Imaging Treat-to-target Strategy vs Conventional Treat-to-target Strategy in Psoriatic Arthritis (NOR-SPRINT)

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

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

Study Overview

• Status: Recruiting
• Conditions: Psoriatic Arthritis
• Intervention / Treatment: Other: Conventional treat-to-target; Other: Imaging informed treat-to-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

• Study Type: Interventional
• Enrollment (Estimated): 202
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Siri Lillegraven, MD, MPH, PhD; Phone Number: +4722451500; Email: siri.lillegraven@diakonsyk.no
• Study Contact Backup: Name: Even Lillejordet, MD; Email: even.lillejordet@diakonsyk.no

Study Locations

• Norway
  • Bergen, Norway, 5021
    • Recruiting
    • Department of Rheumatology, Haukeland University Hospital, Helse Bergen HF
    • Contact: Bjørg-Tilde Fevang, MD PhD
  • Drammen, Norway, 3004
    • Recruiting
    • Department of Rheumatology, Drammen Hospital, Vestre Viken HF
    • Contact: Ada S. Wierød, MD
  • Førde, Norway
    • Recruiting
    • Helse Førde
    • Contact: Anja Myhre Hjelle, MD, PhD
  • Haugesund, Norway, 5504
    • Recruiting
    • Haugesunds Sanitetsforening Revmatismesykehus
    • Contact: Mathias M Braaten, MD
  • Kristiansand, Norway
    • Recruiting
    • Sørlandet Sykehus
    • Contact: Jintana B Andersen, MD PhD
  • Lillehammer, Norway
    • Recruiting
    • Revmatismesykehuset AS
    • Contact: Yi Hu, MD, PhD; Email: Yi.Hu@revmatismesykehuset.no
  • Mo i Rana, Norway, 8613
    • Recruiting
    • Helgelandssykehuset, Mo i Rana
    • Contact: Inger M Hansen, MD
  • Oslo, Norway, 0319
    • Recruiting
    • Department of Rheumatology, Diakonhjemmet Hospital
    • Contact: Even Lillejordet, MD; Phone Number: +22451500; Email: even.lillejordet@diakonsyk.no
  • Sandvika, Norway, 1306
    • Recruiting
    • Martina Hansens Hospital AS
    • Contact: Annicken Slagsvold, MD
  • Tromsø, Norway
    • Recruiting
    • University Hospital of Northern Norway
    • Contact: Gunnstein Bakland, MD, PhD
  • Trondheim, Norway, 7006
    • Recruiting
    • Department of Rheumatology, St Olavs Hospital HF
    • Contact: Agnete Malm Gulati, MD, PhD
  • Ålesund, Norway, 6026
    • Recruiting
    • Department of Rheumatology, Helse Møre og Romsdal HF
    • Contact: Maud-Kristine Aga Ljoså, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Conventional treat-to-target; Conventional treat-to-target follow-up strategy with structured clinical assessment of disease activity	Other: Conventional treat-to-target; 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%
Experimental: Imaging informed treat-to-target; 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; 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

What is the study measuring?

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
Adverse events	Number and nature of adverse events and serious adverse events	0-24 months
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

Other 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, with higher scores Indicating more disease activity	0-24 months
Patient pain assessment	Patient pain assessment on a 0-100 visual analogue scale, with higher scores Indicating more pain	0-24 months
Patient fatigue assessment	Patient fatigue assessment on a 0-100 visual analogue scale, with higher scores Indicating more fatigue	0-24 months
Bath Ankylosing Spondylitis Disease Activity Index	Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), higher scores indicating more disease activity	0-24 months
Patient acceptable symptom state	Patient acceptable symptom state (PASS)	0-24 months
66 joint count for swollen joints	66 joint count for swollen joints	0-24 months
68 joint count for tender joints	68 joint count for tender joints	0-24 months
Tender dactylitis count	Tender dactylitis count	0-24 months
Spondyloarthritis Research Consortium of Canada Enthesitis Index (SPARCC entheseal index)	SPARCC MRI entheseal index	0-24 months
Body surface area of skin psoriasis	Body surface area of skin psoriasis in percentages	0-24 months
Investigator global assessment of skin psoriasis	Investigator global assessment of skin psoriasis	0-24 months
Modified Nail Psoriasis Severity Index (mNAPSI)	Modified Nail Psoriasis Severity Index (mNAPSI)	0-24 months
Physician global assessment of disease activity	Physician global assessment of disease activity on a 0-100 visual analogue scale	0-24 months
C-reactive protein (CRP)	C-reactive protein (CRP), higher scores indicating more inflammation	0-24 months
Erythrocyte sedimentation rate (ESR)	Erythrocyte sedimentation rate (ESR), higher scores indicating more inflammation	0-24 months
Disease activity in Psoriatic arthritis Score (DAPSA)	Disease activity in Psoriatic arthritis Score (DAPSA)	0-24 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.	0-24 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	0-24 months
American College of Rheumatology (ACR) response	American College of Rheumatology (ACR) response	0-24 months
Disease Activity score 28 (DAS-28)	Disease Activity score 28 (DAS-28)	0-24 months
Inflammation assessed musculoskeletal ultrasound	Joints (as specified in protocol); Entheses (as specified in protocol); Tendons (as specified in protocol); Peritenonitis (as specified in protocol)	0 and 24 months
Inflammation assessed by MRI	MRI of total spine and sacroiliac joint, assessed by SPARCC score	12 and 24 months
Joint damage assessed by radiography of hands and feet	Assessed by the modified Sharp van der Heijde Score	24 months
Work Productivity and Activity Impairment Questionnaire (WPAI)	Work Productivity and Activity Impairment Questionnaire (WPAI)	0-24 months
Work participation	Work participation based on data from Statistics Norways's event database (FD Trygd) (social benefits)	0-24 months
Euro Quality of Life 5 Dimensions (EQ-5D)	Euro Quality of Life 5 Dimensions (EQ-5D)	0-24 months
Short Form 36 (SF-36)	Short Form 36 (SF-36)	0-24 months
Psoriatic Arthritis Impact of Disease (PsAID)	Psoriatic Arthritis Impact of Disease (PsAID)	0-24 months
Health Assessment Questionnaire Disability Index (HAQ-DI)	Health Assessment Questionnaire Disability Index (HAQ-DI)	0-24 months
Use of hospital services	Use of hospital services from The Norwegian Patient Register	0-24 months
Medication prescription	Prescription of medication from The Norwegian Prescription Register (pharmaceuticals)	0-24 months
Use of primary care resources	Use of primary care resources based on data from Norway Control and Payment of Health Reimbursement (KUHR) database (primary care services) (d) Municipal patient- and user register (IPLOS) database (nursing services)	0-24 months
Use of nursing services	Use of nursing services based on the municipal patient- and user register (IPLOS) database	0-24 months

Collaborators and Investigators

• Sponsor: Diakonhjemmet Hospital
• Investigators: Principal Investigator: Siri Lillegraven, MD, MPH, PhD, Diakonhjemmet

Study record dates

Study Major Dates

• Study Start (Actual): March 14, 2022
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: March 2, 2022
• First Submitted That Met QC Criteria: March 22, 2022
• First Posted (Actual): March 23, 2022

Study Record Updates

• Last Update Posted (Actual): October 4, 2024
• Last Update Submitted That Met QC Criteria: October 3, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Imaging; Treat-to-target
• Additional Relevant MeSH Terms: Skin Diseases; Joint Diseases; Musculoskeletal Diseases; Skin Diseases, Papulosquamous; Spinal Diseases; Bone Diseases; Spondylarthropathies; Spondylarthritis; Spondylitis; Psoriasis; Arthritis; Arthritis, Psoriatic
• Other Study ID Numbers: NOR-SPRINT protocol ver4_1

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No