ArticleClinical pharmacology and therapeutics2019
Secukinumab Treatment Does Not Alter the Pharmacokinetics of the Cytochrome P450 3A4 Substrate Midazolam in Patients With Moderate to Severe Psoriasis.
Article in Clinical pharmacology and therapeutics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers, 2 of them syntheses that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
8 citing papers in PubMed, 2 syntheses or guidelines pooled it, 14 citations in OpenAlex.
- The Cytokine Release Syndrome and/or the Proinflammatory Cytokines as Underlying Mechanisms of Downregulation of Drug Metabolism and Drug Transport: A Systematic Review of the Clinical Pharmacokinetics of Victim Drugs of this Drug-Disease Interaction Under Different Clinical Conditions.Clinical pharmacokinetics · 2022Pooled it
- A systematic review on disease-drug-drug interactions with immunomodulating drugs: A critical appraisal of risk assessment and drug labelling.British journal of clinical pharmacology · 2022Pooled it
- Secukinumab in the Treatment of Moderate-to-Severe Hidradenitis Suppurativa: Pooled Pharmacokinetics and Safety Results From the SUNSHINE and SUNRISE Phase 3 Studies.International journal of dermatology · 2026Trial
- Longitudinal plasma proteomics identifies diagnostic and response-associated inflammatory and immune biomarkers in psoriasis following secukinumab therapy.Frontiers in immunology · 2026Article
- Circulating IL-17A accumulation reflects effective target blockade with secukinumab in spondyloarthritis.Frontiers in immunology · 2026Article
- Utilization of physiologically-based pharmacokinetic model to assess disease-mediated therapeutic protein-disease-drug interaction in immune-mediated inflammatory diseases.Clinical and translational science · 2022Article
- Influence of Inflammation on Cytochromes P450 Activity in Adults: A Systematic Review of the Literature.Frontiers in pharmacology · 2021Review
- Inflammation is a major regulator of drug metabolizing enzymes and transporters: Consequences for the personalization of drug treatment.Pharmacology & therapeutics · 2020Review
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
This open-label disease-drug-drug interaction study assessed whether blockade of the interleukin (IL)-17A pathway by secukinumab and subsequent downregulation of inflammatory cytokines like IL-6 or high-sensitivity C-reactive protein affects the pharmacokinetics (PKs) of a sensitive probe substrate of the cytochrome P450 3A4 isoform (CYP3A4). The PKs of midazolam, metabolized by CYP3A4, was evaluated before and after 7 and 35 days of treatment initiation of subcutaneous secukinumab at a dose of 300 mg weekly in 24 patients with moderate-to-severe psoriasis. Although demonstrating the expected decrease in downstream inflammatory cytokines, secukinumab had no clinically relevant effects on the PKs of midazolam, provided substantial clinical benefit, and was generally well tolerated. In summary, blockade of IL-17A signaling in patients with moderate-to-severe psoriasis does not significantly affect CYP3A4 enzyme activities and, therefore, the use of secukinumab is unlikely to influence the PKs of CYP3A4 substrates.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.