Imaging Treat-to-target Strategy vs Conventional Treat-to-target Strategy in Psoriatic Arthritis

Study Overview
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Brief Summary
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The main objective is to assess if a treat-to-target strategy implementing structured imaging assessments leads to better patient outcome in terms of sustained remission compared to a conventional treat-to-target strategy in psoriatic arthritis. Main inclusion criteria are: >18 years of age, Clinical diagnosis of psoriatic arthritis (PsA), Fulfillment of ClASsification of Psoriatic Arthritis (CASPAR) criteria, Indication for treatment with disease modifying anti-rheumatic drugs according to treating physician Primary endpoint: Sustained remission, defined as Very Low Disease Activity (VLDA) at 16, 20 and 24 months Secondary endpoints: Individual and composite disease activity measures and remission criteria, inflammation assessed by ultrasound, health related quality of life and adverse events. Study design: A two-arm, parallel-group, single-blind, treatment strategy study where patients are randomized 1:1 to a conventional treat-to-target follow-up strategy with structured clinical assessment of disease activity or an imaging informed treat-to-target follow-up strategy with both structured clinical assessment of disease activity and structured imaging assessment of disease activity. Duration of follow-up is 24 months. All patients are treated according to an algorithm based on current European recommendations. The conventional treatment target, applicable to both arms and the sole target in the conventional arm, is all of: Disease Activity index in Psoriatic Arthritis (DAPSA) remission (≤3), Enthesitis ≤1, Psoriasis Body Surface Area ≤3% Intervention: A treat-to-target treatment strategy incorporating information from ultrasound assessment of joints, tendons and entheses (at every visit), and magnetic resonance imaging (MRI) of spine and sacroiliac (SI)-joints at baseline and 1 year, in addition to clinical information. Specifically, this means that these additional measures will be added to conventional treat to target: If evidence of enthesitis or axial inflammation on imaging the patient will progress directly to biological disease modifying antirheumatic drug in the treatment algorithm If evidence of ongoing inflammation (power Doppler>0) on ultrasound assessment of joints, tendons or enthesis, the patient will be classified as not having reached their treatment target

Detailed Description
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This project addresses the challenges associated with psoriatic arthritis (PsA), which is a diverse disease which is difficult to assess clinically. Ultrasound and magnetic resonance imaging (MRI) visualize inflammation that is not apparent on clinical examination, but whether treating patients according to these findings improves outcomes is unknown. The main objective is to assess if a treat-to-target strategy implementing structured imaging assessments leads to better patient outcome in terms of sustained remission compared to a conventional treat-to-target strategy in psoriatic arthritis. Primary endpoint: Sustained remission, defined as Very Low Disease Activity (VLDA) at all of the 16, 20 and 24 month visits. Secondary endpoints include Individual and composite disease activity measures and remission criteria, inflammation assessed by ultrasound, health related quality of life and adverse events. Study design: A two-arm, parallel-group, single-blind, treatment strategy study where patients are randomized 1:1 to a conventional treat-to-target follow-up strategy with structured clinical assessment of disease activity or an imaging informed treat-to-target follow-up strategy with both structured clinical assessment of disease activity and structured imaging assessment of disease activity. Duration of follow-up is 24 months. All patients are treated according to an algorithm based on current European recommendations. The conventional treatment target, applicable to both arms and the sole target in the conventional arm, is all of: Disease Activity index in Psoriatic Arthritis (DAPSA) remission (≤3), Enthesitis ≤1, Psoriasis Body Surface Area ≤3% Intervention: A treat-to-target treatment strategy incorporating information from ultrasound assessment of joints, tendons and entheses (at every visit), and magnetic resonance imaging (MRI) of spine and sacroiliac (SI)-joints at baseline and 1 year, in addition to clinical information. Specifically, this means that these additional measures will be added to conventional treat to target: If evidence of enthesitis or axial inflammation on imaging the patient will progress directly to biological disease modifying antirheumatic drug in the treatment algorithm If evidence of ongoing inflammation (power Doppler>0) on ultrasound assessment of joints, tendons or enthesis, the patient will be classified as not having reached their treatment target

Official Title
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A NORwegian Randomized Strategy Trial in PsoRiatic Arthritis: ImagiNg Treat-to-target vs Conventional Treat-to-target

Conditions
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Psoriatic Arthritis

Intervention / Treatment
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* Other: Imaging informed treat-to-target
* Other: Conventional treat-to-target


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult (>18 years of age) Clinical diagnosis of PsA Indication for treatment with DMARDs according to treating physician (including having attempted ≥2 non-steroidal anti-inflammatory drugs (NSAIDs) for a minimum of 4 weeks in total in predominantly axial and/or entheseal disease) Fulfillment of CASPAR criteria for PsA Exclusion Criteria: Verified arthritis >1 year prior to inclusion Previous DMARD treatment for PsA Systemic glucocorticoid use within the last 3 months Local glucocorticoid injections within the last 4 weeks Major co-morbidities, including but not limited to relevant malignancies, severe diabetes mellitus, severe infections, uncontrolled hypertension, severe cardiovascular disease (NYHA class III or IV) and/or severe respiratory diseases and cirrhosis. Indications of active or latent tuberculosis (TB) as assessed by chest radiograph and TB interferon gamma release assay (IGRA). Patients with documented adequately treated latent TB can be included. Any other medical condition that according to the treated physician and/or local guidelines makes adherence to treatment protocol impossible Abnormal renal function, defined as serum creatinine >142 µmol/L in female and >168 µmol/L in male, or estimated glomerular filtration rate (eGFR) <40 mL/min/1.73 m2 Abnormal liver function (defined as Aspartate Transaminase (AST) and/or Alanine Transaminase (ALT) >1.5 x upper normal limit), active or recent hepatitis Significant anemia, leukopenia and/or thrombocytopenia Inadequate birth control, pregnancy, and/or breastfeeding (current at screening or planned within the duration of the study) Contraindications to magnetic resonance imaging Severe psychiatric or mental disorders, alcohol abuse or other substance abuse, language barriers or other factors which makes adherence to the study protocol impossible Established or suspected widespread-pain syndrome/fibromyalgia

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A two-arm, parallel-group, single-blind, treatment strategy study where patients are randomized 1:1 to a conventional treat-to-target follow-up strategy with structured clinical assessment of disease activity or an imaging informed treat-to-target follow-up strategy with both structured clinical assessment of disease activity and structured imaging assessment of disease activity.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Conventional treat-to-target<br>Conventional treat-to-target follow-up strategy with structured clinical assessment of disease activity | Other: Conventional treat-to-target<br>* Patients are treated according to an algorithm based on current European recommendations. The conventional treatment target, applicable to both arms and the target in the conventional arm, is all of: Disease Activity index in PSoriatic Arthritis (DAPSA) remission (≤4), Enthesitis ≤1, Psoriasis Body Surface Area ≤3%<br>|
| Experimental: Imaging informed treat-to-target<br>Imaging informed treat-to-target follow-up strategy with both structured clinical assessment of disease activity and structured imaging assessment of disease activity. | Other: Imaging informed treat-to-target<br>* A treat-to-target treatment strategy incorporating information from ultrasound assessment of joints, tendons and entheses (at every visit), and magnetic resonance imaging (MRI) of spine and sacroiliac (SI)-joints at baseline and 1 year, in addition to clinical information Specifically, this means that these additional measures will be added to conventional treat to target: If evidence of enthesitis (power Doppler>0 in enthesis) or axial inflammation (SPARCC score ≥ 2* in SI-joint or SPARCC score ≥ 5 in presence of clinical symptoms of axial disease) on imaging the patient will progress directly to biological disease modifying antirheumatic drug in the treatment algorithm If evidence of ongoing inflammation (power Doppler>0) on ultrasound assessment of joints, tendons or enthesis, the patient will be classified as not having reached their treatment target<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sustained Remission | Sustained remission defined as a combination of Very Low Disease Activity (VLDA) at all of the time points 16, 20 and 24 months. VLDA requires all of the following to be met: Tender joint count (68) ≤ 1, swollen joint count (66) ≤ 1, Psoriasis Body Surface Area ≤ 3, Enthesitis≤ 1, Patient global assessment of disease severity VAS (0-100) ≤ 20, Pain VAS (0-100) ≤ 15 and Health Assessment Questionnaire Disability Index ≤ 0.5. | Sustained remission is defined by the patient meeting VLDA at all of 16, 20 and 24 month follow-up visits | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient global assessment of disease activity | Patient global assessment of disease activity on a 0-100 visual analogue scale (VAS), with higher scores Indicating more disease activity | 12 and 24 months | 
| Patient pain assessment | Patient pain assessment on a 0-100 visual analogue scale, with higher scores Indicating more pain | 12 and 24 months | 
| Patient fatigue assessment | Patient fatigue assessment on a 0-100 visual analogue scale, with higher scores Indicating more fatigue | 12 and 24 months | 
| 66 joint count for swollen joints | Structured 66 joint count for swollen joints | 12 and 24 months | 
| 68 joint count for tender joints | Structured 68 joint count for tender joints | 12 and 24 months | 
| Tender dactylitis count | Structured tender dactylitis count | 12 and 24 months | 
| Spondyloarthritis Research Consortium of Canada Enthesitis Index (SPARCC entheseal index) | SPARCC magnetic resonance imaging entheseal index | 12 and 24 months | 
| Body surface area of skin psoriasis | Body surface area of skin psoriasis in percentage | 12 and 24 months | 
| Modified Nail Psoriasis Severity Index (mNAPSI) | Modified Nail Psoriasis Severity Index (mNAPSI) | 12 and 24 months | 
| Physician global assessment of disease activity | Physician global assessment of disease activity on a 0-100 visual analogue scale, with higher scores Indicating more disease activity | 12 and 24 months | 
| C-reactive protein (CRP) | C-reactive protein (CRP), higher scores indicating more inflammation | 12 and 24 months | 
| Erythrocyte sedimentation rate (ESR) | Erythrocyte sedimentation rate (ESR), higher scores indicating more inflammation | 12 and 24 months | 
| Disease activity in Psoriatic arthritis Score (DAPSA) | Disease activity in Psoriatic arthritis Score (DAPSA), higher scores indicating more disease activity | 12 and 24 months | 
| Minimal Disease Activity (MDA) | Minimal Disease Activity (MDA). MDA is a composite assessment of disease activity state in PsA. It includes 7 components: tender joint count (68) ≤ 1, swollen joint count (66) ≤ 1, Psoriasis Area Severity Index ≤ 1/Body Surface Area ≤ 3, enthesitis≤ 1, patient global assessment of disease activity VAS ≤ 20, pain VAS ≤ 15 and HAQ-DI ≤ 0.5. MDA requires 5 out of 7 components to be met. | 12 and 24 months | 
| Psoriatic Arthritis Disease Activity Score (PASDAS) | Psoriatic Arthritis Disease Activity Score (PASDAS) is a composite disease activity index, with higher scores indicating more disease activity | 12 and 24 months | 
| American College of Rheumatology (ACR) 20 response | American College of Rheumatology (ACR) 20 response is defined as ≥ 20 % improvement in swollen and tender joint counts plus ≥ 20 % improvement in 3 of the 5 remaining ACR core set variables; pain VAS, physician global VAS, Health Assessment Questionnaire Disability Index (HAQ-DI) and CRP/ESR. | 12 and 24 months | 
| Structured assessment of joints by musculoskeletal ultrasound according to a predefined protocol | Structured assessment of joints by musculoskeletal ultrasound according to a predefined protocol | 12 and 24 months | 
| Structured assessment of entheses by musculoskeletal ultrasound according to a predefined protocol | Structured assessment of entheses by musculoskeletal ultrasound according to a predefined protocol | 12 and 24 months | 
| Structured assessment of tendons by musculoskeletal ultrasound according to a predefined protocol | Structured assessment of tendons by musculoskeletal ultrasound according to a predefined protocol | 12 and 24 months | 
| Health Related Quality of Life | Assessed by Short Form 36 (SF-36) questionnaire | 12 and 24 months | 
| Adverse events | Number and nature of adverse events and serious adverse events | 0-24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Imaging, Treat-to-target