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Pharmaceutics Jun 2022Due to ethical and practical reasons, a knowledge gap exists on the pharmacokinetics (PK) of inflammatory bowel disease (IBD)-related drugs in pregnant women with IBD.... (Review)
Review
Due to ethical and practical reasons, a knowledge gap exists on the pharmacokinetics (PK) of inflammatory bowel disease (IBD)-related drugs in pregnant women with IBD. Before evidence-based dosing can be proposed, insight into the PK has to be gained to optimize drug therapy for both mother and fetus. This systematic review aimed to describe the effect of pregnancy and IBD on the PK of drugs used for IBD. One aminosalicylate study, two thiopurine studies and twelve studies with biologicals were included. Most drugs within these groups presented data over multiple moments before, during and after pregnancy, except for mesalazine, ustekinumab and golimumab. The studies for mesalazine, ustekinumab and golimumab did not provide enough data to demonstrate an effect of pregnancy on concentration and PK parameters. Therefore, no evidence-based dosing advice was given. The 6-thioguanine nucleotide levels decreased during pregnancy to 61% compared to pre-pregnancy levels. The potentially toxic metabolite 6-methylmercaptopurine (6-MMP) increased to maximal 209% of the pre-pregnancy levels. Although the PK of the thiopurines changed throughout pregnancy, no evidence-based dosing advice was provided. One study suggested that caution should be exercised when the thiopurine dose is adjusted, due to shunting 6-MMP levels. For the biologicals, infliximab levels increased, adalimumab stayed relatively stable and vedolizumab levels tended to decrease during pregnancy. Although the PK of the biologicals changed throughout pregnancy, no evidence-based dosing advice for biologicals was provided. Other drugs retrieved from the literature search were mesalazine, ustekinumab and golimumab. We conclude that limited studies have been performed on PK parameters during pregnancy for drugs used in IBD. Therefore, more extensive research to determine the values of PK parameters is warranted. After gathering the PK data, evidence-based dosing regimens can be developed.
PubMed: 35745812
DOI: 10.3390/pharmaceutics14061241 -
International Journal of Colorectal... Nov 2022Between people with and without inflammatory bowel disease (IBD), there was no statistically significant difference in the probability of contracting the severe acute... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Between people with and without inflammatory bowel disease (IBD), there was no statistically significant difference in the probability of contracting the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). However, the risk of adverse outcomes in IBD patients after virus infection remains unclear.
METHODS
Eligible studies conducted from January 1, 2020 to March 17, 2022 were obtained by searching PubMed, Embase, and Web of Science. Information was collected in tables from the included studies. Random-effects and fixed-effects models were used as measures for the pooled estimates. All data were estimated by R version 4.1.3.
RESULTS
Twenty-four studies were included. The risk ratio (RR) of adverse outcomes in COVID-19 patients with IBD increased by 32% (RR 1.32; 95% CI 1.06-1.66) relative to COVID-19 patients without IBD. The RR of mortality was higher in COVID-19 patients with IBD from Europe (RR 1.72; 95% CI 1.11-2.67) than in those that were not from Europe (RR 1.00; 95% CI 0.79-1.26; χ = 4.67; P = 0.03). Patients with ulcerative colitis were at higher risk of adverse outcomes after SARS-CoV-2 infection than patients with Crohn's disease patients (RR1.38; 95% CI 1.27-1.50). The IBD drugs treatment was associated with the risk of adverse outcomes, the pooled odds ratio (OR) of mesalazine (1.79; 95% CI 1.59-2.02), immunomodulators (1.30; 95% CI 1.10-1.53), and anti-TNF (0.47; 95% CI 0.41-0.53) were assessed.
CONCLUSION
COVID-19 patients with IBD had an increased risk of adverse outcomes than those without IBD, whereas anti-TNF treatment might reduce the risk.
Topics: Humans; SARS-CoV-2; COVID-19; Tumor Necrosis Factor Inhibitors; Inflammatory Bowel Diseases; Colitis, Ulcerative
PubMed: 36271206
DOI: 10.1007/s00384-022-04265-w -
Annals of Internal Medicine Mar 2022The American College of Physicians (ACP) developed this guideline to provide clinical recommendations on the role of colonoscopy for diagnostic evaluation of colorectal...
Colonoscopy for Diagnostic Evaluation and Interventions to Prevent Recurrence After Acute Left-Sided Colonic Diverticulitis: A Clinical Guideline From the American College of Physicians.
DESCRIPTION
The American College of Physicians (ACP) developed this guideline to provide clinical recommendations on the role of colonoscopy for diagnostic evaluation of colorectal cancer (CRC) after a presumed diagnosis of acute left-sided colonic diverticulitis and on the role of pharmacologic, nonpharmacologic, and elective surgical interventions to prevent recurrence after initial treatment of acute complicated and uncomplicated left-sided colonic diverticulitis. This guideline is based on the current best available evidence about benefits and harms, taken in the context of costs and patient values and preferences.
METHODS
The ACP Clinical Guidelines Committee (CGC) based these recommendations on a systematic review on the role of colonoscopy after acute left-sided colonic diverticulitis and pharmacologic, nonpharmacologic, and elective surgical interventions after initial treatment. The systematic review evaluated outcomes rated by the CGC as critical or important. This guideline was developed using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) method.
TARGET AUDIENCE AND PATIENT POPULATION
The target audience is all clinicians, and the target patient population is adults with recent episodes of acute left-sided colonic diverticulitis.
RECOMMENDATION 1
RECOMMENDATION 2
RECOMMENDATION 3
Topics: Adult; Colonoscopy; Diverticulitis, Colonic; Humans; Physicians; United States
PubMed: 35038270
DOI: 10.7326/M21-2711 -
Journal of Crohn's & Colitis May 2024Patients with inflammatory bowel disease [IBD] have a more than two fold higher risk of venous thromboembolic events [VTE] than the general population. The aetiology is... (Meta-Analysis)
Meta-Analysis
Anti-tumor Necrosis Factor Alpha Versus Corticosteroids: A 3-fold Difference in the Occurrence of Venous Thromboembolism in Inflammatory Bowel Disease-A Systematic Review and Meta-analysis.
BACKGROUND AND AIMS
Patients with inflammatory bowel disease [IBD] have a more than two fold higher risk of venous thromboembolic events [VTE] than the general population. The aetiology is complex, and the role of medication is not precisely defined. We aimed to assess the effects of anti-tumor necrosis factor alpha [anti-TNFα] drugs and conventional anti-inflammatory therapy, namely corticosteroids [CS], immunomodulators [IM], and 5-aminosalicylates [5-ASA] on VTE in IBD.
METHODS
A systematic search was performed in five databases on November 22, 2022. We included studies reporting VTE in the distinct categories of medications, determined the proportions, and calculated the odds ratios [OR] with 95% confidence intervals [CI], using the random-effects model. The risk of bias was evaluated with the Joanna Briggs Institute Critical Appraisal Checklist and the Risk of Bias in Non-randomized Studies of Interventions tool.
RESULTS
The quantitative analysis included 16 observational studies, with data from 91 322 IBD patients. Patients receiving anti-TNFα medication had significantly less VTE [proportion: 0.05, CI: 0.02-0.10], than patients treated with CS [proportion: 0.16, CI: 0.07-0.32], with OR = 0.42 [CI: 0.25-0.71]. IMs resulted in similar proportions of VTE compared with biologics [0.05, CI: 0.03-0.10], with OR = 0.94 [CI: 0.67-1.33]. The proportion of patients receiving 5-ASA having VTE was 0.09 [CI: 0.04-0.20], with OR = 1.00 [CI: 0.61-1.62].
CONCLUSIONS
Biologics should be preferred over corticosteroids in cases of severe flare-ups and multiple VTE risk factors, as they are associated with reduced odds of these complications. Further studies are needed to validate our data.
Topics: Humans; Venous Thromboembolism; Inflammatory Bowel Diseases; Adrenal Cortex Hormones; Tumor Necrosis Factor-alpha; Mesalamine
PubMed: 37952112
DOI: 10.1093/ecco-jcc/jjad193 -
The Turkish Journal of Gastroenterology... Jun 2021To identify risk factors for hypovitaminosis D in inflammatory bowel disease and conduct a comprehensive systematic review with meta-analysis to quantify the impact on... (Meta-Analysis)
Meta-Analysis
BACKGROUND
To identify risk factors for hypovitaminosis D in inflammatory bowel disease and conduct a comprehensive systematic review with meta-analysis to quantify the impact on vitamin D deficiency.
METHODS
We conducted a literature search of studies through PubMed, Embase, Cochrane Library, and Web of Science. In addition, relevant articles were searched manually. Studies were included if the odds ratios (OR) and 95% CI of each risk factor were reported or could be calculated. We will use the fixed-effects or random-effects model to estimate the pooled effect.
RESULTS
Out of 1018 articles, 25 eligible studies were identified, including 5826 participants. The risk factors associated with hypovitaminosis D were non-Caucasian (OR: 3.79, 95% CI: 2.68-5.34), Crohn's disease (OR: 1.38, 95% CI: 1.21-1.56), disease activity (OR: 1.85, 95% CI: 1.61-2.13), inflammatory bowel disease-related surgery (OR: 1.61, 95% CI: 1.38-1.89), exposure to steroid (OR: 1.61, 95% CI: 1.28-2.03), and biologics (OR: 1.78, 95% CI: 1.48-2.14). In 30 ng/mL and adjusted OR subgroup, male (OR: 1.84, 95% CI: 1.47-2.31) and winter season (OR: 2.49, 95% CI: 1.69-3.67) also were risk factors, respectively. 5-aminosalicylic acid (OR: 1.10, 95% CI: 0.74-1.63) and smoking (OR: 1.19, 95% CI: 0.98-1.45) were unrelated to vitamin D deficiency.
CONCLUSIONS
For vitamin D deficiency in inflammatory bowel disease, non-Caucasian, Crohn's disease, disease activity, surgery, exposure to steroid and biologics, males are risk factors, while 5-aminosalicylic acid and smoking are not. The relationship between body mass index, winter season, exposure to immunomodulators, and vitamin D deficiency remains unclear.
Topics: Biological Products; Colitis; Crohn Disease; Humans; Inflammatory Bowel Diseases; Male; Mesalamine; Quality of Life; Risk Factors; Vitamin D; Vitamin D Deficiency; Vitamins
PubMed: 34405817
DOI: 10.5152/tjg.2021.20614 -
BMC Complementary Medicine and Therapies Oct 2020Ulcerative colitis, characterized by diarrhea, bloody stools and abdominal pain, is a chronic, idiopathic inflammatory disease of the colonic mucosa. In recent years,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Ulcerative colitis, characterized by diarrhea, bloody stools and abdominal pain, is a chronic, idiopathic inflammatory disease of the colonic mucosa. In recent years, the incidence of ulcerative colitis presents an increasing trend year by year. Acupuncture, as a potential effective treatment for ulcerative colitis, is widely used in clinical practice.
METHODS
We searched PubMed, the Cochrane Library, Chinese CBM Database, China National Knowledge Infrastructure, Chinese VIP Information, and Wanfang Database from the date of the establishment of each database up to March, 2019. We included randomized controlled clinical trials (RCT) comparing acupuncture versus conventional conventional medicine or comparing acupuncture combined with conventional medicine versus conventional medicine in participants with ulcerative colitis. Two authors screened all references, assessed the risk of bias and extracted data independently. We summarized data using risk ratios (RR) with 95% confidence intervals (CI) for binary outcomes. We performed meta-analyses using random effects model. We assessed overall quality of evidence using GRADE.
RESULTS
We included 13 RCTs (1030 participants, 515 in the acupuncture group and 515 in the control group). Only one study tested head acupuncture, and the other 12 tested body acupuncture. The treatment duration ranged from 14 to 60 days. Seven trials compared acupuncture alone versus conventional medicine, and six compared acupuncture combined with conventional medicine versus conventional medicine. Acupuncture combined with mesalazine showed better clinical effect (improved clinical symptoms, colonoscopy results and stool examination results) (RR 1.25, 95% CI 1.19 to 1.41; 232 participants; 4 trials; low quality evidence) and better colonoscopy curative effect (RR 1.33, 95% CI 1.04 to 1.71; 108 participants; 2 trials; moderate quality evidence) compared to mesalazine. Acupuncture showed better clinical effect compared to the combination of metronidazole and sulfasalazine (RR 1.21, 95%CI 1.10, 1.34; 318 participants; 3 trials; moderate quality evidence). There was no significant difference in the incidence of adverse events between groups.
CONCLUSIONS
Both acupuncture alone and acupuncture combined with conventional medicine may be effective in treating ulcerative colitis compared to conventional medicine. Our findings must be interpreted with caution due to high or unclear risk of bias of the included trials.
Topics: Acupuncture Therapy; Colitis, Ulcerative; Combined Modality Therapy; Humans; Randomized Controlled Trials as Topic
PubMed: 33054760
DOI: 10.1186/s12906-020-03101-4 -
The Cochrane Database of Systematic... Mar 2020Ulcerative colitis is an inflammatory condition affecting the colon, with an annual incidence of approximately 10 to 20 per 100,000 people. The majority of people with... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Ulcerative colitis is an inflammatory condition affecting the colon, with an annual incidence of approximately 10 to 20 per 100,000 people. The majority of people with ulcerative colitis can be put into remission, leaving a group who do not respond to first- or second-line therapies. There is a significant proportion of people who experience adverse effects with current therapies. Consequently, new alternatives for the treatment of ulcerative colitis are constantly being sought. Probiotics are live microbial feed supplements that may beneficially affect the host by improving intestinal microbial balance, enhancing gut barrier function and improving local immune response.
OBJECTIVES
The primary objective was to determine the efficacy of probiotics compared to placebo, no treatment, or any other intervention for the maintenance of remission in people with ulcerative colitis. The secondary objective was to assess the occurrence of adverse events associated with the use of probiotics.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, and two other databases on 31 October 2019. We contacted authors of relevant studies and manufacturers of probiotics regarding ongoing or unpublished trials that may be relevant to the review, and we searched ClinicalTrials.gov. We also searched references of trials for any additional trials.
SELECTION CRITERIA
Randomised controlled trials (RCTs) that compared probiotics against placebo or any other intervention, in both adults and children, for the maintenance of remission in ulcerative colitis were eligible for inclusion. Maintenance therapy had to be for a minimum of three months when remission has been established by any clinical, endoscopic,histological or radiological relapse as defined by study authors.
DATA COLLECTION AND ANALYSIS
Two review authors independently conducted data extraction and 'Risk of bias' assessment of included studies. We analysed data using Review Manager 5. We expressed dichotomous and continuous outcomes as risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CIs). We assessed the certainty of the evidence using the GRADE methodology.
MAIN RESULTS
In this review, we included 12 studies (1473 randomised participants) that met the inclusion criteria. Participants were mostly adults. The studies compared probiotics to placebo, probiotics to 5-aminosalicylic acid (5-ASA) and a combination of probiotics and 5-ASA to 5-ASA. The studies ranged in length from 12 to 52 weeks. The average age of participants was between 32 and 51, with a range between 18 and 88 years. Seven studies investigated a single bacterial strain, and five studies considered mixed preparations of multiple strains. The risk of bias was high in all except three studies due to selective reporting, incomplete outcome data and lack of blinding. This resulted in low- to very low-certainty of evidence. It is uncertain if there is any difference in occurrence of clinical relapse when probiotics are compared with placebo (RR 0.87, 95% CI 0.63 to 1.18; 4 studies, 361 participants; very low-certainty evidence (downgraded for risk of bias, imbalance in baseline characteristics and imprecision)). It is also uncertain whether probiotics lead to a difference in the number of people who maintain clinical remission compared with placebo (RR 1.16, 95% CI 0.98 to 1.37; 2 studies, 141 participants; very low-certainty evidence (downgraded for risk of bias, imbalance in baseline characteristics and imprecision)). When probiotics are compared with 5-ASA, there may be little or no difference in clinical relapse (RR 1.01, 95% CI 0.84 to 1.22; 2 studies, 452 participants; low-certainty evidence) and maintenance of clinical remission (RR 1.06, 95% CI 0.90 to 1.25; 1 study, 125 participants; low-certainty evidence). It is uncertain if there is any difference in clinical relapse when probiotics, combined with 5-ASA are compared with 5-ASA alone (RR 1.11, 95% CI 0.66 to 1.87; 2 studies, 242 participants; very low-certainty evidence (downgraded due to risk of bias and imprecision)). There may be little or no difference in maintenance of remission when probiotics, combined with 5-ASA, are compared with 5-ASA alone (RR 1.05, 95% CI 0.89 to 1.24; 1 study, 122 participants; low-certainty evidence). Where reported, most of the studies which compared probiotics with placebo recorded no serious adverse events or withdrawals due to adverse events. For the comparison of probiotics and 5-ASA, one trial reported 11/110 withdrawals due to adverse events with probiotics and 11/112 with 5-ASA (RR 1.02, 95% CI 0.46 to 2.25; 222 participants; very low-certainty evidence). Discontinuation of therapy was due to gastrointestinal symptoms. One study (24 participants) comparing probiotics combined with 5-ASA with 5-ASA alone, reported no withdrawals due to adverse events; and two studies reported two withdrawals in the probiotic arm, due to avascular necrosis of bilateral femoral head and pulmonary thromboembolism (RR 5.29, 95% CI 0.26 to 107.63; 127 participants; very low-certainty evidence). Health-related quality of life and need for additional therapy were reported infrequently.
AUTHORS' CONCLUSIONS
The effectiveness of probiotics for the maintenance of remission in ulcerative colitis remains unclear. This is due to low- to very low-certainty evidence from poorly conducted studies, which contribute limited amounts of data from a small number of participants. Future trials comparing probiotics with 5-ASA rather than placebo will better reflect conventional care given to people with ulcerative colitis. Appropriately powered studies with a minimum length of 12 months are needed.
Topics: Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Colitis, Ulcerative; Humans; Mesalamine; Middle Aged; Probiotics; Quality of Life; Randomized Controlled Trials as Topic; Recurrence; Remission Induction; Young Adult
PubMed: 32128794
DOI: 10.1002/14651858.CD007443.pub3 -
The Cochrane Database of Systematic... Aug 2020About half of patients with Crohn's disease (CD) require surgery within 10 years of diagnosis. Resection of the affected segment is highly effective, however the...
BACKGROUND
About half of patients with Crohn's disease (CD) require surgery within 10 years of diagnosis. Resection of the affected segment is highly effective, however the majority of patients experience clinical recurrence after surgery. Most of these patients have asymptomatic endoscopic recurrence weeks or months before starting with symptoms. This inflammation can be detected by colonoscopy and is a good predictor of poor prognosis.Therapy guided by colonoscopy could tailor the management and improve the prognosis of postoperative CD.
OBJECTIVES
To assess the effects of prophylactic therapy guided by colonoscopy in reducing the postoperative recurrence of CD in adults.
SEARCH METHODS
The following electronic databases were searched up to 17 December 2019: MEDLINE, Embase, CENTRAL, Clinical Trials.gov, WHO Trial Registry and Cochrane IBD specialized register. Reference lists of included articles, as well as conference proceedings were handsearched.
SELECTION CRITERIA
Randomised controlled trials (RCTs), quasi-RCTs and cohort studies comparing colonoscopy-guided management versus management non-guided by colonoscopy.
DATA COLLECTION AND ANALYSIS
Two review authors independently considered studies for eligibility, extracted the data and assessed study quality. Methodological quality was assessed using both the Cochrane 'Risk of bias' tool for RCTs and Newcastle-Ottawa scale (NOS) for cohort studies. The primary outcome was clinical recurrence. Secondary outcomes included: endoscopic, surgical recurrence and adverse events. We calculated the risk ratio (RR) for each dichotomous outcome and extracted the hazard ratio (HR) for time-to-event outcomes. All estimates were reported with their corresponding 95% confidence interval (CI). Data were analysed on an intention-to-treat (ITT) basis. The overall quality of the evidence was evaluated using GRADE criteria.
MAIN RESULTS
Two RCTs (237 participants) and five cohort studies (794 participants) met the inclusion criteria. Meta-analysis was not conducted as the studies were highly heterogeneous. We included two comparisons. Intensification of prophylactic-therapy guided by colonoscopy versus intensification guided by clinical recurrence One unblinded RCT and four retrospective cohort studies addressed this comparison. All participants received the same prophylactic therapy immediately after surgery. In the colonoscopy-based management group the therapy was intensified in case of endoscopic recurrence; in the control group the therapy was intensified only in case of symptoms. In the RCT, clinical recurrence (defined as Crohn's Disease Activity Index (CDAI) > 150 points) in the colonoscopy-based management group was 37.7% (46/122) compared to 46.1% (21/52) in the control group at 18 months' follow up (RR 0.82, 95% CI: 0.56 to 1.18, 174 participants, low-certainty evidence). There may be a reduction in endoscopic recurrence at 18 months with colonoscopy-based management (RR 0.73, 95% CI 0.56 to 0.95, 1 RCT, 174 participants, low-certainty evidence). The certainty of the evidence for surgical recurrence was very low, due to only four cohort studies with inconsistent results reporting this outcome. Adverse events at 18 months were similar in both groups, with 82% in the intervention group (100/122) and 86.5% in the control group (45/52) (RR 0.95, 95% CI:0.83 to 1.08, 1 RCT, 174 participants, low-certainty of evidence).The most common adverse events reported were alopecia, wound infection, sensory symptoms, systemic lupus, vasculitis and severe injection site reaction. Perforations or haemorrhages secondary to colonoscopy were not reported. Initiation of prophylactic-therapy guided by colonoscopy versus initiation immediately after surgery An unblinded RCT and two retrospective cohort studies addressed this comparison. The control group received prophylactic therapy immediately after surgery, and in the colonoscopy-based management group the therapy was delayed up to detection of endoscopic recurrence. The effects on clinical and endoscopic recurrence are uncertain (clinical recurrence until week 102: RR 1.16, 95% CI 0.73 to 1.84; endoscopic recurrence at week 102: RR 1.16, 95% CI 0.73 to 1.84; 1 RCT, 63 participants, very low-certainty evidence). Results from one cohort study were similarly uncertain (median follow-up 32 months, 199 participants). The effects on surgical recurrence at a median follow-up of 50 to 55 months were also uncertain in one cohort study (RR 0.79, 95% CI 0.38 to 1.62, 133 participants, very low-certainty evidence). There were fewer adverse events with colonoscopy-based management (54.8% (17/31)) compared with the control group (93.8% (30/32)) but the evidence is very uncertain (RR 0.58, 95% CI 0.42 to 0.82; 1 RCT, 63 participants). Common adverse events were infections, gastrointestinal intolerance, leukopenia, pancreatitis and skin lesions. Perforations or haemorrhages secondary to colonoscopy were not reported.
AUTHORS' CONCLUSIONS
Intensification of prophylactic-therapy guided by colonoscopy may reduce clinical and endoscopic postoperative recurrence of CD compared to intensification guided by symptoms, and there may be little or no difference in adverse effects. We are uncertain whether initiation of therapy guided by colonoscopy impacts postoperative recurrence and adverse events when compared to initiation immediately after surgery, as the certainty of the evidence is very low. Further studies are necessary to improve the certainty of the evidence of this review.
Topics: Adalimumab; Adult; Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Asymptomatic Diseases; Azathioprine; Bias; Cohort Studies; Colonoscopy; Crohn Disease; Humans; Immunosuppressive Agents; Mesalamine; Metronidazole; Purines; Randomized Controlled Trials as Topic; Recurrence; Retrospective Studies; Secondary Prevention; Tumor Necrosis Factor-alpha
PubMed: 32746500
DOI: 10.1002/14651858.CD012328.pub2 -
Evidence-based Complementary and... 2022Ulcerative colitis (UC), a chronic inflammatory bowel disease, is characterized by abdominal pain, diarrhea, and mucopurulent bloody stool. In recent years, the...
BACKGROUND
Ulcerative colitis (UC), a chronic inflammatory bowel disease, is characterized by abdominal pain, diarrhea, and mucopurulent bloody stool. In recent years, the incidence and prevalence of UC have been increasing consistently. Five-flavor enteric-coated capsule (FSEC), a licensed Chinese patent medicine, was specifically used to treat UC. This review was aimed to assess the effectiveness and safety of FSEC for the treatment of UC.
METHODS
Six electronic databases were searched from inception to March 2021. Randomized clinical trials (RCTs) comparing FSEC or FSEC plus conventional Western medicine with conventional Western medicine in participants with UC were included. Two authors screened all references, assessed the risk of bias, and extracted data independently. Binary data were presented as risk ratios (RRs) with 95% confidence intervals (CIs) and metric data as mean difference (MD) with 95% CI. The overall certainty of the evidence was assessed by GRADE.
RESULTS
We included 15 RCTs (1194 participants, 763 in the FSEC group and 431 in the control group). The treatment duration ranged from 42 to 64 days. Twelve trials compared FSEC with conventional Western medicine, and two trials compared FSEC plus conventional medicine with conventional medicine. Another trial compared FSEC plus mesalazine with compound glutamine enteric capsules plus mesalazine. FSEC showed a higher clinical effective rate (improved clinical symptoms, colonoscopy results, and stools) (RR 1.12, 95% CI 1.05 to 1.20; 729 participants; 8 trials; low-quality evidence) as well as the effective rate of traditional Chinese medicine (TCM) syndromes (RR 1.10, 95% CI 1.01 to 1.20; 452 participants; 5 trials; low-quality evidence) compared to mesalazine. There was no significant difference in the adverse events between FSEC and control groups.
CONCLUSIONS
FSEC may show effectiveness in UC treatment compared to conventional medicine, and the use of FSEC may not increase the risk of adverse events. Due to the limited number of clinical trials and low methodological quality of the included trials, our findings must be interpreted with discretion.
PubMed: 35069773
DOI: 10.1155/2022/9633048 -
The Cochrane Database of Systematic... May 2020Conventional medications for Crohn's disease (CD) include anti-inflammatory drugs, immunosuppressants and corticosteroids. If an individual does not respond, or loses... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Conventional medications for Crohn's disease (CD) include anti-inflammatory drugs, immunosuppressants and corticosteroids. If an individual does not respond, or loses response to first-line treatments, then biologic therapies such as tumour necrosis factor-alpha (TNF-α) antagonists such as adalimumab are considered for treating CD. Maintenance of remission of CD is a clinically important goal, as disease relapse can negatively affect quality of life.
OBJECTIVES
To assess the efficacy and safety of adalimumab for maintenance of remission in people with quiescent CD.
SEARCH METHODS
We searched the Cochrane IBD Group Specialized Register, CENTRAL, MEDLINE, Embase, and clinicaltrials.gov from inception to April 2019.
SELECTION CRITERIA
We considered for inclusion randomized controlled trials (RCTs) comparing adalimumab to placebo or to an active comparator.
DATA COLLECTION AND ANALYSIS
We analyzed data on an intention-to-treat basis. We calculated risk ratios (RRs) and corresponding 95% confidence intervals (95% CI) for dichotomous outcomes. The primary outcome was failure to maintain clinical remission. We define clinical remission as a Crohn's Disease Activity Index (CDAI) score of < 150. Secondary outcomes were failure to maintain clinical response, endoscopic remission, endoscopic response, histological remission and adverse events (AEs). We assessed biases using the Cochrane 'Risk of bias' tool. We used GRADE to assess the overall certainty of evidence supporting the primary outcome.
MAIN RESULTS
We included six RCTs (1158 participants). We rated four trials at low risk of bias and two trials at unclear risk of bias. All participants had moderate-to-severe CD that was in clinical remission. Four studies were placebo-controlled (1012 participants). Two studies (70 participants) compared adalimumab to active medication (azathioprine, mesalamine or 6-mercaptopurine) in participants who had an ileocolic resection prior to study enrolment. Adalimumab versus placebo Fifty-nine per cent (252/430) of participants treated with adalimumab failed to maintain clinical remission at 52 to 56 weeks, compared with 86% (217/253) of participants receiving placebo (RR 0.70, 95% CI 0.64 to 0.77; 3 studies, 683 participants; high-certainty evidence). Among those who received prior TNF-α antagonist therapy, 69% (129/186) of adalimumab participants failed to maintain clinical or endoscopic response at 52 to 56 weeks, compared with 93% (108/116) of participants who received placebo (RR 0.76, 95% CI 0.68 to 0.85; 2 studies, 302 participants; moderate-certainty evidence). Fifty-one per cent (192/374) of participants who received adalimumab failed to maintain clinical remission at 24 to 26 weeks, compared with 79% (149/188) of those who received placebo (RR 0.66, 95% CI 0.52 to 0.83; 2 studies, 554 participants; moderate-certainty evidence). Eighty-seven per cent (561/643) of participants who received adalimumab reported an AE compared with 85% (315/369) of participants who received placebo (RR 1.01, 95% CI 0.94 to 1.09; 4 studies, 1012 participants; high-certainty evidence). Serious adverse events were seen in 8% (52/643) of participants who received adalimumab and 14% (53/369) of participants who received placebo (RR 0.56, 95% CI 0.39 to 0.80; 4 studies, 1012 participants; moderate-certainty evidence) and withdrawal due to AEs was reported in 7% (45/643) of adalimumab participants compared to 13% (48/369) of placebo participants (RR 0.59, 95% CI 0.38 to 0.91; 4 studies, 1012 participants; moderate-certainty evidence). Commonly-reported AEs included CD aggravation, arthralgia, nasopharyngitis, urinary tract infections, headache, nausea, fatigue and abdominal pain. Adalimumab versus active comparators No studies reported failure to maintain clinical remission. One study reported on failure to maintain clinical response and endoscopic remission at 104 weeks in ileocolic resection participants who received either adalimumab, azathioprine or mesalamine as post-surgical maintenance therapy. Thirteen per cent (2/16) of adalimumab participants failed to maintain clinical response compared with 54% (19/35) of azathioprine or mesalamine participants (RR 0.23, 95% CI 0.06 to 0.87; 51 participants). Six per cent (1/16) of participants who received adalimumab failed to maintain endoscopic remission, compared with 57% (20/35) of participants who received azathioprine or mesalamine (RR 0.11, 95% CI 0.02 to 0.75; 51 participants; very low-certainty evidence). One study reported on failure to maintain endoscopic response at 24 weeks in ileocolic resection participants who received either adalimumab or 6-mercaptopurine (6-MP) as post-surgical maintenance therapy. Nine per cent (1/11) of adalimumab participants failed to maintain endoscopic remission compared with 50% (4/8) of 6-MP participants (RR 0.18, 95% CI 0.02 to 1.33; 19 participants).
AUTHORS' CONCLUSIONS
Adalimumab is an effective therapy for maintenance of clinical remission in people with quiescent CD. Adalimumab is also effective in those who have previously been treated with TNF-α antagonists. The effect of adalimumab in the post-surgical setting is uncertain. More research is needed in people with recent bowel surgery for CD to better determine treatment plans following surgery. Future research should continue to explore factors that influence initial and subsequent biologic selection for people with moderate-to-severe CD. Studies comparing adalimumab to other active medications are needed, to help determine the optimal maintenance therapy for CD.
Topics: Adalimumab; Adolescent; Adult; Aged; Anti-Inflammatory Agents; Azathioprine; Crohn Disease; Drug Administration Schedule; Humans; Immunosuppressive Agents; Maintenance Chemotherapy; Mercaptopurine; Mesalamine; Middle Aged; Patient Dropouts; Placebos; Randomized Controlled Trials as Topic; Time Factors; Treatment Outcome; Tumor Necrosis Factor-alpha; Young Adult
PubMed: 32413933
DOI: 10.1002/14651858.CD012877.pub2