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)

A Multi-center, Open, Randomized, 18-month, Parallel-group, Superiority Study to Compare the Effect of Proactive Therapeutic Drug Monitoring Versus Standard of Care With Regards to Maintenance of Sustained Disease Control Without Flare in Adults With Rheumatoid Arthritis Treated With a Subcutaneous Tumor Necrosis Factor Inhibitor

Status

Active, not recruiting

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT06440629

Acronym

RA-DRUM

Enrollment

387

Registered

2024-06-04

Start date

2024-08-20

Completion date

2027-12-31

Last updated

2026-07-01

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Rheumatoid Arthritis

Keywords

Rheumatoid arthritis, Therapeutic drug monitoring, Tumor necrosis factor inhibitor

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.

Detailed description

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.

Interventions

DRUGTherapeutic 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

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Masking description

The joint assessor will be blinded.

Eligibility

Sex/Gender

ALL

Age

18 Years to 74 Years

Healthy volunteers

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.

Design outcomes

Primary

Measure	Time frame	Description
Sustained disease control over the follow-up period of 18 months without flare	4, 8, 12, 18 months	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)

Secondary

Measure	Time frame	Description
Disease activity assessed by Disease Activity Score using 28 joints C-reactive protein (DAS28-CRP)	4, 8, 12, and 18 months	The DAS28-CRP composite score includes the 28 tender and swollen joint counts, CRP and a Patient Global Assessment of Disease activity (PGA). The DAS28-CRP is calculated as follows: DAS28-CRP = 0.56\√ (tender joints 28) + 0.28\√ (swollen joints 28) + 0.36\ln(CRP (mg/L)+1) + 0.014\PGA + 0.96 High disease activity is defined as a DAS28-CRP value \> 5.1, moderate disease activity as DAS28-CRP \> 3.2 - 5.1, low disease activity as a DAS28-CRP-value of 2.6 - 3.2, and remission as DAS28-CRP \< 2.6 PGA is measured on a 100 mm VAS according to the question: "Considering all the ways your arthritis has affected you, how did you feel your arthritis was over the last week?" (on a 0-100mm Visual Analogue Scale (VAS) with with 0 = excellent and 100 = very poor).
Disease activity measured by 44 joint count	4, 8, 12, and 18 months	44 joint count are included in the original Disease Activity Score (DAS) and in addition to the joints included in DAS28 it includes the MTP joints and the sternoclavicular joints for a more comprehensive valuation of the participants' joints.
Patient Global assessment of disease activity (PGA)	4, 8, 12, and 18 months	PGA is measured on a 100 mm VAS according to the question: "Considering all the ways your arthritis has affected you, how did you feel your arthritis was over the last week?" (on a 0-100mm Visual Analogue Scale (VAS) with with 0 = excellent and 100 = very poor).
Evaluators Global Assessment of Disease Activity (EGA)	4, 8, 12, and 18 months	EGA is measured on a NRS according to the question "Please rate the patient's overall (global) disease activity", with 0 = best and 10 = worst.
Disease activity assessed by Clinical Disease Activity Index (CDAI)	4, 8, 12, and 18 months	CDAI includes the 28 tender and swollen joint counts, Patient Global Assessment of Disease activity (PGA) and Evaluators Global Assessment of Disease Activity (EGA) The formula for CDAI is: swollen joints 28 + tender joints 28 + (PGA (VAS 0-100)/10) + EGA (NRS 0-10). PGA is measured on a 100 mm VAS according to the question: "Considering all the ways your arthritis has affected you, how did you feel your arthritis was over the last week?" (on a 0-100mm Visual Analogue Scale (VAS) with with 0 = excellent and 100 = very poor). EGA is measured on a NRS according to the question "Please rate the patient's overall (global) disease activity", with 0 = best and 10 = worst.
Disease activity assessed by Simple Disease Activity Index (SDAI)	4, 8, 12, and 18 months	SDAI includes the 28 tender and swollen joint counts, Patient Global Assessment of Disease activity (PGA) and Evaluators Global Assessment of Disease Activity (EGA) and C-reactive protein (CRP). The formula for SDAI is: swollen joints 28 + tender joints 28 + (PGA(VAS 0-100)/10) + EGA(NRS 0-10) + (CRP (mg/dL)/10). PGA is measured on a 100 mm VAS according to the question: "Considering all the ways your arthritis has affected you, how did you feel your arthritis was over the last week?" (on a 0-100mm Visual Analogue Scale (VAS) with with 0 = excellent and 100 = very poor). EGA is measured on a NRS according to the question "Please rate the patient's overall (global) disease activity", with 0 = best and 10 = worst.
Remission assessed by American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) remission criteria	4, 8, 12, and 18 months	The ACR/EULAR remission criteria defines a patient in remission when either 1. the patient is in Boolean 2.0 remission with each of the variables tender joint count, swollen joint count and CRP having a value of ≤1 and Patient Global Assessment of Disease activity (PGA) having a value ≤ 2 (PGA on a Visual Analogue Scale (VAS)100mm/10 with 0=best and 100= worst, CRP in mg/dl) OR 2. the SDAI score is ≤ 3.3
Rheumatoid Arthritis Impact of Disease (RAID)	4, 8, 12, and 18 months	The RAID questionnaire includes seven domains with the following relative weights: pain (0.21), functional disability (0.16), fatigue (0.15), emotional well-being (0.12), sleep (0.12), coping (0.12) and physical well-being (0.12) each rated on an Numeric Rating Scale (NRS) (0-10 with 0=best and 10=worst). The rates of each domain are weighted and summed to form a score in the range of 0-10
Evaluation of physical function measured by Modified Health Assessment Questionnaire (MHAQ)	4, 8, 12, and 18 months	The MHAQ includes eight items covering the physical function of patients with inflammatory joint diseases. Each item is scored on a categorical 0-3 scale (0=best and 3= worst) and the sum score is divided by 8 to form the MHAQ score 0.0 to 3.0
Number and type of adverse events (AE)	4, 8, 12, and 18 months	Assessments of AE
Drug survival	4, 8, 12, and 18 months	Drug survival assessed by survival analyses
Drug consumption	18 months	Assessments of drug consumption
Occurrence of anti-drug antibodies (ADAb)	2, 4, 6, 8, 10, 12, 14, 16, 18 months	ADAb will be assessed in all serum samples with adalimumab levels \<3mg/L.
Serum drug levels	2, 4, 6, 8, 10, 12, 14, 16, 18 months	Serum drug levels will be assessed at all visits, both clinical and digital.

Countries

Austria, Italy, Norway, Romania, Sweden, United Kingdom

Contacts

STUDY_DIRECTOREspen A Haavardsholm, Phd, MD

Diakonhjemmet Hospital

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Jul 2, 2026