Category Archives: inflammatory bowel disease

CCFA: Updates in IBD Conference (part 2)

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My notes from Georgia Chapter of CCFA’s conference. There could be errors of omission, transcription and/or errors in context based on my understanding.

Sandy Kim, MD –Children’s Hospital of Pittsburgh

Diet in Inflammatory Bowel Disease: Food for Thought

This was a terrific lecture –though much of the topic has been reviewed recently in this blog: Dietary Therapy for Inflammatory Bowel Disease.

Key points:

  • Changes in diet can change microbiome quickly, within 24 hrs
  • Some diets (eg. more fruit/vegetables/fish) may help lower risk of developing IBD
  • Dietary therapy, especially exclusive enteral nutrition (EEN), is effective therapy for Crohn’s disease
  • Why does EEN work?  It is not clear.  There are some changes in microbiome but decrease or little change overall in microbial diversity
  • Reviewed newer dietary approaches: SCD (www.nimbal.org), CD-TREAT, Crohn’s Disease Exclusion Diet

Related blog posts:

Frank Farraye, MD –Mayo Clinic

Health Maintenance in the Adult Patient with IBD

  • Good Practice: Update Vaccinations in IBD population
  • Recent concerns include measles outbreak, and frequent occurrence of Herpes zoster
  • No evidence that vaccination exacerbates IBD
  • New Hepatitis B Recombination Vaccine (Heplisa-B) -2 doses given over one month (for patients older than 18 years. Seroprotective anti-HBs after two doses: 95.4%
  • Shingrix -new recombinant Zoster vaccine.  Overall efficacy 97.2%.  Frequent adverse reactions
  • Women with IBD should undergo annual cervical cancer screening
  • IBD patients should be seen by dermatology
  • Consider depression screening in IBD patients
  • Counsel patients to quit smoking
  • Consider bone density screening in at risk patients

One audience member (Jeff Lewis, MD) pointed out that more attention needs to be paid to depression and anxiety which are much more common and more frequently health-threatening than issues like vaccination.

Related blog posts:

Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  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.

 

CCFA: Updates in IBD Conference (part 1)

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My notes from a recent Georgia Chapter of CCFA’s conference. There could be errors of omission, transcription and/or errors in context based on my understanding.

Adam Cheifetz, MD —Harvard School of Medicine

Optimizing IBD Treatments

  • Earlier treatment with effective therapies
  • Utilizing therapeutic drug monitoring

Goals are clinical and endoscopic remission

  • Imaging if not visible on endoscopy
  • Biomarker remission -adjunctive goal
  • Symptoms and endoscopy do not have good correlation in Crohn’s disease
  • Endoscopic healing associated with better outcomes
  • Treatment –>assessment –> adjust treatment if goal is not met

Biologic Agents:

  • First agent works best; TNF-exposed patients do not respond as well as TNF-naive patients to subsequent biologic
  • High rate of secondary loss of response

Therapeutic Drug Monitoring:

  • Combination therapy in Sonic study was associated with higher infliximab levels. It appears that optimized monotherapy is as effective as combination therapy (Colombel study).
  • Fistula treatment requires higher biologic levels
  • Lower biologic drug levels associated with development of antidrug antibodies
  • Proactive monitoring –recommended
  • Both infliximab and adalimumab are frequently underdosed, especially in pediatrics –>another reason for proactive monitoring
  • If sicker patients, consider checking TDM at week 10; less sick patients, reasonable to consider TDM at week 14

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.

Anti-TNF Therapy: Might Save Your Health But Not Your Wallet

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A recent study (LE Targownik, EI Benchimol, J Witt et al. Inflamm Bowel Dis 2019; 25: 1718-28) shows that direct health care costs are increased with anti-TNF therapy.

In this retrospective study using the Manitoba IBD Database, the authors examined the direct costs associated with anti-TNF therapy initiation in 928 patients (676 CD, 252 UC).  Only 84 subjects were <18 years.

Key findings:

  • The median costs for health care in the year of anti-TNF initiation increased compared to prior year.  In year prior to initiation, median costs were $4698 for CD and $6364 for UC; in the first year of anti-TNF treatment, costs rose to $39,749 and $49,327 respectively.
  • Costs remained elevated through 5 years of anti-TNF therapy for continuous users with total median of $210,956 and $245,260 respectively
  • There were reductions in non-drug costs. Inpatient and outpatient costs decreased in the year after anti-TNF initiation by 12% and 7% respectively, when excluding the costs of anti-TNFs.  These observed savings are considerably less than the medication expenditures.

Discussion:

  • Costs for medications are likely to improve with the introduction of biosimilars.  Currently these are being used mainly in persons with a new diagnosis due to reticence to switch from originator product in established patients.
  • The authors note that costs were overall higher with infliximab (IFX) than adalimumab (ADA) though “it is possible that patients with higher-severity disease are channeled toward IFX over ADA.”
  • Indirect costs like ability to go to work and achieve educational potential could offset some of the direct costs.  In a prior study in the U.S., ADA treatment was estimated to reduce indirect costs of “nearly $11,000 per person treated.”

Limitations:

  • Some costs were not measured in the study including emergency room visits, over the counter medications and alternative health care use.
  • This was not a randomized study; thus, it is impossible to know what costs of persons with similar disease who were untreated would have been.

My take: This study shows that saving money is not the main reason to use anti-TNF therapies; rather, their effects on improved health and fewer complications.

Related blog posts:

Haystack Rock, Cannon Beach OR

IBD Shorts -October 2019

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Briefly noted:

D Piovani et al. Gastroenterol 2019; 157: 647-59.  This study examined environmental risk factors for inflammatory bowel disease after extensive literature review and assessment of meta-analysis.

9 factors that were associated with increased risk of IBD:

  • smoking (CD)
  • urban living (CD & IBD)
  • appendectomy (CD)
  • tonsillectomy (CD)
  • antibiotic exposure (IBD)
  • oral contraceptive use (IBD)
  • consumption of soft drinks (UC)
  • vitamin D deficiency (IBD)
  • Heliobacter species (non-Helicobacter pylori-like) (IBD)

7 factors that associated with reduced risk of IBD:

  • physical activity (CD)
  • breatfeeding (IBD)
  • bed sharing (CD)
  • tea consumption (UC)
  • high folate levels (IBD)
  • high vitamin D levels (CD)
  • H pylori infection (CD, UC, and IBD)

EL Barnes et al. Inflamm Bowel Dis 2019; 1474-80. In this review which identified 12 studies and 4843 with an IPAA ( ileal pouch-anal anastomosis) for ulcerative colitis, 10.3% were ultimately diagnosed with Crohn’s disease. Link to full text and video explanation: The Incidence and Definition of Crohn’s Disease of the Pouch: A Systematic Review and Meta-analysis

EV Loftus et al. Inflamm Bowel Dis 2019; 1522-31. In this study with 2057 adalimumab-naive patients, “the proportion of patients in HBI remission increased from 29% (573 of 1969; baseline) to 68% (900 of 1331; year 1) and 75% (625 of 831; year 6). Patients stratified by baseline immunomodulator use had similar HBI remission rates.”  Full text: Adalimumab Effectiveness Up to Six Years in Adalimumab-naïve Patients with Crohn’s Disease: Results of the PYRAMID Registry

The following study was summarized in previous blog: Oral Antibiotics For Refractory Inflammatory Bowel Disease  Full text link: Efficacy of Combination Antibiotic Therapy for Refractory Pediatric Inflammatory Bowel Disease

Washington Park, Portland, OR

Fewer Surgeries with Crohn’s Disease

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Briefly noted: NE Burr et al. Clin Gastroenterol Hepatol 2019; 17: 2042-49.

In a retrospective cohort (1994-2013) using a primary care database from England, the authors identified decreasing risk of surgeries with Crohn’s diseae (CD).

  • From 1994-2003, the risk of first surgery dropped from 44% to 21%.
  • The risk of a second resection dropped as well, from 40% in 1994 to 17% in 2003 (with 10-year followup)

The reasons for this reduction are not certain but could include better clinical care or reduction in other risk factors (like smoking).

Atlanta Botanical Garden

Ustekinumab for Ulcerative Colitis (UNIFI Trial)

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A landmark study (BE Sands et al. NEJM 2019; 381: 1201-14) shows that ustekinumab (Stelara) can be an effective therapy for moderate-to-severe ulcerative colitis (UC); it is already an approved, established therapy for Crohn’s disease. This randomized placebo-controlled study included an 8-week induction trial (n=961) followed by a 44-week maintenance trial (n=523) for patients with response.

Clinical remission was defined as a total socre of ≤2 on the Mayo scale (range 0-12) and no subscore >11 on any of the four Mayo scale components.

Key findings:

  • During induction, there was a similar clinical remission rate between those who received 130 mg fixed intravenous dose compared to those who received 6 mg/kg: 15.6% and 15.5% compared to 5.3% for placebo group.
  • During maintenance, among patients receiving 90 mg every 8 weeks the clinical remission rate at 44 weeks was 43.8%, in those with 90 mg every 12 weeks the rate was 38.4%; placebo group was 24.0%.
  • The response to ustekinumab occurred in those with or without previous treatment failure with biologic agents, though response was lower in both induction and maintenance in those with prior treatment failure.  In both phases, at least 59% of participants had failed either or both anti-TNF agents or vedolizumab.
  • In this study, there were similar serious adverse events with ustekinumab compared to placebo.  In the treatment groups, there were two deaths (one from ARDS, one from esophageal varices) and 7 cases of cancer (3 nonmelanoma skin cancer, two colon cancer, one prostate, one renal).  There was one death from testicular cancer in the placebo group. Also four patients in the ustekinumab group had opportunistic infections including CMV in two, legionella in one and HSV in one.

In terms of dosing, the authors note that there was greater improvement in calprotectin values during induction in the group who received 6 mg/kg compared to those who received 130 mg.  At week 44, using more objective and stringent end points (eg. endoscopic improvement), greater clinical benefit was observed with the every 8 week regimen.

Visual abstract from NEJM Twitter Feed:

The following image depicts patients response during the maintenance phase –the lightest color is placebo, followed by every 8 weeks, and then the darkest color is every 12 weeks.  The x-axis measures (left to right) are clinical remission, maintenance of clinical response at week 44, endoscopic improvement, corticosteroid-free remission, and remission at 44 weeks in those with remission after induction.

My take: Ustekinumab is more effective for placebo in patients with ulcerative colitis.  More experience is needed to understand its long-term safety.

Related blog posts:

IBD Shorts: September 2019

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S Olivia et al (including Stanley Cohen from GI Care for Kids) Clin Gastroenterol Hepatol 2019; 17: 2060-7. “A Treat to Target Strategy Using Panenteric Capsule Endoscopy in Pediatric Patients with Crohn’s Disease”  In this prospective study with 48 children with Crohn’s disease, pan-enteric capsule endoscopy (PCE) detected inflammation in 34 (71%) at baseline, 22 (46%) at week 24, and 18 (39%) at week 52.  PCE results were used to manage treatment and resulted in change in therapy in 71% at baseline and 23% at week 24.  Furthermore, PCE increased the proportions of patients in deep remission, up to 58% at week 52.

M Wright, et al. J Pediatr 2019; 210: 220-5. This case report of a 4 year-old boy with a perianal abscess and granulomatous colitis identified a NCF4 mutation causing severe neutrophil dysfunction.  He developed osteomyelitis with anti-TNF therapy and did not respond to vedolizumab. He had an excellent outcome following a hematopoietic stem cell transplantation. This study reinforces the potential benefit of investigating VEO-IBD which could allow more targeted therapy. Related blog post:

P Zapater et al. Inflamm Bowel Dis 2019; 25: 1357-66. This study with 112 patients with Crohn’s disease showed that serum interleukin-10 levels were directly related to infliximab and adalimumab levels.  This suggests that serum anti-TNF levels are significantly influenced by immunological activation.

JE Axelrad et al. Clin Gastroenterol Hepatol 2019; 17: 1311-22.  This study, using the Swedish National Patient Register, showed that gastrointestinal infection increased the odds of developing IBD in a nationwide case-control study.  “Of the patients with IBD, 3105 (7%) had a record of previous gastroenteritis compared with 17,685 control subjects (4.1%). IBD cases had higher odds for an antecedent episode of gastrointestinal infection (aOR 1.64), bacterial gastrointestinal infection (aOR 2.02) and viral gastrointestinal infection (aOR 1.55)…a previous episode of gastroenteriitis remained associated with odds for IBD more than 10 years later (aOR 1.26).”  The authors note that they cannot formally exclude misclassification bias, but it appears that enteric infections contribute to the development of IBD in susceptible individuals.

Good Food and Bad Food for Crohn’s Disease -No Agreement

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As noted in a previous blog (IBD Briefs August 2019), there have been numerous diets proposed to help with Crohn’s disease.   The chart below illustrates the lack of any consensus.

Related blog posts:

Integrating Mental Health into Pediatric IBD Care

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WE Bennett, MD Pfefferkorn. JAMA Pediatr. Published online August 19, 2019. doi:10.1001/jamapediatrics.2019.2669

Full Link: Editorial: “Mental Health Screening as the Standard of Care in Pediatric Inflammatory Bowel Disease” Thanks to Ben Gold for this reference.

An excerpt:

Butwicka and colleagues1 have published a fascinating, landmark cohort study in this issue of JAMA Pediatricsassessing the prevalence of psychiatric diagnoses and symptoms among children with inflammatory bowel disease (IBD) in Sweden. The authors used a rigorous design that compared a cohort of more than 6000 pediatric patients with IBD with hundreds of thousands of healthy controls, as well as a separate cohort comprising the patients’ own siblings who did not have IBD. Butwicka et al1 computed hazard ratios for any psychiatric disorder, as well as for multiple specific disorders, and found a hazard ratio of 1.6 for any psychiatric diagnosis when comparing children with IBD with healthy controls. The statistical analysis is stellar and represents the best data we currently have on the intersection of pediatric IBD and mental health. Their study highlights a substantial risk in a vulnerable population and should trigger revision of guidelines and allocation of resources to support widespread screening and treatment for these dangerous conditions.

Related Article:

A Butwicka et al. JAMA Pediatr. Published online August 19, 2019. doi:10.1001/jamapediatrics.2019.2662 

Full Text Link: Association of Childhood-Onset Inflammatory Bowel Disease With Risk of Psychiatric Disorders and Suicide Attempt

Related blog posts:

Crater Lake, OR

Combination Therapy Associated with Treatment Persistence

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Another large retrospective ‘real-world’ study (C Chen et al. Inflamm Bowel Dis 2019; 1417-27) examined persistence profiles of biologic therapies in newly diagnosed IBD patients.  This study, based on Truven Health MarketScan data (2008-2015) included 5612 patients with Crohn’s disease (CD) and 3533 with ulcerative colitis (UC). There were 1156 persons (20.6%) in the pediatric age range (0-18)

Key findings:

  • Less than half of the patients continued using their initial biologic treatment after 1 year (48.5% of CD cohort and 44.8% of UC cohort).
  • For infliximab (IFX) in the CD cohort, the 1 year continued rate was 47.6% and the 5 year rate was 20.0%. In the UC cohort, the rates were 44.9% and 15.7% respectively.
  • For adalimumab (ADA) in the CD cohort, the 1 year continued rate was 50.9% and the 5 year rate was 9.1%. In the UC cohort, the rates were 45.4% and 7.7% respectively.
  • Combination therapy with immunomodulators (IMM) significantly decreased the risk of discontinuation, especially if IMM was started more than 30 days before the biologic agent (HR 0.22).  Simultaneous starting had HR of 0.32.
  • The major predictors for noncompliance included infection and hospitalization.

Why did combination therapy result in higher medication persistence rates?

  • Potential reasons included improved efficacy by direct inflammatory effects and reduced drug antibodies to TNF antagonists.  It is possible that patients receiving combination therapy had more severe disease and thus less likely to discontinue therapy.

Limitation: This study may overestimate drug discontinuation as some patients may simply have had a dosing delay.

My take: This study shows a higher-than-expected rate of drug discontinuation indicating dissatisfaction related to efficacy, cost or complications. Those receiving immunomodulators (combination therapy) were much less likely to discontinue treatment.

Related blog posts:

Wizard Island, Crater Lake, OR

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