Interleukin-6 Inhibitors and Drug-drug Interactions in Patients With Rheumatoid Arthritis
Status:
Recruiting
Trial end date:
2021-09-30
Target enrollment:
Participant gender:
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.
Phase:
Phase 1/Phase 2
Details
Lead Sponsor:
University of Southern Denmark
Collaborators:
Hospital of South West Jutland King Christian X´Hospital for Rheumatic Diseases Odense Patient Data Explorative Network Odense University Hospital Sygehus Lillebaelt