K Watanabe et al. Clin Gastroenterol Hepatol 2018; 16: 542-9.
The DIAMOND study evaluated monotherapy with adalimumab (n=85) compared with combination therapy of adalimumab with azathioprine (n=91).
- In this subanalysis of patients with moderate and severe Crohn’s disease (CD), endoscopic response (defined by SES-CD drop of at least 8 points or SES-CD <4) was significantly higher at week 26: 71.6% vs 54.4%. The OR for endoscopic response was 2.12 at week 26 with combination therapy.
- At week 52 the endoscopic response difference was not statistically significant: 60% vs. 50%.
- Similarly, mucosal healing was more common (but not statistically significant) in the combination group compared with monotherapy: 20.9% vs 103% at week 26, and 21.5% vs 12.2% at week 52.
- While not statistically significant, the combination group had ADA trough that was higher (7.6 compared with 6.5).
My take: The results described above for endoscopic responses and mucosal healing rates are depicted in figure 2 (I do not have a digital copy of figure or permission to use). After one looks at this figure, depicting the data noted above, there certainly appears to be an advantage for the use of combination therapy in patients with moderate-to-severe CD.
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I have not independently verified the claims on this tweet
From ImproveCareNow: Resources for Mind Body Interventions
The above linked-website has links to many others for patients and providers: meditation, mindfulness, yoga and guided imagery. The links on this page borrowed from Chelly Dykes and KT Park who credits Dr. Sindu Vellanki and Dr Ann Ming Yeh from Stanford.
Literature on these topics (also from ImproveCareNow): Mind Body Interventions and IBD
Mind Body Interventions and IBD – Journal Articles
- Yeh, A. M., Wren, A., & Golianu, B. (2017). Mind–Body Interventions for Pediatric Inflammatory Bowel Disease. Children, 4(4), 22. doi:10.3390/children4040022
- Mindfulness/ Meditation/ Mindfulness based Stress Reduction (MBSR):
- Kabat-Zinn, J., Lipworth, L., Burney, R., & Sellers, W. (1987). Four-Year Follow-Up of a Meditation-Based Program for the Self-Regulation of Chronic Pain: Treatment Outcomes and Compliance. The Clinical Journal of Pain, 3(1), 60.
**Note: This is an overview of MBSR, not IBD specific
- Neilson, K., Ftanou, M., Monshat, K., Salzberg, M., Bell, S., Kamm, M. A., . . . Castle, D. (2016). A Controlled Study of a Group Mindfulness Intervention for Individuals Living With Inflammatory Bowel Disease. Inflammatory Bowel Diseases, 22(3), 694-701.
- Jedel, S., Hoffman, A., Merriman, P., Swanson, B., Voigt, R., Rajan, K., . . . Keshavarzian, A. (2014). A Randomized Controlled Trial of Mindfulness-Based Stress Reduction to Prevent Flare-Up in Patients with Inactive Ulcerative Colitis. Digestion, 89(2), 142-155.
- Hood, M. M., & Jedel, S. (2017). Mindfulness-Based Interventions in Inflammatory Bowel Disease. Gastroenterology Clinics of North America, 46(4), 859-874.
- Berrill, J. W., Sadlier, M., Hood, K., & Green, J. T. (2014). Mindfulness-based therapy for inflammatory bowel disease patients with functional abdominal symptoms or high perceived stress levels. Journal of Crohns and Colitis,8(9), 945-955. doi:10.1016/j.crohns.2014.01.018
- Gerbarg, P. L., Jacob, V. E., Stevens, L., Bosworth, B. P., Chabouni, F., Defilippis, E. M., . . . Scherl, E. J. (2015). The Effect of Breathing, Movement, and Meditation on Psychological and Physical Symptoms and Inflammatory Biomarkers in Inflammatory Bowel Disease.Inflammatory Bowel Diseases,21(12), 2886-2896.
- Keefer, L., Taft, T. H., Kiebles, J. L., Martinovich, Z., Barrett, T. A., & Palsson, O. S. (2013). Gut-directed hypnotherapy significantly augments clinical remission in quiescent ulcerative colitis. Alimentary Pharmacology & Therapeutics,38(7), 761-771.
- Mawdsley, J. E., Jenkins, D. G., Macey, M. G., Langmead, L., & Rampton, D. S. (2008). The Effect of Hypnosis on Systemic and Rectal Mucosal Measures of Inflammation in Ulcerative Colitis. The American Journal of Gastroenterology,103(6), 1460-1469.
- Shaoul, R., Sukhotnik, I., & Mogilner, J. (2009). Hypnosis as an Adjuvant Treatment for Children With Inflammatory Bowel Disease. Journal of Developmental & Behavioral Pediatrics,30(3), 268.
- Vlieger, A., Govers, A., Frankenhuis, C., & Benninga, M. (2010). Hypnotherapy for children with functional abdominal pain or irritable bowel syndrome: Long term follow-up. European Journal of Integrative Medicine,2(4), 191.
IBS + Yoga:
- Schumann, D., Anheyer, D., Lauche, R., Dobos, G. Langhorst, J., Cramer, H. Effect of Yoga in the Therapy of Irritable Bowel Syndrome: A Systematic Review. Clin. Gastroenterol. Hepatol. 2016, 14, 1720-1731.
- Selvan, S. R., Kavuri, V., Selvan, P., Malamud, A., & Raghuram, N. (2015). Randomized clinical trial study of Yoga therapy for Irritable Bowel Syndrome (IBS). European Journal of Integrative Medicine,7, 23.
- Kuttner, L., Chambers, C., Hardial, J., Israel, D., Jacobson, K., Evans, K. A Randomized Trial of Yoga for Adolescents with Irritable Bowel Syndrome. Pain Research & Management 2006, 11, 217-223.
- Evans, S., Lung, K., Seidman, L., Sternlieb, B., Zeltzer, L., & Tsao, J. (2014). (567) Iyengar yoga for adolescents and young adults with irritable bowel syndrome (IBS). J. Pediatri. Gastroenterol. Nutri. 2014, 59, 244-253.
IBD + Yoga:
- Sharma, P., Poojary, G., Dwivedi, S. N., & Deepak, K. K. (2015). Effect of Yoga-Based Intervention in Patients with Inflammatory Bowel Disease. International Journal of Yoga Therapy,25(1), 101-112.
- Alicia Leiby (abstract only, not published) http://acgblog.org/2014/10/14/a-randomized-controlled-trial-of-yoga-in-pediatric-inflammatory-bowel-disease-preliminary-findings/
- Arruda, J., Bogetz, A., Wren, A., Vellanki, S., Yeh, AM. Is yoga an acceptable adjunctive therapy in the treatment of adolescents with inflammatory bowel disease? Manuscript in Preparation.
Briefly noted: Y Hanada et al. Clin Gastroenterol Hepatol 2018; 16: 528-33.
In this retrospective review with 9247 patients with IBD, the incidence of bacterial pathogens (non-C diff) identified was <3% of those who were tested; in this group (n=25), Aeromonas was detected in 8,Salmonella in 7, Plesiomonas in 4, Campylobacter in 2, and Yersinia in 2. From authors: “These infections did not have a significant negative impact on patient outcomes. Given these findings, routine testing for infections other than CDI is not recommended.”
A recent retrospective study (NE Burr et al. Clin Gastroenterol Hepatol 2018; 16: 534-41) with 3517 patient’s with Crohn’s disease (CD) and 5349 with ulcerative colitis (UC) examined the frequency of opioid prescriptions and the relationship to fatal outcomes.
- Compared to 1990-93, the period of 2010-13 saw a sharp rise in the use of opiods in England: 10% compared to 30%.
- Prescription of strong opioids (>3 prescriptions per calendar year) was associated with premature mortality: Hazard ratio 2.18 for CD and 3.3 for UC.
This study is in agreement with other data showing increasing use of opiate prescriptions worldwide for chronic noncancer pain (although there has been a drop in the past year). As with other studies of patients with inflammatory bowel disease, this study shows an association between opioid use and mortality.
My take: Needing an opioid may be a marker for more severe disease. Whether the opioid use directly contributes to mortality remains unclear.
Full Text Link: ACG Clinical Guideline: Management of Crohn’s Disease. GR Lichtenstein et al. Am J Gastroenterol 2018; 113:481–517
A few of the recommendations from Table 1:
- (Insurance companies –please read this one): #1 Fecal calprotectin is a helpful test that should be considered to help differentiate the presence of IBD from irritable bowel syndrome (IBS) (strong recommendation, moderate level of evidence).
- #9 Perceived stress, depression, and anxiety, which are common in IBD, are factors that lead to decreased health-related quality of life in patients with
Crohn’s disease, and lead to lower adherence to provider recommendations. Assessment and management of stress, depression, and anxiety should be
included as part of the comprehensive care of the Crohn’s disease patient (strong recommendation, very low level of evidence)
- #24, 25 Anti-TNF agents (inﬂiximab, adalimumab, certolizumab pegol) should be used to treat Crohn’s disease that is resistant to treatment with corticosteroids (strong recommendation, moderate level of evidence). Anti-TNF agents should be given for Crohn’s disease refractory to thiopurines or methotrexate (strong recommendation, moderate level of evidence).
- #26 Combination therapy of inﬂiximab with immunomodulators (thiopurines) is more effective than treatment with either immunomodulators alone or
inﬂximab alone in patients who are naive to those agents (strong recommendation, high level of evidence).
- #27 For patients with moderately to severely active Crohn’s disease and objective evidence of active disease, anti-integrin therapy (with vedolizumab) with
or without an immunomodulator is more effective than placebo and should be considered to be used for induction of symptomatic remission in patients with
Crohn’s disease (strong recommendation, high level of evidence).
- #30 Ustekinumab should be given for moderate-to-severe Crohn’s disease patients who failed previous treatment with corticosteroids, thiopurines, methotrexate, or anti-TNF inhibitors or who have had no prior exposure to anti-TNF inhibitors (strong recommendation, high level of evidence).
- #46 Oral 5-aminosalicylic acid has not been demonstrated to be effective for maintenance of medically induced remission in patients with Crohn’s disease,
and is not recommended for long-term treatment (strong recommendation, moderate level of evidence).
- # 58 In high-risk patients, anti-TNF agents should be started within 4 weeks of surgery in order to prevent postoperative Crohn’s disease recurrence
(conditional recommendation, low level of evidence).
From Table 2:
- #9 Symptoms of Crohn’s disease do not correlate well with the presence of active inﬂammation, and therefore should not be the sole guide for therapy. Objective evaluation by endoscopic or cross-sectional imaging should be undertaken periodically to avoid errors of under– or over treatment.
- #23 Routine use of serologic markers of IBD to establish the diagnosis of Crohn’s disease is not indicated.
- #30 Small bowel imaging should be performed as part of the initial diagnostic workup for patients with suspected Crohn’s disease.
- #44 Insufﬁcient data exist to support the safety and efﬁcacy of switching patients in stable disease maintenance from one biosimilar to another of the same biosimilar molecule.
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.
Briefly noted: B Gonzalez-Suarez et al. IBD 24: 775-80.
In 47 patients with established (n=32) or suspected Crohn’s disease (n=15), MRE was first performed to exclude strictures and then subsequently capsule endoscopy (CE) (with patency capsule in 10 patients). Key finding: Small bowel lesions were found in 36 of 47 with CE compared with 21 of 47 with MRE (76.6% vs 44.7%, P=0.001)
Related blog post: Head-to-Head: Capsule endoscopy compared to colonoscopy
A recent retrospective study (K Queliza et al. JPGN 2018; 66: 620-23) describes seven patients with granulomatous disease in the upper GI tract who were diagnosed with ulcerative colitis.
This study examined patients at a single center between 2007-2016 with ages ranging from 2 years to 17 years. Median time of followup is not provided. Two patients required colectomy. All patients had non-casseating granulomas identified in either the stomach or duodenum (or both) along with moderate to severe pancolitis. All of the patients had extensive investigations, generally cross-sectional imaging (MRE or CT) or capsule endoscopy
- “The final classification of IBD was based on expert opinion from gastroenterologists, radiologists, and pathologists upon thorough review of the medical records.”
My take: This study highlights the confusion of the essentially binary classification of IBD into either Crohn’s disease or ulcerative colitis, when in fact there are hundreds of genetic mutations which give rise to inflammatory bowel disease. Given that granulomas are a hallmark of Crohn’s disease and there are no pathognomic features of ulcerative colitis, only time will tell if these patients have an ulcerative colitis phenotype. I wonder how many centers would take exception to this classification and describe these patients as ‘indeterminate’ colitis/IBDU (IBD unclassified).
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