Category Archives: inflammatory bowel disease

Upper endoscopy useful for identifying Crohn’s disease

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In a large pediatric study, the value of upper endoscopy in detecting Crohn’s disease (CD) is evident (JPGN 2012: 54: 753-57).

While the majority of pediatric patients with suspected inflammatory bowel disease probably undergo both upper endoscopy and colonoscopy, the added value of upper endoscopy remains unclear.  In this retrospective study with 171 pediatric patients (70 with CD, 33 with UC, 68 Non-IBD), 11% of children with CD had the diagnosis established based “solely” on the finding of granulomatous inflammation in upper intestinal tract (along with clinical symptoms).

Other key findings:

  • Presence of histologic gastric inflammation in CD patients compared to control patients was significantly higher (p<0.0001) but not significantly higher compared to UC patients (p=0.19).
  • Duodenal inflammation was highly suggestive of CD compared with both UC and non-IBD patients.  This occurred in 19% of CD patients compared with 0% and 1% in the other groups respectively.
  • 21 children (30%) had granulomas identified in upper GI tract (19 in stomach).  In 8 (11%), the diagnosis was changed based on this finding.  Prior to histology, the tenative diagnosis: 2 UC, 4 IC, 2 non-IBD.
One curious finding was a the presence of “perianal abscess/fistula” with similar frequency in CD patients and UC patients based on their Table 2 Patient Characteristics.
Additional references:
  • -IBD 2009; 15: 1101-4.  Presence of UGI disease in IBD.
  • -JPGN 2007; 44: 653.  NASPGHAN report on discriminating/labelling UC vs. Crohn’s.
  • -JPGN 2002; 35: 636-40. Advocates panendoscopy for all new IBD.  Granulomas in 28% of EGDs & 71% of UC pts c some abnl on EGD; 82% Crohn’s c abnl EGD.
  • -JPGN 2005; 41: abstract 181 (page 549).  UGI identified granulomas in 15% that were not identified elsewhere.
  • -JPGN 2004; 39: 257-61. Diagnostic role of EGD for pediatric IBD.
  • Magnetic resonance enterography for Crohn’s disease

Colonic disease and PSC

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While primary sclerosing cholangitis (PSC) has been associated with inflammatory bowel disease, and ulcerative colitis (UC) in particular, the pathogenesis of this relationship has not been established.  A fascinating observation on this relationship is that an inflamed colon is important in PSC development (Clin Gastroenterol Hepatol 2012; 10: 439-41).

In this study which reviewed 2754 Irish patients with IBD, 59 (2.2%) had PSC.  PSC incidence correlated with increasing colonic involvement.  Among the 13 patients with Crohn’s disease, none had isolated small bowel disease.  The second part of the study involved a review of 82 separate PSC patients attending the Irish National liver transplant unit.  The majority of ulcerative colitis patients had a pancolitis; all 10 PSC patients with Crohn’s disease had colonic involvement.

Since PSC occurs without IBD, colonic inflammation is not necessary for PSC development.  However, in patients with IBD, colonic inflammation is very important.  In fact, in a previous study of 53 PSC-IBD patients, no UC patient status post a colectomy had recurrent liver disease following liver transplantation whereas seven patients with intact colons had recurrent disease following liver transplantation.

The authors speculate that bacterial translocation along with subsequent portal bacteremia may be an important step in pathogenesis among these patients.

Additional references/previous posts:

Quantifying Risk of PML with Natalizumab

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Given the limited number of treatment options for inflammatory bowel disease, when Natalizumab became available, there was a great deal of enthusiasm.  This quickly diminished as reports of progressive multifocal leukoencephalopathy (PML) emerged.  So far, I have not prescribed this agent.

Due to its efficacy for multiple sclerosis and IBD, there has been continued interest in understanding the risk for PML (NEJM 2012; 366: 1870-80, editorial pg 1938-39).

Key findings:

  • 212 cases of PML among 99,571 patients treated with natalizumab (2.1 cases per 1000)
  • Three main risk factors: positive JC-virus antibody, previous use of immunosuppressants, and receiving natalizumab more than 2 years

Patients who were negative for anti-JC virus antibodies had an incidence of 0.09 cases or less per 1000 patients.  Among patients who test positive for anti-JC virus antibodies, the risk remained <1 per 1000 patients if no use of immunosuppressants and 2 per 1000 if prior use of immunosuppressants during the first two years of therapy.  The risks were five-fold higher after 2 years in both groups.

While the risks are becoming more clear, the benefits of natalizumab are fairly well-established for multiple sclerosis.  Natalizumab decreased the annualized rate of relapse among patients with relapsing–remitting multiple sclerosis by 68%.

Additional references:

  • -NEJM 2009; 361: 1067, 1075, 1081.  Asymptomatic detection of JC virus common in urine noted in patients Rx’d with natalizumab (19% baseline to 63% on Rx); actual leukoencephalopathy ~1/1000 patients.
  • -Gastroenterol 2007; 132: 1672.  ENCORE trial.
  • -JPGN 2007; 44: 185. n=31 children/adolescents.  55% response, 29% remission; dosed at 3mg/kg.
  • -IBD 2007; 13: 2.  n=79.  Trial of combination natalizumab & infliximab.
  • -NEJM 2006; 354: 899, 911, 924.  Natalizumab slows progression of MS.  Risk of PML due to JC virus 1:1000 in 18 months of Rx.
  • -NEJM 2005; 353: 1912/1965.  Natalizumab not significantly effective for Crohn’s in this study
  • -NEJM 2005; 353: 362, 369, 375, 414.  3 cases of PML associated with Natalizumab
  • -JPGN 2004; 39: S49 [abstract 0107].  Natalizumab in 38 adolescents was effective (Hyams et al).
  • -Gastroenterol 2004; 126: 1574-81. review.  Natalizumab benefitted subjects with elevated CRP. (dosing 300mg every 4 weeks.)
  • -NEJM 2003; 24-32 & 68.  Natalizumab improved response rates in pts c Crohn’s dz (similar to infliximab).  Drug blocks alpha4 integrins which are required for lymphocytes to enter the intestine.
  • -Gastroenterol 2001; 121: 268-74. Infusion of 3mg/kg decreases CDAI in Crohn’s dz.

Improve Care Now

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Several years ago, “ImproveCareNow” Network was established with a goal of improving the quality of care children with inflammatory bowel disease. https://improvecarenow.org/ (http://www.youtube.com/watch?v=beG2eMROWqg)

Documentation of some outcomes of this effort have now been published (Pediatrics 2012; 129: e1030-e1041).  In this study from six U.S. centers, data from 843 children with Crohn’s disease and Ulcerative Colitis were available.  Centers were eligible to participate if they did not have extensive quality improvement (QI) experience and if they were able to enroll >75% of their IBD patients.  During the course of the study (2007-2010), there were increases in the proportion of patients with measurement of thiopurine methyltransferase (TPMT) before initiation of thiopurines, increased percentage of individuals receiving an appropriate thiopurine dosage, and an increased percentage of patients with inactive disease.  In Crohn’s disease, the number with inactive disease changed from 55% to 68%; in ulcerative colitis, the number increased from 61% to 72%.  

This study shows significant progress in these patients and the potential benefit of a more-structured approach.  However, some of the improvements in these outcomes may not be to process improvements. 

Study limitations:

  • The study does not document the rate of inactive disease in non-participating centers; thus there is not an adequate control population.  Given more widespread use of biologic therapies, this may account for much of the improvement in outcomes.   In fact, the study does not describe the percentage of patients receiving thiopurines or biologic agents.
  • The use of the physician global assessment (PGA) as indicative of disease activity.  The authors acknowledge that “PGA ….is a relatively subjective measure.”  A more reliable measure of disease activity like a stool calprotectin, endoscopy, or imaging study improvement would have been helpful.  
  • Better documentation or better outcomes? It is not clear whether some of the improvement reflects better documentation or improved care delivery.

Despite the limitations of this study, it is a good starting point.  The goal of improving the care of patients is shared by almost all physicians.  One way to start making a difference is measuring specific outcomes and targeting specific goals/checklists. Going forward with QI there are many QI hurdles: 

  • Defining optimal care is nearly impossible, there are few trials comparing efficacy & difficult to judge risk/benefit ratio of many therapies.
  • Difficulty selecting appropriate outcome measures -indications for hospitalization and surgery are not clear-cut in many cases.  Surgery may be an appropriate treatment rather than a negative outcome. 
  • Risk adjustment is an imperfect science.

Goals with Quality Improvement:

  • Plan-Do-Study-Act cycles.
  • Learning from high-performing centers -benchmarking

Warranted vs unwarranted variations:
Unwarranted: selecting inadequate dosing of medications, failure to check for TB before remicade/biologics, failure to consider drug interactions, failure to discuss options with families
Warranted: variation due to differences in disease (eg budesonide for ileitis but not pancolitis), variation driven by patient preferences (eg. using NG instead of corticosteroids)

“When you can measure what you are speaking about and express it in numbers, you know something about it; but when you cannot express it in numbers, your knowledge is of a meagre and unsatisfactory kind” –Lord Kelvin 1883

“Not everything that counts can be counted, and not everything that can be counted counts.” –Albert Einstein

Additional references on quality improvement:

  • Free Self Management Handbook endorsed by ImproveCareNow:

https://improvecarenow.org/patients/self-management-handbook

  • -JPGN 2009; 49: 272.  Review of quality measures/history.
  • -Kohn LT, et al. To Err is Human: Building Safer Health System.  Nat’l Academy Press; 2000
  • -Crossing the quality chasm.  Wash DC: Nat’l Academy Press; 2001.
  • -Clin Gastro & Hep 2010; 8: 709.  Quality indicator sets in cirrhosis.
  • -J Pediatr 2005; 146: 744-50.  Bucuvalas JC et al.  Adjusting calcinerin inhibitor dosing
  • -IBD guidelines: www.cincinnatichildrens.org/svc/alpha/health-policy/ev-based/ibd.htm
  • -JPGN 2009; 49: 297.  Variation in care in pediatric Crohn disease. (Our center participated in this study)
  • -J Pediatr 2009; 154: 582.  Ventilator assoc pneumonia reduced w bundle of hand hygiene, elevated HOB, not changing ventilator circuits except when soiled & mouth care
  • -“The Learning Curve”(Atul Gawande) in The Best American Essays 2003 -some CF ctrs outperform, extending life expectancy ~14yrs.
  • -” A Surgeons Notes on Performance-Atul Gawande
    -NEJM 2007; 357: 2652.  Nice editorial.
  • www.icsi.org
  • www.qualityforum.org
  • www.ambulatoryqualityalliance.org
  • www.ncqa.org
  • www.cms.hhs.gov/hospitalqualityinit

Comments from lead author forwarded to blog:

Thanks for including our recent paper in your blog.  I agree with the study limitations as you mentioned, but wanted to put a couple of things in context.  We actually thought very hard about the issue of a control group, and specifically how to determine what the remission rate would be without the intervention.  We could not come up with a reasonable comparator (very few people/groups outside of ICN even know what the remission rate of their population is).  One very rough measure (which we did not feel was legitimate to include) is the rate of remission for new sites as they are joining the collaborative.  Established sites with complete participation have better outcomes than newer sites or sites that participate less fully, suggesting that at least a significant portion of the effect is due to the QI intervention rather than secular trend.  As far as the objective measures for outcomes, I know you realize that we are not able to mandate specific objective evaluations for a QI/observational research study, so we may never be able to use mucosal healing (for example) as our measure of remission.  However you probably noticed in the paper that we did demonstrate improvements in objective measures including sPCDAI, PUCAI and use of corticosteroids.  Certainly improvements in process measures may have been due in part to better documentation, but it is unlikely that objective outcome measures improved due to documentation. Thanks again for sharing our work with your audience.

Disease modifying treatment in IBD

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As noted in this blog (Only one chance to make first impression) and other sites as well, many have argued for early “top down” treatment to try to modify the natural history of Crohn’s disease (CD).  Early in the course of CD when an inflammatory process predominates, theoretically, treatment at this time point can prevent the development of intestinal fibrosis/strictured IBD phenotype.

Support for this approach can now be extrapolated from a mouse model as well (Inflamm Bowel Dis 2012; 18: 460-71).  In this study, the authors eliminated an inflammatory stimulus, Salmonella typhimurium, with levofloxacin treatment.  Treatment was initiated at sequential time points during infection.  Subsequently, the effects of the inflammation on the development of fibrosis was determined by examining histopathology; in addition, the effects on mRNA expression and protein expression were determined.  The time course of a number of cytokines is followed including TNFα, TGFβ, IL12p40, IL-17, IL-1β, and IL-6. While intestinal fibrosis developed even in those with early treatment, early treatment lessened, but did not eliminate, the development of fibrosis.

Since no effective antifibrotics exist and fibrosis may autopropagate even in the absence of inflammation, the authors postulate that early effective treatment has the best opportunity to alter the natural history.

Inadequate treatment of anemia in IBD

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In some patients with inflammatory bowel disease (IBD), treatment of anemia associated with IBD sometimes results in more symptomatic benefit than treatment of the IBD.  Yet, anemia remains common in IBD, both in children and adults (Inflamm Bowel Dis 2012; 18: 513-19).

Using a cross-sectional observational study design, a tertiary adult and pediatric IBD center reviewed consecutive clinic patients in April 2009.  The prevalence of anemia was 70% (41/59) children, 42% (24/54) adolescents, and 40% (49/124) adult.  In addition, iron deficiency anemia was more common in the pediatric population: 36/41 children and 20/23 adolescents.  In the adults with anemia, only 55% (27/49) were iron deficient.  One of the key determinants of anemia was disease activity.

Interestingly, among patients with iron deficiency, younger age was inversely associated with treatment with iron therapy: 13% of children, 30% of adolescents, and 48% of adults.

Other important aspects of anemia in IBD:

  • Anemic patients can have quality of life scores as poor as those seen in malignancy
  • Almost all IBD patients will respond to either oral or parenteral iron.  Erythropoetin reserved for patients who do not respond to parenteral iron.

Additional references:

  • -NEJM 2005; 352: 1011. Anemia algorithm.  If transferrin saturation <16%, check ferritin.  If ferritin less than 30, then patient with Fe-deficiency; if >100, anemia of chronic disease.  If 30-100, could check soluble transferrin receptor (level of sTranReceptor/log ferritin < 1 is c/w anemia of chronic disease whereas when > 2, c/w combined Fe-def anemia and anemia of chronic disease)
  • -JPGN 2010; 51: 708. 25-50% still anemic 1yr post IBD diagnosis.
  • -IBD 2007; 13: 1545-53. Guidelines for anemia mgt w IBD. Max oral absorption is 10-20mg/day; thus IV iron often needed. Goal for iron Rx is transferrin saturation of 15-50% and ferritin > 30 mcg/L (>100 if active inflammation). Anemia of chronic disease likely if TS <16% and ferritin > 100. Rec IV iron Rx prior to use of Epo. IV iron effective alone in 70-80%. Epo if no response to IV iron & Hgb <10. Consider folic acid & B12 deficiency if high MCV. AZA/6MP usually associated with pancytopenia not isolated anemia.
  • -Gastroenterology 2011; 141: 846. Ferric carboxymaltose better than iron sucrose (Ferrlecit/Venofer) b/c can use higher dose & give more rapidly.

Infliximab for children with Ulcerative Colitis

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A large multicenter study of patients 6-17 years of age has shown that infliximab (IFX) can be effective for ulcerative colitis (UC) (Clin Gastroenterol Hepatol 2012; 10: 391-99). Our pediatric GI group was part of this multicenter study which enrolled 60 patients. Stanley Cohen was lead CCDHC investigator and is one of the authors.

At week 8, 44 patients (73.3%) had a clinical response to IFX.  This group of ‘responders’ were eligible for the maintenance phase of the study and were divided into a q8 week treatment group (Q8) and a q12 week treatment group (Q12).  During the maintenance phase, patients who had lost response were eligible to have a dose escalation from 5 mg/kg/dose to 10 mg/kg/dose. At week 54,  patients receiving every Q8 had a remission rate of 38% (8 of 21) whereas among the Q12 responder group only 18% (4 of 22) were in remission.  Overall, the authors projected that if the entire cohort had been placed on every 8 week treatment, the response would have been 28% at week 54; in addition, analysis with ‘real-world’ dose adjustments could achieve a 42.8% remission rate.

The main serious adverse events reported during the study was worsening of UC.  Two patients were receiving immunomodulators during the study. Five of 60 patients required a colectomy within the 54-week study period.

The risk/benefit ratio of TNF antagonists for UC has been discussed in related posts (see below).

Previous related posts:

TNF antagonists and UC

Only one chance to make first impression

Additional references:

  • -Am J Gastroenterol (Oussalah A et al) 2010; 105: 2617-25. Multicenter study of IFX for UC.
  • -Gastroenterology 2010; 138: 2282. Severe pediatric UC. 25/33 responded to IFX. colectomy rate 19% at 1 year.

Magnetic resonance enterography for Crohn’s disease

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Magnetic resonance enterography (MRE) has increasingly been recognized as an effective way to characterize small bowel disease in Crohn’s disease (Inflamm Bowel Dis 2012; 18: 520-28).

In this retrospective pediatric study, 95 patients with Crohn’s disease underwent MRE from 2006-2009.  As expected, terminal ileal disease was the most common site of involvement with 54%; this was followed by ileum with 19%, and jejunum with 17%.  Other findings included solitary jejunal inflammation (3.7%), small bowel stenosis (1.9%) fistula (1%), and abscess (1%).  Specific evidence of inflammation included contrast enhancement, bowel wall thickening or derangement of bowel wall shape.  The images in the article are excellent.

The main advantage of MRE over CT enterography (CTE) is the lack of ionizing radiation.  In addition, MRE can better detect soft tissue contrast suggestive of bowel wall edema.  This helps distinguish acute from chronic inflammation.  Obtaining an MRE is technically more challenging and more costly.  The youngest patient in the study was seven; though the authors note that the youngest patient they have performed MRE was six.

Additional references:

  • More imaging needed?
  • -JPGN 2010; 51: 603.  MRE for suspected IBD.  Useful in pediatric Crohn’s disease.
  • -IBD 2009; 15: 1635. U/S compared favorably with endoscopy in correlating postoperative recurrence with Crohn’s.
  • -Clin Gastro Hepatol 2006; 3: 1221. MRI as accurate in evaluating ileocolonic disease with flareups as endoscopy.
  • -IBD 2004; 10: 452-61. U/S was very helpful in identifying disease and complications.

Drug levels for inflammatory bowel disease

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In many conditions, drug levels are helpful to make sure the patient receives an adequate dose for the indication.  When we treat infections or seizures, drug levels predict the effectiveness of the medication and allow dosing adjustments to improve responses as well as to lower toxicity. Drug levels are helpful in inflammatory bowel disease (IBD) as well.  Drug levels may help with thiopurine dosing and with infliximab (IFX) dosing.

Infliximab (IFX) levels can guide therapy (Scand J Gastroeneterol 2011; 46: 310-18). This study examined 106 patients (85 with CD and 21 with UC) over a ten-year period. In this cohort, patients received concurrent hydrocortisone, acetaminophen, and cetirizine to prevent acute reactions and to try to limit anti-infliximab antibodies (ATI), also called anti-human antichimeric antibodies (HACA).  Infusion intervals ranged from 4-12 weeks.

69% of Crohn’s patients maintained response to IFX and 48% of UC patients.  Infliximab trough levels were significantly increased among patients who maintained their response.  A cutoff value of 0.5 μg/mL was defined as clinically relevant for IFX trough concentrations for Crohn’s patients and for UC the cutoff was 0.8 μg/mL .  Trough levels below this cutoff were 86% sensitive and 85% specific for identifying loss of response.  The overall accuracy for the test was 87% in identifying loss of response.

Also, ATIs were significantly higher in CD patients who had lost response to infliximab.  Patients who had been “re-treated,” were significantly more likely to have developed ATIs.  “Re-treated” was defined as having interruption of IFX treatment more than 6 months.

These specific cutoff values apply to the radioimmunoassay technique for measuring IFX and ATI.  These values may not extrapolate to ELISA assays.  At the same time, the findings suggest a practical approach in patients with symptoms while receiving IFX:

  • Check IFX level (at trough or at 4 weeks)
  • If low level and no ATI, likely to respond to dose escalation
  • If low level but positive for ATI, not likely to respond to dose escalation
  • Do not assume symptoms are due to drug failure; reassess with imaging &/or scope. Consider alternate etiologies (eg infections, stricture, celiac, IBS).
  • Cotherapy with an immunomodulator reduces ATIs and boosts levels of IFX.
More usage of IFX and ATI levels is likely; however, cost issues preclude frequent measurements.

Additional references:

  • Only one chance to make first impression.  Previous blog entry on use of infliximab.
  • -Clin Gastro & Hepatology 2011; 9: 395. Do not assume symptoms are due to drug failure -reassess with imaging &/or scope. Consider alternate etiologies (eg infections, stricture, celiac, IBS). Check IFX level –if >12 @ 4weeks or >1.4 mcg/mL at trough –>predicts good response.  If +HACA, ~90% response with alternative TNF.  In those with low level, 86% responded to dose escalation.
  • -DDW 2011, Abstract #772. If loss of response to IFX, **confirm active dz (labs, scope) & not due to CDT. **check HACA –if +, only 10-20% chance of responding to dose escalation; better chance of responding to similar agent **check IFX week 4 level, if low (& neg HACA) then 90% respond to dose escalation
  • -NEJM 2010; 362:1383-1395. SONIC study.  Patients with moderate-to-severe Crohn’s disease who were treated with infliximab plus azathioprine or infliximab monotherapy were more likely to have a corticosteroid-free clinical remission than those receiving azathioprine monotherapy.
  • -Gut 2010; 59: 49-54. Trough IFX levels in UC. n=115. Antibody status can only be measured at trough levels. Undetectable trough level (<1.4 mcg/mL) associated with lower remission (15% vs 69%) and lower endoscopic response (28% vs 76%) & higher colectomy rate (55% vs. 7%).
  • -Gastroenterology 2010; 139: 344 (review of above Gut article). Similar to Crohn’s disease: 82% remission with detectable trough vs 6% w/o detectable level.
  • –Lancet 354 (9194): 1932–9. doi:10.1016/S0140-6736(99)05246-0. PMID 10622295.”Infliximab (chimeric anti-tumour necrosis factor alpha monoclonal antibody) versus placebo in rheumatoid arthritis patients receiving concomitant methotrexate: a randomised phase III trial. ATTRACT Study Group”.
  • -Am J Gastroenterol 2010; 105: 1133-39. If lack/loss of response, may need dose escalation with humira or Cimzia (q2weeks):
  • -IBD 2011; 17: 141-51. Loss of response to biologics.
  • -Gastro & Hep 2008; 4: 12. “primary nonresponse can be determined after 2 doses” in table reiterating AGA consensus guidelines. 85% of responders show benefit by 2weeks & all responders benefit c/in 6 weeks (Am J Gastro 2001; 96: S303). Worsening Sx despite infliximab indicates need to look for stricture, infxn, etc.
  • -Clin Gastro & Hep 2006; 4: 1248. Clinical remission associated with measurable infliximab troughs; thus, if no measurable trough, increase dose or shorten interval. If level detected & no response, unlikely to respnd to TNF class. Also, concurrent immunomodulators were not helpful.
  • -Am J Gastro 2010; 105: 2617 (Oussalah et al). 2-3yrs 41% IFX failure in UC. withdrawal of AZA increase loss of response –7x more likely
  • -Am J Gastro ; 105: 1133-40. n=155. 23% ATI -92% respond to med change, 17% respond to dose change. Level <12 @ 4weeks, 86% respond to dose change
  • -Gut 2010; 59: 1363. n=121. Co-treatment helped reduce complications & flares relative to monotherapy (& azathioprine appeared to be more effective than methotrexate).

Vitamin D, IBD, and Causality

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The importance of vitamin D has been noted in this blog previously (Common to be “D-ficient” ).  Now a study implicates vitamin D as a risk factor for developing inflammatory bowel disease, especially for Crohn’s disease (Gastroenterology 2012: 142: 482-89).  It is known that vitamin D influences innate immunity.  As such, it may play a role in the susceptibility to Crohn’s disease (CD) and Ulcerative colitis (UC).

This prospective study included 72,719 women (age 40-73) enrolled in the Nurses’ Health Study.  Research subjects completed an assessment of diet and lifestyle along with 25-hydroxy vitamin D [25(OH)D] levels.  The 25(OH)D levels were predicted; this prediction was based on a validated model which included vitamin D intake, sun exposure, race, and body mass index (J Natl Cancer Inst 2006; 98: 451-9).  This model was validated against directly measured 25(OH)D levels.

During nearly 1.5 million person-years of followup, 122 incident cases of CD and 123 cases of UC occurred.  The adjusted hazard ratio (HR) for the highest quartile of 25(OH)D was 0.54 for CD and 0.65 for UC compared to the lowest quartile.  Compared with a level less than 20, the highest quartile HR was 0.38 for CD and 0.57 for UC.

In addition, the authors identified a significant inverse association between dietary supplemental vitamin D and UC; an insignificant reduction in CD risk was noted with dietary intake.  Although it is difficult to determine causality, these data convincingly show that ‘healthy’ levels of vitamin D are associated with a lower risk of IBD.