Evaluation of an integrated yoga program in patients with inflammatory bowel disease: A pilot study.

BACKGROUND: The effects of integrated yoga programs on mental health outcomes in inflammatory bowel disease (IBD) have not been well explored. To explore the acceptability, implementation and effectiveness of an integrated eight-week yoga program plus aromatherapy massage in patients with IBD. METHODS: Nine participants with documented IBD were recruited from a gastroenterology clinic in Calgary, Alberta, Canada to participate in an integrated yoga program weekly for eight weeks with outcomes assessed at baseline and week 8. Primary outcomes were assessed using Theory of Planned Behaviour as a guiding theory to identify salient beliefs from qualitative analysis of a semi-structured interview, survey items measuring the strength of beliefs and a daily log was used to capture adherence and adverse events. Secondary outcomes were collected using validated survey tools examining anxiety, depression, stress, sleep quality, and physical and mental quality of life. RESULTS: Attitude, subjective norm and perceived behavioral control beliefs pertinent to the yoga intervention and daily practice were identified. Participants reported feeling the intervention was very helpful; however, felt guilt about not completing daily practices which decreased confidence and intention to continue with the practice. An average of 55.6% of in-person sessions were attended and decreased over time. Participants practiced on average of 5.4 days per week. Depression and mental health scores improved at week 8 from baseline. CONCLUSIONS: We were able to identify key salient beliefs of IBD patients in regard to an integrated yoga plus aromatherapy massage intervention. This intervention appears to be acceptable and further research should explore its potential to improve mental and physical health outcomes including IBD symptoms.

Efficacy of Pharmacological Agents for Ulcerative Proctitis: A Systematic Literature Review.

BACKGROUND: Ulcerative proctitis is a common and often highly symptomatic form of inflammatory bowel disease. We performed a systematic review to assess the efficacy of different therapies in the management of patients with ulcerative proctitis. METHODS: We identified randomized controlled trials in adults with ulcerative proctitis treated with oral or topical therapies for induction of response or remission, or prevention of relapse. RESULTS: A total of 32 randomized controlled trials were included [27 induction/2839 participants, five maintenance/334 participants]. Follow-up varied from 3 to 8 weeks for induction, and from 6 to 24 months for maintenance of remission. 5-Aminosalicylic acid [5-ASA] suppository was the most frequently evaluated treatment [14/32, 43.7%], followed by steroid enema [7/32, 21.9%]. Topical 5-ASA demonstrated effectiveness for induction of clinical response or remission and prevention of relapse in several studies. Combined topical steroids and 5-ASA was more effective than topical 5-ASA or topical steroids alone to induce response [100% of patients for combination vs 70% for beclomethasone alone and 76% for 5-ASA alone]. One observational study suggested azathioprine may be effective in patients with ulcerative proctitis. Only two cohort studies evaluated the efficacy of tumour necrosis factor inhibitors in ulcerative proctitis. Small molecules, anti-integrins and anti-interleukin therapies have not been evaluated in isolated ulcerative proctitis. CONCLUSION: The role of topical 5-ASA as a treatment for ulcerative proctitis has been confirmed in this systematic literature review, for induction and maintenance of remission. Future trials are needed to investigate the efficacy of more recent and upcoming drug classes in patients with ulcerative proctitis.

Comparative efficacy and safety of biologic therapies for moderate-to-severe Crohn's disease: a systematic review and network meta-analysis.

BACKGROUND: Data are needed to inform the positioning of biologic therapy in the treatment of moderate-to-severe Crohn's disease, both first line and after previous biologic exposure. We aimed to assess the comparative efficacy and safety of biologics in patients with Crohn's disease. METHODS: We did a systematic review and network meta-analysis of phase 2 and phase 3 randomised controlled trials done in adults (≥18 years) with moderate-to-severe Crohn's disease (Crohn's Disease Activity Index [CDAI] 220-450) treated with tumour necrosis factor (TNF) antagonists, anti-integrin, anti-interleukin (IL)-12 and IL-23p40, or anti-IL23p19 agents, either alone or in combination with immunosuppressants, as their first-line biologic or after previous biologic exposure, compared with placebo or an active comparator. The minimum duration of therapy was 14 days for trials reporting induction of remission in active disease and 22 weeks in trials reporting maintenance of remission. We searched Medline, EMBASE, the Cochrane CENTRAL Register of Controlled Trials, conference proceedings, trial registries, and unpublished data from inception to June 3, 2021, without any language restrictions. Summary estimates of the primary and secondary outcomes were extracted from the published reports; individual patient-level data were not sought. The primary endpoint was induction of clinical remission in patients with active disease (CDAI <150) and maintenance of remission in patients with response to induction therapy, with data extracted from published reports. A network meta-analysis with multivariate consistency model random-effects meta-regression was done, with rankings based on surface under the cumulative ranking curve (SUCRA) values. FINDINGS: The search strategy yielded 18 382 citations, of which 31 trials were eligible for inclusion. On the basis of 15 randomised controlled trials including 2931 biologic-naive patients, infliximab monotherapy (odds ratio [OR] 4·53 [95% CI 1·49-13·79]), infliximab combined with azathioprine (7·49 [2·04-27·49]), adalimumab (3·01 [1·25-7·27]), and ustekinumab (2·63 [1·10-6·28]) were associated with significantly higher odds of inducing remission compared to certolizumab pegol (all moderate confidence); infliximab and azathioprine combination therapy was also associated with significantly higher odds of inducing remission than vedolizumab (3·76 [1·01-14·03]; low confidence). On the basis of ten randomised controlled trials including 2479 patients with previous biologic exposure, adalimumab after loss of response to infliximab (OR 2·82 [95% CI 1·20-6·62]; low confidence), and risankizumab (2·10 [1·12-3·92]; moderate confidence), were associated with higher odds of inducing remission than vedolizumab. No differences between active interventions were observed in maintenance trials. Most trials were at low or uncertain risk of bias. INTERPRETATION: Although biologic treatment choices in patients with moderate-to-severe Crohn's disease must be individualised for each patient, this analysis suggests that either infliximab with azathioprine or adalimumab might be preferred as a first-line therapy, and adalimumab (after infliximab loss of response) or risankizumab might be preferred as a second-line therapy, for induction of clinical remission. FUNDING: None.

Effects of Apremilast, an Oral Inhibitor of Phosphodiesterase 4, in a Randomized Trial of Patients With Active Ulcerative Colitis.

BACKGROUND & AIMS: New oral therapeutic agents are needed for patients with ulcerative colitis (UC) who are unresponsive or intolerant to conventional therapy. METHODS: We performed a double-blind, phase 2 trial of adults with active UC for 3 months or more who were naïve to biologic therapy or had been failed by, could not tolerate, or had contraindications to conventional therapies. The study was performed at 61 sites in 14 countries (screening from January 2015 through May 2017). Patients were randomly assigned to groups given apremilast 30 mg (n = 57), apremilast 40 mg (n = 55), or placebo (n = 58) twice daily for 12 weeks; patients were then randomly assigned to groups that received apremilast, 30 or 40 mg twice daily, for an additional 40 weeks. Endoscopies were performed and biopsies were collected during the screening phase, at week 12, and at week 52. Blood and fecal samples were also collected and analyzed throughout the study. The primary endpoint was clinical remission at week 12, defined as a total Mayo score of 2 or less, with no individual subscore above 1. RESULTS: Clinical remission was achieved at week 12 by 31.6% of patients in the 30 mg apremilast group and 12.1% of patients in the placebo group (P = .01). However, only 21.8% of patients in the 40 mg apremilast group achieved clinical remission at week 12 (P = .27 compared with placebo). Differences in clinical remission between the 30 mg and 40 mg apremilast groups were associated with differences in endoscopic improvement. Both apremilast groups had similar improvements from baseline in Mayo score components (stool frequency score, rectal bleeding score, physician's global assessment). The 30 mg and 40 mg apremilast groups had greater median percent reductions in C-reactive protein (measured by a high-sensitivity blood test) and fecal calprotectin through week 12 than the placebo group. At week 52, clinical remission was achieved by 40.4% of patients initially assigned to the apremilast 30 mg group and 32.7% of patients initially assigned to the apremilast 40 mg group. The most frequent apremilast-associated adverse events were headache and nausea. CONCLUSIONS: Although the primary endpoint of clinical remission was not met in this phase 2 trial, a greater proportion of patients with active UC who received apremilast (30 mg or 40 mg) had improvements in clinical and endoscopic features, and markers of inflammation, at 12 weeks. Clinical remission was maintained to week 52 in up to 40% of patients who continued apremilast until that time point. ClinicalTrials.gov no: NCT02289417.

Pregnant Women with Inflammatory Bowel Disease Are at Increased Risk of Vitamin D Insufficiency: A Cross-Sectional Study.

BACKGROUND AND AIMS: Vitamin D insufficiency is prevalent in individuals with inflammatory bowel disease [IBD], as well as in pregnant women; however, the prevalence of vitamin D insufficiency in pregnant women with IBD is unknown. This study assessed the prevalence of vitamin D insufficiency in pregnant women with IBD and the adequacy of recommended supplementation. METHODS: A cross-sectional study was conducted in pregnant women with inflammatory bowel disease [Crohn's disease = 61, ulcerative colitis = 41] and without inflammatory bowel disease [n = 574]. Chi square tests and log binomial regression were used to examine the prevalence of vitamin D insufficiency. Covariates included ethnicity and season. Adequacy of vitamin D supplementation during pregnancy was also assessed. RESULTS: The prevalence of vitamin D insufficiency [25-OHD ≤75 nmol/L] in those with Crohn's disease was 50.8% (95% confidence interval [CI]: 38.4%-63.2%) and 60.9% [95% CI: 45.3%-74.7%] with ulcerative colitis compared with 17.4% [95% CI: 14.6%-20.8%] without inflammatory bowel disease. Women with inflammatory bowel disease were more likely to be vitamin D insufficient after adjusting for ethnicity and season (Crohn's disease-adjusted relative risk [aRR] = 2.98,;: 2.19-4.04; ulcerative colitis-aRR = 3.61; 95% CI: 2.65-4.93). Despite vitamin D supplementation, 32.3% [95% CI: 17.8%-51.2%] of those with Crohn's disease, 58.3% [95% CI: 37.1%-76.9%] of those with with ulcerative colitis, and 10.8% [95% CI: 6.9%-16.6%] of those without inflammatory bowel disease were still vitamin D insufficient. CONCLUSIONS: Pregnant women with inflammatory bowel disease are at increased risk of vitamin D insufficiency compared with those without inflammatory bowel disease. The current guidelines for vitamin D supplementation may be inadequate for pregnant women with inflammatory bowel disease.

Modern management of perianal fistulas in Crohn's disease: future directions.

Perianal fistulae in patients with Crohn's disease (CD) can be associated with significant morbidity resulting in negative impact on quality of life. The last two decades have seen significant advancements in the management of perianal fistulas in CD, which has evolved into a multidisciplinary approach that includes gastroenterologists, colorectal surgeons, endoscopists and radiologists. Despite the introduction of new medical therapies such as antitumour necrosis factor and novel models of care delivery, the best fistula healing rates reported with combined medical and surgical approaches are approximately 50%. More recently, newer biologics, cell-based therapies as well as novel endoscopic and surgical techniques have been introduced raising new hopes that outcomes can be improved upon. In this review, we describe the modern management and the most recent advances in the management of complex perianal fistulising CD, which will likely impact clinical practice. We will explore optimal use of both older and newer biological agents, as well as new data on cell-based therapies. In addition, new techniques in endoscopic and surgical approaches will be discussed.

Interpreting Registrational Clinical Trials of Biological Therapies in Adults with Inflammatory Bowel Diseases.

BACKGROUND: The use of biologics to treat inflammatory bowel disease is supported by robust randomized controlled trials in both ulcerative colitis and Crohn's disease. Nonetheless, an understanding of the principles of clinical trial design is necessary to extrapolate study findings to clinical practice. METHODS: We conducted a review of inflammatory bowel disease registrational clinical trials of biologics to determine how differences in trial design potentially influence results and interpretation. RESULTS: Registrational trials of biological agents have used diverse patient populations, outcome measures, and designs, which makes comparisons of results among studies difficult. Key differences among trials include patient populations, choice of symptom-based measures or objective outcomes as endpoints, and overall trial design. Additional factors, including analytical methods, can also influence the interpretation of outcomes. CONCLUSIONS: The most robust evidence is derived from comparative effectiveness trials. In the absence of these, clinicians should be aware of the various methodological issues which could impact interpretation of efficacy and safety outcomes, including differences in patient population, study design, and analytic methodology.

Type I interferons for induction of remission in ulcerative colitis.

BACKGROUND: Interferons (IFNs) are cytokines which possess immunoregulatory properties and have been used to successfully treat a number of chronic inflammatory disorders. It has been postulated that Type I IFNs may be able to re-establish the Th1/Th2 balance in Th2 predominant diseases like ulcerative colitis. OBJECTIVES: To systematically evaluate the efficacy and safety of type I IFN therapy for induction of remission in ulcerative colitis. SEARCH METHODS: We searched MEDLINE, EMBASE, CENTRAL, the Cochrane IBD/FBD group specialised register, and ClinicalTrials.gov from inception to August 8, 2014. Reference lists of trials and review articles, as well as recent proceedings from major gastroenterology meetings were manually searched. SELECTION CRITERIA: Randomised controlled trials of type I IFNs for induction of remission in UC were included. The study population included patients of any age with active ulcerative colitis. There were no exclusions based on type, dose or duration of IFN treatment. DATA COLLECTION AND ANALYSIS: Two independent authors reviewed studies for eligibility, extracted the data and assessed study quality using the Cochrane risk of bias tool. The overall quality of the evidence supporting the outcomes was evaluated using the GRADE criteria. The primary outcome was induction of remission of ulcerative colitis. Secondary outcomes included: time to remission, mean change in disease activity index score, clinical, histological or endoscopic improvement, improvement in quality of life, and adverse events. We calculated the risk ratio (RR) and corresponding 95% confidence interval (CI) for dichotomous outcomes. We calculated the mean difference and corresponding 95% confidence interval for continuous outcomes. Meta-analysis was performed using RevMan 5.3.5 software. MAIN RESULTS: Six studies were eligible for inclusion (517 patients). Five studies compared type I IFNs to placebo injections (485 patients) and a single study compared IFNs to prednisolone enemas in patients with left-sided colitis (32 patients). The active comparator study was rated as high risk of bias due to an open-label design. Three studies were rated as unclear risk of bias for random sequence generation and allocation concealment. Two studies described as double blind were rated as unclear risk of bias for blinding. There was no significant benefit of type I IFNs over placebo for inducing clinical remission or improvement in patients with active ulcerative colitis. Thirty-six per cent (87/242) of patients in the type I IFNs group achieved clinical remission by 8 to 12 weeks compared to 30% (36/120) of placebo patients (RR 1.16, 95% CI 0.84 to 1.58; 4 studies, 362 patients). A GRADE analysis indicated that the overall quality of the evidence supporting the outcome clinical remission was moderate due to sparse data (123 events). Fifty-six per cent (149/264) of patients in the type I IFNs group improved clinically by 8 to 12 weeks compared to 48% (77/161) of placebo patients (RR 1.16, 95% CI 0.96 to 1.40; 4 studies, 425 patients). A GRADE analysis indicated that the overall quality of the evidence supporting the outcome clinical improvement was moderate due to sparse data (226 events). Patients who received type I IFNs were significantly more likely to withdraw from the studies due to adverse events than those who received placebo. Seven per cent (18/42) of type I IFNs patients withdrew due to adverse events compared to 2% (3/152) of placebo patients (RR 3.16, 95% CI 1.06 to 9.40). A GRADE analysis indicated that the overall quality of the evidence supporting the outcome withdrawal due to adverse events was low due to very sparse data (21 events). The study comparing type I IFNs to prednisolone enemas found no difference between the treatment groups in quality of life or disease activity scores. Common adverse events included headaches, arthralgias, myalgias, fatigue, back pain, nausea, application site reactions, rigors, and fevers. There were no statistically significant differences in the other secondary outcomes. AUTHORS' CONCLUSIONS: Moderate quality evidence suggests that type I IFNs are not effective for the induction of remission in UC. In addition, there are concerns regarding the tolerability of this class of treatment.

Living with inflammatory bowel disease: A Crohn's and Colitis Canada survey.

BACKGROUND: Despite improvements in therapies for inflammatory bowel diseases (IBDs), patient quality of life continues to be significantly impacted. OBJECTIVE: To assess the impact of IBD on patients and families with regard to leisure, relationships, mental well-being and financial security, and to evaluate the quality and availability of IBD information. METHODS: An online survey was advertised on the Crohn's and Colitis Canada website, and at gastroenterology clinics at the University of Alberta Hospital (Edmonton, Alberta) and University of Calgary Hospital (Calgary, Alberta). RESULTS: The survey was completed by 281 IBD patients and 32 family members. Among respondents with IBD, 64% reported a significant or major impact on leisure activities, 52% a significant or major impact on interpersonal relationships, 40% a significant or major impact on financial security, and 28% a significant or major impact on planning to start a family. Patient information needs emphasized understanding disease progression (84%) and extraintestinal symptoms (82%). There was a strong interest in support systems such as health care insurance (70%) and alternative therapies (66%). The most common source of information for patients was their gastroenterologist (70%); however, most (70%) patients preferred to obtain their information from the Crohn's and Colitis Canada website. CONCLUSIONS: The impact of IBD on interpersonal relationships and leisure activities was significant among IBD patients and their families. Understanding the disease, but also alternative treatment options, was of high interest. Currently, there is a discrepancy between interest in information topics and their availability. Respondents reported a strong desire to obtain information regarding disease progression, especially extraintestinal symptoms.

Cannabis use provides symptom relief in patients with inflammatory bowel disease but is associated with worse disease prognosis in patients with Crohn's disease.

BACKGROUND: Cannabinoids are used by patients with inflammatory bowel disease (IBD) to alleviate their symptoms. Little is known on patient motivation, benefit, or risks of this practice. Our aim was to assess the extent and motives for Cannabis use in patients with IBD and the beneficial and adverse effects associated with self-administration of Cannabis. METHODS: Consecutive patients with IBD (n = 313) seen in the University of Calgary from July 2008 to March 2009 completed a structured anonymous questionnaire covering motives, pattern of use, and subjective beneficial and adverse effects associated with self-administration of Cannabis. Subjects who had used Cannabis specifically for the treatment of IBD or its symptoms were compared with those who had not. Logistic regression analysis was used to identify variables predictive of poor IBD outcomes, specifically surgery or hospitalization for IBD. RESULTS: Cannabis had been used by 17.6% of respondents specifically to relieve symptoms associated with their IBD, the majority by inhalational route (96.4%). Patients with IBD reported that Cannabis improved abdominal pain (83.9%), abdominal cramping (76.8%), joint pain (48.2%), and diarrhea (28.6%), although side effects were frequent. The use of Cannabis for more than 6 months at any time for IBD symptoms was a strong predictor of requiring surgery in patients with Crohn's disease (odds ratio = 5.03, 95% confidence interval = 1.45-17.46) after correcting for demographic factors, tobacco smoking status, time since IBD diagnosis, and biological use. Cannabis was not a predictor for hospitalization for IBD in the previous year. CONCLUSIONS: Cannabis use is common in patients with IBD and subjectively improved pain and diarrheal symptoms. However, Cannabis use was associated with higher risk of surgery in patients with Crohn's disease. Patients using Cannabis should be cautioned about potential harm, until clinical trials evaluate efficacy and safety.

Polyunsaturated fatty acids in inflammatory bowel diseases: a reappraisal of effects and therapeutic approaches.

Recent epidemiological studies highlight the key role of the type of consumed unsaturated fatty acid and the development of ulcerative colitis (UC). We aimed to review the potential mechanisms behind the antiinflammatory effects of unsaturated fatty acids on intestinal inflammation, to discuss their potential limitations, and to propose a new reappraisal of polyunsaturated fatty acids (PUFAs) in the pathophysiology of inflammatory bowel disease (IBD). A literature search using PubMed was carried out to identify relevant studies (basic science, epidemiological studies, or clinical trials) with unsaturated fatty acids and IBD. Only articles published in English were included. IBD patients exhibit an altered lipid metabolism. While in vitro and in vivo studies have demonstrated the antiinflammatory properties of n-3 polyunsaturated fatty acids in experimental models IBD, results of clinical trials have been disappointing. In addition, the impact of fatty acid on innate immunity as an alternative therapeutic approach is explored. This may offer insight into therapeutic avenues for designing n-3 PUFA diet therapy for IBD.

Optimizing the safety of biologic therapy for IBD.

The introduction of biologic therapy for the treatment of IBD has substantially changed its management. The safety concerns associated with biologic therapies include the increased risk of infection, autoimmunity, development of lymphoma and demyelinating disease, and the risk of worsening heart failure. There are several strategies for minimizing the risks associated with biologic therapies. Pretreatment strategies include taking a proper history from the patient, physical examination of the patient, screening for latent tuberculosis and ruling out sepsis. Vaccination of patients against vaccine preventable diseases is also recommended. During treatment, patients should be closely monitored and any symptoms that develop should be dealt with early. Education of physicians and patients is also important to allow the early detection of any adverse events.

Sequential therapies for Crohn's disease: optimizing conventional and biologic strategies.

The current guidelines for the management of Crohn's disease (CD) suggest a stepwise approach to treatment according to the severity of clinical presentation. The use of tumor necrosis factor (TNF) antagonists are currently reserved for patients who do not respond to conventional nonbiological therapies such as corticosteroids and immunosuppressants. However, as TNF-alpha antagonists have the potential to produce mucosal healing in CD, earlier more aggressive treatment with biologics has been advocated. Anti-TNF therapy may be most beneficial in the early stages of inflammatory disease, before patients develop complications such as fibrostenotic or penetrating disease. Thus, the use of the more aggressive "top-down" strategy involving early introduction of biologics has been explored. Emerging data suggest that earlier use of biological therapy is associated with improved clinical outcomes and potential disease-modifying effects. Future studies are warranted and will likely lead to the expanded use of such agents in the treatment of CD.

Biologic therapy in Crohn's disease: state of the art.

PURPOSE OF REVIEW: This review is intended to appraise the evolution and latest developments in treatment strategies and management of patients with Crohn's disease. RECENT FINDINGS: The last 24 months has further established the role of anti-tumor necrosis factor therapy in Crohn's disease with two new agents demonstrating efficacy in well designed randomized controlled trials. Furthermore, other important strategies have been identified including inhibition of leukocyte trafficking and blocking of interleukin-12 and 23. Along with the evolution in drug therapies there has been more extensive investigation on the best means to use these new agents. SUMMARY: Biologic therapy has changed and will continue to transform the way we treat patients with Crohn's disease. Treatment success has been redefined. The challenges will be to utilize these agents in the best algorithms possible to benefit not only short-term but also long-term outcomes.