Effect of Proactive Therapeutic Drug Monitoring on Maintenance of Sustained Disease Control in Adults With Rheumatoid Arthritis on a Subcutaneous TNF Inhibitor: The Rheumatoid Arthritis Therapeutic DRUg Monitoring Trial (RA-DRUM)

NCT06440629 | Recruiting Phase 4 DMC

• 1 other identifier: EU CT No 2023-510184-35-00
• Study Type: interventional
• Target: 350
• Locations: 6 countries
• Sites: 22

Brief Summary

The goal of this clinical trial is to compare therapeutic drug monitoring (TDM) versus Standard of care in patients with rheumatoid arthritis treated with a subcutaneous tumor necrosis factor inhibitor (adalimumab). The main question it aims to answer is: Is TDM superior to standard of care in order to maintain sustained disease control without flares? Participants will be followed with blood sampling every second month, measuring serum drug levels and anti-drug antibodies of the TNFi. In the TDM-group, the researchers will adjust the dosage of the TNFi based on knowledge on optimal therapeutic ranges. In the Standard of care group, the TNFi will be administered according to standard of care without knowledge of serum drug levels or anti-drug antibodies.

Conditions

Rheumatoid Arthritis

Keywords

Rheumatoid arthritis; Therapeutic drug monitoring; Tumor necrosis factor inhibitor

Outcome Measures

Primary Outcomes (1)

• Sustained disease control over the follow-up period of 18 months without flare

  A flare defined as either of the following: A combination of an increase in Disease Activity Score using 28 joints C-reactive protein (DAS28-CRP) ≥ 1.2, or ≥ 0.6 if DAS28-CRP ≥ 3.2, AND ≥ 2 swollen joints on examination of 44 joints OR Consensus between patient and physician that a disease flare has occurred, leading to a major change\* in treatment \*Please see protocol for the definition of a major change in treatment (due to word restrictions)

  4, 8, 12, 18 months

Secondary Outcomes (14)

• Disease activity assessed by Disease Activity Score using 28 joints C-reactive protein (DAS28-CRP)

  4, 8, 12, and 18 months

• Disease activity measured by 44 joint count

  4, 8, 12, and 18 months

• Patient Global assessment of disease activity (PGA)

  4, 8, 12, and 18 months

• Evaluators Global Assessment of Disease Activity (EGA)

  4, 8, 12, and 18 months

• Disease activity assessed by Clinical Disease Activity Index (CDAI)

  4, 8, 12, and 18 months

Other Outcomes (8)

• European Quality of Life 5 Dimensions (EQ-5D)

  2, 4, 6, 8, 10, 12, 14, 16, 18 months

• 36-Item Short-form health survey (SF-36)

  2, 4, 6, 8, 10, 12, 14, 16, 18 months

• Work Productivity and Activity Impairment Questionnaire: Rheumatoid Arthritis (WPAI:RA)

  2, 4, 6, 8, 10, 12, 14, 16, 18 months

Study Arms (2)

TDM-group

EXPERIMENTAL

In the TDM-group, the TNFi dose will be adjusted in order to keep the drug level within the therapeutic range

Drug: Therapeutic drug monitoring (TDM) of adalimumab

Standard of Care group

NO INTERVENTION

In the Standard of Care group, TNFi will be administered according to standard of care without knowledge of serum drug levels or ADAb

Interventions

Therapeutic drug monitoring (TDM) of adalimumab DRUG

In the TDM-group, the adalimumab dose will be adjusted according to the following algorithms in order to keep the drug level within the therapeutic range: * Serum drug level within therapeutic range : keep dose * Low drug levels, ADAb undetectable or low levels : Decrease dosing interval by one week to a maximum of 40 mg/week * Low drug levels, ADAb high levels : Switch to another therapy * High drug levels : Increase dosing interval by one week up to a maximum of 6 weeks

TDM-group

Eligibility Criteria

• Age: 18 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• A clinical diagnosis of RA
• ≥ 18 and under 75 years of age at screening
• On stable therapy with standard dose of a SC TNFi (adalimumab) for a minimum of 3 months and a maximum of 24 months
• In low disease activity or remission (DAS28-CRP under 3.2) and indication for continuation of treatment according to the treating physician
• Subject capable of understanding and signing an informed consent form

You may not qualify if:

• Major comorbidities, such as previous malignancies within the last 5 years, uncontrolled diabetes mellitus, severe infections (including HIV), uncontrollable hypertension, severe cardiovascular disease (NYHA class 3 or 4), severe respiratory diseases, demyelinating disease, significant chronic widespread pain syndrome, significant renal or hepatic disease, and/or other diseases or conditions which either contraindicate treatment with SC TNFi or make adherence to the protocol difficult
• Hypersensitivity to sc TNFi (adalimumab).
• Pregnancy, or subject considering becoming pregnant during the study period
• Psychiatric or mental disorders, alcohol abuse or other substance abuse, language barriers, or other factors that makes adherence to the study protocol difficult
• Changes in csDMARD co-medication, including dose changes of csDMARD or changes in the dose of corticosteroids within the last 2 months
• Co-medication with bDMARD, tsDMARD, or other immunosuppressive drugs (excluding csDMARD and corticosteroids ≤ 7.5 mg prednisolone (or equivalent) once daily).
• Active participation in any other interventional study.
• In need of live vaccines during the study period.

Sponsors & Collaborators

• Alesund Hospital: collaborator
• St. Olavs Hospital: collaborator
• Helse Stavanger HF: collaborator
• Drammen sykehus: collaborator
• University Hospital of North Norway: collaborator
• Førde Hospital Trust: collaborator
• Hospital of Southern Norway Trust: collaborator
• Haukeland University Hospital: collaborator
• Ostfold Hospital Trust: collaborator
• Lillehammer Hospital for Rheumatic Diseases: collaborator
• Vestre Viken Hospital Trust: collaborator
• Haugesund Rheumatism Hospital: collaborator
• Betanien Hospital: collaborator
• Helgeland Hospital Trust: collaborator
• Nordlandssykehuset HF: collaborator
• Carol Davila University of Medicine and Pharmacy: collaborator
• Humanitas Research Hospital IRCCS, Rozzano-Milan: collaborator
• Sahlgrenska University Hospital: collaborator
• Diakonhjemmet Hospital: lead
• Oslo University Hospital: collaborator
• Karolinska University Hospital: collaborator
• Queen Mary University of London: collaborator
• Medical University of Vienna: collaborator

Study Sites (22)

Medical University Vienna

Vienna, A-1090, Austria

RECRUITING

Humanitas Research Hospital

Milan, Italy

RECRUITING

Diakonhjemmet sykehus

Oslo, N-0319, 0319, Norway

RECRUITING

Ålesund Hospital

Ålesund, 6017, Norway

RECRUITING

Haukeland University Hospital

Bergen, 5009, Norway

RECRUITING

Nordland Hospital Trust

Bodø, 8005, Norway

RECRUITING

Drammen Hospital

Drammen, 3004, Norway

RECRUITING

Førde Hospital Trust

Førde, 6812, Norway

RECRUITING

Haugesund Rheumatism Hospital

Haugesund, 5528, Norway

RECRUITING

Hospital of Southern Norway Trust

Kristiansand, 4615, Norway

RECRUITING

Lillehammer Hospital for Rheumatic Diseases

Lillehammer, 2609, Norway

RECRUITING

Helgeland Hospital Trust

Mo i Rana, 8613, Norway

RECRUITING

Østfold Hospital Trust

Moss, 1535, Norway

RECRUITING

Martina Hansen's Hospital

Sandvika, Norway

RECRUITING

Betanien Hospital

Skien, 3722, Norway

RECRUITING

Stavanger University Hospital

Stavanger, 4019, Norway

RECRUITING

University Hospital of North Norway

Tromsø, 9019, Norway

RECRUITING

St.Olavs Hospital

Trondheim, 7030, Norway

RECRUITING

Carol Davila University of Medicine and Pharmacy Bucharest

Bucharest, Romania

RECRUITING

Sahlgrenska Universitetssjukehuset

Gothenburg, 41345, Sweden

RECRUITING

Karolinska University Hospital

Stockholm, 141 86, Sweden

RECRUITING

Queen Mary

London, SW15 5PN, SW15 5PN, United Kingdom

RECRUITING

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Adalimumab

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Espen A Haavardsholm, Phd, MD

  Diakonhjemmet Hospital

  STUDY DIRECTOR

Central Study Contacts

Ingrid Jyssum, PhD, MD

CONTACT

+4722451500; ingrid.jyssum@gmail.com

Silje W Syversen, PhD, MD

CONTACT

+4722451500; s.w.syversen@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: The joint assessor will be blinded.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 23, 2024
• First Posted: June 4, 2024
• Study Start: August 20, 2024
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: February 5, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: 10 years after publishing
• Access Criteria: The data will only be made available after submission of a project plan outlining the reason for the request and any proposed analyses, and will have to be approved by the RA-DRUM steering group. Project proposals can be submitted to the corresponding author. Data sharing will have to follow appropriate regulations.

Locations

GB (1); NO (16); IT (1); SE (2); AU (1); RO (1)