Complementary and alternative medications in the management of inflammatory bowel disease.

The use of complementary and alternative medications (CAM), products, and therapies not considered to be part of conventional medicine is common among patients with inflammatory bowel disease (IBD). Patients often turn to these therapies as they are considered natural and safe, with significant benefit reported beyond disease control. There is emerging evidence that some of these therapies may have anti-inflammatory activity; however, robust evidence for their efficacy in modulating disease activity is currently lacking. Patients often avoid discussing the use of CAM with their physicians, which may lead to drug interactions and/or reduced adherence with conventional therapy. It is important for physicians to be aware of the commonly used CAM and current evidence behind these therapies in order to better counsel their patients about their use in the management of IBD. This narrative review provides an overview of the evidence of the more commonly used CAM in patients with IBD.

The impact of pregnancy on biologic therapies for the treatment of inflammatory bowel disease.

Active inflammatory bowel disease during conception and pregnancy has been associated with adverse materno-fetal outcomes. Patients are often unduly concerned about the adverse effects of biologic medications on the growing fetus, however, continuing therapy is advised, with potential risks of therapy outweighed by the risks of active maternal disease. A number of physiological changes associated with pregnancy can alter the absorption, distribution and elimination of these therapies, which may impact on their safety and efficacy. We review the current evidence regarding the effects of pregnancy on the pharmacokinetics of biologic therapies, as well as drug concentration measurements during pregnancy and at time of delivery. A greater understanding of the impact of pregnancy on the pharmacokinetics of biologic therapies and the emerging utilisation of drug concentration monitoring during pregnancy may lead to improved materno-fetal outcomes in patients with inflammatory bowel disease.

Pregnant women with IBD are more likely to be adherent to biologic therapies than other medications.

BACKGROUND: There are differences in the efficacy and safety profiles of medications used to treat IBD that may impact a woman's perceived risk of medication exposure during pregnancy, potentially leading to medication non-adherence, poor disease-control and adverse pregnancy outcomes. AIM: To assess whether medication adherence patterns differ by drug class during pregnancy and influence birth outcomes for women with IBD. METHODS: Of 143 491 women, a validated case definition was used to identify 370 women with IBD in five administrative health databases in Alberta, Canada (2012-2015). Women who had ≥2 consecutive medications prescription for maintenance therapy for IBD in the year prior to pregnancy were included (n = 230). Prescription-based medication possession ratio ≥0.8 defined adherence. Chi-squared tests were used to compare adherence patterns by drug class and outcomes. RESULTS: Of the 159/230 women who were adherent during the year prior to pregnancy, 20 (12.6%; 95% CI: 8.2%, 18.8%) were not adherent and 21 (13.2%; 95% CI: 8.7%, 19.5%) discontinued their medications during pregnancy. Medication adherence during pregnancy differed significantly by drug class. A greater proportion of women on biologics (41.5%; 95% CI 32.9%, 50.7%) were adherent during pregnancy than women on thiopurines (22.9%; 95% CI 16.1%, 31.5%; P = 0.006); adherence was not significantly different for 5-aminosalicylates (35.6%; 95% CI 27.4%, 44.8%; P = 0.204). Women were more likely to be adherent to biologics (49.3%, 95% CI 37.3%, 61.3%) than thiopurines (20.9%; 95% CI 12.6%, 32.6%; P = 0.014) and 5-aminosalicylates (29.9%; 95% CI 19.9%, 42.1%; P = 0.030) in the first trimester. This was similar in the third trimester. In the second trimester, adherence pattern did not significantly differ by drug class (biologics vs thiopurines: P = 0.348; biologics vs 5-aminosalicylate: P = 0.999). Infants born to women with IBD (adherent: RR 1.58. 95% CI 1.02, 2.27; non-adherent: RR 1.32, 95% CI 0.97, 1.81) were more likely to be admitted into the neonatal intensive care unit than the general obstetric population, but this was not significantly different between women who were adherent or not adherent to their IBD medication (P = 0.711). CONCLUSION: Almost a quarter of women with IBD who were previously adherent to medical therapy were not adherent during pregnancy. Adherence pattern differed by drug class.

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.

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.

Oral budesonide for induction of remission in ulcerative colitis.

BACKGROUND: Corticosteroids remain one of the most popular medication choices for the induction of remission in ulcerative colitis and Crohn's disease. While corticosteroids may improve symptoms, they do not always result in mucosal healing and have significant adverse effects. Steroids which act topically, with less systemic side-effects may be more desirable. Oral budesonide, a topically acting corticosteroid with extensive first pass hepatic metabolism, is effective in Crohn's disease and in enema formulation for left-sided ulcerative colitis. Data are limited regarding the role of oral budesonide in ulcerative colitis. OBJECTIVES: To systematically review the safety and efficacy of oral budesonide for induction of remission in ulcerative colitis. SEARCH STRATEGY: Electronic searching of the MEDLINE and EMBASE databases was performed. Two authors independently reviewed all identified titles and abstracts. Full text articles of all potentially relevant studies were retrieved. Reference lists of review articles were searched in an attempt to identify additional studies. Abstracts of the major gastroenterology scientific meetings, held over the past 3 years, were hand searched. The ClinicalTrials.gov website as well as the Cochrane Registry of Controlled Trials was searched to identify any ongoing trials. Direct communication with pharmaceutical manufacturers was established to identify any ongoing or unpublished studies. SELECTION CRITERIA: Randomized controlled trials of oral budesonide for the induction of remission in ulcerative colitis, with either a parallel arm or cross-over design, were considered eligible for inclusion. There were no exclusions based on patient age or the type, dose or duration of budesonide therapy. The primary outcome was the induction of clinical remission in ulcerative colitis. Secondary outcomes included clinical, histologic and endoscopic improvement, endoscopic mucosal healing, change in disease activity index scores, adverse events and study withdrawals. DATA COLLECTION AND ANALYSIS: Studies were reviewed for eligibility, data were extracted and quality assessed by 2 independent investigators. It was not possible to perform a meta-analysis of the included studies due to significant heterogeneity, with each study comparing budesonide to a different control medication. MAIN RESULTS: Three studies met the inclusion criteria. Oral budesonide was significantly less likely to induce clinical remission than oral mesalamine after 8 weeks of therapy (RR 0.72, 95% CI 0.57 to 0.91). There was no significant benefit of oral budesonide in comparison to placebo for inducing clinical remission after 4 weeks of treatment (RR 1.41, 95% CI 0.59 to 3.39). A small pilot study reported no statistically significant difference in endoscopic remission between budesonide and prednisolone (RR 0.75, 95% CI 0.23 to 2.42). The study was small and not powered to evaluate the impact of budesonide on clinical remission. Suppression of plasma cortisol was significantly more common in prednisolone treated patients (RR 0.02, 95% CI 0.0 to 0.33). Two multicenter studies are ongoing. AUTHORS' CONCLUSIONS: At present, there is no evidence to recommend the clinical use of oral budesonide for the induction of remission in active ulcerative colitis. Mesalamine is superior to budesonide for the treatment of active ulcerative colitis.