Infliximab for medical induction of remission in Crohn's disease.
Ontology highlight
ABSTRACT:
SUBMITTER: Gordon M
PROVIDER: S-EPMC10658649 | biostudies-literature | 2023 Nov
REPOSITORIES: biostudies-literature
Publications
Infliximab for medical induction of remission in Crohn's disease.
Gordon Morris M Sinopoulou Vassiliki V Akobeng Anthony K AK Radford Shellie J SJ Eldragini Mohsen Ebrahim Abdelhamid Ali MEAA Darie Ana-Maria AM Moran Gordon William GW
The Cochrane database of systematic reviews 20231120
<h4>Background</h4>Infliximab is a monoclonal antibody that binds and neutralises tumour necrosis factor-alpha (TNF-α), which is present in high levels in the blood serum, mucosa and stool of people with Crohn's disease.<h4>Objectives</h4>To evaluate the benefits and harms of infliximab alone or in combination with another agent for induction of remission in Crohn's disease compared to placebo or active medical therapies.<h4>Search methods</h4>On 31 August 2021 and 4 March 2023, we searched CENT ...[more]
Similar Datasets
Project description:AimsA strategy based on therapeutic drug monitoring and population pharmacokinetic (popPK) models would likely increase the rate of clinical remission (CR) after infliximab (IFX) induction in patients with Crohn's disease (CD). This study aimed to evaluate the relationship between early IFX levels and antibodies to infliximab (ATI) and CR at week 14 and simulate the probability of attaining the identified exposure target.MethodsPatients with CD (n = 140) treated with IFX were enrolled to develop the popPK model. Of these, 43 moderate-to-severe patients with CD were followed up at week 14. Simulations were performed on patients with different dosage regimens and covariates.ResultsIFX levels >20.08 μg/mL at week 2, >18.44 μg/mL at week 6, and >3.08 μg/mL at week 14 were linked to CR. A one-compartment model fit the data best. The covariates influencing clearance were fat free mass, albumin and ATI levels. To achieve IFX levels >20.08 μg/mL at week 2, ≥400 mg IFX was predicted to be required in over 50% patients with 45-70 kg and 35-45 g/L albumin, except for patients with 70 kg and 30 g/L albumin.ConclusionIFX levels >20.08 μg/mL at week 2 and absence of ATI at week 14 are associated with CR. Optimising IFX induction dosing will be critical to achieve the target of early IFX levels associated with CR.
| S-EPMC11384982 | biostudies-literature
Project description:BackgroundBoth exclusive enteral nutrition (EEN) and infliximab (IFX) are recommended as induction therapy for pediatric Crohn's disease (CD). Our aim was to compare long-term disease outcomes of patients initially received with either IFX or EEN.MethodsMedical records of newly diagnosed, therapy naïve pediatric patients with CD received with IFX or EEN as induction therapy were retrospectively enrolled. Pediatric Crohn's disease activity index (PCDAI), Crohn's disease endoscopic index of severity (CDEIS), and other clinical data were compared pre- and postinduction therapy in two groups. The sustained remission rates and time coupled with body mass index (BMI) and height for age (HFA) changes were evaluated during more than 2-year long-term follow-up.ResultsWe collected data from 58 children with CD used IFX (23) or EEN (35) as induction remission therapy from January 2015 through June 2021 in our single-center. The median follow-up after starting IFX or EEN was 12.2 months (6.5-18.0months) and 18.9 months (7.1-30.7months), respectively. The proportion clinical and endoscopic remission in EEN (88.57% and 68.75%) was similar with that of IFX (73.91% and 80.77%) after induction therapy. No significant differences were also observed in BMI and HFA recovery between two groups. Among those who achieved clinical or endoscopic remission or endoscopic response, the sustained remission rates and time did not reveal any significant differences for those 10 patients who used 6-mercaptopurine/methotrexate (6-MP/MTX) or 14 patients who used IFX as maintenance treatment during longitudinal follow-up.ConclusionsOur study suggested that EEN treatment is similar with IFX therapy in short-term outcomes, and EEN+6-MP/MTX treatment is comparable with IFX+IFX therapy in long-term outcomes.
| S-EPMC9462978 | biostudies-literature
Project description:BackgroundCrohn's disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract, in which the pathogenesis is believed to be partly influenced by the gut microbiome. Probiotics can be used to manipulate the microbiome and have therefore been considered as a potential therapy for CD. There is some evidence that probiotics benefit other gastrointestinal conditions, such as irritable bowel syndrome and ulcerative colitis, but their efficacy in CD is unclear. This is the first update of a Cochrane Review previously published in 2008.ObjectivesTo assess the efficacy and safety of probiotics for the induction of remission in CD.Search methodsThe following electronic databases were searched: MEDLINE (from inception to 6 July 2020), Embase (from inception to 6 July 2020), the Cochrane Central Register of Controlled Trials (CENTRAL), The Cochrane IBD Review Group Specialised Trials Register, World Health Organization (WHO) International Clinical Trials Registry, and ClinicalTrials.gov.Selection criteriaRandomised controlled trials (RCTs) that compared probiotics with placebo or any other non-probiotic intervention for the induction of remission in CD were eligible for inclusion.Data collection and analysisTwo review authors independently extracted data and assessed the methodological quality of included studies. The primary outcome was clinical remission. Risk ratios (RRs) and 95% confidence intervals (CIs) were calculated for dichotomous outcomes.Main resultsThere were two studies that met criteria for inclusion. One study from Germany had 11 adult participants with mild-to-moderate CD, who were treated with a one-week course of corticosteroids and antibiotics (ciprofloxacin 500 mg twice daily and metronidazole 250 mg three times a day), followed by randomised assignment to Lactobacillus rhamnosus strain GG (two billion colony-forming units per day) or corn starch placebo. The other study from the United Kingdom (UK) had 35 adult participants with active CD (CDAI score of 150 to 450) randomised to receive a synbiotic treatment (comprised of freeze-dried Bifidobacterium longum and a commercial product) or placebo. The overall risk of bias was low in one study, whereas the other study had unclear risk of bias in relation to random sequence generation, allocation concealment, and blinding. There was no evidence of a difference between the use of probiotics and placebo for the induction of remission in CD (RR 1.06; 95% CI 0.65 to 1.71; 2 studies, 46 participants) after six months. There was no difference in adverse events between probiotics and placebo (RR 2.55; 95% CI 0.11 to 58.60; 2 studies, 46 participants). The evidence for both outcomes was of very low certainty due to risk of bias and imprecision.Authors' conclusionsThe available evidence is very uncertain about the efficacy or safety of probiotics, when compared with placebo, for induction of remission in Crohn's disease. There is a lack of well-designed RCTs in this area and further research is needed.
| S-EPMC7389339 | biostudies-literature
Project description: Not available
| S-EPMC6953260 | biostudies-literature
Project description:BackgroundCrohn's disease (CD) is a chronic inflammatory disease of the gastrointestinal tract, and immune response modulation is the main treatment strategy to induce remission in active CD. Certolizumab pegol (CZP) is a tumor necrosis factor-alfa (TNF-α) inhibitor which regulates impaired immune response.ObjectivesThe primary objectives were to evaluate the efficacy and safety of CZP for the induction of remission in CD.Search methodsWe searched MEDLINE, Embase, CENTRAL, the Cochrane IBD group specialized register, trials registers and other sources from inception to 28 January 2019. Moreover, we contacted the pharmaceutical company that manufactures CZP.Selection criteriaWe included randomized controlled trials comparing CZP with placebo or no treatment in active CD patients.Data collection and analysisWe used standard Cochrane methodological procedures. The main outcomes selected for GRADE analysis were clinical remission at week 8 (Crohn's Disease Activity Index [CDAI] ≤150), clinical response at week 8 (CDAI reduction ≥ 100 or clinical remission), and serious adverse events. The Mantel-Haenszel random-effects method was applied for the statistical analyses. For dichotomous outcomes, we calculated the risk ratio (RR) and corresponding 95% confidence interval (95% CI).Main resultsFour studies involving 1485 participants with moderate to severe CD met the inclusion criteria and were used in the meta-analyses. All studies included active CD patients with CDAI ranging from 220 to 450. Most patients were adults over 18 years of age. One study was identified as high risk of bias due to a non-identical placebo while the other studies were judged to be at low risk of bias.CZP (100 mg to 400 mg every 2 to 4 weeks) was shown to be superior to placebo for achieving clinical remission at week 8 (RR 1.36, 95% CI 1.11 to 1.66; moderate certainty evidence). The raw numbers of participants achieving clinical remission at week 8 were 26.9% (225/835) and 19.8% (129/650) in the CZP and the placebo groups, respectively.CZP was shown to be superior to placebo for achieving clinical response at week 8 (RR 1.29, 95% CI 1.09 to 1.53; moderate certainty evidence). In raw numbers, clinical response at week 8 was achieved in 40.2% (336/835) and 30.9% (201/650) of participants in the CZP and the placebo groups, respectively.In raw numbers, serious adverse events were observed in 8.7% (73/835) and 6.2% (40/650) of participants in the CZP and the placebo groups, respectively (RR 1.35, 95% CI 0.93 to 1.97; moderate certainty evidence). Serious adverse events included worsening Crohn's disease, infections, and malignancy.Authors' conclusionsModerate certainty evidence suggests that CZP is effective for induction of clinical remission and clinical response in participants with active CD patients. It is uncertain whether the risk of serious adverse events differs between CZP and placebo as the 95% CI includes the possibility of a small decrease or doubling of events. Future studies are needed to evaluate the long-term efficacy and safety of CZP in CD patients.
| S-EPMC6718195 | biostudies-literature
Project description:Abstract This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: The objectives of this systematic review are to evaluate the efficacy and safety of CZP for induction of remission in CD.
| S-EPMC6486011 | biostudies-literature
Project description: Not available
| S-EPMC6494424 | biostudies-literature
Project description: Not available
| S-EPMC10351211 | biostudies-literature
Project description:Background and aimsIt is unclear whether early symptom improvement in Crohn's disease [CD] provides any prognostic information for patients long-term. This paper aims to investigate the relationship between early patient-reported outcomes [PROs] after completion of induction of infliximab, and their relationship with long-term clinical remission [CR] and endoscopic remission [ER].MethodsThis post-hoc analysis [Clinicaltrials.gov: NCT02096861] used data from 220 CD patients to evaluate the relationship of Weeks 6 and 14 PRO variables and Week 54 clinical remission (Crohn's Disease Activity Index [CDAI <150), PRO2 remission (mean score abdominal pain [AP] ≤1 and stool frequency [SF] ≤1.5), and endoscopic remission (Simple Endoscopic Score-CD [SES-CD <3). Multivariable logistic regression models adjusted for confounders were used to assess the relationships between post-induction PROs and outcomes of interest.ResultsPatients with moderate or severe AP after induction had reduced odds of achieving 1-year CR and PRO2 remission compared with those with mild AP (adjusted odds ratio [aOR] for CR 0.31, 95% confidence interval [CI] 0.17-0.57, p = 0.0002). Similarly, patients with moderately to severely elevated SF after induction had reduced odds of 1-year CR and PRO2 remission compared with patients with less SF [aOR for CR 0.31, 95% CI 0.16-0.58, p = 0.0003]. No significant differences were found when comparing higher Weeks 6 or 14 PRO scores of AP and/or SF with lower PRO scores in the odds of achieving 1-year ER.ConclusionsPost-induction PROs of AP and SF strongly predict likelihood of 1-year CR but are not associated with 1-year ER. Clinical symptoms alone should not be relied upon when assessing response to therapies for CD.
| S-EPMC8491840 | biostudies-literature
Project description: Not available
| S-EPMC9099217 | biostudies-literature