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)

NCT ID: NCT06440629

Last Updated: 2025-11-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE4

Total Enrollment

350 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-08-20

Study Completion Date

2027-12-31

Brief Summary

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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.

Detailed Description

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There is a considerable variation in serum drug levels among rheumatoid arthritis (RA) patients on tumor necrosis factor inhibitors (TNFi), and a high number develop neutralizing anti-drug antibodies (ADAb). Sub-therapeutic drug levels and ADAb formation are major contributors to TNFi treatment failure and disease flare. Proactive therapeutic drug monitoring (TDM), i.e., individualized drug dosing based on regular assessments of serum drug levels and ADAb, has the potential to optimize the efficacy and safety of TNFi treatment.

The aim of the RA-DRUM trial is to assess whether TDM is superior to standard of care in order to maintain sustained disease control without flares in patients with RA treated with the SC TNFi adalimumab.

Participants will be randomized to:

* Administration of TNFi based on proactive TDM (TDM group)
* Administration of TNFi based on standard of care without knowledge of serum drug levels or ADAb status (Standard of care group)

Participants will be followed for 18 months with on-site visits at baseline, 4, 8, 12 and 18 months and digital visits at 2, 6, 10, 14, and 16 months. Blood sampling for serum drug levels and anti-drug antibodies will be done at all visits.

Conditions

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Rheumatoid Arthritis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

The joint assessor will be blinded.

Study Groups

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TDM-group

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

Group Type EXPERIMENTAL

Therapeutic drug monitoring (TDM) of adalimumab

Intervention Type 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

Standard of Care group

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

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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Therapeutic drug monitoring (TDM) of adalimumab

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

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. A clinical diagnosis of RA
2. ≥ 18 and under 75 years of age at screening
3. On stable therapy with standard dose of a SC TNFi (adalimumab) for a minimum of 3 months and a maximum of 24 months
4. In low disease activity or remission (DAS28-CRP under 3.2) and indication for continuation of treatment according to the treating physician
5. Subject capable of understanding and signing an informed consent form

Exclusion Criteria

1. 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
2. Hypersensitivity to sc TNFi (adalimumab).
3. Pregnancy, or subject considering becoming pregnant during the study period
4. Psychiatric or mental disorders, alcohol abuse or other substance abuse, language barriers, or other factors that makes adherence to the study protocol difficult
5. Changes in csDMARD co-medication, including dose changes of csDMARD or changes in the dose of corticosteroids within the last 2 months
6. Co-medication with bDMARD, tsDMARD, or other immunosuppressive drugs (excluding csDMARD and corticosteroids ≤ 7.5 mg prednisolone (or equivalent) once daily).
7. Active participation in any other interventional study.
8. In need of live vaccines during the study period.
Minimum Eligible Age

18 Years

Maximum Eligible Age

74 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Oslo University Hospital

OTHER

Sponsor Role collaborator

Karolinska University Hospital

OTHER

Sponsor Role collaborator

Queen Mary University of London

OTHER

Sponsor Role collaborator

Medical University of Vienna

OTHER

Sponsor Role collaborator

Alesund Hospital

OTHER

Sponsor Role collaborator

St. Olavs Hospital

OTHER

Sponsor Role collaborator

Helse Stavanger HF

OTHER_GOV

Sponsor Role collaborator

Drammen sykehus

OTHER

Sponsor Role collaborator

University Hospital of North Norway

OTHER

Sponsor Role collaborator

Førde Hospital Trust

OTHER

Sponsor Role collaborator

Hospital of Southern Norway Trust

OTHER

Sponsor Role collaborator

Haukeland University Hospital

OTHER

Sponsor Role collaborator

Ostfold Hospital Trust

OTHER

Sponsor Role collaborator

Lillehammer Hospital for Rheumatic Diseases

OTHER

Sponsor Role collaborator

Vestre Viken Hospital Trust

OTHER

Sponsor Role collaborator

Haugesund Rheumatism Hospital

OTHER

Sponsor Role collaborator

Betanien Hospital

OTHER

Sponsor Role collaborator

Helgeland Hospital Trust

OTHER

Sponsor Role collaborator

Nordlandssykehuset HF

OTHER

Sponsor Role collaborator

Carol Davila University of Medicine and Pharmacy

OTHER

Sponsor Role collaborator

Humanitas Research Hospital IRCCS, Rozzano-Milan

OTHER

Sponsor Role collaborator

Sahlgrenska University Hospital

OTHER

Sponsor Role collaborator

Diakonhjemmet Hospital

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Espen A Haavardsholm, Phd, MD

Role: STUDY_DIRECTOR

Diakonhjemmet Hospital

Locations

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Medical University Vienna

Vienna, , Austria

Site Status RECRUITING

Humanitas Research Hospital

Milan, , Italy

Site Status NOT_YET_RECRUITING

Diakonhjemmet sykehus

Oslo, N-0319, Norway

Site Status RECRUITING

Ålesund Hospital

Ålesund, , Norway

Site Status RECRUITING

Haukeland University Hospital

Bergen, , Norway

Site Status RECRUITING

Nordland Hospital Trust

Bodø, , Norway

Site Status RECRUITING

Drammen Hospital

Drammen, , Norway

Site Status RECRUITING

Førde Hospital Trust

Førde, , Norway

Site Status RECRUITING

Haugesund Rheumatism Hospital

Haugesund, , Norway

Site Status RECRUITING

Hospital of Southern Norway Trust

Kristiansand, , Norway

Site Status RECRUITING

Lillehammer Hospital for Rheumatic Diseases

Lillehammer, , Norway

Site Status RECRUITING

Helgeland Hospital Trust

Mo i Rana, , Norway

Site Status RECRUITING

Østfold Hospital Trust

Moss, , Norway

Site Status RECRUITING

Martina Hansen's Hospital

Sandvika, , Norway

Site Status RECRUITING

Betanien Hospital

Skien, , Norway

Site Status RECRUITING

Stavanger University Hospital

Stavanger, , Norway

Site Status RECRUITING

University Hospital of North Norway

Tromsø, , Norway

Site Status RECRUITING

St.Olavs Hospital

Trondheim, , Norway

Site Status RECRUITING

Carol Davila University of Medicine and Pharmacy Bucharest

Bucharest, , Romania

Site Status RECRUITING

Sahlgrenska Universitetssjukehuset

Gothenburg, , Sweden

Site Status RECRUITING

Karolinska University Hospital

Stockholm, , Sweden

Site Status RECRUITING

Queen Mary

London, SW15 5PN, United Kingdom

Site Status RECRUITING

Countries

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Austria Italy Norway Romania Sweden United Kingdom

Central Contacts

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Ingrid Jyssum, PhD, MD

Role: CONTACT

+4722451500

Silje W Syversen, PhD, MD

Role: CONTACT

+4722451500

Facility Contacts

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Helga Lechner-Radner, PhD, MD

Role: primary

+43 1 40400-43010

Elisa Gremese, MD PhD

Role: primary

Ingrid Jyssum, PhD, MD

Role: primary

+4722451500

Silje W Syversen, PhD, MD

Role: backup

+4722451500

Astrid B Langhammer, MD

Role: primary

+4770105000

Anne- Kristine Halse, MD, PhD

Role: primary

+4755975000

Sonja Pedersen, MD

Role: primary

+4775534000

Fillip Skovlund, MD

Role: primary

Pawel F Mienik, MD, PhD

Role: primary

+4757839000

Svanaug Skorpe, MD

Role: primary

+4752805000

Jintana B Andersen, MD, PhD

Role: primary

+4738073000

Eldri K Strand, MD

Role: primary

+4761279500

Petya S Galabova, MD

Role: primary

+4775660000

Anne J Haugen, MD, PhD

Role: primary

+4769860000

Anne B Haaversen, MD

Role: primary

+4767500800

Christine Stillum, MD

Role: primary

+4735900700

Kjartan Bryne, MD

Role: primary

+4751518000

Trude J Bruun, MD

Role: primary

+4777626000

Mari Hoff, MD, PhD

Role: primary

+4772573000

Bianca Dumirescu, MD PHD

Role: primary

+40722204389

Anna Karin Ekwall, MD, PhD

Role: primary

Aikaterini Chatzidionysiou, MD, PhD

Role: primary

Michele Bombardieri, MD, PhD

Role: primary

Provided Documents

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Document Type: Study Protocol

View Document

Other Identifiers

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EU CT No 2023-510184-35-00

Identifier Type: -

Identifier Source: org_study_id

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