseases

  • The authors recommend more vegetables and fruits with CD (but low insoluble fiber if stricture present)
  • “Prudent to reduce intake of red and processed meat” with UC
  • “Prudent to increase dietary omega-3 fatty acids” from marine fish but not from dietary supplements with UC
  • ‘Prudent to use a low FODMAP diet for patients with persistent symptoms for CD and UC despite resolution of inflammation’

M Collins et al Clinical Gastroenterol Hepatol 2020; 18: 1393-1403.Management of Patients With Immune Checkpoint Inhibitor-Induced Enterocolitis: A Systematic Review

This study reviews colitis induced by immune checkpoint inhibitors which are similar to young patients with inherent CTLA4b deficiency.

Related blog posts:

Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure.  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 Practice Guidelines: Probiotics NOT Helpful for Most GI Conditions

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Here is a link to the EPUB draft of AGA clinical report (G Su et al. Gastroenterology DOI: https://doi.org/10.1053/j.gastro.2020.05.059): AGA Clinical Practice Guidelines on the Role of Probiotics in the Management of Gastrointestinal Disorders

Here is a link to the pre-draft technical review by GA Preidis et al. Gastroenterology DOI: https://doi.org/10.1053/j.gastro.2020.05.060 AGA Technical Review on the Role of Probiotics in the Management of Gastrointestinal Disorders

  • The report recommends NOT using probiotics outside of clinical trials for irritable bowel syndrome, Clostridium difficile infection treatment, Crohn’s disease, and gastroenteritis.
  • It recommends a specific probiotic for pouchitis and for prevention of necrotizing enterocolitis in preterm infants <37 weeks and 3 probiotics for patients who are receiving antibiotics (to prevent Clostridium difficile infection)

CNN summary: Probiotics don’t do much for most people’s gut health despite the hype, review finds

“While our guideline does highlight a few use cases for probiotics, it more importantly underscores that the public’s assumptions about the benefits of probiotics are not well-founded,” said Dr. Grace L. Su, a professor of medicine and chief of gastroenterology at the University of Michigan, Ann Arbor, in a news statement. She was the chair of the panel that issued the new guidance….

“The industry is largely unregulated and marketing of product is often geared directly at consumers without providing direct and consistent proof of effectiveness,” said the new guidelines. “This has led to widespread use of probiotics with confusing evidence for clinical efficacy,” it said…

“Not all probiotics are created equal. Some probiotic strains and mixtures are very effective for some types of diseases and should not be overlooked due to studies that lump all probiotics together as one”

My take: Probiotics are overhyped and underperform for most conditions. This report suggests that most people should NOT be taking probiotics.

Related blog posts:

How to Get Rid of the Placebo Effect in Inflammatory Bowel Disease Trials

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A recent study (M Duijvestein et al. Clin Gastroenterol Hepatol 2020; 18: 1121-32, editorial 1030-32) analyzed data from recent randomized, double-blind, placebo-controlled trials for Crohn’s disease (CD).  In these induction trials fro eldelumab, filgotinib, risankizumab, and ustekinumab, the authors found very low rates of placebo response (n=188 in placebo arms).

Key findings:

  • Based on endoscopic assessment of CD activity, response rate to placebo was 16.2%; response indicated >50% reduction in the simple endoscopic score for CD.
  • The rate of remission was 5.2%
  • Even lower rates of response were noted in those with elevated CRP at baseline (OR 0.93) and those with history of anti-TNF therapy (OR 0.31)

Commentary:

  • The key to lowering the placebo response are to use objective biologic markers rather than relying exclusively on clinical symptoms.
  • Central reading of endoscopic endpoints also is thought to minimize placebo effect
  • The editorial notes that the use of placebo in clinical trials “must be justified by the importance of the additional scientific value gained, and placebo should be used in trials only if there is genuine equipoise between the active treatment and placebo.”
  • “Because of ethical questions concerning placebo and the emergence of head-to-head trials, placebo arms may disappear from future IBD trials.”

My take: In reality, very few individuals with CD improve without adequate treatment.  Use of objective criteria is crucial to finding out what really works, both in clinical trials and in clinical practice.

Related blog posts:

IBD Updates: Depression and Crohn’s Disease, Blood Tests in Pediatric IBD

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LW Gaines et al. Inflamm Bowel Dis 2020; 26: 423-8. In this study with 3307 adults with Crohn’s disease (CD) and baseline demographics, CD activity and an affective-cognitive index of depression, the authors used structural equation models to determine the likelihood of whether depression triggers CD activity or whether CD activity triggers depression.  Key findings: “The hypothesis that an affective-cognitive depression predicts patient-reported exacerbation of CD is 218 times more likely to account for the data than the converse.”   (Depression is likely to increase CD activity rather than be due to CD activity).

JJ Ashton et al. Inflamm Bowel Dis 2020; 26: 469-76. Among 256 patients (dx 2013-17) in Southhampton-PIBD database, there were 151 with CD, 95 with UC and 10 IBD-unclassified.  Key findings:

  • 9% presented with all normal blood tests (tests analyzed if available: CRP, ESR, Albumin, platelets, packed cell volume, wbc, ALT)
  • Normal labs were more common with UC compared to CD: 14.4% vs 5.3%

RC Ungaro et al. AP&T; 2020; DOI: 10.1111/apt.15685.  (Thanks to Ben Gold for this reference).  Systematic review with meta-analysis: efficacy and safety of early biologic treatment in adult and paediatric patients with Crohn’s disease. A total of 18 471 patients were studied, with  a median follow-up of 64 weeks (range 10-416). Meta-analysis found that early use of biologics was associated with higher rates of clinical remission (OR 2.10 [95% CI: 1.69-2.60], n = 2763, P < 0.00001), lower relapse rates (OR 0.31 [95% CI: 0.14-0.68], n = 596, P = 0.003) and higher mucosal healing rates (OR 2.37 [95% CI: 1.78-3.16], n = 994, P < 0.00001) compared with late/conventional management. Conclusions: Early biologic treatment is associated with improved clinical outcomes in both adult and paediatric CD patients, not only in prospective clinical trials but also in real-world settings.

RS Boneh et al. Dietary Therapies Induce Rapid Response and Remission in Pediatric Patients With Active Crohn’s Disease Clin Gastroenterol Hepatol (online April 14, 2020, in press) Thanks to KT Park’s Twitter feed for this reference.

  • Methods: We collected data from the multicenter randomized trial of the CD exclusion diet (CDED). We analyzed data from 73 children with mild to moderate CD (mean age, 14.2±2.7 y) randomly assigned to groups given either exclusive enteral nutrition (EEN, n=34) or the CDED with 50% (partial) enteral nutrition (n=39). Patients were examined at baseline and at weeks 3 and 6 of the diet. Remission was defined as CD activity index scores below 10 and response was defined as a decrease in score of 12.5 points or clinical remission. Inflammation was assessed by measurement of C-reactive protein.
  • Results: At week 3 of the diet, 82% of patients in the CDED group and 85% of patients in the EEN group had a dietary remission (DiRe). Median serum levels of C-reactive protein had decreased from 24 mg/L at baseline to 5.0 mg/L at week 3 (P<.001). Among the 49 patients in remission at week 6, 46 patients (94%) had a DiRe and 81% were in clinical remission by week 3. In multivariable analysis, remission at week 3 increased odds of remission by week 6 (odds ratio, 6.37; 95% CI, 1.6–25; P=.008) whereas poor compliance reduced odds of remission at week 6 (odds ratio, 0.75; 95% CI, 0.012–0.46; P=.006).
  • Conclusions: For pediatric patients with active CD, dietary therapies (CDED and EEN) induce a rapid clinical response (by week 3).

Related blog posts:

Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure.  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

 

Efficacy of Anti-TNF Agents for Internal Fistulas and Study of Antibiotics and Development of IBD

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G Bougen et al. Clin Gastroenterol Hepatol 2020; 18: 628-36.  This retrospective study (n=156, median age 32 years) found that anti-TNF therapy delays or prevents surgery for almost half of patients with Crohn’s disease who had luminal fistulas.  Key findings:

  • With a median followup of 3.5 years, “68 patients (43.6%) underwent a major abdominal surgery.”
  • Fistula healing occurred on average 1 year after the introduction of anti-TNF treatment
  • The presence of a stricture or abscess increased the likelihood of surgery.
  • Three patients died from intestinal adenocarcinomas, one patient died from melanoma (6 months after initiation of anti-TNF therapy), one patient died from sepsis (3 months after initiation of anti-TNF therapy, and 32 patients (20.5%) developed an intestinal abscess.

My take: Therapy with anti-TNF agent, in the setting of a luminal fistula, is a reasonable option, especially in the absence of a concurrent stricture.

FS Troelsen, S Jick. Inflamm Bowel Dis 2020; 26: 440-7, editorial 448-9. Using a UK database, the authors identified 461 cases of ulcerative colitis (UC) and 863 cases of Crohn’s disease (CD) and then matched each case to 4 controls. Key findings:

  • There was no association between ever use of antibiotics and UC, OR 1.02 or CD, OR 1.01 compared to never use of antibiotics
  • CD was associated with antibiotic exposure before age 5 (OR 2.2) in analysis restricted to individuals followed from birth
  • A slight increase was seen for CD in ever users of quinolones (OR 1.76, CI 1.00-3.11) and metronidazole (OR 1.43, CI 0.87-2.34)

In the editorial, Charles Bernstein notes that “it may be that specific types of antibiotics…at specific times in a person’s life have differential risks for IBD development. Also, it may be that what triggers IBD in children is different than what triggers IBD later in life.”

Duke University -late Fall 2019