Clinical trial NCT05291819: Imaging Treat-to-target Strategy vs Conventional Treat-to-target Strategy in Psoriatic Arthritis
Official title: A NORwegian Randomized Strategy Trial in PsoRiatic Arthritis: ImagiNg Treat-to-target vs Conventional Treat-to-target
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Psoriatic Arthritis
Keywords: Imaging
Treat-to-target
Lead sponsor: Diakonhjemmet Hospital
Sponsor class: OTHER
First posted: 2022-03-23
Enrollment: 202
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: TREATMENT

Brief summary: 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: 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

Eligibility criteria: Inclusion Criteria:

1. Adult (\>18 years of age)
2. Clinical diagnosis of PsA
3. 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)
4. Fulfillment of CASPAR criteria for PsA

Exclusion Criteria:

1. Verified arthritis \>1 year prior to inclusion
2. Previous DMARD treatment for PsA
3. Systemic glucocorticoid use within the last 3 months
4. Local glucocorticoid injections within the last 4 weeks
5. 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.
6. 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.
7. Any other medical condition that according to the treated physician and/or local guidelines makes adherence to treatment protocol impossible
8. 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
9. Abnormal liver function (defined as Aspartate Transaminase (AST) and/or Alanine Transaminase (ALT) \>1.5 x upper normal limit), active or recent hepatitis
10. Significant anemia, leukopenia and/or thrombocytopenia
11. Inadequate birth control, pregnancy, and/or breastfeeding (current at screening or planned within the duration of the study)
12. Contraindications to magnetic resonance imaging
13. Severe psychiatric or mental disorders, alcohol abuse or other substance abuse, language barriers or other factors which makes adherence to the study protocol impossible
14. Established or suspected widespread-pain syndrome/fibromyalgia

Primary outcomes:
measure: Sustained Remission
timeFrame: Sustained remission is defined by the patient meeting VLDA at all of 16, 20 and 24 month follow-up visits
Secondary outcomes:
measure: Patient global assessment of disease activity
timeFrame: 12 and 24 months
measure: Patient pain assessment
timeFrame: 12 and 24 months
measure: Patient fatigue assessment
timeFrame: 12 and 24 months
measure: 66 joint count for swollen joints
timeFrame: 12 and 24 months
measure: 68 joint count for tender joints
timeFrame: 12 and 24 months
measure: Tender dactylitis count
timeFrame: 12 and 24 months
measure: Spondyloarthritis Research Consortium of Canada Enthesitis Index (SPARCC entheseal index)
timeFrame: 12 and 24 months
measure: Body surface area of skin psoriasis
timeFrame: 12 and 24 months
measure: Modified Nail Psoriasis Severity Index (mNAPSI)
timeFrame: 12 and 24 months
measure: Physician global assessment of disease activity
timeFrame: 12 and 24 months
measure: C-reactive protein (CRP)
timeFrame: 12 and 24 months
measure: Erythrocyte sedimentation rate (ESR)
timeFrame: 12 and 24 months
measure: Disease activity in Psoriatic arthritis Score (DAPSA)
timeFrame: 12 and 24 months
measure: Minimal Disease Activity (MDA)
timeFrame: 12 and 24 months
measure: Psoriatic Arthritis Disease Activity Score (PASDAS)
timeFrame: 12 and 24 months
measure: American College of Rheumatology (ACR) 20 response
timeFrame: 12 and 24 months
measure: Structured assessment of joints by musculoskeletal ultrasound according to a predefined protocol
timeFrame: 12 and 24 months
measure: Structured assessment of entheses by musculoskeletal ultrasound according to a predefined protocol
timeFrame: 12 and 24 months
measure: Structured assessment of tendons by musculoskeletal ultrasound according to a predefined protocol
timeFrame: 12 and 24 months
measure: Health Related Quality of Life
timeFrame: 12 and 24 months
measure: Adverse events
timeFrame: 0-24 months
Other outcomes:
measure: Patient global assessment of disease activity
timeFrame: 0-24 months
measure: Patient pain assessment
timeFrame: 0-24 months
measure: Patient fatigue assessment
timeFrame: 0-24 months
measure: Bath Ankylosing Spondylitis Disease Activity Index
timeFrame: 0-24 months
measure: Patient acceptable symptom state
timeFrame: 0-24 months
measure: 66 joint count for swollen joints
timeFrame: 0-24 months
measure: 68 joint count for tender joints
timeFrame: 0-24 months
measure: Tender dactylitis count
timeFrame: 0-24 months
measure: Spondyloarthritis Research Consortium of Canada Enthesitis Index (SPARCC entheseal index)
timeFrame: 0-24 months
measure: Body surface area of skin psoriasis
timeFrame: 0-24 months
measure: Investigator global assessment of skin psoriasis
timeFrame: 0-24 months
measure: Modified Nail Psoriasis Severity Index (mNAPSI)
timeFrame: 0-24 months
measure: Physician global assessment of disease activity
timeFrame: 0-24 months
measure: C-reactive protein (CRP)
timeFrame: 0-24 months
measure: Erythrocyte sedimentation rate (ESR)
timeFrame: 0-24 months
measure: Disease activity in Psoriatic arthritis Score (DAPSA)
timeFrame: 0-24 months
measure: Minimal Disease Activity (MDA)
timeFrame: 0-24 months
measure: Psoriatic Arthritis Disease Activity Score (PASDAS)
timeFrame: 0-24 months
measure: American College of Rheumatology (ACR) response
timeFrame: 0-24 months
measure: Disease Activity score 28 (DAS-28)
timeFrame: 0-24 months
measure: Inflammation assessed musculoskeletal ultrasound
timeFrame: 0 and 24 months
measure: Inflammation assessed by MRI
timeFrame: 12 and 24 months
measure: Joint damage assessed by radiography of hands and feet
timeFrame: 24 months
measure: Work Productivity and Activity Impairment Questionnaire (WPAI)
timeFrame: 0-24 months
measure: Work participation
timeFrame: 0-24 months
measure: Euro Quality of Life 5 Dimensions (EQ-5D)
timeFrame: 0-24 months
measure: Short Form 36 (SF-36)
timeFrame: 0-24 months
measure: Psoriatic Arthritis Impact of Disease (PsAID)
timeFrame: 0-24 months
measure: Health Assessment Questionnaire Disability Index (HAQ-DI)
timeFrame: 0-24 months
measure: Use of hospital services
timeFrame: 0-24 months
measure: Medication prescription
timeFrame: 0-24 months
measure: Use of primary care resources
timeFrame: 0-24 months
measure: Use of nursing services
timeFrame: 0-24 months
Locations:
city: Bergen
country: Norway
facility: Department of Rheumatology, Haukeland University Hospital, Helse Bergen HF
city: Drammen
country: Norway
facility: Department of Rheumatology, Drammen Hospital, Vestre Viken HF
city: Førde
country: Norway
facility: Helse Førde
city: Haugesund
country: Norway
facility: Haugesunds Sanitetsforening Revmatismesykehus
city: Kristiansand
country: Norway
facility: Sørlandet Sykehus
city: Lillehammer
country: Norway
facility: Revmatismesykehuset AS
city: Mo i Rana
country: Norway
facility: Helgelandssykehuset, Mo i Rana
city: Oslo
country: Norway
facility: Department of Rheumatology, Diakonhjemmet Hospital
city: Sandvika
country: Norway
facility: Martina Hansens Hospital AS
city: Tromsø
country: Norway
facility: University Hospital of Northern Norway
city: Trondheim
country: Norway
facility: Department of Rheumatology, St Olavs Hospital HF
city: Ålesund
country: Norway
facility: Department of Rheumatology, Helse Møre og Romsdal HF
Study officials:
affiliation: Diakonhjemmet
name: Siri Lillegraven, MD, MPH, PhD
role: PRINCIPAL_INVESTIGATOR
References: