Psoriatic Arthritis
Conditions
Keywords
Imaging, Treat-to-target
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
Interventions
OTHERImaging 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
OTHERConventional 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%
Sponsors
Diakonhjemmet Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Sustained Remission | Sustained remission is defined by the patient meeting VLDA at all of 16, 20 and 24 month follow-up visits | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Tender dactylitis count | 12 and 24 months | Structured tender dactylitis count |
| Health Related Quality of Life | 12 and 24 months | Assessed by Short Form 36 (SF-36) questionnaire |
| Adverse events | 0-24 months | Number and nature of adverse events and serious adverse events |
| Patient global assessment of disease activity | 12 and 24 months | Patient global assessment of disease activity on a 0-100 visual analogue scale (VAS), with higher scores Indicating more disease activity |
| Patient pain assessment | 12 and 24 months | Patient pain assessment on a 0-100 visual analogue scale, with higher scores Indicating more pain |
| Patient fatigue assessment | 12 and 24 months | Patient fatigue assessment on a 0-100 visual analogue scale, with higher scores Indicating more fatigue |
| 66 joint count for swollen joints | 12 and 24 months | Structured 66 joint count for swollen joints |
| Spondyloarthritis Research Consortium of Canada Enthesitis Index (SPARCC entheseal index) | 12 and 24 months | SPARCC magnetic resonance imaging entheseal index |
| Body surface area of skin psoriasis | 12 and 24 months | Body surface area of skin psoriasis in percentage |
| Modified Nail Psoriasis Severity Index (mNAPSI) | 12 and 24 months | Modified Nail Psoriasis Severity Index (mNAPSI) |
| 68 joint count for tender joints | 12 and 24 months | Structured 68 joint count for tender joints |
| C-reactive protein (CRP) | 12 and 24 months | C-reactive protein (CRP), higher scores indicating more inflammation |
| Erythrocyte sedimentation rate (ESR) | 12 and 24 months | Erythrocyte sedimentation rate (ESR), higher scores indicating more inflammation |
| Disease activity in Psoriatic arthritis Score (DAPSA) | 12 and 24 months | Disease activity in Psoriatic arthritis Score (DAPSA), higher scores indicating more disease activity |
| Minimal Disease Activity (MDA) | 12 and 24 months | 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) | 12 and 24 months | 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 | 12 and 24 months | 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. |
| Structured assessment of joints by musculoskeletal ultrasound according to a predefined protocol | 12 and 24 months | Structured assessment of joints 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 entheses by musculoskeletal ultrasound according to a predefined protocol |
| Structured assessment of tendons by musculoskeletal ultrasound according to a predefined protocol | 12 and 24 months | Structured assessment of tendons by musculoskeletal ultrasound according to a predefined protocol |
| Physician global assessment of disease activity | 12 and 24 months | Physician global assessment of disease activity on a 0-100 visual analogue scale, with higher scores Indicating more disease activity |
Other
| Measure | Time frame | Description |
|---|---|---|
| Joint damage assessed by radiography of hands and feet | 24 months | Assessed by the modified Sharp van der Heijde Score |
| Work Productivity and Activity Impairment Questionnaire (WPAI) | 0-24 months | Work Productivity and Activity Impairment Questionnaire (WPAI) |
| Work participation | 0-24 months | Work participation based on data from Statistics Norways's event database (FD Trygd) (social benefits) |
| Euro Quality of Life 5 Dimensions (EQ-5D) | 0-24 months | Euro Quality of Life 5 Dimensions (EQ-5D) |
| Short Form 36 (SF-36) | 0-24 months | Short Form 36 (SF-36) |
| Patient global assessment of disease activity | 0-24 months | Patient global assessment of disease activity on a 0-100 visual analogue scale, with higher scores Indicating more disease activity |
| Health Assessment Questionnaire Disability Index (HAQ-DI) | 0-24 months | Health Assessment Questionnaire Disability Index (HAQ-DI) |
| Use of hospital services | 0-24 months | Use of hospital services from The Norwegian Patient Register |
| Medication prescription | 0-24 months | Prescription of medication from The Norwegian Prescription Register (pharmaceuticals) |
| Use of primary care resources | 0-24 months | 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) |
| Use of nursing services | 0-24 months | Use of nursing services based on the municipal patient- and user register (IPLOS) database |
| Psoriatic Arthritis Impact of Disease (PsAID) | 0-24 months | Psoriatic Arthritis Impact of Disease (PsAID) |
| Patient pain assessment | 0-24 months | Patient pain assessment on a 0-100 visual analogue scale, with higher scores Indicating more pain |
| Patient fatigue assessment | 0-24 months | Patient fatigue assessment on a 0-100 visual analogue scale, with higher scores Indicating more fatigue |
| Bath Ankylosing Spondylitis Disease Activity Index | 0-24 months | Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), higher scores indicating more disease activity |
| Patient acceptable symptom state | 0-24 months | Patient acceptable symptom state (PASS) |
| 66 joint count for swollen joints | 0-24 months | 66 joint count for swollen joints |
| 68 joint count for tender joints | 0-24 months | 68 joint count for tender joints |
| Tender dactylitis count | 0-24 months | Tender dactylitis count |
| Spondyloarthritis Research Consortium of Canada Enthesitis Index (SPARCC entheseal index) | 0-24 months | SPARCC MRI entheseal index |
| Body surface area of skin psoriasis | 0-24 months | Body surface area of skin psoriasis in percentages |
| Investigator global assessment of skin psoriasis | 0-24 months | Investigator global assessment of skin psoriasis |
| Modified Nail Psoriasis Severity Index (mNAPSI) | 0-24 months | Modified Nail Psoriasis Severity Index (mNAPSI) |
| Physician global assessment of disease activity | 0-24 months | Physician global assessment of disease activity on a 0-100 visual analogue scale |
| C-reactive protein (CRP) | 0-24 months | C-reactive protein (CRP), higher scores indicating more inflammation |
| Erythrocyte sedimentation rate (ESR) | 0-24 months | Erythrocyte sedimentation rate (ESR), higher scores indicating more inflammation |
| Disease activity in Psoriatic arthritis Score (DAPSA) | 0-24 months | Disease activity in Psoriatic arthritis Score (DAPSA) |
| Minimal Disease Activity (MDA) | 0-24 months | 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) | 0-24 months | Psoriatic Arthritis Disease Activity Score (PASDAS) is a composite disease activity index, with higher scores indicating more disease activity |
| American College of Rheumatology (ACR) response | 0-24 months | American College of Rheumatology (ACR) response |
| Disease Activity score 28 (DAS-28) | 0-24 months | Disease Activity score 28 (DAS-28) |
| Inflammation assessed musculoskeletal ultrasound | 0 and 24 months | 1. Joints (as specified in protocol) 2. Entheses (as specified in protocol) 3. Tendons (as specified in protocol) 4. Peritenonitis (as specified in protocol) |
| Inflammation assessed by MRI | 12 and 24 months | MRI of total spine and sacroiliac joint, assessed by SPARCC score |
Countries
Norway
Contacts
Primary ContactSiri Lillegraven, MD, MPH, PhD
Backup ContactEven Lillejordet, MD
Outcome results
None listed