A recent article discusses how a British model is an inspiration. “Bethany Townsend made a bold move posting photos of herself in a bikini with colostomy bags on full display….Millions of people have seen her picture on the Crohn’s and Colitis UK page.”
If you want, take a look; here’s the link: British bikini model
Previously Tofacitnib, an oral Janus kinase inhibitor, has shown promise as an emerging treatment for inflammatory bowel disease (Tofacitinib –a JAK Inhibitor for UC | gutsandgrowth). So, a recent large study in tofacitinib use in rheumatoid arthritis caught my attention, specifically with regards to the potential risks of treatment (NEJM 2014; 370: 2377-86).
This double-blind study randomly assigned 958 patients (mean age ~49 years) to receive 5 mg or 10 mg of tofacitinib twice daily or weekly methotrexate. This study, called ORAL Start, examined the effectiveness of these drugs over a 24 month period in patients with active moderate-to-severe rheumatoid arthritis naive to therapeutic doses of methotrexate.
Key findings:
Related blog post: Source Article: Methotrexate Safety | gutsandgrowth
A recent study identifies a new biomarker for Crohn’s disease (CD) (Inflamm Bowel Dis 2014; 20: 1037-48).
The authors examined a cohort of 208 newly diagnosed pediatric CD and 43 non-IBD controls for ileal/rectal expression of FcγRIA mRNA. In addition, in a smaller cohort of 26 newly diagnosed CD patients, 83 established CD patients and 30 non-IBD controls the authors measured peripheral blood polymorphonuclear neutrophil (PMN) CD64 index.
Key findings:
Take-home point: This study shows in pediatrics, as in adults IBD patients, that PMN CD64 index is associated with mucosal inflammation; high levels are associated with clinical relapse. Serum biomarkers are likely to complement stool biomarkers like fecal calprotectin.
One other point the authors make: “studies have found that 57% to 59% of CD have concurrent IBS.” Thus, there is a need for biomarkers to distinguish whether patients with clinical symptoms are experiencing an inflammatory relapse.
Related blog post: Calprotectin: Part of diagnostic algorithm for IBD …
Two other studies in same issue:
“Alterations in the Intestinal Microbiome (Dysbiosis) as a Predictor of Relapse After Infliximab Withdrawal in Crohn’s disease” pages 978-86. N=33 CD patients. Key finding: “CD-associated dysbiosis, characterized by a decrease in Firmicutes, correlates with the time-to-relapse after infliximab withdrawal.”
“Tissue Studies in Screened First-degree Relatives Reveal a Distinct Crohn’s Disease Phenotype” pages 1049-56. N=38 asymptomatic relatives. Key finding: based on histologic scoring 61% were normal, 26% had minor lesions, and 13% had evidence of active disease. This study indicates that screening relatives may identify a subset with early biologic disease.
This month I learned from a recent publication (Inflamm Bowel Dis 2014; 20: 1120-23) that Crohn’s disease without ileal resection does not seem to increase the risk of Vitamin B12 (cobalamin) deficiency. To reach this conclusion, the authors did an extensive literature search and identified 42 relevant articles with 3732 IBD patients.
Key findings:
Take home message: Crohn’s disease, regardless of disease location, did not increase the risk of B12 deficiency in the absence of ileal resections >20 cm.
Related blog posts:
Since the introduction of anti-tumor necrosis factor therapies (anti-TNFs), the benefit of using these agents in combination with immunomodulators or as monotherapy has shifted a few times based on the latest studies. The most influential recent studies had been SONIC and UC Success which indicated that combination therapy for Crohn’s and Ulcerative Colitis, respectively, was more effective and without more adverse effects than monotherapy. A recent study may create some additional uncertainty in this line of thought (Gastroenterol 2014; 146: 941-49).
The author performed a pooled analysis of data from 1594 patients with Crohn’s disease (CD). Studies included CLASSIC I and II, CHARM, GAIN, EXTEND, and ADHERE. In total, these studies provided 3050 patient-years of exposure. For individual patients, the median followup period was 1.5 years.
Key findings:
In the discussion, the authors state “the data suggest that the increased risk likely is attributed to the immunomodulator therapy.”
A related editorial (884-86) helps dissect the articles strengths/limitations as well as implications.
Strengths:
Limitations:
Implications:
Also noted: “Risk of Cancer in Patients with Inflammatory Bowel Diseases: A Nationwide Population-based Cohort Study with 30 Years of Follow-up Evaluation” (Clin Gastroenterol Hepatol 2014; 13: 265-73). n=13,756 patients with CD and 35,152 with UC. Key findings –among CD patients, the excess risk was largely due to extra-intestinal cancers such as hematological malignancies (SIR 1.9) and smoking-related malignancies (SIR 1.5). Associations between UC and gastrointestinal/extraintestinal cancers were weaker (both SIRs were 1.1); the risk of gastrointestinal cancers decreased over the course of the study.
Related blog posts:
According to a recent study (Clin Gastroenterol Hepatol 2014; 12: 821-27), “in a large mulit-institutional IBD cohort, a low plasma level of 25(OH)D was associated with an increased risk of cancer, especially colorectal cancer.” The study reviewed data from 2809 patients who vitamin D levels check (total cohort 11,028 persons with IBD); nearly a third had vitamin [25(OH)D] levels less than 20 ng/mL. The median followup was 11 years. During this period, 7% developed cancer (excluding nonmelanoma skin cancer). Vitamin D deficiency was associated with an adjusted odds ratio of 1.82 of increased cancer risk.
Like so many other studies, this study is another reason for vitamin D manufacturers to feel pretty good. The associated editorial provides some helpful context (pgs 828-30). The evidence regarding vitamin D dates back to at least 1980 when there was an observed higher incidence of colorectal cancer (CRC) mortality in regions with low solar radiation levels. Similar findings were noted with breast cancer.
There is biologic plausibility to the importance of vitamin D with regard to cancer as it is involved in “cell signaling, cell proliferation, cell apoptosis, cell adhesion, angiogenesis and it can up-regulate tumor suppressor genes.” A number of reviews have shown an inverse relationship to vitamin D levels and CRC risk.
The editorial points out a number of potential flaws. “For instance, those who had vitamin D measured may have been among the more ill patients…they may have been the most malnourished.” “Whether patients had concurrent …primary sclerosing cholangitis was also omitted.”
Take-home message (from editorial): “Although the authors have identified an association, for several reasons it may be spurious…the jury is still out as to what impact maintaining normal vitamin D levels may have on reducing inflammation and modulating cancer risk in chronic inflammatory diseases. However, it is healthful to have adequate vitamin D.” In Manitoba, the authors recommend that all of their patients receive vitamin D supplementation. In areas with more sun, checking levels may be worthwhile.
Related 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.
Recently ESPGHAN assembled an international group of European experts in pediatric inflammatory bowel disease (PIBD) to establish practice recommendations (JPGN 2014; 58: 795-806). Their aim was “to revise the original Porto criteria using an evidence-based approach and consensus process to yield specific practice recommendations for the diagnosis of PIBD.”
Before detailing some of their recommendations, I want to state my main criticism: these recommendations do not consider cost or cost-effectiveness. This is important since we do not live in a world where costs are irrelevant.
Some specific recommendations/observations:
1. “We recommend performing small bowel imaging in all suspected cases of IBD at diagnosis; this may be deferred in typical UC.” In addition, all suspected cases of IBD should undergo esophagogastroduodenoscopy (EGD) and ileocolonoscopy. “The diagnostic yield of an EGD to diagnose Crohn’s disease (CD) in patients with an otherwise normal workup [ileocolonoscopy/small bowel imaging] is ~7.5%. ”
2. The authors clarify the use of IBD-unclassified (IBD-U). “IBD-U should be …for patients with colitis and highly atypical findings.” Atypical findings for ulcerative colitis: include rectal sparing, and cecal patch (present in 2% of pediatric patients with left-sided colitis). Table 3 suggests that if at least one “class 2” (rare feature) exists or at least 2 “class 3” (uncommon) feature exists, then labeling IBD-U is appropriate.
Rare (Class 2):
Uncommon (Class 3):
3. Crohn’s disease, according to Table 3, should be diagnosed with any of the following:
4. “Normal blood tests do not exclude the diagnosis of IBD”… Fecal markers (eg. calprotectin) are “extremely sensitive in the detection of mucosal inflammation but are not specific for IBD.”
5.”Although small bowel imaging is encouraged in all of the patients with suspected IBD, it is essential in pediatric patients with CD, IBD-U, or atypical UC.” Magnetic resonance enterography (MRE) is currently the imaging modality of choice in PIBD. Wireless capsule endoscopy (WCE) is a “useful alternative.” The authors advocate for imaging because it may “detect small intestinal involvement…and identify disease complications.”
6. Evaluation for primary immune deficiency should be performed in all cases of PIBD diagnosed <2 years of age.
While the authors acknowledge that “clinical considerations may require taking a course of action that varies from these criteria,” nevertheless, they are likely to influence clinical practice. My personal belief is that there are many situations in which small bowel imaging will not result in changes in clinical care. Furthermore, many patients, especially younger patients, would require anesthesia in order to complete a MRE which is an added burden. In addition, with the added emphasis on assessing response to therapy, one could envision that some patients would be better served with imaging after implementing treatment.
Related blog posts:
Here’s the link (Enteral Nutrition Study) from a summary of the study in Healio Gastroenterology (from their twitter feed) and an excerpt:
Frivolt K. Aliment Pharmacol Ther. 2014;39:1398-1407.
A retrospective study of all pediatric Crohn’s disease (CD) patients treated with exclusive enteral nutrition (EEN) at a children’s hospital in Munich between January 2004 and June 2011. Fifty-two included patients (mean age, 13.2 years; 59.6% male) had newly diagnosed CD (n=40) or had relapsed (n=12) while maintaining treatment for at least 3 months….The first course of EEN showed a higher median starting wPCDAI score compared with the second (59 vs. 40; P<.0001), as well as higher remission rates after 3 months (92% vs. 77%). Relapse rates after 1 year were comparable (67% vs. 70%), but fewer relapses occurred in the first 120 days after the first EEN course compared with the second (25% vs. 45%).
Of 48 patients with NOD2 genotype, 44 went into remission with EEN; 11 of 12 patients carrying R702W or G908R genotype relapsed within 1 year; and there were significantly lower rates of relapse in patients with wild-type (60%) or 1007fs (50%) mutations.
Related blog posts:
As alluded to in a previous post (CCFA Conference Notes 2014 (part 2) | gutsandgrowth), there has been increasing discussion and efforts aimed at mucosal healing (MH) because it is associated with improved clinical outcomes in patient’s with Crohn’s disease (CD). Even before its print publication, this study (Clin Gastroenterol Hepatol 2014; 12: 978-85) by William Sandborn’s group has influenced the discussion.
This retrospective study analyzed 67 patients with CD (2011-2012). These 67 were selected from a population of 510 patients seen at UCSD who had at least several endoscopies and ulcers seen at the initial procedure. In this cohort of 67 patients, the median disease duration was 9.8 years. Only 26 (38.8%) were naive to both immunosuppressives and biologics at referral.
Key findings:
The authors conclude that “serial endoscopic procedures to guide treatment to the goal of MH is feasible in clinical practice.” Ultimately the goal is to influence the natural history of Crohn’s disease.
Study limitations:
From Dr. Sandborn: (from Healio Gastro summary):
“Evidence has accumulated that the complications of Crohn’s disease [CD] … are due to chronic inflammation that has not been fully treated,” William J. Sandborn, MD, chief of the gastroenterology division and director at the University of California, San Diego, IBD Center, told Healio.com. “This in turn has led to the concept of ‘treat to target’ in which patients are assessed with endoscopy for active inflammation prior to making important changes in therapy, and then reassessed with endoscopy within 4 to 6 months to ensure that the therapy change healed the bowel and resolved the inflammation.
“If active disease persists at endoscopy, even in the absence of clinical symptoms, then therapy is intensified and this cycle is repeated until mucosal healing (MH) is achieved.”
Take-home message: This study is one of many that are likely to influence the practice of clinicians to prove that the treatment is exerting a biologic effect and not solely improvement in clinical scoring indices. With the emergence of multiple modalities to assess improvement, including biomarkers and imaging, it is not clear that repeated endoscopy will be the best assessment tool.
Related blog post: EXTEND & MUSIC: Optimizing Crohn Disease Care …
Also noted:
Clin Gastroenterol Hepatol 2014; 12: 986-94. “Association Between Telephone Activity and Features of Patients with Inflammatory Bowel Disease.” The authors found that 15% of patients were responsible for half of all telephone calls. These patients were more likely to be seen in ED and hospitalized.
Clin Gastroenterol Hepatol 2014; 12: 929-34. “Histologic Remission: The Ultimate Therapeutic Goal in Ulcerative Colitis?” This article reviews definitions for histologic remission and highlights questions that need to be addressed before histologic remission is used more widely as a clinical endpoint in trials and in practice.
Briefly noted:
“Physician Knowledge Regarding Concomitant Antibiotic and Oral Contraceptive Use in Patients with IBD.” Gastroenterology & Hepatology 2014; 10: 302-06.
Key finding:
Previous studies suggested that antibiotics reduced OCP efficacy. The authors note that “more recent, prospective, pharmacokinetic studies in women demonstrate no evidence of an interaction between OCPs and most antibiotics, with the exception of rifampin.” (J Am Acad Dermatol 2002; 46: 917-23)
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.
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