Dataset Information

Effects of concomitant immunomodulators on the pharmacokinetics, efficacy and safety of adalimumab in patients with Crohn's disease or ulcerative colitis who had failed conventional therapy.

ABSTRACT:

Background

Adalimumab is approved for use in patients with moderate to severe Crohn's disease (CD) or ulcerative colitis (UC) who have not achieved disease control with conventional therapies including corticosteroids and/or immunomodulators (IMM).

Aim

To analyse six studies that examined efficacy, pharmacokinetics and safety of combination IMM/adalimumab therapy, compared with adalimumab monotherapy in patients with inadequate disease control on conventional therapy.

Methods

Patients with moderate to severe CD or UC from randomised, double-blind, placebo-controlled trials were analysed. Adalimumab was added to background therapy; patients were categorised as receiving adalimumab monotherapy (CD induction, n = 245, maintenance, n = 185; UC induction, n = 213, maintenance, n = 157) or combination therapy (CD induction, n = 139, maintenance, n = 139; UC induction, n = 140, maintenance, n = 100) according to baseline immunomodulator use. Efficacy was reported for the intent-to-treat populations from each study, with remission defined as CD activity index <150 for CD and Mayo score ?2 with no subscore >1 for UC. Safety was assessed via adverse events.

Results

The proportions of patients achieving remission were similar for adalimumab monotherapy and immunomodulator combination therapy in all studies. Median adalimumab concentrations at week 4 or 8 were numerically but not significantly higher with adalimumab combination therapy vs. monotherapy in the CD and UC studies respectively. Incidence and rate of adverse events was similar for adalimumab monotherapy and combination therapy.

Conclusions

Post hoc analysis of six randomised, controlled trials demonstrated no efficacy benefits with immunomodulator/adalimumab combination therapy, compared with adalimumab monotherapy in CD and UC patients with inadequate disease control on conventional therapy; the safety of the two treatment approaches was comparable.

SUBMITTER: Colombel JF

PROVIDER: S-EPMC5157781 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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Publications

Effects of concomitant immunomodulators on the pharmacokinetics, efficacy and safety of adalimumab in patients with Crohn's disease or ulcerative colitis who had failed conventional therapy.

Colombel J-F JF Jharap B B Sandborn W J WJ Feagan B B Peyrin-Biroulet L L Eichner S F SF Robinson A M AM Mostafa N M NM Zhou Q Q Thakkar R B RB

Alimentary pharmacology & therapeutics 20161107 1

<h4>Background</h4>Adalimumab is approved for use in patients with moderate to severe Crohn's disease (CD) or ulcerative colitis (UC) who have not achieved disease control with conventional therapies including corticosteroids and/or immunomodulators (IMM).<h4>Aim</h4>To analyse six studies that examined efficacy, pharmacokinetics and safety of combination IMM/adalimumab therapy, compared with adalimumab monotherapy in patients with inadequate disease control on conventional therapy.<h4>Methods</ ...[more]

PMID: 27883215

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Project description:Background/aimsVedolizumab is indicated for moderately-to-severely active ulcerative colitis (UC) and Crohn's disease (CD). Because multiple factors may result in different pharmacokinetics and clinical efficacies, understanding determinants of vedolizumab clearance may enhance dose and treatment strategies. The aim was to characterize vedolizumab pharmacokinetics in Asian and non-Asian UC and CD patients.MethodsPopulation pharmacokinetic analysis for repeated measures, using data from 5 studies, was conducted using nonlinear mixed-effects modeling. A Bayesian estimation approach in NONMEM 7.3 was utilized to leverage the predominantly sparse data available for this analysis with results from a prior population pharmacokinetic analysis of vedolizumab.ResultsVedolizumab pharmacokinetics were described by a 2-compartment model with parallel linear and nonlinear elimination. Using reference covariate values, linear elimination half life of vedolizumab was 24.7 days for anti-vedolizumab antibody (AVA)-negative patients and 18.1 days for AVA-positive patients; linear clearance (CLL) was 0.165 L/day for AVA-negative patients and 0.246 L/day for AVA-positive patients; central (Vc) and peripheral compartment volumes of distribution were 3.16 L and 1.84 L, respectively. Interindividual variabilities (percent coefficient of variation) were 30.8% for CLL and 19% for Vc; interoccasion variability on CLL was 20.3%; residual variance was 17.8%. For albumin, body weight and AVA, only extreme values were identified as potentially clinically important predictors of CLL. The effect of race (Asian/non-Asian) and diagnosis (UC/CD) on CLL was negligible and likely not of clinical importance.ConclusionsPharmacokinetic parameters were similar in Asian and non-Asian patients with moderately-to-severely active UC and CD. This analysis supports use of vedolizumab flat-fixed dosing in these patients. (Clinicaltrials.gov Identifiers: NCT00783718 (GEMINI 1); NCT00783692 (GEMINI 2). CCT 101; NCT02039505 and CCT-001; NCT02038920).

Dataset Information

Effects of concomitant immunomodulators on the pharmacokinetics, efficacy and safety of adalimumab in patients with Crohn's disease or ulcerative colitis who had failed conventional therapy.

Background

Aim

Methods

Results

Conclusions

Publications

Effects of concomitant immunomodulators on the pharmacokinetics, efficacy and safety of adalimumab in patients with Crohn's disease or ulcerative colitis who had failed conventional therapy.

Similar Datasets

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