SynthesisRheumatology international2012
Interleukin-6 and cytochrome-P450, reason for concern?
Synthesis in Rheumatology international, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06383338 (A Prospective Feasibility Study Investigating PhEnoconversion of CYP3A4, CYP2C19 and CYP2D6 Genotype in Paediatric and Adolescent and Young Adult patientS With an acUte diagnosiS of Hodgkin or Non-Hodgkin Lymphoma.), which is not on this map. Cited by 33 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
A Prospective Feasibility Study Investigating PhEnoconversion of CYP3A4, CYP2C19 and CYP2D6 Genotype in Paediatric and Adolescent and Young Adult patientS With an acUte diagnosiS of Hodgkin or Non-Hodgkin Lymphoma.
Who cites it
33 citing papers in PubMed, 66 citations in OpenAlex.
- Frailty as a Marker for the Plasma Concentrations of Direct Oral Anticoagulants in Older Patients: Results of an Exploratory Study.Drugs & aging · 2023Trial
- Anti-interleukin-6 antibody clazakizumab in late antibody-mediated kidney transplant rejection: effect on cytochrome P450 drug metabolism.Transplant international : official journal of the European Society for Organ Transplantation · 2021Trial
- Therapeutic protein-drug interaction assessment for daclizumab high-yield process in patients with multiple sclerosis using a cocktail approach.British journal of clinical pharmacology · 2016Trial
- Cytochrome P450 (CYP) 1 enzymes in acute lung injury: from molecular insights to therapeutic implications.Redox report : communications in free radical research · 2025Review
- Phenoconversion of CYP3A4, CYP2C19 and CYP2D6 in Pediatrics, Adolescents and Young Adults With Lymphoma: Rationale and Design of the PEGASUS Study.Clinical and translational science · 2025Article
- Evaluation of the potential impact on pharmacokinetics of various cytochrome P450 substrates of increasing IL-6 levels following administration of the T-cell bispecific engager glofitamab.CPT: pharmacometrics & systems pharmacology · 2024Article
- COVID-19: A Review of Potential Treatments (Corticosteroids, Remdesivir, Tocilizumab, Bamlanivimab/Etesevimab, and Casirivimab/Imdevimab) and Pharmacological Considerations.Journal of pharmacy practice · 2023Review
- Investigation of CYP2E1 and Caspase-3 Gene Expressions in COVID-19 patients.Gene reports · 2022Article
- Drug Interactions for Patients with Respiratory Diseases Receiving COVID-19 Emerged Treatments.International journal of environmental research and public health · 2021Review
- Liver transplantation during global COVID-19 pandemic.World journal of clinical cases · 2021Review
- Management of COVID-19 in patients with seizures: Mechanisms of action of potential COVID-19 drug treatments and consideration for potential drug-drug interactions with anti-seizure medications.Epilepsy research · 2021Review
- Pharmacological mechanism of immunomodulatory agents for the treatment of severe cases of COVID-19 infection.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2021Review
- Potential Drug Interactions of Repurposed COVID-19 Drugs with Lung Cancer Pharmacotherapies.Archives of medical research · 2021Review
- Clinically Significant Drug Interactions Between Psychotropic Agents and Repurposed COVID-19 Therapies.CNS drugs · 2021Review
- Cardiac Corrected QT Interval Changes Among Patients Treated for COVID-19 Infection During the Early Phase of the Pandemic.JAMA network open · 2021Article
- Potential Effects of COVID-19 on Cytochrome P450-Mediated Drug Metabolism and Disposition in Infected Patients.European journal of drug metabolism and pharmacokinetics · 2021Review
- Effect of Pregnane X Receptor onAnimals : an open access journal from MDPI · 2021Article
- Article
- Spontaneous Spinal Epidural Hematoma During Simultaneous Tocilizumab and Warfarin Use in a Patient With Rheumatoid Arthritis: Is There a Drug Interaction Between Tocilizumab and Oral Anticoagulants?Archives of rheumatology · 2020Article
- Evaluating Potential Disease-Mediated Protein-Drug Interactions in Patients With Moderate-to-Severe Plaque Psoriasis Receiving Subcutaneous Guselkumab.Clinical and translational science · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Interleukin 6 (IL-6) plays a central role in the immunopathogenesis of rheumatoid arthritis (RA) and tocilizumab [TCZ] (an anti-IL-6 receptor antibody) has been shown to be effective in the treatment of the condition. As up-regulation of IL-6 reduces the activity of cytochrome P450 (CYP) enzymes, blockade of this cytokine may enhance CYP function. This may lead to reduced bioavailability of CYP-metabolized drugs. Due to the increasing use of TCZ, we undertook a systematic literature review to explore such interactions. Our search was conducted in MEDLINE, EMBASE, Web of Science, FDA and EMEA websites for in vitro and in vivo studies, clinical trials and reviews mentioning TCZ and CYP on the basis of the title and abstract. Appropriate articles were further screened based on full-text review to select only those reporting IL-6, TCZ and their potential interaction with CYP-metabolized drugs. Two in vitro studies showed that TCZ-reversed IL-6 induced reduction of CYP isozymes. CYP3A4 mRNA expression was most reduced by IL-6 followed by CYP2C9 and CYP2C19. This change was prevented with TCZ. Three clinical studies investigated the interaction showing simvastatin (CYP3A4 substrate) bioavailability reduced by TCZ and omeprazole bioavailability was decreased by TCZ-induced CYP2C19 activity. The bioavailability of dextromethorphan (CYP2D6 and CYP3A4 substrates) was shown to be unaffected by TCZ treatment. The observed increase in CYP isozyme activity by TCZ is of clinical relevance as the bioavailability of the CYP isozyme substrates were decreased in vivo. As CYP3A4 is the isozyme responsible for the largest proportion of drug metabolism, it is probable that the bioavailability of other drugs may be reduced by TCZ. Thus, clinicians should exercise caution when co-prescribing TCZ and CYP-metabolized drugs. More studies are required to investigate this interaction further.
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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.