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Efficacy and Safety of Infliximab in Pediatric Crohn Disease: A Systematic Review and Meta-Analysis.

ABSTRACT: Background:Crohn disease is an inflammatory bowel disease with intermittent symptoms relating to damage to the gastrointestinal tract. Compared with adult-onset Crohn disease, the childhood-onset form is more likely to be severe. Infliximab has shown efficacy in adult patients. Objective:To examine the efficacy and safety of infliximab in pediatric Crohn disease, by means of a systematic review. Data Sources:Three databases (MEDLINE, Embase, and Cochrane Central Register of Controlled Trials) and regulatory documents were searched from inception to December 2017. Clinical trial registries, conference abstracts, and reference lists were searched to March 2018. Study Selection and Data Extraction:Randomized controlled trials (RCTs) and prospective cohort studies that compared infliximab with active control were included in the analysis. Two reviewers independently performed screening, extracted data, and assessed risk of bias. The primary outcomes were induction and maintenance of endoscopic remission and severe adverse effects. Data Synthesis:Three eligible RCTs comparing different dose regimens, 16 prospective cohort studies comparing infliximab with other therapies (adalimumab, exclusive enteral nutrition, or standard of care), and 3 prospective cohort studies comparing different infliximab regimens were identified. Meta-analysis of the RCTs showed no significant difference between infliximab every 8 weeks compared with longer intervals for maintenance of clinical remission (risk ratio [RR] 1.76, 95% confidence interval [CI] 0.98-3.19). Meta-analyses of the prospective cohort studies showed no significant differences between infliximab and adalimumab for maintenance of endoscopic remission (RR 1.07, 95% CI 0.60-1.92), between infliximab and exclusive enteral nutrition for induction of clinical remission (RR 1.09, 95% CI 0.82-1.45), or between infliximab and standard of care for maintenance of clinical remission at 6 and 12 months (RR 1.12, 95% CI 0.58-2.17, and RR 1.24, 95% CI 0.84-1.84, respectively). Conclusions:Current evidence suggested comparable efficacy for infliximab and other therapies; however, the available literature was limited by risk of bias and small sample size. Further prospective studies are needed to confirm the efficacy and safety of this drug in pediatric Crohn disease.

SUBMITTER: Li S

PROVIDER: S-EPMC6592657 | biostudies-literature | 2019 May-Jun

REPOSITORIES: biostudies-literature

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Efficacy and Safety of Infliximab in Pediatric Crohn Disease: A Systematic Review and Meta-Analysis.

Li Sophia S Reynaert Christopher C Su Annie Ling AL Sawh Sonja S

The Canadian journal of hospital pharmacy 20180630 3

<h4>Background</h4>Crohn disease is an inflammatory bowel disease with intermittent symptoms relating to damage to the gastrointestinal tract. Compared with adult-onset Crohn disease, the childhood-onset form is more likely to be severe. Infliximab has shown efficacy in adult patients.<h4>Objective</h4>To examine the efficacy and safety of infliximab in pediatric Crohn disease, by means of a systematic review.<h4>Data sources</h4>Three databases (MEDLINE, Embase, and Cochrane Central Register of ...[more]

PMID: 31258168

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Project description:Background: Crohn disease (CD) is a chronic inflammatory disease that affects quality of life. There are several drugs available for the treatment of CD, but their relative efficacy is unknown due to a lack of high-quality head-to-head randomized controlled trials. Aim: To perform a mixed comparison of the efficacy and safety of biosimilars, biologics and JAK1 inhibitors for CD. Methods: We searched PubMed, Web of Science, embase and the Cochrane Library for randomized controlled trials (RCTs) up to Dec. 28, 2020. Only RCTs that compared the efficacy or safety of biosimilars, biologics and JAK1 inhibitors with placebo or another active agent for CD were included in the comparative analysis. Efficacy outcomes were the induction of remission, maintenance of remission and steroid-free remission, and safety outcomes were serious adverse events (AEs) and infections. The Bayesian method was utilized to compare the treatments. The registration number is CRD42020187807. Results: Twenty-eight studies and 29 RCTs were identified in our systematic review. The network meta-analysis demonstrated that infliximab and adalimumab were superior to certolizumab pegol (OR 2.44, 95% CI 1.35-4.97; OR 2.96, 95% CI 1.57-5.40, respectively) and tofacitinib (OR 2.55, 95% CI 1.27-5.97; OR 3.10, 95% CI 1.47-6.52, respectively) and revealed the superiority of CT-P13 compared with placebo (OR 2.90, 95% CI 1.31-7.59) for the induction of remission. Infliximab (OR 7.49, 95% CI 1.85-34.77), adalimumab (OR 10.76, 95% CI 2.61-52.35), certolizumab pegol (OR 4.41, 95% CI 1.10-21.08), vedolizumab (OR 4.99, 95% CI 1.19-25.54) and CT-P13 (OR 10.93, 95% CI 2.10-64.37) were superior to filgotinib for the maintenance of remission. Moreover, infliximab (OR 3.80, 95% CI 1.49-10.23), adalimumab (OR 4.86, 95% CI 1.43-16.95), vedolizumab (OR 2.48, 95% CI 1.21-6.52) and CT-P13 (OR 5.15, 95% CI 1.05-27.58) were superior to placebo for steroid-free remission. Among all treatments, adalimumab ranked highest for the induction of remission, and CT-P13 ranked highest for the maintenance of remission and steroid-free remission. Conclusion: CT-P13 was more efficacious than numerous biological agents and JAK1 inhibitors and should be recommended for the treatment of CD. Further head-to-head RCTs are warranted to compare these drugs.

Project description:ObjectivesSubtherapeutic drug concentrations contribute to both primary and secondary nonresponse to infliximab in children with Crohn disease (CD). The aim of this study was to evaluate treatment outcomes and infliximab concentrations at infusions 2 and 3 with an objective to establish infliximab targets during induction for primary responders.MethodsSingle-center, prospective cohort of anti- tumor necrosis factor-alpha naïve CD patients younger than 22 years starting infliximab. Clinical response was defined with the weighted pediatric CD activity index at the fourth infusion. Rates of biological response (>50% improvement in fecal calprotectin) and maintenance concentrations ≥5 μg/mL were secondary outcomes.ResultsWe enrolled 72 patients with CD with 70 of 72 receiving infliximab monotherapy. Clinical response, biological response, and start of maintenance concentrations ≥5 μg/mL were achieved in 64%, 54%, and 22%, respectively. The median (interquartile range) infliximab concentrations at infusion 2 and 3 in clinical responders were 27.8 μg/mL (19.5-40) and 14 μg/mL (8.3-24) compared to 18.8 μg/mL (9.1-23, P < 0.001) and 7.8 μg/mL (4-13.2, P < 0.01) in nonresponders. Receiver operating characteristic analysis determined that an infliximab concentration ≥15.9 μg/mL at infusion 3 was associated with clinical response (area under the curve [AUC] 0.73), whereas an infusion 3 level ≥18 μg/mL was associated with a start of maintenance concentration >5 μg/mL (AUC 0.85). Independent predictors for infusion 3 levels <18 μg/mL included pretreatment prednisone, low body mass index, elevated erythrocyte sedimentation rate and C-reactive protein, hypoalbuminemia, and an infusion 2 infliximab level <29 μg/mL.ConclusionsWe found that infusion 2 (≥29 μg/mL) and infusion 3 (≥18 μg/mL) infliximab concentrations were strongly associated with improved early outcomes and higher first maintenance dose levels.

Project description:Vancomycin and teicoplanin are the glycopeptides currently in use for the treatment of infections caused by invasive beta-lactam-resistant gram-positive organisms. We conducted a systematic review and meta-analysis of randomized controlled trials that have compared vancomycin and teicoplanin administered systemically for the treatment of suspected or proven infections. A comprehensive search of trials without year, language, or publication status restrictions was performed. The primary outcome was all-cause mortality. Two reviewers independently extracted the data. Risk ratios (RRs) with 95% confidence intervals (CIs) were pooled by using the fixed-effect model (RRs of >1 favor vancomycin). Twenty-four trials were included. All-cause mortality was similar overall (RR, 0.95; 95% CI, 0.74 to 1.21), and there was no significant heterogeneity. In trials that used adequate allocation concealment, the results favored teicoplanin (RR, 0.82; 95% CI, 0.63 to 1.06), while in trials with unknown methods or inadequate concealment, the results favored vancomycin (RR, 3.61; 95% CI, 1.27 to 10.30). The latter trials might have recruited more severely ill patients. No other variable affected the RRs for mortality, including the assessment of glycopeptides administered empirically or for proven infections, neutropenia, the participant's age, and drug dosing. There were no significant differences between teicoplanin and vancomycin with regard to clinical failure (RR, 0.92; 95% CI, 0.81 to 1.05), microbiological failure (RR, 1.24; 95% CI, 0.93 to 1.65), and other efficacy outcomes. Lower RRs (in favor of teicoplanin) for clinical failure were observed with a lower risk of bias and when treatment was initiated for infections caused by gram-positive organisms rather than empirically. Total adverse events (RR, 0.61; 95% CI, 0.50 to 0.74), nephrotoxicity (RR, 0.44; 95% CI, 0.32 to 0.61), and red man syndrome were significantly less frequent with teicoplanin. Teicoplanin is not inferior to vancomycin with regard to efficacy and is associated with a lower adverse event rate than vancomycin.

Dataset Information

Efficacy and Safety of Infliximab in Pediatric Crohn Disease: A Systematic Review and Meta-Analysis.

Publications

Efficacy and Safety of Infliximab in Pediatric Crohn Disease: A Systematic Review and Meta-Analysis.

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