Tag Archives: Ulcerative colitis

Dr. YouTube for IBD Dietary Advice

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K Gkikas et al. Inflamm Bowel Dis 2024; Volume 30, March 2024, 347–356. Open Access! YouTube as a Source of Information for Food, Diet-Related Items, and Advisory Comments for the Management of Inflammatory Bowel Disease

The authors assessed videos discussing dietary aspects (food, diet-related items, and advisory comments [FODRIACs]) on YouTube. Of 1800 videos screened, a total of 160 were included in the final analysis.

Background: “Currently, the only well-established dietary treatment in IBD is exclusive enteral nutrition (EEN), which is used for induction of remission mostly in pediatric CD.5,6 Over the past 2 decades, several food-based exclusion diets have been suggested as potential treatments for CD and UC, some of which demonstrated promising efficacy signals such as the CD-TREAT (Crohn’s disease treatment with eating) diet and the CDED (Crohn’s disease exclusion diet).7-9 Nonetheless, current societal guidelines do not recommend the use of any solid food–based exclusion diet as a treatment option for the induction or maintenance of clinical remission in IBD.6“

Key findings:

  • Foods pertinent to a prudent dietary pattern (ie, fish, chicken, avocado, blueberries), foods high in pre- and probiotics, and certain food exclusion diets (eg, SCD) were primarily portrayed as beneficial.
  • Foods often associated with a Western dietary pattern, including processed foods, high-sugar foods and high-fat foods, red meat, and alcohol, were considered detrimental for disease outcomes in patients with IBD.
  • Neutral opinions were expressed about fiber and vegetables.
  • There was a higher video interaction rate and number of likes in patient-generated videos compared with videos from healthcare professionals.
  • Only 3% of all patient videos and 35% of videos from healthcare professionals cited any form of scientific evidence.
  • Problems with diet advice is that extensive dietary restrictions and adherence to extreme diets may lead to the development of disordered eating as well as nutrient deficiencies (nutritionist involvement is important to avoid this). In addition, reliance on unproven diets may lead some patients to forgo proven therapies.

My take: Though there are some overlapping advice in these videos, much of the dietary advice on YouTube (and elsewhere) is conflicting. In part, this reflects the lack of evidence-based dietary guidelines for IBD. Physicians should review information on dietary therapies at diagnosis and request that families contact them (or well-qualified nutritionists) when considering dietary modifications.

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Delayed Commentary

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I was a little disappointed (aka first world problem) that this commentary appeared in the February print edition of The Journal of Pediatrics about 4 months after the publication of the analyzed study. This blog commented on this study in October: Disparities Are Abundant in Pediatrics -4 Studies on IBD, SUID, Specialty Referrals and in the NICU re: J Smith et al. J Pediatr 2023; 260: 113522.

DJ Spencer. J Pediatr 2024; DOI:https://doi.org/10.1016/j.jpeds.2023.113839. Open Access! Understanding Health Outcomes in Pediatric Inflammatory Bowel Diseases: Contributing Factors that Aren’t so Black and White

“In this issue of The Journal, Smith et al report the results of an historical cohort analysis of 519 children and adolescents with newly diagnosed IBD (2013-2020)… Smith et al ask the question of whether the greater rate of complicated disease in Black patients is related more to delayed diagnosis or access to therapy rather than inherent race-based differences in response to treatment.”

Key points:

  • “In this study, Smith et al importantly identified no difference in initiating standard medical therapies based on race. Specifically, they report no difference in initial corticosteroid usage, time to initiation of maintenance therapy, or time to initiate antitumor necrosis factor therapy. In patients receiving biologics, both Black and White patients received similar loading doses and frequency of therapeutic drug monitoring.”
  • “Despite comparable disease presentation and approach to medical therapy in this study cohort, Black patients strikingly remained only one-half as likely to reach corticosteroid-free remission at 12 months compared with White patients (OR 0.52, 95% CI 0.3-0.9).”
  • ” Black patients were less likely to be seen in gastroenterology specialty clinic for follow-up, more likely to present to the emergency department, and more likely to be hospitalized.”
  • “This study described poorer outcomes in Black patients despite similar treatments. However, the authors fail to arrive at a definitive answer as to why this is the case.”

My take: Black patients, even when offered similar IBD treatment, clearly experience inferior outcomes. While access and social determinants of health are important, there may be biological/phenotypic factors (eg. more aggressive disease) that are involved as well. More studies are needed. This editorial is a helpful review -the timing of the editorial in the print edition many months later, though, is a head-scratcher.

Unrelated topic: CDC COVID-19 Recommendation

The Centers for Disease Control and Prevention announced new isolation guidance for Covid-19 this week. At the start of the pandemic, people were recommended to stay home for 10 days after testing positive. At the height of the Omicron wave, that was revised to 5 days. This week, isolation time was revised to 24 hours without a fever and symptoms improving, which is similar to the recommendations for other illnesses.

St Johns Honeymoon Beach

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Spice It Up! Curcumin for Ulcerative Colitis (2024)

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S Ben-Horin et al. Clin Gastroenterol Hepatol 2024; 22: 347-356. Open Access! Curcumin-QingDai Combination for Patients With Active Ulcerative Colitis: A Randomized, Double-Blinded, Placebo-Controlled Trial

This two part study involved a small open-label trial of combination curcumin-QingDai (CurQD) with 10 patients and a placebo-controlled trial with 42 patients with active ulcerative colitis (UC) over 8 weeks.

Background: “Curcumin and QingDai (QD, Indigo) are herbal compounds previously found to be effective in mild–moderate and moderate–severe ulcerative colitis (UC), respectively, but data on their use still are limited.” Curcumin has purported anti-inflammatory and antioxidant properties through downregulation of nuclear factor-kB, regulation the JAK/STAT pathways, and through its effects on the NLRP3 inflammasome. Qing Dai, also known as indigo naturalis, is a traditional Chinese medicine that has demonstrated efficacy in promoting recovery from colitis in animal models and prior human trials, potentially acting through activation of the aryl hydrocarbon receptor.

Methods: CurQD was administered as 3 capsules of 500 mg herbal extract dry powder QD (a total of 1.5 g) and 3 capsules of 500 mg dry powder curcumin (a total of 1.5 g)

Key findings:

  • Clinical response was observed in 85.7% vs 30.7% (P < .001), clinical remission in 14 of 28 (50%) vs 1 of 13 (8%; P = .01), a 50% calprotectin reduction in 46.4% vs 15.4% (P = .08), and endoscopic improvement in 75% vs 20% (P = .036) in the CurQD and placebo groups, respectively. 
  • In the maintenance arm, 11/15 responders in the CurQD arm maintained remission for an additional 8 weeks with just curcumin alone.

The editorial (pg 235 ) notes the following:

  • The number of patients in the study is small and safety and effectiveness of these agents is not certain. Qing Dai has been associated with a rare risk of pulmonary arterial hypertension (especially with long-term use). Thus, further studies are needed.
  • “Although it may be preferrable to use these agents in combination with therapies with established efficacy, should the patients’ choice be to use alternative therapy as sole agents for treatment, it is important for us to continue to maintain a trusting physician-patient relationship to ensure that our patients are achieving the treatment targets they need to maximize long-term favorable outcomes, irrespective of the therapeutic agent of choice.”

My take: Curcumin (with combination of Qing Dai for induction) was superior to placebo in achieving meaningful clinical outcomes including clinical response, remission, calprotectin improvement and endoscopic improvement. For future studies, I would favor an active comparator like mesalamine rather than placebo.

Related blog post: Spice It Up? Curcumin for Ulcerative Colitis (2015)

IBD Updates: Dual Advanced Therapies in Pediatrics, IL23 agents/Psoriasis

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A Yerushalmy-Feler et al. Inflammatory Bowel Diseases, Volume 30, Issue 2, February 2024, Pages 159–166. Open Access! Dual Biologic or Small Molecule Therapy in Refractory Pediatric Inflammatory Bowel Disease (DOUBLE-PIBD): A Multicenter Study from the Pediatric IBD Porto Group of ESPGHAN

In this retrospective study with 62 children (35 Crohn’s disease, 27 ulcerative colitis) with extensive and severe IBD that was refractory to various therapies, the authors examined the outcomes of combination therapies: the dual therapy included an anti-tumor necrosis factor agent and vedolizumab in 30 children (48%), anti-tumor necrosis factor and ustekinumab in 21 (34%) children, vedolizumab and ustekinumab in 8 (13%) children, and tofacitinib with a biologic in 3 (5%) children.

Key findings:

  • Clinical remission was observed in 21 (35%), 30 (50%), and 38 (63%) children at 3, 6, and 12 months, respectively.
  • Normalization of C-reactive protein and decrease in fecal calprotectin to <250 µg/g were achieved in 75% and 64%, respectively, at 12 months 
  • Twenty-nine (47%) children sustained adverse events, 8 of which were regarded as serious and led to discontinuation of therapy in 6.
  • Among the 43% that were receiving steroids at the start of dual therapy, twenty (74%) of them could be successfully weaned within 3 months after the initiation of dual therapy.
  • Only 2 of 23 (8.7%) had endoscopic healing

My take (borrowed partly from authors):

  1. “Dual biologic therapy may be effective in children with refractory IBD. The potential efficacy should be weighed against the risk of serious adverse events” and affordability.
  2. “There are currently no data for identifying the patients that are more likely to benefit from dual therapy….The ideal selection of dual biologic regimens remains to be determined.”

A Al-Janabi et al. JAMA Dermatol. 2024;160(1):71-79. doi:10.1001/jamadermatol.2023.4846 Open Access! Risk of Paradoxical Eczema in Patients Receiving Biologics for Psoriasis

This study examined more than 13,000 patients enrolled in a prospective cohort study from the British Association of Dermatologists Biologics and Immunomodulators Register for adults treated with biologics for plaque psoriasis.

Key findings:

  •  A total of 273 exposures (1%) were associated with paradoxical eczema.
  • The adjusted incidence rates were 0.94 per 100 000 person-years for TNF inhibitors, 0.80 per 100 000 person-years for IL-12/23 inhibitors, and 0.56 per 100 000 person-years for IL-23 inhibitors.  IL-23 inhibitors were associated with a lower risk of paradoxical eczema (hazard ratio [HR], 0.39)

My take (from authors): The overall incidence of paradoxical eczema was low in biologic-treated patients with psoriasis. The risk was lowest in patients receiving IL-23 inhibitors. Increasing age, female sex, and history of AD or hay fever were associated with higher risk of paradoxical eczema.

Chattahoochee River in Sandy Springs, GA

AGA Guideline on Pouchitis Management

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Key recommendations

  • AGA recommends metronidazole and/or ciprofloxacin as preferred treatment of pouchitis with duration of treatment 2-4 weeks.
  • For Crohn’s-like disease of the pouch, AGA guideline recommends using either ileal-release budesonide or advanced immunosuppressive agents (eg. Biological therapies and small molecule therapies)
  • “In patients with cuffitis, topical therapies should be the first-line therapy, such as mesalamine suppositories, corticosteroid suppositories, or corticosteroid ointment applied directly to the cuff. Biological therapies and small molecule therapies are recommended in refractory cases

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Increased Risk of Suicide in Patients with IBD

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At a lot of IBD conferences, there is often a lot of focus on health maintenance including discussions on optimizing immunization levels and nutrition. It is often striking how, in comparison, so little attention is focused on emotional health which seems to cause a much greater health burden.

CS Tse et al. Inflamm Bowel Dis 2024; 30: 150-153. Increased Risks for Suicide, Self-Harm, Substance Use, and Psychiatric Disorders in Adults With Inflammatory Bowel Disease: A Nationwide Study in the United States From 2007 to 2017

Background: Patients with IBD are also at an increased risk for chronic opioid use, depression, anxiety, sleep disturbance, and disease-related disability (eg, unemployment), all known risk factors for suicide

Methods: This cross-sectional study uses the Nationwide Emergency Department Sample of the Healthcare Cost and Utilization Project (HCUP) as a public domain representing 80% of the U.S. population. This analysis included more than 260 million emergency department visits across the United States from 2007 to 2017.

Key findings:

  • Inflammatory bowel disease conferred >10-fold risk for suicide deaths, self-harm, substance use, and psychiatric disorders.
  • The absolute numbers of self-harm rates were low (<1% of all-cause inflammatory bowel disease emergency department visits; total 56 suicide deaths). This amounts to about 5 suicide deaths per year (compared to 0.5 per year for patients with celiac disease.
  • The risk of self-harm was higher in patients with Crohn’s disease than ulcerative colitis (RR, 3.3; 95% CI, 1.2-5.4), though the suicide risk was not statistically different (RR, 2.3; 95% CI, 0.8-4.5).
From Table 2: RR of self-harm, suicide, psychiatric disorders, and substance use of adults with inflammatory bowel disease compared with celiac disease in the United States from 2007 to 2017. 
The authors found that rates of self-harm and suicide were the same for patients with celiac disease as the general population (RR 1.0).

My take: Attention to mental health is important component of good care for patients with inflammatory bowel disease.

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Immune Mediated Disorders Associated with TNF Inhibitors Can Involve the Liver Too

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Yesterday’s post highlighted immune-mediated disorders likely caused by anti-TNF therapy; this includes rheumatoid arthritis, psoriasis, hidradenitis suppurativa, and chronic recurrent multifocal osteomyelitis. Anti-TNF inhibitors can be the reason for drug-induced liver disease (DILI) including autoimmune hepatitis (AIH) as well. 

  • In one study, 8% of children receiving anti-TNF therapy developed a new elevation in ALT.
  • Most often liver enzyme elevation is mild and transient
  • Differential diagnosis for persistent elevation can be due to DILI, autoimmune liver disease (eg. PSC, AIH), or rarely due to a combination (autoimmune drug-induced liver disease). The latter can improve with drug cessation and with corticosteroid treatment.

Some slides on this topic (courtesy of William. Balistreri):

My take: Serious liver injury related to anti-TNF therapy is rare. When liver enzymes are persistently elevated, consider DILI including anti-TNF agents.

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Is PPI Use Detrimental Before or After a Diagnosis of Inflammatory Bowel Disease?

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N Singh et al. Inflamm Bowel Dis 2023; 29: 1871-1878. Proton Pump Inhibitor Use Before and After a Diagnosis of Inflammatory Bowel Disease

The authors retrospectively utilized the University of Manitoba IBD Epidemiology Database includes all Manitobans diagnosed with IBD between 1984 and 2018 (n=5920). Key findings:

  • Rates of PPI use in control subjects increased gradually from 1.5% to 6.5% over 15 years
  • Persons with IBD had a higher rate of PPI use, peaking up to 17% within 1 year of IBD diagnosis with a rate ratio (RR) of 3.1

The authors noted an abrupt increase in PPI use within 6 months of an IBD diagnosis which could indicate that IBD-related symptoms are being mistakenly treated with a PPI or that IBD may increase reflux-related symptoms. Given the higher rate of PPI use in pre-IBD diagnosis patients, compared to controls, the authors note that “it is possible that their [PPI] use enhances the likelihood of an IBD diagnosis by their role in altering the gut microbiota.” In addition, they note that “a case-control study found that PPIs were associated with an increased risk of pediatric IBD” (NR Schwartz et al. J Pediatr Pharmacol Ther 2019; 24: 489-496).

My take: PPIs are being used more frequently. Whether PPIs are detrimental before or after a diagnosis with IBD is not clear.

Chattahoochee River at Island Ford

IBD Updates

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  1. Allopurinol makes thiopurines more effective. A Vasudevan et al. AP&T 2023; https://doi.org/10.1111/apt.17831 Clinical trial: Combination allopurinol-thiopurine versus standard thiopurine in patients with IBD escalating to immunomodulators (the DECIDER study)

This was  a multicenter, randomized, placebo-controlled trial to compare the efficacy and safety of thiopurine-allopurinol versus thiopurine with placebo for adults commencing a thiopurine for IBD in 102 patients. Allopurinol was dosed at 100 mg. Key findings:

  • A higher proportion achieved the primary outcome (improved clinical score and fecal calprotectin <150) in the thiopurine-allopurinol group (50% vs 35%, p = 0.14) and fewer participants stopped their allocated therapy due to adverse events (11% vs 29%, p = 0.02

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2. Newer treatments and lower colectomy rates in pediatric UC. D Ley et al. AJG 2023; 118:1997-2004 New Therapeutic Strategies Are Associated With a Significant Decrease in Colectomy Rate in Pediatric Ulcerative Colitis. Thanks to Ben Gold for this reference.

Medication exposure and disease outcomes were compared between 3 diagnostic periods: 1988 to 1993 (period [P] 1; pre-IS era), 1994 to 2000 (P2; pre-anti-TNF era), and 2001 to 2011 (P3; anti-TNF era).

  • Key finding: The risk of colectomy at 5 years decreased significantly over time (P1, 17%; P2, 19%; and P3, 9%; P = 0.045, P-trend = 0.027) and between the pre-anti-TNF era (P1 + P2, 18%) and the anti-TNF era (P3, 9%) (P = 0.013). 

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3. More data indicating that anti-TNF therapy does not increase post-operative complications. D Bajzat et al. Inflamm Bowel Dis 2023; 29: 1971-1980. Safety Analysis of Preoperative Anti-TNF-α Therapy in Pediatric IBD After Intestinal Resection: A Systematic Review and Meta-analysis

In this systematic review, the authors identified 8 eligible articles with 526 pediatric patients with IBD. Key finding: “There is no significant association between preoperative anti-TNF-α therapy and postoperative complications in children with IBD after intestinal resection.”

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Pics from Island Ford/Chattahoochee River

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