Dataset Information

Evaluating Potential Disease-Mediated Protein-Drug Interactions in Patients With Moderate-to-Severe Plaque Psoriasis Receiving Subcutaneous Guselkumab.

ABSTRACT: This open-label, multicenter, phase I therapeutic protein-drug interaction study was designed to evaluate the potential effect of guselkumab, a fully human anti-interleukin-23 immunoglobulin G1 lambda monoclonal antibody, on the pharmacokinetics of a cocktail of representative cytochrome P450 (CYP) probe substrates (midazolam (CYP3A4), S-warfarin (CYP2C9), omeprazole (CYP2C19), dextromethorphan (CYP2D6), and caffeine (CYP1A2)). Fourteen participants with psoriasis received a single subcutaneous dose of guselkumab 200 mg on day 8 and an oral probe cocktail on days 1, 15, and 36. Blood samples were collected for measuring plasma concentrations of these probe substrates on days 1, 15, and 36. No consistent trends in observed maximum plasma concentration and area under the curve from time 0 to infinity values of each probe CYP-substrate before (day 1) and after guselkumab treatment (days 15 and 36) could be identified in each individual patient, suggesting that the use of guselkumab in patients with psoriasis is unlikely to influence the systemic exposure of drugs metabolized by CYP isozymes (CYP3A4, CYP2C9, CYP2C19, CYP2D6, and CYP1A2). The probe cocktail was generally well-tolerated when administered in combination with guselkumab in patients with psoriasis. Clinicaltrials.gov Identifiers: NCT02397382.

SUBMITTER: Zhu Y

PROVIDER: S-EPMC7719363 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Evaluating Potential Disease-Mediated Protein-Drug Interactions in Patients With Moderate-to-Severe Plaque Psoriasis Receiving Subcutaneous Guselkumab.

Zhu Yaowei Y Xu Yan Y Zhuang Yanli Y Piantone Alexa A Shu Cathye C Chen Dion D Zhou Honghui H Xu Zhenhua Z Sharma Amarnath A

Clinical and translational science 20200528 6

This open-label, multicenter, phase I therapeutic protein-drug interaction study was designed to evaluate the potential effect of guselkumab, a fully human anti-interleukin-23 immunoglobulin G1 lambda monoclonal antibody, on the pharmacokinetics of a cocktail of representative cytochrome P450 (CYP) probe substrates (midazolam (CYP3A4), S-warfarin (CYP2C9), omeprazole (CYP2C19), dextromethorphan (CYP2D6), and caffeine (CYP1A2)). Fourteen participants with psoriasis received a single subcutaneous ...[more]

PMID: 32407591

Similar Datasets

Project description:BackgroundReal-life data on patients with psoriasis treated with guselkumab are few and are needed to compare with trial-based data. We investigated the effect of clinical factors on real-world effectiveness of guselkumab.MethodsThis multicentre study retrospectively included 135 patients with psoriasis treated with guselkumab from June 2018 until November 2020. Effectiveness was assessed using the degree of improvement in the Psoriasis Area and Severity Index (PASI) scores at baseline and after 4, 12, 20, 28, and 36 weeks. Predictors of effectiveness were also evaluated.ResultsAt week 36, 67% of the patients achieved PASI 75. Multivariate logistic regression analysis revealed that heavier patients were less likely to achieve PASI 75 at week 4 than patients with lower body weights. Fewer patients exposed to only one biologic achieved PASI 75 at weeks 4, 20, 28, and 36 [odds ratio (OR) = 0.08 (95% CI, 0.01-0.48), 0.21 (95% CI, 0.05-0.74), 0.04 (95% CI, 0.00-0.35), and 0.07 (95% CI, 0.00-0.68), respectively] than biologic-naïve patients. Patients previously treated with more than one biologic were less likely to achieve PASI 75 at weeks 12, 20, 28, and 36 [OR = 0.05 (95% CI, 0.01-0.22), 0.03 (95% CI, 0.01-0.16), 0.00 (95% CI, 0.00-0.03), and 0.00 (95% CI, 0.00-0.044), respectively] than biologic-naïve patients. Patients with previous anti-interleukin (IL)-17 exposure, rather than tumour necrosis factor-α and IL-12/23 inhibitors, had lower PASI improvements to guselkumab than biologic-naïve patients at weeks 12, 20, and 28 [OR = 0.19 (95% CI, 0.03-0.90), 0.10 (95% CI, 0.02-0.55), and 0.03 (95% CI, 0.00-0.29), respectively].ConclusionsThe effectiveness of guselkumab was compromised in a real-world setting. Delayed onset of therapeutic response was noted in heavier patients. Biologic exposure, the number of previously used biologics, and previous exposure to IL-17 inhibitors were clinical predictors of a reduced response to guselkumab. Physicians may share this information with patients to make treatment decisions.

Dataset Information

Evaluating Potential Disease-Mediated Protein-Drug Interactions in Patients With Moderate-to-Severe Plaque Psoriasis Receiving Subcutaneous Guselkumab.

Publications

Evaluating Potential Disease-Mediated Protein-Drug Interactions in Patients With Moderate-to-Severe Plaque Psoriasis Receiving Subcutaneous Guselkumab.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets