Background
Corticosteroids are often preferred over enteral nutrition (EN) as induction therapy for Crohn's disease (CD). Prior meta‐analyses suggest that corticosteroids are superior to EN for ...induction of remission in CD. Treatment failures in EN trials are often due to poor compliance, with dropouts frequently due to poor acceptance of a nasogastric tube and unpalatable formulations. This systematic review is an update of a previously published Cochrane review.
Objectives
To evaluate the effectiveness and safety of exclusive EN as primary therapy to induce remission in CD and to examine the importance of formula composition on effectiveness.
Search methods
We searched MEDLINE, Embase and CENTRAL from inception to 5 July 2017. We also searched references of retrieved articles and conference s.
Selection criteria
Randomized controlled trials involving patients with active CD were considered for inclusion. Studies comparing one type of EN to another type of EN or conventional corticosteroids were selected for review.
Data collection and analysis
Data were extracted independently by at least two authors. The primary outcome was clinical remission. Secondary outcomes included adverse events, serious adverse events and withdrawal due to adverse events. For dichotomous outcomes, we calculated the risk ratio (RR) and 95% confidence interval (CI). A random‐effects model was used to pool data. We performed intention‐to‐treat and per‐protocol analyses for the primary outcome. Heterogeneity was explored using the Chi2 and I2 statistics. The studies were separated into two comparisons: one EN formulation compared to another EN formulation and EN compared to corticosteroids. Subgroup analyses were based on formula composition and age. Sensitivity analyses included publications and poor quality studies. We used the Cochrane risk of bias tool to assess study quality. We used the GRADE criteria to assess the overall quality of the evidence supporting the primary outcome and selected secondary outcomes.
Main results
Twenty‐seven studies (1,011 participants) were included. Three studies were rated as low risk of bias. Seven studies were rated as high risk of bias and 17 were rated as unclear risk of bias due to insufficient information. Seventeen trials compared different formulations of EN, 13 studies compared one or more elemental formulas to a non‐elemental formula, three studies compared EN diets of similar protein composition but different fat composition, and one study compared non‐elemental diets differing in glutamine enrichment. Meta‐analysis of 11 trials (378 participants) demonstrated no difference in remission rates. Sixty‐four per cent (134/210) of patients in the elemental group achieved remission compared to 62% (105/168) of patients in the non‐elemental group (RR 1.02, 95% CI 0.88 to 1.18; GRADE very low quality). A per‐protocol analysis (346 participants) produced similar results (RR 1.04, 95% CI 0.91 to 1.18). Subgroup analyses performed to evaluate the different types of elemental and non‐elemental diets (elemental, semi‐elemental and polymeric) showed no differences in remission rates. An analysis of 7 trials including 209 patients treated with EN formulas of differing fat content (low fat: < 20 g/1000 kCal versus high fat: > 20 g/1000 kCal) demonstrated no difference in remission rates (RR 1.03; 95% CI 0.85 to 1.26). Very low fat content (< 3 g/1000 kCal) and very low long chain triglycerides demonstrated higher remission rates than higher content EN formulas. There was no difference between elemental and non‐elemental diets in adverse event rates (RR 1.00, 95% CI 0.63 to 1.60; GRADE very low quality), or withdrawals due to adverse events (RR 1.29, 95% CI 0.80 to 2.09; GRADE very low quality). Common adverse events included nausea, vomiting, diarrhea and bloating.
Ten trials compared EN to steroid therapy. Meta‐analysis of eight trials (223 participants) demonstrated no difference in remission rates between EN and steroids. Fifty per cent (111/223) of patients in the EN group achieved remission compared to 72% (133/186) of patients in the steroid group (RR 0.77, 95% CI 0.58 to 1.03; GRADE very low quality). Subgroup analysis by age showed a difference in remission rates for adults but not for children. In adults 45% (87/194) of EN patients achieved remission compared to 73% (116/158) of steroid patients (RR 0.65, 95% CI 0.52 to 0.82; GRADE very low quality). In children, 83% (24/29) of EN patients achieved remission compared to 61% (17/28) of steroid patients (RR 1.35, 95% CI 0.92 to 1.97; GRADE very low quality). A per‐protocol analysis produced similar results (RR 0.93, 95% CI 0.75 to 1.14). The per‐protocol subgroup analysis showed a difference in remission rates for both adults (RR 0.82, 95% CI 0.70 to 0.95) and children (RR 1.43, 95% CI 1.03 to 1.97). There was no difference in adverse event rates (RR 1.39, 95% CI 0.62 to 3.11; GRADE very low quality). However, patients on EN were more likely to withdraw due to adverse events than those on steroid therapy (RR 2.95, 95% CI 1.02 to 8.48; GRADE very low quality). Common adverse events reported in the EN group included heartburn, flatulence, diarrhea and vomiting, and for steroid therapy acne, moon facies, hyperglycemia, muscle weakness and hypoglycemia. The most common reason for withdrawal was inability to tolerate the EN diet.
Authors' conclusions
Very low quality evidence suggests that corticosteroid therapy may be more effective than EN for induction of clinical remission in adults with active CD. Very low quality evidence also suggests that EN may be more effective than steroids for induction of remission in children with active CD. Protein composition does not appear to influence the effectiveness of EN for the treatment of active CD. EN should be considered in pediatric CD patients or in adult patients who can comply with nasogastric tube feeding or perceive the formulations to be palatable, or when steroid side effects are not tolerated or better avoided. Further research is required to confirm the superiority of corticosteroids over EN in adults. Further research is required to confirm the benefit of EN in children. More effort from industry should be taken to develop palatable polymeric formulations that can be delivered without use of a nasogastric tube as this may lead to increased patient adherence with this therapy
We compared the efficacy of adalimumab, infliximab, ustekinumab, and vedolizumab on the ability to achieve endoscopic healing (EH) after one-year of therapy in moderate-severe Crohn's disease (CD).
...Pooled analysis of patient-level data from 299 patients with CD from four clinical trials. Proportions of patients treated with each biologic were compared for achieving one-year complete endoscopic healing (EH) (SES-CD<3), and ileal and colonic EH separately (SES-CD=0). Multivariate logistic regression was used to model the relationship between biologics and one-year outcomes, adjusted for disease duration, concomitant corticosteroid use, and prior anti-TNF failure.
Compared to vedolizumab 4/56 (7.1%), adalimumab 17/61 (27.9%), aOR: 5.79 (95% CI: 1.77-18.95), p=0.004 and infliximab 39/141 (27.7%), aOR: 4.59 (95% CI: 1.48-14.22), p=0.008 had superior rates of one-year EH. No significant difference was observed between vedolizumab and ustekinumab. Similar results were observed among biologic-naïve patients. Among patients with baseline ileal SES-CD ≥3, no significant differences were observed between biologics for one-year ileal EH. However for large (>0.5cm) ileal ulcers, infliximab 20/49 (40.8%) had superior rates of no ileal ulcers compared to vedolizumab 2/23 (8.7%), aOR: 5.39 (95% CI: 1.03-28.05), p=0.045. No other differences were observed. For colonic disease, compared to ustekinumab 9/31 (29.0%), adalimumab 30/48 (62.5%), aOR: 3.97 (95% CI: 1.45-10.90), p=0.007 had superior rates of one-year EH in the colon, with similar trends observed for infliximab (55/105 (52.4%), aOR: 2.08 (95% CI: 0.82-5.27), p=0.121. No other differences were observed.
In this post-hoc analysis, TNFα antagonists were overall superior to vedolizumab and ustekinumab for achieving one-year EH in moderate-severe CD patients.
We assessed the real-world effectiveness and safety of vedolizumab (VDZ) in moderate-severe Crohn's disease (CD).
Retrospective cohort study of seven medical centers, from May 2014 to December 2015. ...Adults with moderate-severe CD treated with VDZ, with follow-up after initiation of therapy, were included. Using the multivariable Cox proportional hazard analyses, we identified independent predictors of clinical remission or mucosal healing with VDZ. Rates of serious infection (requiring antibiotics, resulting in discontinuation of VDZ, hospitalization or death) and serious adverse events (discontinuation of VDZ, hospitalization or death) were described quantitatively.
We included 212 patients with moderate-severe CD (median age 34 years; 40% male; 90% tumor necrosis factor (TNF)-antagonist exposed) with a median follow-up (IQR) of 39 weeks (25-53). Twelve-month cumulative rates of clinical remission, mucosal healing, and deep remission (clinical remission+mucosal healing) were 35%, 63%, and 26%, respectively. Individuals with prior TNF-antagonist exposure (hazard ratio (HR) 0.40; 95% confidence interval (CI): 0.20-0.81), smoking history (HR 0.47; 95% CI: 0.25-0.89), active perianal disease (HR 0.49; 95% CI: 0.27-0.88), and severe disease activity (HR 0.54; 95% CI: 0.31-0.95) were less likely to achieve clinical remission. Those with prior TNF-antagonist exposure (HR 0.29; 95% CI: 0.12-0.73), and severe disease activity (HR 0.54; 95% CI: 0.31-0.95) were less likely to achieve mucosal healing. During 160 patient years of follow-up (PYF) and 1,433 VDZ infusions, 5 patients developed infusion reactions (3.5 per 1,000 infusions), 21 developed serious infections (13 per 100 PYF), and 17 developed serious adverse events (10 per 100 PYF). A minority of adverse events required discontinuation of therapy (6 per 100 PYF).
VDZ is a safe and effective treatment option for moderate-severe CD in routine practice. Clinical remission and deep remission (clinical remission and mucosal healing) can be achieved in 1/3 of individuals, and a minority of individuals require discontinuation of therapy due to adverse events.
Cases of inflammatory bowel disease (IBD) during treatment with interleukin (IL)-17 antagonists have been reported from trials in psoriasis, psoriatic arthritis, and ankylosing spondylitis. The aim ...of this study was to assess the overall risk for development of IBD due to IL-17 inhibition.
Systematic review and meta-analysis of studies conducted 2010-2018 of treatment with IL-17 antagonists in patients with psoriasis, psoriatic arthritis, ankylosing spondylitis, and rheumatoid arthritis. We compared risk of IBD development in anti-IL-17 treated patients compared to placebo treatments. We also computed incident rates of IBD overall. A 'worst case scenario' defining subjects ambiguous for prevalent versus incident cases for the latter was also applied.
Sixty-six studies of 14,390 patients exposed to induction and 19,380 patients exposed to induction and/or maintenance treatment were included. During induction, 11 incident cases of IBD were reported, whereas 33 cases were diagnosed during the entire treatment period. There was no difference in the pooled risk of new-onset IBD during induction studies for both the best-case risk difference (RD) 0.0001 (95% CI: -0.0011, 0.0013) and worst-case scenario RD 0.0008 (95% CI: -0.0005, 0.0022). The risk of IBD was not different from placebo when including data from maintenance and long-term extension studies RD 0.0007 (95% CI: -0.0023, 0.0036) and RD 0.0022 (95% CI: -0.0010, 0.0055), respectively.
The risk for development of IBD in patients treated with IL-17 antagonists is not elevated. Prospective surveillance of patients treated with IL-17 antagonists with symptom and biomarker assessments is warranted to assess for onset of IBD in these patients.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Differences in 1-year outcomes among early and delayed responders have been demonstrated with some therapies in ulcerative colitis. However, it is unclear whether similar differences exist in ...patients with Crohn's disease (CD) treated with biologic therapies.
This was a post hoc analysis of patient-level data from the SEAVUE clinical trial program. Ustekinumab-treated and adalimumab-treated patients with clinical response at week 8, defined as a reduction in Crohn's Disease Activity Index (CDAI) score of at least 100 points from baseline or CDAI score <150, were deemed early responders and their outcomes were compared with delayed responders (week 8 nonresponders who subsequently responded at week 16) and nonresponders (no response at week 8 or 16). The primary outcome assessed was clinical remission at week 56, defined as CDAI <150.
A total of 373 participants (187 treated with ustekinumab and 186 treated with adalimumab) were included in this analysis. The overall rate of delayed clinical response was low in the SEAVUE clinical trial program (13.1%). No differences were observed for week 56 clinical remission among early vs delayed responders to ustekinumab or adalimumab nor were there significant differences for secondary outcomes assessed. Delayed responders to ustekinumab and adalimumab had a significant decline in C-reactive protein by week 8 when compared with nonresponders.
Among patients with moderate-to-severe CD, early and delayed responders to adalimumab and ustekinumab have similar 1-year clinical outcomes. Biomarker decline can be observed through the initial 8 weeks of therapy in patients who will eventually be delayed responders, which may help differentiate from nonresponders.
We performed a systematic review to investigate whether patients with Crohn's disease (CD) and permanent ileostomy (PI) have been included in clinical trials evaluating biologics and small molecules.
...MEDLINE, Embase and Cochrane library (CENTRAL) data bases were searched from inception to May 16, 2022 for placebo controlled induction and/or maintenance randomized controlled trials assessing biologics and oral small molecules in adult patients with active CD.
Of the 81 induction and maintenance trials assessing biologics and oral small molecules in CD, none permitted the enrollment of patients with PI. Patients with CD and PI have been universally excluded from pharmaceutical trials of biologics and small molecules to date.
There is an urgent need to identify barriers to enrollment and develop eligibility and outcome measures enabling the inclusion of patients with CD and PI into clinical trials.
Previous or current infection with Helicobacter pylori (exposure) has been reported to protect against eosinophilic esophagitis (EoE), perhaps owing to H pylori-induced immunomodulation. However, ...findings vary. We performed a systematic review and meta-analysis of comparative studies to define the association between H pylori exposure and EoE more clearly.
We searched 4 large databases to identify comparative clinical studies that included sufficient detail to determine the odds or risk of EoE (primary outcome) or esophageal eosinophilia (secondary outcome) among individuals exposed to H pylori (exposed) vs individuals who were tested and found to be unexposed. Estimates were pooled using a random-effects model. Meta-regression and sensitivity analyses were planned a priori. Studies were evaluated for quality, risk of bias, publication bias, and heterogeneity.
We analyzed 11 observational studies comprising data on 377,795 individuals worldwide. H pylori exposure vs nonexposure was associated with a 37% reduction in odds of EoE (odds ratio, 0.63; 95% CI, 0.51-0.78) and a 38% reduction in odds of esophageal eosinophilia (odds ratio, 0.62; 95% CI, 0.52-0.76). Fewer prospective studies found a significant association between H pylori exposure and EoE (P = .06) than retrospective studies. Effect estimates were not affected by study location, whether the studies were performed in pediatric or adult populations, time period (before vs after 2007), or prevalence of H pylori in the study population.
In a comprehensive meta-analysis, we found evidence for a significant association between H pylori exposure and reduced odds of EoE. Studies are needed to determine the mechanisms of this association.
Technological advances now permit self-management strategies using mobile applications which could greatly benefit patient care. The purpose of this study was to investigate whether the use of the ...inflammatory bowel disease (IBD) digital health monitoring platform, HealthPROMISE, leads to better quality of care and improved health outcomes in IBD patients. IBD patients were recruited in gastroenterology clinics and asked to install the HealthPROMISE application onto their smartphones. Patient satisfaction, quality of care, quality of life, patient symptoms, and resource utilization metrics were collected throughout the study and sent directly to their healthcare teams. Patients with abnormal symptom/SIBDQ scores were flagged for their physicians to follow up. After one-year, patient outcome metrics were compared to baseline values. Overall, out of 59 patients enrolled in the study, 32 patients (54%) logged into the application at least once during the study period. The number of IBD-related ER visits/hospitalizations in the year of use compared to the prior year demonstrated a significant decrease from 25% of patients (8/32) to 3% (1/32) (
p
= 0.03). Patients also reported an increase in their understanding of the nature/causes of their condition after using the application (
p
= 0.026). No significant changes were observed in the number of quality indicators met (
p
= 0.67) or in SIBDQ scores (
p
= 0.48). Given the significant burden of IBD, there is a need to develop effective management strategies. This study demonstrated that digital health monitoring platforms may aid in reducing the number of ER visits and hospitalizations in IBD patients.
Background
Recent evidence suggests that exposures in early life that are known to influence microbiome development may affect the risk of developing inflammatory bowel disease (IBD). Cesarean ...section has been associated with altered colonization of commensal gut flora and is thought to predispose to immune-mediated diseases later in life.
Aims
To evaluate the risk of IBD, Crohn’s Disease (CD), and Ulcerative Colitis (UC) according to mode of delivery (C-section vs vaginal delivery).
Methods
A systematic search was performed in PubMed and Embase. The primary outcome was the risk of IBD in individuals delivered vaginally compared to those born by C-section. Secondary outcomes were UC and CD risk according to mode of delivery and IBD risk in individuals born by emergent compared to elective C-section. Publication bias was evaluated by funnel plots and Egger’s test. Study’s quality was characterized using the Newcastle–Ottawa Scale.
Results
Ten studies fulfilled the inclusion criteria, of which seven were population-based. No publication bias was detected. Overall, 14.164 IBD patients and 4.206.763 controls were included. Being born by C-section was not associated with increased risk of IBD OR 1.01, 95% CI (0.81–1.27),
p
= 0.92, CD OR 1.15, 95% CI (0.94–1.42),
p
= 0.18 or UC OR 0.94, 95% CI (0.61–1.45),
p
= 0.79. No differences were found between emergent and elective C-section in IBD OR 1.05, 95% CI (0.59–1,87),
p
= 0.87. Substantial heterogeneity was found in statistical analysis, and further studies are needed.
Conclusion
Overall, the risk of developing IBD was not affected by mode of delivery.
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