Rheumatoid ArthritisNOR-DRUMNCT03074656
The Norwegian Drug Monitoring Study
A study testing Therapeutic drug monitoring in people with Rheumatoid Arthritis and Spondyloarthritis, run by Diakonhjemmet Hospital at 21 sites in Norway.
Trial summary
Infliximab and other TNF-inhibitors have revolutionised the treatment of several immunological inflammatory diseases. Still, more than half of the patients either do not respond sufficiently to infliximab therapy or loose efficacy over time. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Rheumatoid Arthritis, Spondyloarthritis, Ankylosing Spondylitis
- What is being tested?
- Therapeutic drug monitoring
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 611 participants
- Where
- 21 sitesNorway
- Study dates
- 1 Mar 2017to 14 Dec 2020
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- NOR-DRUM A
- A clinical diagnosis of one of the following; rheumatoid arthritis, spondyloarthritis (including ankylosing spondylitis), psoriatic arthritis*, ulcerative colitis, Crohn's disease or chronic plaque psoriasis
- Male or non-pregnant female
- ≥18 and < 75 years of age at screening
- A clinical indication to start INX
- Subject not in remission according to diagnosis-specific disease activity scores
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- Subject capable of understanding and signing an informed consent form
- Patients with psoriatic arthritis with predominantly axial manifestations should be included and assessed as spondyloarthritis
- NOR-DRUM B
- A clinical diagnosis of one of the following; rheumatoid arthritis, spondyloarthritis (including ankylosing spondylitis), psoriatic arthritis*, ulcerative colitis, Crohn's disease or chronic plaque psoriasis
- Male or non-pregnant female
- ≥18 and < 75 years of age at screening
- On maintenance therapy with infliximab for a minimum of 30 weeks and a maximum of 3 years
- A clinical indication for further infliximab treatment
- Subject capable of understanding and signing an informed consent form
- Patients with psoriatic arthritis and predominantly axial manifestations should be included and assessed as spondyloarthritis
Who cannot join
- NOR-DRUM A
- Major co-morbidities, such as previous malignancies within the last 5 years, severe 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, laboratory abnormalities or significant renal or hepatic disease and/or other diseases or conditions where treatment with infliximab is either found contra-indicated by the clinician or which make adherence to the protocol difficult
- A positive screening for TB and hepatitis
- Inadequate birth control, 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 which makes adherence to the study protocol difficult
- Prior use of infliximab within the last 6 months
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- NOR-DRUM B
- Major co-morbidities, such as previous malignancies within the last 5 years, severe diabetes mellitus, severe infections, uncontrollable hypertension, severe cardiovascular disease (NYHA class 3 or 4), severe respiratory diseases, demyelinating disease, significant chronic widespread pain syndrome, laboratory abnormalities or significant renal or hepatic disease and/or other diseases or conditions where treatment with infliximab is either found contra-indicated by the clinician or which make adherence to the protocol difficult
- Inadequate birth control, 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 which makes adherence to the study protocol difficult
Trial locations and contacts
21 sites in 1 country.
21 sites in 1 country
Norway21 sites
Ålesund, HELSE MØRE OG ROMSDAL HF
Ålesund
Sørlandet Sykehus, Arendal
Arendal
Haukeland, HELSE BERGEN HF,
Bergen
Bodø, NORDLANDSSYKEHUSET
Bodø
Drammen, VESTRE VIKEN HF
Drammen
Elverum, SYKEHUSET INNLANDET HF
Elverum
Helse Førde Hf
Førde
Hamar, SYKEHUSET INNLANDET HF
Hamar
HAUGESUND SANITETSFORENING revmatismesykehus
Haugesund
Haugesund Sjukehus
Haugesund
SØRLANDET SYKEHUS HF Kristiansand
Kristiansand
REVMATISMESYKEHUSET AS, Lillehammer
Lillehammer
Sykehuset Østfold Moss
Moss, 1535
Akershus University Hospital
Oslo, Lørenskog, 1478
Rikshospitalet
Oslo, 0372
Diakonhjemmet Sykehus
Oslo, 0687
Betanien Hospital
Skien
Stavanger Universitetssjukehus
Stavanger
Sykehuset Vestfold, Tønsberg
Tønsberg
Tromsø, UNIVERSITETSSYKEHUSET NORD-NORGE HF
Tromsø
St Olavs Hospital
Trondheim
About this study
Official title: A NORwegian Multicentre Randomised Controlled Trial Assessing the Effectiveness of Tailoring Infliximab Treatment by Therapeutic DRUg Monitoring - The NOR-DRUM Study
Infliximab and other TNF-inhibitors have revolutionised the treatment of several immunological inflammatory diseases. Still, more than half of the patients either do not respond sufficiently to infliximab therapy or loose efficacy over time. The large individual variation in the serum drug concentrations on standard doses and the development of anti-drug antibodies are thought to be main reasons for these treatment failures. An individualised treatment strategy based on systematic assessments of serum drug concentrations, therapeutic drug monitoring, has been proposed as a clinical tool to optimise efficacy of infliximab treatment. Therapeutic drug monitoring seems reasonable both from a clinical and an economical point of view, but the effectiveness of this treatment strategy still remain to be shown. The NOR-DRUM study is planned as a national, randomised controlled multicentre trial in two parts aiming to assess the effectiveness of therapeutic drug monitoring in order to achieve remission in patients with immunological inflammatory diseases starting infliximab treatment (part A) and in order to maintain disease control in patients on maintenance infliximab treatment (part B). The results of the NOR-DRUM study will hopefully contribute to an implementation of a personalised medicine approach to treatment with infliximab and other biological drugs.
- Conditions
- Rheumatoid Arthritis, Spondyloarthritis, Ankylosing Spondylitis, Crohn Disease, Ulcerative Colitis, Psoriasis
- Being tested
- Therapeutic drug monitoring, Standard care
- Keywords
- infliximab, therapeutic drug monitoring, anti drug antibodies, TDM
- Medical subject headings
- Arthritis, Rheumatoid, Spondylarthritis, Spondylitis, Ankylosing, Crohn Disease, Colitis, Ulcerative, Psoriasis, Arthritis, Psoriatic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Therapeutic drug monitoringOther
Treatment algorithm based on assessments of serum drug levels and anti-drug antibodies
Standard careOther
Treatment algorithm based on standard clinical assessments, without knowledge of serum drug levels and anti-drug antibodies
| Study group | Role | What they receive |
|---|---|---|
| Therapeutic drug monitoring | Experimental | Administration of infliximab according to a treatment strategy based on therapeutic drug monitoring and assessments of anti-drug antibodies Receives: Other: Therapeutic drug monitoring |
| Standard care | Active comparator | Administration of infliximab according to standard clinical care, without knowledge of drug levels or status of anti-drug antibodies Receives: Other: Standard care |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of patients in remission defined by disease specific composite scores Study part A
Definition of remission: DAS 28 score <2.6 in patients with RA and PsA, ASDAS score <1.3 in patients with SpA, Mayo score of ≤2 with no sub scores >1 in patients with UC, HBI score of ≤4 in CD and PASI score of ≤4 in patients with Ps.
Measured: 30 weeks
Sustained disease control throughout the study period without disease worsening defined by disease specific composite scores Study part B
Definition of disease worsening: RA/PsA: Change DAS28 of ≥ 1.2 and min DAS 3.2 SpA: Increase in ASDAS of ≥1.1 and min ASDAS of 2.1 UC: Increase in Partial Mayo score of ≥ 3 and min score of ≥ 5 CD: Increase in HBI of ≥ 4 points and min score of 7 Ps: Increase in PASI of ≥ 3 points and min PASI score of 5 Or: Patient and investigator consensus on disease worsening
Measured: 52 weeks
Secondary outcomes (35)
Time to sustained remission (Part A)
Remission at all following visit
Measured: Assessed at all time points up to 30 weeks
Patient's and physician's global assessment of disease activity (Part A and B)
Visual analogue scale (VAS) 0 mm-100 mm (100 mm worst outcome)
Measured: 30 weeks (A) and 52 weeks (B)
ESR (Part A and B)
0-100 mmHg
Measured: 30 weeks (A) and 52 weeks (B)
CRP (Part A and B)
mg/L
Measured: 30 weeks (A) and 52 weeks (B)
Occurrence of anti-drug antibodies (Part A and B)
Defined as ADAb ≥15 µg/L
Measured: 30 weeks (A) and 52 weeks (B)
Occurrence of drug discontinuation (Part A and B)
Infliximab discontinuation
Measured: 30 weeks (A) and 52 weeks (B)
Cost effectiveness, QALY
Part A and B (Incremental Quality adjusted life years (QALYs) of the intervention arm and active comparator)
Measured: 30 weeks (A) and 52 weeks (B)
Cost effectiveness, ICERs
Part A and B (Cost-effectiveness ratios (ICERs) of the intervention arm and active comparator)
Measured: 30 weeks (A) and 52 weeks (B)
Health utility (EQ-5D)
EuroQol 5 (EQ-5D) dimensions The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The patient is asked to indicate his/her health state by ticking the box next to the most appropriate statement in each of the five dimensions. This decision results in a 1-digit number that expresses the level selected for that dimension. The digits for the five dimensions can be combined into a 5-digit number that describes the patient's health state
Measured: 30 weeks (A) and 52 weeks (B)
Quality of life (SF-36)
The SF-36 is a multi-purpose, short-form health survey with 36 questions. The SF-36 will be scored according to RAND 36-Item Health Survey 1.0 to form eight measures scores 0-100 (100 worst outcome): physical functioning, bodily pain, role limitations due to physical health problems, role limitations due to personal or emotional problems, emotional well-being, social functioning, energy/fatigue, and general health perceptions.
Measured: 30 weeks (A) and 52 weeks (B)
Safety (adverse events frequency)
A and B
Measured: 30 weeks (A) and 52 weeks (B)
Time to disease worsening
Part B
Measured: 52 weeks
Proportion of patients in remission, diagnostic subgroups (overall in B)
RA/PsA: DAS28 remission, SDAI remission, ACR/EULAR remission, SpA: ASDAS inactive disease, UC: PMS, CD: HBI, Ps PASI
Measured: 30 weeks (A) and 52 weeks (B)
Serum drug level
Trough level
Measured: Assessed at all time points up to 30 weeks
Proportion of patients with improvement defined by disease specific composite scores (Part A)
- Improvement in RA and PsA Improvement is defined as a decrease in DAS28 of ≥1.2 from baseline
- Improvement in SpA Improvement is defined as a decrease in ASDAS of ≥1.1 from baseline
- Improvement in UC Improvement in UC is defined as a decrease in the partial Mayo score of ≥ 3 points from baseline or a partial Mayo score of 0
- Improvement in CD Improvement in CD is defined as a decrease in HBI of ≥ 4 points from baseline
- Improvement in Ps Improvement in Ps is defined as PASI 50 (A 50% decrease in the PASI obtained at baseline)
- Patient and investigators consensus on improvement
Measured: 14 weeks
Time to remission (Part A)
Definition of remission: DAS 28 score <2.6 in patients with RA and PsA, ASDAS score <1.3 in patients with SpA, Mayo score of ≤2 with no sub scores >1 in patients with UC, HBI score of ≤4 in CD and PASI score of ≤4 in patients with Ps.
Measured: Assessed at all time points up to week 30
DAS28 (RA and PsA only)
The 28-joint Disease Activity Score (DAS28) includes the 28- tender joint counts (TJC28), 28-swollen joint counts (SJC28), Erythrocyte Sedimentation Rate (ESR) and Patient Global Assessment (PGA) on a VAS
According to DAS28, the following cut-points are used:
High disease activity: DAS28 > 5.1 Moderate disease activity: 5.1 ≥ DAS28>3.2 Low disease activity: 3.2 ≥ DAS28 ≥ 2.6 In remission: DAS28 < 2.6
Measured: 30 weeks (A) and 52 weeks (B)
Partial Mayo score
The Mayo score consists of four components (rectal bleeding, stool frequency, physician rating of disease activity, and mucosal appearance at endoscopy) rated from 0-3 that are summed to give a total score that ranges from 0-12. The non-invasive partial Mayo score (PMS) does not require an endoscopy, and thereby ranging from 0-9.
Remission is defined as a partial Mayo score of ≤ 2 with no individual subscore >1
Measured: 30 weeks (A) and 52 weeks (B)
SDAI (RA and PsA only)
The Simplified Disease Activity Index (SDAI) includes TCJ28, SJC28, PGA, PhGA and CRP. In remission: SDAI ≤ 3.3. High values denotes worse outcomes. High values denotes worse outcomes.
Measured: 30 weeks (A) and 52 weeks (B)
EULAR response (RA and PsA only)
Defined according to EULAR definition
Measured: 30 weeks (A)
ACR/EULAR remission
- TJC28 ≤ 1
- SJC28 ≤ 1
- CRP ≤ 10 (mg/l)
- PGA ≤ 14
Measured: 30 weeks (A)
ACR response
If a patient experiences a flare and treatment is escalated, the ACR response rates ACR20, ACR50, ACR70 and ACR90 as well as ACR remission rates will be calculated.
An ACR20 response is defined if the following criteria are fulfilled:
- 20% improvement in RAI AND
- 20% improvement in swollen joint count 44 AND
- 20% improvement in at least 3 of 5 other core set items
The other core set items consist of:
- Investigator global assessment of disease activity
- Patient global assessment of disease activity
- Patient pain
- Disability
- ESR/CRP
Measured: 30 weeks (A)
DAPSA (PsA only)
Disease Activity index for PSoriatic Arthritis (DAPSA) is calculated as follows: TJC68 + SJC66 + CRP(mg/L)/10 + PGA(0-100)/10+VAS Pain(0-100)/10. High values denotes worse outcomes.
Measured: 30 weeks (A) and 52 weeks (B)
BASDAI (SpA only)
The Bath Ankylosing Spondylitits Disease Activity Index (BASDAI) includes six questions pertaining to the five major symptoms of ankylosing spondylitis: fatigue (Q1), spinal pain (Q2), joint pain/swelling (Q3), areas of localized tenderness (Q4), morning stiffness duration (Q5) and morning stiffness severity (Q6). Each question is scored on an NRS (0-10).
Measured: 30 weeks (A) and 52 weeks (B)
ASDAS
The Ankylosing Spondylitis Disease Activity Score (ASDAS) is computed based on patient reported outcomes (components of BASDAI) and the CRP. The ASDAS-CRP is calculated as follows:
ASDAS-CRP=0.121*total back pain + 0.0110*patient global + 0.073*peripheral pain/swelling + 0.058*duration of morning stiffness + 0.579*ln(CRP+1 High values denotes worse outcomes
Measured: 30 weeks (A) and 52 weeks (B)
Partial Mayo Score (UC only)
The Mayo score consists of four components (rectal bleeding, stool frequency, physician rating of disease activity, and mucosal appearance at endoscopy) rated from 0-3 that are summed to give a total score that ranges from 0-12. The non-invasive partial Mayo score (PMS) does not require an endoscopy, and thereby ranging from 0-9.
Remission is defined as a partial Mayo score of ≤ 2 with no individual subscore >1
Measured: 30 weeks (A) and 52 weeks (B)
Harvey-Bradshaw Index (CD only)
The Harvey-Bradshaw index (HBI) consists of five domains, general well-being (0-4), abdominal pain (0-3), number of liquid soft stools per day, abdominal mass (0-3) and number of predefined complications. The scores of each sub-domain is summed up to compute the HBI.
Remission is defined as a HBI score ≤ 4 points.
Measured: 30 weeks (A) and 52 weeks (B)
Psoriasis Area and Severity Index (PASI) (Ps only)
A PASI 50/75 means a 50% /75% reduction in the PASI score. Complete clearance is defined as PASI=0, mild to moderate psoriasis is defined as PASI < 10, moderate to severe psoriasis between 10 and 20 and severe psoriasis above 20.
Remission is defined as PASI <4
Measured: 30 weeks (A) and 52 weeks (B)
Modified Health Assessment Questionnaire
Each item of the Modified Health Assessment Questionnaire (MHAQ) is scored on a categorical 0-3 scale and the sum score is divided by 8 to form the MHAQ score 0.0 to 3.0 (3.0 worst outcome possible)
Measured: 30 weeks (A) and 52 weeks (B)
Rheumatoid Arthritis Impact of Disease (RA only)
The Rheumatoid Arthritis Impact of Disease (RAID) score is calculated based on seven numerical rating scales (NRS) questions. Each NRS is assessed as a number between 0 and 10. The seven NRS correspond to pain, function, fatigue, sleep, emotional wellbeing, physical wellbeing and coping/self-efficacy.
Measured: 30 weeks (A) and 52 weeks (B)
Psoriatic Arthritis Impact of Disease (PsAID) score
Psoriatic Arthritis Impact of Disease (PsAID) score is a questionnaire with 9 domains of health. The nine domains with relative weights are: pain (0.174), fatigue (0.131), skin (0.121), work and/or leisure activities (0.110), function (0.107), discomfort (0.098), sleep (0.089), coping (0.087) and anxiety (0.085), each rated on an NRS (0-10). The rates of each domain are weighted and summed to form a score in the range of 0-10 (10 worst outcome possible). The final RAID score is computed. The scale 0-10 where higher figures indicate worse status.
Measured: 30 weeks (A) and 52 weeks (B)
Inflammatory Bowel Disease Questionnaire (IBDQ)
The Inflammatory Bowel Disease Questionnaire (IBDQ) is widely used tool to measure health-related quality of life in patients with inflammatory bowel diseases. The questionnaire consists of 32 questions scored in four domains: bowel symptoms, emotional health, systemic systems and social function. The total IBDQ score is the sum of all the question scores, ranging 32 to 224 (224 worst possible)
Measured: 30 weeks (A) and 52 weeks (B)
Total drug consumption
mg/kg/ week
Measured: 30 weeks (A) and 52 weeks (B)
Dermatology Life Quality Index (DLQI)
The Dermatology Life Quality Index (DLQI) consists of 10 questions concerning patients' perception of the impact of skin diseases on different aspects of their health-related quality of life over the last week. It has been validated for adult dermatology patients aged 16 years and older. The items of the DLQI encompass aspects of symptoms and feelings, daily activities, leisure, work or school, personal relationships and the side effects of treatment. Each question is scored on a 4-point Likert scale: Not at all/Not relevant=0, A little=1, A lot=2 and Very much=3. Scores of individual items (0-3) are added to yield a total score (0-30); higher scores mean greater impairment of patient's QoL. The DLQI will only be presented to patients with chronic plaque psoriasis.
Measured: 30 weeks (A) and 52 weeks (B)
Calprotectin
Faecal calprotectin is an inflammatory marker for IBD. It is measured in mg/kg
Measured: 30 weeks (A) and 52 weeks (B)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Mar 2017
- Study start1 Mar 2017
- Primary completion14 Dec 2020
- Study completion14 Dec 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Rheumatoid ArthritisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 611 participants (actual)
Sponsor and investigators
- Lead sponsor
- Diakonhjemmet Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Oslo University Hospital, University Hospital, Akershus
- Responsible party
- Principal investigator, Espen A. Haavardsholm, MD PhD, Diakonhjemmet Hospital
- Investigators
- Espen A Haavardsholm, MD, PhD, Principal investigator, Diakonhjemmet HospitalTore K Kvien, MD, PhD, Study director, Diakonhjemmet Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03074656
- Sponsor's protocol ID
- DIA2016-1
- Acronym
- NOR-DRUM
- Status last verified
- Mar 2021
- First submitted
- 10 Feb 2017
- Last updated
- 8 Mar 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Holly T, Kirkesaether Brun M, Jorgensen KK, Goll GL, Sexton J, Gehin JE, Kvien TK, Jahnsen J, Provan SA, Bolstad N, Aas E, Haavardsholm EA, Kristiansen IS, Syversen SW, Hagen G. Cost-effectiveness of proactive therapeutic drug monitoring of maintenance infliximab treatment in patients with immune-mediated inflammatory diseases: results from a randomised controlled trial. RMD Open. 2026 Mar 19;12(1):e006329. doi: 10.1136/rmdopen-2025-006329.
PubMed 41856561Syversen SW, Jorgensen KK, Goll GL, Brun MK, Sandanger O, Bjorlykke KH, Sexton J, Olsen IC, Gehin JE, Warren DJ, Klaasen RA, Noraberg G, Bruun TJ, Dotterud CK, Ljosa MKA, Haugen AJ, Njalla RJ, Zettel C, Ystrom CM, Bragnes YH, Skorpe S, Thune T, Seeberg KA, Michelsen B, Blomgren IM, Strand EK, Mielnik P, Torp R, Mork C, Kvien TK, Jahnsen J, Bolstad N, Haavardsholm EA. Effect of Therapeutic Drug Monitoring vs Standard Therapy During Maintenance Infliximab Therapy on Disease Control in Patients With Immune-Mediated Inflammatory Diseases: A Randomized Clinical Trial. JAMA. 2021 Dec 21;326(23):2375-2384. doi: 10.1001/jama.2021.21316.
PubMed 34932077Syversen SW, Goll GL, Jorgensen KK, Sandanger O, Sexton J, Olsen IC, Gehin JE, Warren DJ, Brun MK, Klaasen RA, Karlsen LN, Noraberg G, Zettel C, Ljosa MKA, Haugen AJ, Njalla RJ, Bruun TJ, Seeberg KA, Michelsen B, Strand EK, Skorpe S, Blomgren IM, Bragnes YH, Dotterud CK, Thune T, Ystrom CM, Torp R, Mielnik P, Mork C, Kvien TK, Jahnsen J, Bolstad N, Haavardsholm EA. Effect of Therapeutic Drug Monitoring vs Standard Therapy During Infliximab Induction on Disease Remission in Patients With Chronic Immune-Mediated Inflammatory Diseases: A Randomized Clinical Trial. JAMA. 2021 May 4;325(17):1744-1754. doi: 10.1001/jama.2021.4172.
PubMed 33944876Syversen SW, Goll GL, Jorgensen KK, Olsen IC, Sandanger O, Gehin JE, Warren DJ, Sexton J, Mork C, Jahnsen J, Kvien TK, Bolstad N, Haavardsholm EA. Therapeutic drug monitoring of infliximab compared to standard clinical treatment with infliximab: study protocol for a randomised, controlled, open, parallel-group, phase IV study (the NOR-DRUM study). Trials. 2020 Jan 6;21(1):13. doi: 10.1186/s13063-019-3734-4.
PubMed 31907007
Study at a glance
From the registry record, last updated by the sponsor on 8 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A NORwegian Multicentre Randomised Controlled Trial Assessing the Effectiveness of Tailoring Infliximab Treatment by Therapeutic DRUg Monitoring - The NOR-DRUM Study
- ClinicalTrials.gov ID
- NCT03074656
- Acronym / sponsor ID
- NOR-DRUM / DIA2016-1
- Conditions
- Rheumatoid Arthritis, Spondyloarthritis, Ankylosing Spondylitis, Crohn Disease, Ulcerative Colitis, Psoriasis
- Keywords
- infliximab, therapeutic drug monitoring, anti drug antibodies, TDM
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 611 participants (actual)
- Lead sponsor
- Diakonhjemmet HospitalUniversity, hospital or other
- Collaborators
- Oslo University Hospital, University Hospital, Akershus
- Study start
- 1 Mar 2017 (actual)
- Primary completion
- 14 Dec 2020 (actual)
- Study completion
- 14 Dec 2020 (actual)
- First posted
- 9 Mar 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Infliximab and other TNF-inhibitors have revolutionised the treatment of several immunological inflammatory diseases. Still, more than half of the patients either do not respond sufficiently to infliximab therapy or loose efficacy over time. The large individual variation in the serum drug concentrations on standard doses and the development of anti-drug antibodies are thought to be main reasons for these treatment failures. An individualised treatment strategy based on systematic assessments of serum drug concentrations, therapeutic drug monitoring, has been proposed as a clinical tool to optimise efficacy of infliximab treatment. Therapeutic drug monitoring seems reasonable both from a clinical and an economical point of view, but the effectiveness of this treatment strategy still remain to be shown. The NOR-DRUM study is planned as a national, randomised controlled multicentre trial in two parts aiming to assess the effectiveness of therapeutic drug monitoring in order to achieve remission in patients with immunological inflammatory diseases starting infliximab treatment (part A) and in order to maintain disease control in patients on maintenance infliximab treatment (part B). The results of the NOR-DRUM study will hopefully contribute to an implementation of a personalised medicine approach to treatment with infliximab and other biological drugs.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Therapeutic drug monitoring | Experimental | Other: Therapeutic drug monitoringAdministration of infliximab according to a treatment strategy based on therapeutic drug monitoring and assessments of anti-drug antibodies |
| Standard care | Active comparator | Other: Standard careAdministration of infliximab according to standard clinical care, without knowledge of drug levels or status of anti-drug antibodies |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- NOR-DRUM A
- A clinical diagnosis of one of the following; rheumatoid arthritis, spondyloarthritis (including ankylosing spondylitis), psoriatic arthritis*, ulcerative colitis, Crohn's disease or chronic plaque psoriasis
- Male or non-pregnant female
- ≥18 and < 75 years of age at screening
- A clinical indication to start INX
Key exclusion criteria (10 listed)
- NOR-DRUM A
- Major co-morbidities, such as previous malignancies within the last 5 years, severe 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, laboratory abnormalities or significant renal or hepatic disease and/or other diseases or conditions where treatment with infliximab is either found contra-indicated by the clinician or which make adherence to the protocol difficult
- A positive screening for TB and hepatitis
- Inadequate birth control, 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 which makes adherence to the study protocol difficult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Therapeutic drug monitoringTreatment algorithm based on assessments of serum drug levels and anti-drug antibodies | Other | Therapeutic drug monitoring |
| Standard careTreatment algorithm based on standard clinical assessments, without knowledge of serum drug levels and anti-drug antibodies | Other | Standard care |
Primary outcome
Proportion of patients in remission defined by disease specific composite scores Study part A
Time frame: 30 weeks
Definition of remission: DAS 28 score <2.6 in patients with RA and PsA, ASDAS score <1.3 in patients with SpA, Mayo score of ≤2 with no sub scores >1 in patients with UC, HBI score of ≤4 in CD and PASI score of ≤4 in patients with Ps.
Sustained disease control throughout the study period without disease worsening defined by disease specific composite scores Study part B
Time frame: 52 weeks
Definition of disease worsening: RA/PsA: Change DAS28 of ≥ 1.2 and min DAS 3.2 SpA: Increase in ASDAS of ≥1.1 and min ASDAS of 2.1 UC: Increase in Partial Mayo score of ≥ 3 and min score of ≥ 5 CD: Increase in HBI of ≥ 4 points and min score of 7 Ps: Increase in PASI of ≥ 3 points and min PASI score of 5 Or: Patient and investigator consensus on disease worsening
35 secondary outcomes
Time to sustained remission (Part A)
Time frame: Assessed at all time points up to 30 weeks
Patient's and physician's global assessment of disease activity (Part A and B)
Time frame: 30 weeks (A) and 52 weeks (B)
ESR (Part A and B)
Time frame: 30 weeks (A) and 52 weeks (B)
CRP (Part A and B)
Time frame: 30 weeks (A) and 52 weeks (B)
Occurrence of anti-drug antibodies (Part A and B)
Time frame: 30 weeks (A) and 52 weeks (B)
Occurrence of drug discontinuation (Part A and B)
Time frame: 30 weeks (A) and 52 weeks (B)
Cost effectiveness, QALY
Time frame: 30 weeks (A) and 52 weeks (B)
Cost effectiveness, ICERs
Time frame: 30 weeks (A) and 52 weeks (B)
Health utility (EQ-5D)
Time frame: 30 weeks (A) and 52 weeks (B)
Quality of life (SF-36)
Time frame: 30 weeks (A) and 52 weeks (B)
Safety (adverse events frequency)
Time frame: 30 weeks (A) and 52 weeks (B)
Time to disease worsening
Time frame: 52 weeks
Proportion of patients in remission, diagnostic subgroups (overall in B)
Time frame: 30 weeks (A) and 52 weeks (B)
Serum drug level
Time frame: Assessed at all time points up to 30 weeks
Proportion of patients with improvement defined by disease specific composite scores (Part A)
Time frame: 14 weeks
Time to remission (Part A)
Time frame: Assessed at all time points up to week 30
DAS28 (RA and PsA only)
Time frame: 30 weeks (A) and 52 weeks (B)
Partial Mayo score
Time frame: 30 weeks (A) and 52 weeks (B)
SDAI (RA and PsA only)
Time frame: 30 weeks (A) and 52 weeks (B)
EULAR response (RA and PsA only)
Time frame: 30 weeks (A)
ACR/EULAR remission
Time frame: 30 weeks (A)
ACR response
Time frame: 30 weeks (A)
DAPSA (PsA only)
Time frame: 30 weeks (A) and 52 weeks (B)
BASDAI (SpA only)
Time frame: 30 weeks (A) and 52 weeks (B)
ASDAS
Time frame: 30 weeks (A) and 52 weeks (B)
Partial Mayo Score (UC only)
Time frame: 30 weeks (A) and 52 weeks (B)
Harvey-Bradshaw Index (CD only)
Time frame: 30 weeks (A) and 52 weeks (B)
Psoriasis Area and Severity Index (PASI) (Ps only)
Time frame: 30 weeks (A) and 52 weeks (B)
Modified Health Assessment Questionnaire
Time frame: 30 weeks (A) and 52 weeks (B)
Rheumatoid Arthritis Impact of Disease (RA only)
Time frame: 30 weeks (A) and 52 weeks (B)
Psoriatic Arthritis Impact of Disease (PsAID) score
Time frame: 30 weeks (A) and 52 weeks (B)
Inflammatory Bowel Disease Questionnaire (IBDQ)
Time frame: 30 weeks (A) and 52 weeks (B)
Total drug consumption
Time frame: 30 weeks (A) and 52 weeks (B)
Dermatology Life Quality Index (DLQI)
Time frame: 30 weeks (A) and 52 weeks (B)
Calprotectin
Time frame: 30 weeks (A) and 52 weeks (B)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Mar 2021.
- Derived from this study: PubMed 41856561Holly T, Kirkesaether Brun M, Jorgensen KK, Goll GL, Sexton J, Gehin JE, Kvien TK, Jahnsen J, Provan SA, Bolstad N, Aas E, Haavardsholm EA, Kristiansen IS, Syversen SW, Hagen G. Cost-effectiveness of proactive therapeutic drug monitoring of maintenance infliximab treatment in patients with immune-mediated inflammatory diseases: results from a randomised controlled trial. RMD Open. 2026 Mar 19;12(1):e006329. doi: 10.1136/rmdopen-2025-006329.
- Derived from this study: PubMed 34932077Syversen SW, Jorgensen KK, Goll GL, Brun MK, Sandanger O, Bjorlykke KH, Sexton J, Olsen IC, Gehin JE, Warren DJ, Klaasen RA, Noraberg G, Bruun TJ, Dotterud CK, Ljosa MKA, Haugen AJ, Njalla RJ, Zettel C, Ystrom CM, Bragnes YH, Skorpe S, Thune T, Seeberg KA, Michelsen B, Blomgren IM, Strand EK, Mielnik P, Torp R, Mork C, Kvien TK, Jahnsen J, Bolstad N, Haavardsholm EA. Effect of Therapeutic Drug Monitoring vs Standard Therapy During Maintenance Infliximab Therapy on Disease Control in Patients With Immune-Mediated Inflammatory Diseases: A Randomized Clinical Trial. JAMA. 2021 Dec 21;326(23):2375-2384. doi: 10.1001/jama.2021.21316.
- Derived from this study: PubMed 33944876Syversen SW, Goll GL, Jorgensen KK, Sandanger O, Sexton J, Olsen IC, Gehin JE, Warren DJ, Brun MK, Klaasen RA, Karlsen LN, Noraberg G, Zettel C, Ljosa MKA, Haugen AJ, Njalla RJ, Bruun TJ, Seeberg KA, Michelsen B, Strand EK, Skorpe S, Blomgren IM, Bragnes YH, Dotterud CK, Thune T, Ystrom CM, Torp R, Mielnik P, Mork C, Kvien TK, Jahnsen J, Bolstad N, Haavardsholm EA. Effect of Therapeutic Drug Monitoring vs Standard Therapy During Infliximab Induction on Disease Remission in Patients With Chronic Immune-Mediated Inflammatory Diseases: A Randomized Clinical Trial. JAMA. 2021 May 4;325(17):1744-1754. doi: 10.1001/jama.2021.4172.
- Derived from this study: PubMed 31907007Syversen SW, Goll GL, Jorgensen KK, Olsen IC, Sandanger O, Gehin JE, Warren DJ, Sexton J, Mork C, Jahnsen J, Kvien TK, Bolstad N, Haavardsholm EA. Therapeutic drug monitoring of infliximab compared to standard clinical treatment with infliximab: study protocol for a randomised, controlled, open, parallel-group, phase IV study (the NOR-DRUM study). Trials. 2020 Jan 6;21(1):13. doi: 10.1186/s13063-019-3734-4.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Espen A Haavardsholm, MD, PhD principal investigator
Diakonhjemmet Hospital
Tore K Kvien, MD, PhD study director
Diakonhjemmet Hospital
21 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Therapeutic drug monitoring in people with Rheumatoid Arthritis and Spondyloarthritis, run by Diakonhjemmet Hospital at 21 sites in Norway.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 21 sites in Norway. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of patients in remission defined by disease specific composite scores Study part A (time frame: 30 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03074656, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Mar 2021.