Tag Archives: Ulcerative colitis

Cancers Complicating Inflammatory Bowel Disease

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In several prior posts, the issue of cancer and inflammatory bowel disease (IBD) has been discussed.  In my view, even the word “cancer” is so scary that it can make people make bad choices (related: Facts, “Misfearing” and Women’s Health | gutsandgrowth).  An up-to-date succinct summary (Laurent Beaugerie, M.D., Ph.D., and Steven H. Itzkowitz, M.D. N Engl J Med 2015; 372:1441-1452) provides a fairly good overview of “Cancers Complicating Inflammatory Bowel Disease.”

Key points:

  • “Smokers are overrepresented among the patients with Crohn’s disease…results in an excess rate of smoking related cancers.” (Smoking also is associated with more aggressive Crohn’s)
  • Colorectal cancers risk factors (Table 1), specific to IBD, include coexisting primary sclerosing cholangitis (PSC), and increasing duration & extent of colonic IBD.
  • A “progressive decrease in the excess risk of colorectal cancer in patients with IBD has been noted over time.”  This may be due to better control of inflammation, surveillance, and colectomy.  Still, the risk of colorectal cancer in patients with IBD is 1.5 to 2 times greater than the general population risk.
  • Small-bowel adenocarcinoma –risk is 20-30 times that of the general population, typically arises more than 8 years after diagnosis.  Absolute risk in those with disease more than 8 years is estimated at “0.5 per 1000 patient-years.”
  • Intestinal lymphomas –absolute risk is about 0.1 per 1000 patient-years.
  • Cholangiocarcinoma (CCA)–absolute risk is approximately “0.08 per 1000 patient-years.” CCA is mainly evident in patients with PSC who have a risk ~160 times the general population and lifelong risk of 5-10%.
  • Non-Hodgkin’s lymphoma –“whether TNF-alpha antagonists promote lymphomas by themselves in patients with IBD is difficult to assess…” A recent study found no excess risk in patients receiving TNF-alpha antagonists after adjustments for cotreatments.
  • Skin Cancers –nonmelanoma skin cancer, though not life-threatening, occur more often in those with current thiopurine usage.
  • HPV-Related Cervical Cancer –“it is still unclear whether the risk of HPV-related cervical cancer is intrinsically increased in woman with IBD or independently worsened by exposure to an immunosuppressant.”
  • Thiopurines: “after adjustment for confounders, current use of thiopurines for IBD has been shown to be associated with an overall relative risk of cancer of 1.3 to 1.7.”
  • TNF-alpha antagonists: “There is no overall excess risk of cancer in patients treated with TNF-alpha antagonists for IBD.”  However, more long-term data are needed.

Recommendations:

  • Figure 2 provides recommendations for colorectal cancer surveillance based on the American Gastroenterological Association (AGA), British Society of Gastroenterology (BSG) and European Crohn’s and Colitis Organisation (ECCO) recommendations. Typically, 8-10 years after diagnosis of colitis, starting surveillance (with chromoendoscopy if available) is recommended.  In patients with Crohn’s disease, “the excess risk appears when more than 30 to 50% of the colonic surface is ever involved.” However, with PSC, the excess risk of colorectal cancer is significant at the time of diagnosis.
  • For cholangiocarcinoma screening in those with PSC, “most experts recommend noninvasive annual imaging of the biliary tract (MRCP or ultrasound) and serum CA 19-9.”
  • For HPV, vaccination is recommended and regular Papanicolaou tests

Take-home message: Some cancers are increased in association with IBD.  However, the medications, particularly immunosuppressants, may reduce the incidence of inflammation-related cancers…or promote immunosuppression-related cancers.

Related blog posts:

Sandy Springs

Sandy Springs

Working on Transition Readiness

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A recent study (Gray WN, et al. Inflamm Bowel Dis 2015; 21: 1125-31) examines preparedness of patients with inflammatory bowel disease (IBD) on the verge of transitioning to adult gastroenterologists from pediatric gastroenterologists.

Using a population of 195 patients (16-25 years), the authors used the Transition Readiness Assessment Questionnaire (TRAQ).  Scoring system:

  • 5= Yes, I always do this when I need to
  • 4= Yes, I have started doing this
  • 3= No, but I am learning to do this
  • 2= No, but I want to learn
  • 1= No, I do not know how

Specific Readiness Skills & Mean Scores (more complete data listed in Table 3):

  • Taking medicines correctly and on own 4.66
  • Arranging for ride to medical appointment 4.39
  • Managing money and budgeting 3.69
  • Calling doctor about unusual change in health 3.64
  • Reordering and getting refills on time 3.60
  • Calling doctor’s office to schedule an appointment 3.09
  • Getting financial help with school or work 2.92
  • Knowing what health insurance covers 2.60
  • Applying for health insurance if coverage lost 2.44

Key finding: “Only 5.6% older adolescents/young adults …met our institutional benchmark.”

To help with transition readiness the authors recommend the CDHNF/NASPGHAN Transition Checklist for parents and starting on transition issues between 12-15 years of age.  Transition checklist available here: Transitioning a Patient With IBD From Pediatric to Adult Care –this is a simple 2-page handout!

Conclusion: Most patients need more work on transition readiness.  If patients are not prepared, it is more likely that this will lead to medical setbacks.

Briefly noted:

“Exercise Decreases Risk of Future Active Disease in Patients with Inflammatory Bowel Disease in Remission” Inflammatory Bowel Dis 2015; 21: 1063-71. This prospective study used the CCFA’s Partners’ internet-based cohort. 227 of 1308 (17.4%) Crohn’s disease (CD) patients and 135 of 549 (24.6%) Ulcerative colitis/indeterminate colitis (UC/IC) patients developed active disease after 6 months.  Key finding: Higher exercise level was associated with decreased risk of active disease for CD (adjusted relative risk 0.72) and UC/IC (adjusted relative risk 0.78).  Take-home point: While there are several limitations to this study, it does seem likely that regular physical exercise is a good idea (not just in patients with IBD).  In this population, subjective markers of disease activity (sCDAI and SCCAI) improved in those who exercised more.

Zoo Atlanta

Zoo Atlanta

Increasing Inflammatory Bowel Disease Among U.S. Patients From India

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An interesting epidemiology study (Malhotra R, et al. Clin Gastroenterol Hepatol 2015; 13: 683-89) shows a high prevalence of inflammatory bowel disease among U.S. residents with Indian Ancestry.

Using a national pathology database on 1,027,977 subjects who had ileocolonic biopsies from 2008-2013, the authors identified 30,812 patients who were diagnosed with inflammatory bowel disease (IBD): 20,308 with ulcerative colitis (UC), 7706 with Crohn’s disease (CD), and 2798 with indeterminate colitis (IC).

Key findings:

  • Among patients with Indian ancestry, the overall prevalence of IBD was 9.1% (n=197 compared with 1960 controls) compared with 4.3% for those of Jewish ethnicity, 2.4% for hispanic ethnicity, and 1.4% for East Asian ethnicity.  The adjusted odds ratio for patients with Indian ancestry was 2.5.
  • In addition, UC was predominant, accounting for 153 of the 197 cases; 26 were diagnosed with CD and 18 were IC.  IBD and UC were highest in subjects with roots in Gujarat.

Take-home point (from authors): “Considering the reported relatively low prevalence of IBD in India, these findings suggest that genetic factors may interact with new environmental conditions to trigger the expression of disease.”

Related blog post: Emigration -One Way to Acquire IBD

Briefly Noted:

Rungoe C, et al. “Inflammatory Bowel Disease and Cervical Neoplasia: A Population-Based Nationwide Cohort Study” Clin Gastroenterol Hepatol 2015; 13: 693-700. Using a Dutch national cohort with more than 27,000 patients, the authors showed a “2-way association between IBD, notably CD, and neoplastic lesions of the uterine cervix.” Overall the risk was mildly increased; for CD, the incidence rate ratio of cervical cancer was 1.53 (CI 1.04-2.27).

Reinisch W, et al. “Factors Associated with Poor Outcomes in Adults with Newly Diagnosed Ulcerative Colitis” Clin Gastroenterol Hepatol 2015; 13: 635-42. The tables in this article summarize clinical characteristics, biologic markers, and treatment factors associated with poor outcomes.  For clinical factors, younger age at diagnosis and age >65 years increase the risk for more severe disease. For biomarkers, increased CRP, ESR, and cal protection were associated with higher risk of progressing to colectomy. For treatment factors, not surprisingly, failing to respond to therapy and absence of mucosal healing were associated with higher risk of progressing to colectomy.

Chattahoochee River National Recreation Area

Chattahoochee River National Recreation Area

Toronto Consensus: Practice Guidelines for Nonhospitalized Ulcerative Colitis

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A group of 23 experts followed a rigorous process over a 1-year period to assess the quality of evidence and develop consensus statements regarding the medical management of ulcerative colitis (UC) in adults (Bressler B, Marshall JK et al. Gastroenterol 2015; 148: 1035-58, editorial 877-80).

The need for updated guidelines has emerged due to practice variation related in part to a wider availability of treatments and diagnostic tools. It is recognized that early institution of effective therapy is associated with the best outcomes.  In addition, due to the chronic nature of ulcerative colitis and the potential for reduced durability of biologic agents, careful decision-making can improve response.

Table 4 in the article summarizes the recommendations.  I will list a few:

1. Thiopurines:

  • “In patients with UC, we recommend against the use of thiopurine monotherapy to induce complete remission.”
  • In selected patients, “we suggest thiopurine monotherapy as an option to maintain complete corticosteroid-free remission.”

2. Anti-TNF therapy:

  • “In patients with UC who fail to respond to thiopurines or corticosteroids, we recommend anti-TNF therapy to induce complete corticosteroid-free remission.”
  • “When starting anti-TNF therapy, we recommend it be combined with a thiopurine or methotrexate rather than used as monotherapy to induce complete remission.”
  • For UC patients with suboptimal response or for those who lose response to anti-TNF therapy, “we recommend dose intensification.”  Dose optimization should be informed by therapeutic drug monitoring.

3. Vedolizumab

  • Vedolizumab is recommended with primary anti-TNF failure (rather than switching to an alternative anti-TNF), whereas either a 2nd anti-TNF or vedolizumab is recommended with secondary anti-TNF failure based on therapeutic drug monitoring.

4. Fecal microbial transplant (FMT)

  • “We recommend against FMT…outside the setting of a clinical trial.”

5. 5-ASA and Corticosteroids

  • Rectal 5-ASA is recommended at 1 g daily for mild-to-moderate ulcerative proctitis.  5-ASA enemas are recommended for mild-to-moderate left-sided ulcerative colitis.
  • In patients with moderate-to-severe UC, corticosteroids are recommended as 1st line therapy for induction of remission but not for maintaining remission.  In addition, corticosteroids are recommended as 2nd-line agents for inducing remission in those with mild-to-moderate disease who do not respond to 5-ASA products.

With all of the treatments, the authors recommend followup to assure response to therapy; this followup ranges from within 2 weeks for steroids, to 4-8 weeks with 5-ASA products, to 8-14 weeks for biologic agents.

Overall, the emphasis of this consensus statement is on maximizing the response to biologic agents.  By optimizing dosing and using combination therapy, the treatment guidelines aim to lower rates of antidrug antibody formation.  This in turn should improve results and is in agreement with data from both the SONIC study and the UC-SUCCESS study.

The editorial comments that methotrexate “may be an attractive option for young male patients;” however, “the absence of data on risk of malignancy with methotrexate in IBD may reflect lower frequency of use for this indication.”

While these guidelines will be useful, there are many unanswered questions (discussed in editorial).

  • In patients on combination therapy, what is the optimal dose of the immunomodulator?
  • When or Should the immunomodulator be withdrawn?
  • For secondary failure, should a 2nd anti-TNF be used prior to vedolizumab?
  • How should these guidelines be tailored for the pediatric population (or the elderly)?
  • What is the optimal monitoring for UC patients with regard to biomarkers and endoscopy?
  • What is the appropriate role of therapeutic drug monitoring?

Bottomline: These guidelines are likely to promote the use of more combination therapy and help define the current role of vedolizumab.

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.

How to Incorporate Budesonide Foam into UC Treatment Algorithm

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A recent study (Sandborn WJ, et al. Gastroenterol 2015; 148: 740-50, editorial 701-4) shows that budesonide foam can be helpful for patients with ulcerative proctitis and ulcerative proctosigmoiditis.

Design: Two identical randomized, double-blind, placebo-controlled trials examined the use of budesonide foam in 546 patients with mild to moderate ulcerative proctitis or ulcerative proctosigmoiditis.  Patients had at least 5 cm of involved mucosa but no more than 40 cm. Dosing: 2 mg/25 mL twice daily for 2 weeks, then once daily for 4 weeks. The primary endpoint of remission was defined as an endoscopy subscore of ≤1, rectal bleeding subscore of 0, and improvement or no change from baseline in stool frequency subscore of the Mayo score. It is noted that about 90% of patients had moderate Mayo endoscopy subscore at baseline.

Key findings:

  • Combining the results of the studies, 41.2% achieved the primary end point of remission at the end of 6 weeks, compared with 24.0% of placebo patients.
  • There were 10 patients (3.7%) with low morning cortisol (compared with 0.7% of placebo-treated patients) and 14% who had abnormal ACTH testing at 6 weeks (compared with 4% of placebo-treated patients), though there no reported signs/symptoms of adrenal suppression present.

The associated editorial suggests that budesonide could be implemented in patients who did not respond to 5-ASA topical therapy (suppository for proctitis and enema for proctosigmoiditis).  In addition, the editorial questions whether a single night-time administration may be more effective by maximizing adherence.

Bottomline: Budesonide foam was superior to placebo in this study and may eliminate the need for systemic steroid use.  As the editorial suggests, 5-ASA topical therapy likely should be considered as first-line treatment.

Related blog post: Budesonide for Ulcerative Colitis

Early Look At Entyvio (Vedolizumab) in Pediatrics

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From DDW 2015 and HealioGastro: Entyvio shows promise in pediatric patients

First study, abstract 321:

Namita Singh, MD, of Cedars Sinai Medical Center in New York, … presented results of a prospective observational study in which they initiated Entyvio (vedolizumab, Takeda; 6 mg/kg, maximum 300 mg) — off label — via intravenous infusion in pediatric patients…The primary clinical outcomes was clinical remission at week 6 (PUCAI ≤ 10; PCDAI ≤ 10).

The study looked at 23 patients (15 with Crohn’s; eight with ulcerative colitis) enrolled between June 2014 and October 2014; median age of vedolizumab initiation was 14 years.

At 88%, the patients with ulcerative colitis had a higher rate of remission than those with Crohn’s who were at 40% [at week 6]. This trend sustained at week 14 and Singh said all patients with ulcerative colitis were in remission at week 14.

Week 6 and week 14 remission rates overall were 46.6% and 54.5%, respectively, and week 6 remission predicted week 14 remission (P < .05).

“Week 6 remission is associated with week 14 remission,” Singh said. “This suggests that we can determine early in therapy whether a patient will be a primary responder to therapy. If not, then perhaps we should move on to another therapy.”

“Longer duration from last anti-TNF exposure is associated with higher remission rates,” Singh said.

Second study, abstract 322:

Ronen Stein, MD, from the Perelman School of Medicine at the University of Pennsylvania, also presented data on vedolizumab therapy in patients with severe pediatric IBD…In this single center, prospective observational cohort study, the primary endpoint was a decrease in PCDAI/PUCAI from baseline to weeks 6, 14 and 22 and secondary endpoints were changes in albumin, hematocrit and CRP as well as remission at the same time points.

Patients received vedolizumab infusions (300 mg) at weeks 0, 2 and 6 for induction and maintenance through week 22.

The researchers included children aged 13 years to 21 years (n = 17) with IBD who weighed 40 kg or more and had a past failure on TNF-alpha inhibitor therapy. Of these patients, 15 had Crohn’s disease and two had unclassified IBD (IBD-U).

More than three-quarters started on systemic corticosteroids at baseline; more than one quarter were on immunomodulators. Seven patients had previous abdominal surgery and 59% of patients had failed more than one biologic therapy…

At each time point in question, this study saw improvement of PCDAI (P < .001 at week 6; P < .05 at week 14; P < .0001 at week 22).

“Starting at week 6, there was a significant decrease in PCDAI that was sustained for weeks 14 and 22.”

Five patients reached remission at week 6.

“There really is no pattern to tell us which patients will be in remission at week 6. They have pretty different characteristics,” Stein said.

Briefly noted:

Link: Case description/images of 9 year old with gastric Crohn’s

Related blog posts:

I love Ria’s Bluebird –the best pancakes ever!

I Love the place: the best pancakes ever!

Brains and Bowels: Kids with IBD Do Fine in School

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Screen Shot 2015-05-04 at 8.11.32 PM

A recent study (Singh H, et al. J Pediatr 2015; 166: 1128-33) showed that overall academic performance was not affected for children with inflammatory bowel disease (IBD).

Study characteristics:

University of Manitoba Database IBD population (n=337) was matched by age, sex, and area of residence to 10 randomly selected controls (n=3093).

Key findings:

  • There were no significant differences in the 2 groups in standardized scores or enrollment in grade 12
  • Lower socioeconomic status and diagnosis with a mental health problem (6-month before or after IBD diagnosis) were independent predictors of worse outcomes

Akin to the quote above, I’ve often felt that it is difficult to think clearly when having severe bowel dysfunction.  At the same time, some of our patients accomplish so much despite their physical setbacks.

Bottomline: This study provides reassurance that children with IBD should be able to complete their course work.

Chicago

Chicago

 

Emigration -One Way to Acquire Inflammatory Bowel Disease

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A recent study (Shitrit AB, et al. Inflamm Bowel Ds 2015; 21: 631-35) highlights the phenomenon of acquiring inflammatory bowel disease (IBD) by moving from a non-developed country to a developed country; the implication is that the changes in environment and diet predispose towards the development of IBD.

This study examined Ethiopian Jews who migrated to Israel.  Using a case-control study, the authors compared 32 Ethiopian immigrants to 33 Ashkenazi patients with IBD.

Key findings:

  • No Ethiopian immigrants had a positive family history compared with 42% of Ashkenazi group.
  • Crohn’s disease was more prevalent in the Ethiopian immigrants: 94% versus 73%.
  • The Ethiopian immigrants lived in Israel for at least 8 years before developing IBD an da median duration of 13 years.

The study discusses the difficulty of diagnosing IBD in rural Africa but speculates that rather than an underdiagnosis of IBD, it is likely to have a true low prevalence of IBD.

Take-home message: It takes many years for the environment exposures to allow for the development of IBD.  Additional work is needed to establish the clinical, genetic, and microbial factors that influence the acquisition of IBD in immigrants to developing countries.  Understanding the susceptibility of immigrants would have widespread application.

Related blog posts:

Accelerated Infliximab Dosing in Acute Severe Ulcerative Colitis -plus one link

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A small retrospective study (n=50) suggests that more rapid induction with infliximab may improve response and lower colectomy rate in acute severe ulcerative colitis (UC).

Link: Accelerated Infliximab in Acute UC

Here’s the abstract:

Background & Aims

Administration of infliximab to patients with acute severe ulcerative colitis (ASUC) (rescue therapy) can reduce the rate of early colectomy (within 12 months), but long-term rates of colectomy are the same as those of the pre-biologic era for these patients. The half-life of infliximab is shorter in patients with ASUC than in patients with non-severe UC, so more frequent dosing might be required to produce a therapeutic effect.

Methods

We performed a retrospective analysis of 50 hospitalized patients who received infliximab for steroid-refractory ASUC at a single academic center from September 2005 through 2013. In 2011 an accelerated dosing strategy for infliximab was introduced; we compared outcomes of standard and accelerated dosing regimens. One group of patients (n = 35) were placed on a standard dosing regimen for infliximab and then given the drug at 0, 2, and 6 weeks and then every 8 weeks thereafter. A second group (n = 15) were placed on an accelerated regimen and received 3 induction doses of infliximab within a median period of 24 days. Rates of colectomy were compared between the groups during induction and follow-up periods.

Results

There were no differences between groups in median baseline levels of C-reactive protein, albumin, or hemoglobin. The rate of colectomy during induction therapy was significantly lower with the accelerated regimen (6.7%, 1 of 15) than with the standard regimen (40%, 14 of 35) (Fisher exact test, P = .039). The standard regimen was associated with shorter time to colectomy (log-rank test, P = .042). Among patients who completed induction therapy, subsequent need for colectomy was similar between the groups during the follow-up period. Multivariate analysis showed that factors independently associated with successful induction therapy were level of albumin (g/L) when the treatment began (P = .003) and the accelerated dosing regimen (P = .03).

Conclusions

In patients with ASUC, an accelerated infliximab induction strategy reduces the need for early colectomy. An intensified infliximab dosing strategy in response to clinical or laboratory signs of breakthrough inflammation merits consideration in prospective studies.

One other link: IBD and College: Do the two play nicely (from Jeremy Adler and UofM) -describes college transition issues for our IBD patients.  Probably the most important piece of advice: “Take your medicine.”  Many really good kids decide to see what happens off therapy, often to their detriment.

Increased Narcotic Usage in Pediatric Patients with IBD

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A summary from the AGA Journals Blog of a recent article highlights the increased use of chronic narcotics, not related to surgery, in pediatric patients with IBD.

Here’s a link:  Chronic Use of Narcotics in Children with IBD and here’s an excerpt:

Jessie P. Buckley et al used data from a large insurance claims database, collected from 2010 through 2011, to compare the prescription narcotic use among children (younger than 18 years old) with and without IBD who were not undergoing surgery. Buckley et al also searched for factors associated with narcotic treatment of pediatric patients with IBD.

Of 4344 children with IBD during the study period, 63% had Crohn’s disease, and 37% had ulcerative colitis.

Buckley et al found that 5.6% among children with IBD vs 2.3% in the general population received chronic narcotic therapy. Associations between IBD and narcotic use revealed a particularly high burden among children with concomitant anxiety or depression.

Cover of Clinical Gastroenterology & Hepatology

Cover of Clinical Gastroenterology & Hepatology –The pills look cool but wrong age depicted