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

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

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.

Conventional treat-to-target follow-up strategy with structured clinical assessment of disease activity

Imaging informed treat-to-target follow-up strategy with both structured clinical assessment of disease activity and structured imaging assessment of disease activity.

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

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%

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

Patient global assessment of disease activity on a 0-100 visual analogue scale (VAS), with higher scores Indicating more disease activity

Patient fatigue assessment on a 0-100 visual analogue scale, with higher scores Indicating more fatigue

Physician global assessment of disease activity on a 0-100 visual analogue scale, with higher scores Indicating more disease activity

Disease activity in Psoriatic arthritis Score (DAPSA), higher scores indicating more disease activity

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.

Psoriatic Arthritis Disease Activity Score (PASDAS) is a composite disease activity index, with higher scores indicating more disease activity

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.

Patient global assessment of disease activity on a 0-100 visual analogue scale, with higher scores Indicating more disease activity

Patient fatigue assessment on a 0-100 visual analogue scale, with higher scores Indicating more fatigue

Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), higher scores indicating more disease activity

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.

Psoriatic Arthritis Disease Activity Score (PASDAS) is a composite disease activity index, with higher scores indicating more disease activity

Joints (as specified in protocol) Entheses (as specified in protocol) Tendons (as specified in protocol) Peritenonitis (as specified in protocol)

Work participation based on data from Statistics Norways's event database (FD Trygd) (social benefits)

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)

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