Short summary

Patients with rheumatoid arthritis have increased levels of inflammatory cytokines e.g. IL-6. With this study we aim to assess if drug metabolism changes in patients with rheumatoid arthritis when an interleukin (IL)-6 inhibitor is initiated.

In a clinical pharmacokinetic study, a drug cocktail, to assess the drug-metabolizing enzyme activity, will be administered to patients with rheumatoid arthritis before and after initiation of an IL-6 inhibitor.

This will uncover whether inhibition of IL-6 causes altered drug metabolism in patients with rheumatoid arthritis, which may change dosing and monitoring of drugs taken concomitantly with glucose lowering drugs.

Rationale

With this study we wish to assess if drug metabolism changes in patients with rheumatoid arthritis when an interleukin (IL)-6 inhibitor is initiated.

Patients with rheumatoid arthritis have an increased level of inflammation in the body which can lead to decreased expression and activity of drug metabolizing enzymes in the liver. This will lead to a decreased metabolism and excretion of drugs. The inflammation is driven by a number of proinflammatory cytokines e.g., IL-6.

We hypothesise that patients with rheumatoid arthritis initiating treatment with an IL-6-receptor inhibitor (anti-IL-6R) will obtain a normalization of the activated IL-6-pathway resulting in increased expression and activity of drug metabolizing enzymes and hence increased metabolism. Ultimately, this normalization of drug metabolism could lead to insufficient efficacy of a wide variety of drugs.

The current trial is a part of translational research; with results from in vitro hepatocyte studies, clinical trials and register-based studies we will provide new knowledge on the proposed association between inflammation and drug metabolism and the mechanisms behind. This knowledge will lead to changes in the way we dose, and monitor drugs administered concomitantly with anti-inflammatory drugs and can provide additional tools for personalizing therapy of the increasing group of adults suffering from chronic inflammatory diseases.

Description of the cohort

Patients with rheumatoid arthritis are recruited at Odense University Hospital, Hospital South West Jutland, and Danish Hospital for Rheumatic Diseases in Sønderborg. The indication to initiate treatment with an IL-6 inhibitor will be based on current guidelines.

Data and biological material

Clinical data and blood and urine samples will be obtained throughout the study.

Collaborating researchers and departments

Department of Rheumatology, Odense University Hospital

• MD, Kasper Søltoft
• Department of Rheumatology, Hospital of South West Jutland
• MD, Niels Jacob Kock
• Danish Hospital for Rheumatic Diseases
• MD, Professor, Oliver Hendricks