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

Sponsor
University of Southern Denmark
Study ID
NCT04842981
Phase
PHASE1/PHASE2
Status
Terminated

Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - 75 Years
Healthy Volunteers
Not accepted

Interventions

  • Tocilizumab — DRUG
    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.
  • Sarilumab — DRUG
    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.

Study Details

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.

Key Dates

Start date
May 25, 2021
Status verified
Jan 2023
Primary completion
Sep 30, 2022
Completion
Sep 30, 2022

Study Design

Enrollment
3 participants (actual)
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE

Arms

  • Experimental: Interleukin 6 receptor antibody
    Tocilizumab, 162 mg subcutaneous, once every week OR Sarilumab, 200 mg subcutaneous, once every two weeks.

Primary Outcome Measure

Short-term change in CYP3A4 activity assessed by midazolam metabolic ratio. [ Time Frame: 3 weeks ]

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