Secukinumab Treatment Does Not Alter the Pharmacokinetics of the Cytochrome P450 3A4 Substrate Midazolam in Patients With Moderate to Severe Psoriasis

Bruin, Gerard; Hasselberg, Anke; Koroleva, Irina; Milojevic, Julie; Calonder, Claudio; Soon, Rachel L.; Woessner, Ralph; Pariser, David M.; Boutouyrie‐Dumont, Bruno

doi:10.1002/cpt.1558

Cited by 12 publications

(16 citation statements)

References 18 publications

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“…Accordingly, blockade of IL-4/IL-13 by dupilumab (Dupixent; Table 2) in patients with atopic dermatitis did not affect CYP activity to a clinically relevant extent 51 (Table 3). Similar results were obtained in patients with psoriasis, with the antipsoriatic IL-23 antagonists guselkumab (Tremfya), 52 risankizumab (Skyrizi), 53 or tildrakizumab (Ilumya), 54 or the IL-17A antagonists secukinumab (Cosentyx), 55 (Table 3) brodalumab (Siliq), or ixekizumab (Taltz) 7 . The findings from the studies with IL-23 inhibitors were also in line with absence of in vitro IL-23 effects on CYP enzyme expression.…”

Section: T a B L E 3 Continuedsupporting

confidence: 64%

Not your usual drug‐drug interactions: Monoclonal antibody–based therapeutics may interact with antiseizure medications

et al. 2021

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Therapeutic monoclonal antibodies (mAbs) have emerged as the fastest growing drug class. As such, mAbs are increasingly being co-prescribed with other drugs, including antiseizure medications (ASMs). Although mAbs do not share direct targets or mechanisms of disposition with small-molecule drugs (SMDs), combining therapeutics of both types can increase the risk of adverse effects and treatment failure. The primary goal of this literature review was identifying mAb-ASM combinations requiring the attention of professionals who are treating patients with epilepsy. Systematic PubMed and Embase searches were performed for terms relating to mAbs, ASMs, drug interactions, and their combinations. Additional information was obtained from documents from the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA).

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Section: T a B L E 3 Continuedsupporting

confidence: 64%

Not your usual drug‐drug interactions: Monoclonal antibody–based therapeutics may interact with antiseizure medications

et al. 2021

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“…Indeed, these studies all showed that pharmacological inhibition of IL-6 restored CYP3A activity, with a significant decrease in simvastatin exposure of approximately 55 and 57% after the administration of sarilumab ( Lee, Daskalakis, et al, 2017 ) or tocilizumab ( Schmitt et al, 2011 ), respectively. Conversely, several other biotherapies targeting proinflammatory cytokines, such as TNF-ɑ ( Deng et al, 2018 ; Frye, Schneider, Frye, & Feldman, 2002 ), IL-17 ( Bruin et al, 2019 ), or IL-23 ( Khalilieh et al, 2018 ; Khatri et al, 2019 ) did not influence CYP activity. However, any effect of such biologics needs to be verified for various diseases with varying levels of proinflammatory cytokines, as the magnitude of these disease-dependent drug interactions are per se affected by the underlying disease.…”

Section: Pharmacological Consequences Of Inflammation-induced Metabolmentioning

confidence: 97%

“…These data suggest that blockade of the IL-6-dependent pathway reversed the suppression of CYP3A4 activity induced by inflammation and confirm the key role of IL-6 in the downregulation of CYP activity. Conversely, the antihuman IL-17A monoclonal antibody sekukinumab failed to modify the pharmacokinetic profile of midazolam in patients with moderate to severe psoriasis ( Bruin et al, 2019 ). Similarly, the antihuman IL-23 antibody risankizumab did not affect the in vivo activity of CYP1A2, CYP2C9, CYP2C19, CYP2D6, or CYP3A in patients with moderate plaque psoriasis ( Khatri et al, 2019 ).…”

Section: How To Integrate the Inflammatory Status In Personalized Medmentioning

confidence: 99%

Inflammation is a major regulator of drug metabolizing enzymes and transporters: Consequences for the personalization of drug treatment

Stanke‐Labesque

Gautier-Veyret

Chhun

et al. 2020

Pharmacology & Therapeutics

131

147

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Inflammation is an evolutionary process that allows survival against acute infection or injury. Inflammation is also a pathophysiological condition shared by numerous chronic diseases. In addition, inflammation modulates important drug-metabolizing enzymes and transporters (DMETs), thus contributing to intra- and interindividual variability of drug exposure. A better knowledge of the impact of inflammation on drug metabolism and its related clinical consequences would help to personalize drug treatment. Here, we summarize the kinetics of inflammatory mediators and the underlying transcriptional and post-transcriptional mechanisms by which they contribute to the inhibition of important DMETs. We also present an updated overview of the effect of inflammation on the pharmacokinetic parameters of most of the drugs that are DMET substrates, for which therapeutic drug monitoring is recommended. Furthermore, we provide opinions on how to integrate the inflammatory status into pharmacogenetics, therapeutic drug monitoring, and population pharmacokinetic strategies to improve the personalization of drug treatment for each patient.

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“…Moreover, OKT3 (also known as muromonab, a CD3 receptor antibody) treatment transiently increased CyA through concentration, and authors suggested that OKT3 inhibits CYP3A4 metabolic activity by inducing transient cytokine release (Vasquez and Pollak, 1997). No changes were observed in drugs PK parameters before and after monoclonal antibodies administration, possibly because CYP metabolic activity was similar in psoriasis disease and in healthy volunteers (Bruin et al, 2019;Khatri et al, 2019). However, these therapies are used for a variety of diseases, with different levels of proinflammatory markers.…”

Section: Therapies With Immunomodulator Anti-tnf-α and -Mabsmentioning

confidence: 99%

Influence of Inflammation on Cytochromes P450 Activity in Adults: A Systematic Review of the Literature

et al. 2021

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Background: Available in-vitro and animal studies indicate that inflammation impacts cytochromes P450 (CYP) activity via multiple and complex transcriptional and post-transcriptional mechanisms, depending on the specific CYP isoforms and the nature of inflammation mediators. It is essential to review the current published data on the impact of inflammation on CYP activities in adults to support drug individualization based on comorbidities and diseases in clinical practice.Methods: This systematic review was conducted in PubMed through 7th January 2021 looking for articles that investigated the consequences of inflammation on CYP activities in adults. Information on the source of inflammation, victim drugs (and CYPs involved), effect of disease-drug interaction, number of subjects, and study design were extracted.Results: The search strategy identified 218 studies and case reports that met our inclusion criteria. These articles were divided into fourteen different sources of inflammation (such as infection, autoimmune diseases, cancer, therapies with immunomodulator…). The impact of inflammation on CYP activities appeared to be isoform-specific and dependent on the nature and severity of the underlying disease causing the inflammation. Some of these drug-disease interactions had a significant influence on drug pharmacokinetic parameters and on clinical management. For example, clozapine levels doubled with signs of toxicity during infections and the concentration ratio between clopidogrel’s active metabolite and clopidogrel is 48-fold lower in critically ill patients. Infection and CYP3A were the most cited perpetrator of inflammation and the most studied CYP, respectively. Moreover, some data suggest that resolution of inflammation results in a return to baseline CYP activities.Conclusion: Convincing evidence shows that inflammation is a major factor to be taken into account in drug development and in clinical practice to avoid any efficacy or safety issues because inflammation modulates CYP activities and thus drug pharmacokinetics. The impact is different depending on the CYP isoform and the inflammatory disease considered. Moreover, resolution of inflammation appears to result in a normalization of CYP activity. However, some results are still equivocal and further investigations are thus needed.

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Secukinumab Treatment Does Not Alter the Pharmacokinetics of the Cytochrome P450 3A4 Substrate Midazolam in Patients With Moderate to Severe Psoriasis

Cited by 12 publications

References 18 publications

Not your usual drug‐drug interactions: Monoclonal antibody–based therapeutics may interact with antiseizure medications

Not your usual drug‐drug interactions: Monoclonal antibody–based therapeutics may interact with antiseizure medications

Inflammation is a major regulator of drug metabolizing enzymes and transporters: Consequences for the personalization of drug treatment

Influence of Inflammation on Cytochromes P450 Activity in Adults: A Systematic Review of the Literature

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