Personalised dosing of certolizumab pegol based on serum concentration in rheumatoid arthritis patients

Lead Investigator: Johanna Elin Gehin, Oslo University Hospital
Title of Proposal Research: Personalised dosing of certolizumab pegol based on serum concentration in rheumatoid arthritis patients
Vivli Data Request: 9053
Funding Source: EU -Horizon Europe 2020
Potential Conflicts of Interest: Partner SQUEEZE -Horizon Europe funded project
Post-Doctoral fellowship funded by Horizon Europe
Funding from Horizon Europe will be declared in any subsequent publication.
Dr. Goll additionally reports: Speakers bureaus AbbVie/Abbott, Galapagos, Pfizer, UCB, advisory board Pfizer, AbbVie/Abbott, Galapagos, Pfizer, UCB.
Funding and conflicts of interest will be declared in any subsequent publications.
Dr. Jyssum additionally reports: PhD-project funded by Norwegian Regional Health authorities
Planned post-Doctoral fellowship funded by Horizon Europe
Funding from Norwegian Regional Health authorities and Horizon Europe will be declared in any subsequent publication.

Summary of the Proposed Research:

Rheumatoid arthritis is a chronic disease where the patient’s own immune system induces painful and destructive inflammation in the joints of the hands and feet. Rheumatoid arthritis is a limiting, potentially disabling disease to patients, and is associated with significant costs to society, both related to treatment and disability. In the last two decades, drugs that reduce the activity of the immune system have revolutionized the treatment of rheumatoid arthritis. Tumor necrosis factor (TNF) inhibitors, is a class of drugs that suppress tumor necrosis factor (TNF), a substance in your body that causes inflammation. Certolizumab pegol is one of five TNF inhibitors in common use.

With modern treatment such as TNF inhibitors, low disease activity or even remission is realistic in patients with rheumatoid arthritis. However, all TNF inhibitors are expensive treatments and not all patients respond adequately. One way to improve treatment effect of TNF inhibitors is to personalize treatment based on each patient’s drug level in blood. If the drug level is low, the patient increases the drug dose, and if the drug level is high, the patient reduces the drug dose. This strategy, where we aim for a predefined therapeutic drug concentration interval, is called therapeutic drug monitoring, TDM. Personalised dosing based on TDM may improve treatment effect and cost-effectiveness in patients treated with TNF inhibitors. This was shown in the randomised clinical Norwegian Drug Monitoring (NOR-DRUM) trials, conducted by our research group. The trials showed that TDM leads to better outcomes in the maintenance phase of treatment with the TNF inhibitor infliximab in patients with immune-mediated inflammatory diseases, including patients with rheumatoid arthritis. Infliximab is the only TNF inhibitor administered intravenously in a hospital setting. We do not know if TDM also improves outcomes in patients treated with other TNF inhibitors (such as certolizumab pegol), which are administered by the injection of the drug by a syringe or autoinjector into the fatty layer of tissue under the skin, by the patients themselves.

We are planning a clinical trial to investigate the possible benefit of TDM of TNF inhibitors administered by injection under the skin in rheumatoid arthritis. Certolizumab pegol will be included in the trial. Before we can conduct the trial, we need to know which certolizumab pegol serum levels to aim for, and how changes in dosing affects serum levels. Access to data from existing trials will help establish this. The impact of certolizumab pegol dose and a range of covariates (i.e. independent variables that can influence the outcome of a given statistical trial, but which are not of direct interest) on serum certolizumab pegol levels will be assessed by comparing mean/median and change in certolizumab pegol levels between groups and by statistical methods which allow more complex comparisons.

By optimising treatment with TNF inhibitors by personalised dosing, the proposed research has potential to improve treatment and quality of life for a large group of patients with rheumatoid arthritis. This project is part of the SQUEEZE project, which is a European research consortium investigating personalised medicine for rheumatoid arthritis. SQUEEZE is funded by the European Union (Horizon 2022), https://squeeze-project.eu/

Requested Studies:

A Phase III Multicentre, Double Blind, Placebo-controlled, Parallel Group 52-week Study to Assess the Efficacy and Safety of 2 Dose Regimens of Lyophilised CDP870 as Additional Medication to Methotrexate in the Treatment of Signs and Symptoms and Preventing Structural Damage in Patients With Active Rheumatoid Arthritis Who Have an Incomplete Response to Methotrexate
Data Contributor: UCB
Study ID: NCT00152386
Sponsor ID: C87027

A Phase III Multi-center, Double-blind, Placebo-controlled, Parallel Group 24-Week Study to Assess the Efficacy and Safety of Two Dose Regimens of Liquid Certolizumab Pegol as Additional Medication to Methotrexate in the Treatment of Signs and Symptoms of Rheumatoid Arthritis and in Prevention of Joint Damage in Patients With Active Rheumatoid Arthritis Who Have an Incomplete Response to Methotrexate.
Data Contributor: UCB
Study ID: NCT00160602
Sponsor ID: C87050

A Phase III Multi-centre, Open-label, follow-on Study to CDP870-027, to Assess the Efficacy and Safety of Lyophilized CDP870 an Engineered Human Anti-TNF PEG Conjugate, as Additional Medication to Methotrexate, in the Treatment of Signs and Symptoms and Preventing Structural Damage in Patients With Active Rheumatoid Arthritis
Data Contributor: UCB
Study ID: NCT00175877
Sponsor ID: C87028

A Phase III Multi-center, Open-label, Follow-up Study, to Assess the Safety and Efficacy of Liquid Certolizumab Pegol as Additional Medication to Methotrexate, in the Treatment of Signs and Symptoms and in the Prevention of Joint Damage in Patients With Active Rheumatoid Arthritis Who Participated in Study CDP870-050
Data Contributor: UCB
Study ID: NCT00160641
Sponsor ID: C87051