Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Oslo University Hospital | OTHER |
| Karolinska University Hospital | OTHER |
| Queen Mary University of London | OTHER |
| Medical University of Vienna |
Not provided
Not provided
Not provided
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:
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.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| TDM-group | Experimental | In the TDM-group, the TNFi dose will be adjusted in order to keep the drug level within the therapeutic range |
|
| 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 |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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:
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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). |
| Measure | Description | Time Frame |
|---|---|---|
| European Quality of Life 5 Dimensions (EQ-5D) | The EQ-5D is a utility instrument for measurement of health-related quality of life. It consists of 5 dimensions. Each dimension is scored on a level from 1 to 5: LEVEL 1: indicating no problem LEVEL 2: indicating slight problems LEVEL 3: indicating moderate problems LEVEL 4: indicating severe problems LEVEL 5: indicating unable to/extreme The health state is referred to by a 5-digit code, e.g. state 11111 indicates no problems on any of the five dimensions, while state 55555 indicate extreme problems on all of the five dimensions. |
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Espen A Haavardsholm, Phd, MD | Diakonhjemmet Hospital | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Medical University Vienna | Vienna | A-1090 | Austria | |||
| Humanitas Research Hospital |
A de-identified patient data set can be made available to researchers upon reasonable request.
10 years after publishing
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.
Not provided
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Apr 19, 2024 | May 29, 2024 |
Not provided
| OTHER |
| Alesund Hospital | OTHER |
| St. Olavs Hospital | OTHER |
| Helse Stavanger HF | OTHER_GOV |
| Drammen sykehus | OTHER |
| University Hospital of North Norway | OTHER |
| Førde Hospital Trust | OTHER |
| Hospital of Southern Norway Trust | OTHER |
| Haukeland University Hospital | OTHER |
| Ostfold Hospital Trust | OTHER |
| Lillehammer Hospital for Rheumatic Diseases | OTHER |
| Vestre Viken Hospital Trust | OTHER |
| Haugesund Rheumatism Hospital | OTHER |
| Betanien Hospital | OTHER |
| Helgeland Hospital Trust | OTHER |
| Nordlandssykehuset HF | OTHER |
| Carol Davila University of Medicine and Pharmacy | OTHER |
| Humanitas Research Hospital IRCCS, Rozzano-Milan | OTHER |
| Sahlgrenska University Hospital | OTHER |
Not provided
Not provided
Not provided
The joint assessor will be blinded.
Not provided
|
| 4, 8, 12, and 18 months |
| Disease activity measured by 44 joint count | 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. | 4, 8, 12, and 18 months |
| Patient Global assessment of disease activity (PGA) | 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). | 4, 8, 12, and 18 months |
| Evaluators Global Assessment of Disease Activity (EGA) | 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. | 4, 8, 12, and 18 months |
| Disease activity assessed by Clinical Disease Activity Index (CDAI) | 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. | 4, 8, 12, and 18 months |
| Disease activity assessed by Simple Disease Activity Index (SDAI) | 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. | 4, 8, 12, and 18 months |
| Remission assessed by American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) remission criteria | The ACR/EULAR remission criteria defines a patient in remission when either
| 4, 8, 12, and 18 months |
| Rheumatoid Arthritis Impact of Disease (RAID) | 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 | 4, 8, 12, and 18 months |
| Evaluation of physical function measured by Modified Health Assessment Questionnaire (MHAQ) | 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 | 4, 8, 12, and 18 months |
| Number and type of adverse events (AE) | Assessments of AE | 4, 8, 12, and 18 months |
| Drug survival | Drug survival assessed by survival analyses | 4, 8, 12, and 18 months |
| Drug consumption | Assessments of drug consumption | 18 months |
| Occurrence of anti-drug antibodies (ADAb) | ADAb will be assessed in all serum samples with adalimumab levels <3mg/L. | 2, 4, 6, 8, 10, 12, 14, 16, 18 months |
| Serum drug levels | Serum drug levels will be assessed at all visits, both clinical and digital. | 2, 4, 6, 8, 10, 12, 14, 16, 18 months |
| 2, 4, 6, 8, 10, 12, 14, 16, 18 months |
| 36-Item Short-form health survey (SF-36) | The SF-36 is a multi-purpose, short-form health survey with 36 questions. It yields an 8- scale profile of functional health and well-being scores as well as psychometrically-based physical and mental health summary measures and a preference-based health utility index (SF-6D). It is a generic measure, as opposed to one that targets a specific age, disease, or treatment group. Accordingly, the SF-36 has proven useful in surveys of general and specific populations, comparing the relative burden of diseases, and in differentiating the health benefits produced by a wide range of different treatments. | 2, 4, 6, 8, 10, 12, 14, 16, 18 months |
| Work Productivity and Activity Impairment Questionnaire: Rheumatoid Arthritis (WPAI:RA) | The Work Productivity and Activity Impairment (WPAI) questionnaire is a tool that assesses impairments in both work and daily activities. It consists of six items that determine employment status and measure absenteeism caused by health issues, presenteeism, and overall health-related impairment in both paid work and regular activities over the preceding 7 days. The questionnaire yields four outcomes: i) the percentage of work time missed due to health; ii) the percentage of impairment experienced while working due to health in the past 7 days; iii) the percentage of overall work impairment; iv) activity impairment resulting from health issues. Participants will be asked to answer the Work Productivity and Activity Impairment Questionnaire: Rheumatoid Arthritis V2.0. | 2, 4, 6, 8, 10, 12, 14, 16, 18 months |
| Rheumatoid arthritis flare questionnaire (RA-FQ) | The RA-FQ was developed by the Omeract group to identify and measure flares in patients with RA. It encompasses pain, physical impairment, fatigue, stiffness, and participation, and the score is calculated as the sum of responses for the 5 items (maximum 50). | 2, 4, 6, 8, 10, 12, 14, 16, 18 months |
| Adherence | At each visit (every two months), the participant will fill out a questionnaire assessing compliance in into the eCRF. | 2, 4, 6, 8, 10, 12, 14, 16, 18 months |
| Co-medication | Registration of co-medication will be made at each clinical visit. | 4, 8, 12, and 18 months |
| Consentration of C-reactive protein (CRP) | C-reactive protein (CRP) will be measured at all clinical visits. | 4, 8, 12, and 18 months |
| Erythrocyte sedimentation rate (ESR) | Erythrocyte sedimentation rate (ESR) will be measured at all clinical visits. | 4, 8, 12, and 18 months |
| Milan |
| Italy |
| Diakonhjemmet sykehus | Oslo | N-0319 | 0319 | Norway |
| Ålesund Hospital | Ålesund | 6017 | Norway |
| Haukeland University Hospital | Bergen | 5009 | Norway |
| Nordland Hospital Trust | Bodø | 8005 | Norway |
| Drammen Hospital | Drammen | 3004 | Norway |
| Førde Hospital Trust | Førde | 6812 | Norway |
| Haugesund Rheumatism Hospital | Haugesund | 5528 | Norway |
| Hospital of Southern Norway Trust | Kristiansand | 4615 | Norway |
| Lillehammer Hospital for Rheumatic Diseases | Lillehammer | 2609 | Norway |
| Helgeland Hospital Trust | Mo i Rana | 8613 | Norway |
| Østfold Hospital Trust | Moss | 1535 | Norway |
| Martina Hansen's Hospital | Sandvika | Norway |
| Betanien Hospital | Skien | 3722 | Norway |
| Stavanger University Hospital | Stavanger | 4019 | Norway |
| University Hospital of North Norway | Tromsø | 9019 | Norway |
| St.Olavs Hospital | Trondheim | 7030 | Norway |
| Carol Davila University of Medicine and Pharmacy Bucharest | Bucharest | Romania |
| Sahlgrenska Universitetssjukehuset | Gothenburg | 41345 | Sweden |
| Karolinska University Hospital | Stockholm | 141 86 | Sweden |
| Queen Mary | London | SW15 5PN | SW15 5PN | United Kingdom |
| Prot_000.pdf |
| ID | Term |
|---|---|
| D001172 | Arthritis, Rheumatoid |
| ID | Term |
|---|---|
| D001168 | Arthritis |
| D007592 | Joint Diseases |
| D009140 | Musculoskeletal Diseases |
| D012216 | Rheumatic Diseases |
| D003240 | Connective Tissue Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D000068879 | Adalimumab |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
Not provided
Not provided