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The Norwegian Drug Monitoring Study (NOR-DRUM)

Primary Purpose

Rheumatoid Arthritis, Spondyloarthritis, Ankylosing Spondylitis

Status
Completed
Phase
Not Applicable
Locations
Norway
Study Type
Interventional
Intervention
Therapeutic drug monitoring
Standard care
Sponsored by
Diakonhjemmet Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Rheumatoid Arthritis focused on measuring infliximab, therapeutic drug monitoring, anti drug antibodies, TDM

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

NOR-DRUM A

  1. 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
  2. Male or non-pregnant female
  3. ≥18 and < 75 years of age at screening
  4. A clinical indication to start INX
  5. Subject not in remission according to diagnosis-specific disease activity scores

  6. 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

  1. 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
  2. Male or non-pregnant female
  3. ≥18 and < 75 years of age at screening
  4. On maintenance therapy with infliximab for a minimum of 30 weeks and a maximum of 3 years
  5. A clinical indication for further infliximab treatment

  6. 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

Exclusion Criteria:

NOR-DRUM A

  1. 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
  2. A positive screening for TB and hepatitis
  3. Inadequate birth control, 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 which makes adherence to the study protocol difficult
  5. Prior use of infliximab within the last 6 months

NOR-DRUM B

  1. 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
  2. Inadequate birth control, pregnancy or subject considering becoming pregnant during the study period
  3. Psychiatric or mental disorders, alcohol abuse or other substance abuse, language barriers or other factors which makes adherence to the study protocol difficult

Sites / Locations

  • Akershus University Hospital
  • Sørlandet Sykehus, Arendal
  • Haukeland, HELSE BERGEN HF,
  • Bodø, NORDLANDSSYKEHUSET
  • Drammen, VESTRE VIKEN HF
  • Elverum, SYKEHUSET INNLANDET HF
  • Helse Førde Hf
  • Hamar, SYKEHUSET INNLANDET HF
  • HAUGESUND SANITETSFORENING revmatismesykehus
  • Haugesund Sjukehus
  • SØRLANDET SYKEHUS HF Kristiansand
  • REVMATISMESYKEHUSET AS, Lillehammer
  • Sykehuset Østfold Moss
  • Rikshospitalet
  • Diakonhjemmet Sykehus
  • Betanien Hospital
  • Stavanger Universitetssjukehus
  • Tromsø, UNIVERSITETSSYKEHUSET NORD-NORGE HF
  • St Olavs Hospital
  • Sykehuset Vestfold, Tønsberg
  • Ålesund, HELSE MØRE OG ROMSDAL HF

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Therapeutic drug monitoring

Standard care

Arm Description

Administration of infliximab according to a treatment strategy based on therapeutic drug monitoring and assessments of anti-drug antibodies

Administration of infliximab according to standard clinical care, without knowledge of drug levels or status of anti-drug antibodies

Outcomes

Primary Outcome Measures

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.
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

Secondary Outcome Measures

Time to sustained remission (Part A)
Remission at all following visit
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)
ESR (Part A and B)
0-100 mmHg
CRP (Part A and B)
mg/L
Occurrence of anti-drug antibodies (Part A and B)
Defined as ADAb ≥15 µg/L
Occurrence of drug discontinuation (Part A and B)
Infliximab discontinuation
Cost effectiveness, QALY
Part A and B (Incremental Quality adjusted life years (QALYs) of the intervention arm and active comparator)
Cost effectiveness, ICERs
Part A and B (Cost-effectiveness ratios (ICERs) of the intervention arm and active comparator)
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
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.
Safety (adverse events frequency)
A and B
Time to disease worsening
Part B
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
Serum drug level
Trough level
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
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.
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
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
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.
EULAR response (RA and PsA only)
Defined according to EULAR definition
ACR/EULAR remission
TJC28 ≤ 1 SJC28 ≤ 1 CRP ≤ 10 (mg/l) PGA ≤ 14
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
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.
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).
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
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
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.
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
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)
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.
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.
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)
Total drug consumption
mg/kg/ week
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.
Calprotectin
Faecal calprotectin is an inflammatory marker for IBD. It is measured in mg/kg

Full Information

First Posted
February 10, 2017
Last Updated
March 4, 2021
Sponsor
Diakonhjemmet Hospital
Collaborators
Oslo University Hospital, University Hospital, Akershus
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1. Study Identification

Unique Protocol Identification Number
NCT03074656
Brief Title
The Norwegian Drug Monitoring Study
Acronym
NOR-DRUM
Official Title
A NORwegian Multicentre Randomised Controlled Trial Assessing the Effectiveness of Tailoring Infliximab Treatment by Therapeutic DRUg Monitoring - The NOR-DRUM Study
Study Type
Interventional

2. Study Status

Record Verification Date
March 2021
Overall Recruitment Status
Completed
Study Start Date
March 1, 2017 (Actual)
Primary Completion Date
December 14, 2020 (Actual)
Study Completion Date
December 14, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Diakonhjemmet Hospital
Collaborators
Oslo University Hospital, University Hospital, Akershus

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No

5. Study Description

Brief 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. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rheumatoid Arthritis, Spondyloarthritis, Ankylosing Spondylitis, Crohn Disease, Ulcerative Colitis, Psoriasis, Psoriatic Arthritis
Keywords
infliximab, therapeutic drug monitoring, anti drug antibodies, TDM

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
611 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Therapeutic drug monitoring
Arm Type
Experimental
Arm Description
Administration of infliximab according to a treatment strategy based on therapeutic drug monitoring and assessments of anti-drug antibodies
Arm Title
Standard care
Arm Type
Active Comparator
Arm Description
Administration of infliximab according to standard clinical care, without knowledge of drug levels or status of anti-drug antibodies
Intervention Type
Other
Intervention Name(s)
Therapeutic drug monitoring
Intervention Description
Treatment algorithm based on assessments of serum drug levels and anti-drug antibodies
Intervention Type
Other
Intervention Name(s)
Standard care
Intervention Description
Treatment algorithm based on standard clinical assessments, without knowledge of serum drug levels and anti-drug antibodies
Primary Outcome Measure Information:
Title
Proportion of patients in remission defined by disease specific composite scores Study part A
Description
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.
Time Frame
30 weeks
Title
Sustained disease control throughout the study period without disease worsening defined by disease specific composite scores Study part B
Description
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
Time Frame
52 weeks
Secondary Outcome Measure Information:
Title
Time to sustained remission (Part A)
Description
Remission at all following visit
Time Frame
Assessed at all time points up to 30 weeks
Title
Patient's and physician's global assessment of disease activity (Part A and B)
Description
Visual analogue scale (VAS) 0 mm-100 mm (100 mm worst outcome)
Time Frame
30 weeks (A) and 52 weeks (B)
Title
ESR (Part A and B)
Description
0-100 mmHg
Time Frame
30 weeks (A) and 52 weeks (B)
Title
CRP (Part A and B)
Description
mg/L
Time Frame
30 weeks (A) and 52 weeks (B)
Title
Occurrence of anti-drug antibodies (Part A and B)
Description
Defined as ADAb ≥15 µg/L
Time Frame
30 weeks (A) and 52 weeks (B)
Title
Occurrence of drug discontinuation (Part A and B)
Description
Infliximab discontinuation
Time Frame
30 weeks (A) and 52 weeks (B)
Title
Cost effectiveness, QALY
Description
Part A and B (Incremental Quality adjusted life years (QALYs) of the intervention arm and active comparator)
Time Frame
30 weeks (A) and 52 weeks (B)
Title
Cost effectiveness, ICERs
Description
Part A and B (Cost-effectiveness ratios (ICERs) of the intervention arm and active comparator)
Time Frame
30 weeks (A) and 52 weeks (B)
Title
Health utility (EQ-5D)
Description
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
Time Frame
30 weeks (A) and 52 weeks (B)
Title
Quality of life (SF-36)
Description
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.
Time Frame
30 weeks (A) and 52 weeks (B)
Title
Safety (adverse events frequency)
Description
A and B
Time Frame
30 weeks (A) and 52 weeks (B)
Title
Time to disease worsening
Description
Part B
Time Frame
52 weeks
Title
Proportion of patients in remission, diagnostic subgroups (overall in B)
Description
RA/PsA: DAS28 remission, SDAI remission, ACR/EULAR remission, SpA: ASDAS inactive disease, UC: PMS, CD: HBI, Ps PASI
Time Frame
30 weeks (A) and 52 weeks (B)
Title
Serum drug level
Description
Trough level
Time Frame
Assessed at all time points up to 30 weeks
Title
Proportion of patients with improvement defined by disease specific composite scores (Part A)
Description
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
Time Frame
14 weeks
Title
Time to remission (Part A)
Description
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.
Time Frame
Assessed at all time points up to week 30
Title
DAS28 (RA and PsA only)
Description
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
Time Frame
30 weeks (A) and 52 weeks (B)
Title
Partial Mayo score
Description
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
Time Frame
30 weeks (A) and 52 weeks (B)
Title
SDAI (RA and PsA only)
Description
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.
Time Frame
30 weeks (A) and 52 weeks (B)
Title
EULAR response (RA and PsA only)
Description
Defined according to EULAR definition
Time Frame
30 weeks (A)
Title
ACR/EULAR remission
Description
TJC28 ≤ 1 SJC28 ≤ 1 CRP ≤ 10 (mg/l) PGA ≤ 14
Time Frame
30 weeks (A)
Title
ACR response
Description
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
Time Frame
30 weeks (A)
Title
DAPSA (PsA only)
Description
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.
Time Frame
30 weeks (A) and 52 weeks (B)
Title
BASDAI (SpA only)
Description
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).
Time Frame
30 weeks (A) and 52 weeks (B)
Title
ASDAS
Description
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
Time Frame
30 weeks (A) and 52 weeks (B)
Title
Partial Mayo Score (UC only)
Description
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
Time Frame
30 weeks (A) and 52 weeks (B)
Title
Harvey-Bradshaw Index (CD only)
Description
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.
Time Frame
30 weeks (A) and 52 weeks (B)
Title
Psoriasis Area and Severity Index (PASI) (Ps only)
Description
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
Time Frame
30 weeks (A) and 52 weeks (B)
Title
Modified Health Assessment Questionnaire
Description
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)
Time Frame
30 weeks (A) and 52 weeks (B)
Title
Rheumatoid Arthritis Impact of Disease (RA only)
Description
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.
Time Frame
30 weeks (A) and 52 weeks (B)
Title
Psoriatic Arthritis Impact of Disease (PsAID) score
Description
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.
Time Frame
30 weeks (A) and 52 weeks (B)
Title
Inflammatory Bowel Disease Questionnaire (IBDQ)
Description
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)
Time Frame
30 weeks (A) and 52 weeks (B)
Title
Total drug consumption
Description
mg/kg/ week
Time Frame
30 weeks (A) and 52 weeks (B)
Title
Dermatology Life Quality Index (DLQI)
Description
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.
Time Frame
30 weeks (A) and 52 weeks (B)
Title
Calprotectin
Description
Faecal calprotectin is an inflammatory marker for IBD. It is measured in mg/kg
Time Frame
30 weeks (A) and 52 weeks (B)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 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 Exclusion Criteria: 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 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Espen A Haavardsholm, MD, PhD
Organizational Affiliation
Diakonhjemmet Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Tore K Kvien, MD, PhD
Organizational Affiliation
Diakonhjemmet Hospital
Official's Role
Study Director
Facility Information:
Facility Name
Akershus University Hospital
City
Oslo
State/Province
Lørenskog
ZIP/Postal Code
1478
Country
Norway
Facility Name
Sørlandet Sykehus, Arendal
City
Arendal
Country
Norway
Facility Name
Haukeland, HELSE BERGEN HF,
City
Bergen
Country
Norway
Facility Name
Bodø, NORDLANDSSYKEHUSET
City
Bodø
Country
Norway
Facility Name
Drammen, VESTRE VIKEN HF
City
Drammen
Country
Norway
Facility Name
Elverum, SYKEHUSET INNLANDET HF
City
Elverum
Country
Norway
Facility Name
Helse Førde Hf
City
Førde
Country
Norway
Facility Name
Hamar, SYKEHUSET INNLANDET HF
City
Hamar
Country
Norway
Facility Name
HAUGESUND SANITETSFORENING revmatismesykehus
City
Haugesund
Country
Norway
Facility Name
Haugesund Sjukehus
City
Haugesund
Country
Norway
Facility Name
SØRLANDET SYKEHUS HF Kristiansand
City
Kristiansand
Country
Norway
Facility Name
REVMATISMESYKEHUSET AS, Lillehammer
City
Lillehammer
Country
Norway
Facility Name
Sykehuset Østfold Moss
City
Moss
ZIP/Postal Code
1535
Country
Norway
Facility Name
Rikshospitalet
City
Oslo
ZIP/Postal Code
0372
Country
Norway
Facility Name
Diakonhjemmet Sykehus
City
Oslo
ZIP/Postal Code
0687
Country
Norway
Facility Name
Betanien Hospital
City
Skien
Country
Norway
Facility Name
Stavanger Universitetssjukehus
City
Stavanger
Country
Norway
Facility Name
Tromsø, UNIVERSITETSSYKEHUSET NORD-NORGE HF
City
Tromsø
Country
Norway
Facility Name
St Olavs Hospital
City
Trondheim
Country
Norway
Facility Name
Sykehuset Vestfold, Tønsberg
City
Tønsberg
Country
Norway
Facility Name
Ålesund, HELSE MØRE OG ROMSDAL HF
City
Ålesund
Country
Norway

12. IPD Sharing Statement

Plan to Share IPD
Undecided
Citations:
PubMed Identifier
34932077
Citation
Syversen 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.
Results Reference
derived
PubMed Identifier
33944876
Citation
Syversen 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.
Results Reference
derived
PubMed Identifier
31907007
Citation
Syversen 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.
Results Reference
derived

Learn more about this trial

The Norwegian Drug Monitoring Study

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