Interleukin-6 Inhibitors and Drug-drug Interactions in Patients With Rheumatoid Arthritis

Summary

With this study the investigators aim 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. The investigators hypothesize 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 investigators will perform a clinical pharmacokinetic trial. The study will include patients with active rheumatoid arthritis and a need to initiate treatment with an IL-6 receptor antibody. Patients will ingest a 6-drug cocktail consisting of probes for specific CYP enzymes. Plasma and urine will be drawn over 6 hours to determine concentrations of the drugs and their metabolites. Patients will then initiate IL-6 receptor antibody treatment and to assess both short- and long-term impact of altered inflammation, the same 6-drug cocktail will be ingested, and concentrations measured, after three weeks and three months. To help understand the mechanism and the putative involvement of inflammation, markers of inflammation such as cytokines, transcription factors, etc. will also be assesses.

Conditions

• Arthritis, Rheumatoid
• Interaction

Interventions

DRUG

Tocilizumab

Tocilizumab and Sarilumab are considered equal. Patients are assigned the treatment based on national and local guidelines. Intervention will be administered according to the approved posology.

DRUG

Sarilumab

Tocilizumab and Sarilumab are considered equal. Patients are assigned the treatment based on national and local guidelines. Intervention will be administered according to the approved posology.

Sponsors & Collaborators

• Odense University Hospital

  collaborator OTHER

• Esbjerg Hospital - University Hospital of Southern Denmark

  collaborator OTHER

• King Christian X´Hospital for Rheumatic Diseases

  collaborator OTHER

• Sygehus Lillebaelt

  collaborator OTHER

• Odense Patient Data Explorative Network

  collaborator OTHER

• University of Southern Denmark

  lead OTHER

Principal Investigators

• Ann-Cathrine Dunvald, MD · University of Southern Denmark

Study Design

Allocation

NA

Purpose

BASIC_SCIENCE

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Max Age

75 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2021-05-25

Primary Completion

2022-09-30

Completion

2022-09-30

Countries

• Denmark

Study Locations