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)

Phase 4RecruitingNCT06440629

Diakonhjemmet Hospital350 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Interventions

Therapeutic drug monitoring (TDM) of adalimumabDRUG

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

Eligibility

Sex: ALLMin age: 18 YearsMax age: 74 Years

Medical Language ↔ Plain English

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.

Locations (22)

Medical University Vienna

Vienna, Austria

RECRUITING

Humanitas Research Hospital

Milan, Italy

RECRUITING

Diakonhjemmet sykehus

Oslo, N-0319, Norway

RECRUITING

Ålesund Hospital

Ålesund, Norway

RECRUITING

Haukeland University Hospital

Bergen, Norway

RECRUITING

Nordland Hospital Trust

Bodø, Norway

RECRUITING

Drammen Hospital

Drammen, Norway

RECRUITING

Førde Hospital Trust

Førde, Norway

RECRUITING

Haugesund Rheumatism Hospital

Haugesund, Norway

RECRUITING

Hospital of Southern Norway Trust

Kristiansand, Norway

RECRUITING

...and 12 more locations

Outcomes

Primary Outcomes

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)

Time frame: 4, 8, 12, 18 months

Secondary Outcomes

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

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).