Rheumatoid ArthritisJAKPOTNCT04084223
JAKPOT (JAK Inhibitors and Predictors of Outcome in RheumaToid Arthritis)
A study testing Ultrasound in people with Rheumatoid Arthritis, run by University Hospital, Montpellier at 1 site in France.
Trial summary
Rheumatoid arthritis (RA) is a chronic, progressive autoimmune disease associated with inflammation and destruction of joints and systemic effects, which result in significant impact on patient's quality of life and function. Sustained remission or low disease activity is the target to achieve in RA management. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Rheumatoid Arthritis
- What is being tested?
- Ultrasound
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 51 participants
- Where
- 1 siteFrance
- Study dates
- 10 Oct 2019to 24 Sep 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patient ≥18 years
- 2010 (American College of Rheumatology) ACR-EULAR classification criteria for RA for ≥3 months
- Inadequate response to MTX (or other csDMARD) for ≥3 months, at stable dosage for ≥1 month
- Active disease defined by DAS28>3,2 AND presence of ≥2 US synovitis with Power-Doppler≥2,
- Starting a treatment with JAKi (baricitinib or tofacitinib),
- Patients previously treated with biologic (stopped for inadequate response or safety) could be included. Biologics will be stopped before entering in the study: Abatacept and all TNF (tumor necrosis factor) inhibitors: no use within 4 weeks before baseline visit; Rituximab: no use within 6 months before baseline visit.
- Informed signed consent
Who cannot join
- Patient not treated before by MTX (or other csDMARD). Patients with a contraindication or in whom MTX was stopped due to safety issue could be included. Patients treated by MTX will have MTX during the follow-up, others will be treated by JAKi monotherapy,
- Patients with a contraindication to baricitinib or tofacitinib (current infection, recent attenuated vaccine injection, cancer <5 years…) or treated previously with baricitinib or tofacitinib,
- Patients treated by glucocorticoids ≥10 mg/day and unstable dosage for <1 month or with ≥1 glucocorticoids injection <1 month.
- RA with Steinbrocker class IV damage status
- General exclusion criteria (pregnancy, breast feeding…)
- Refusal to participate in the study
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Added Value of Early Collected Ultrasound As Compared to Clinical Evaluation to Predict Definite Clinical Outcome and Therapeutic Response in Rheumatoid Arthritis Patients Treated by JAK Inhibitors
Rheumatoid arthritis (RA) is a chronic, progressive autoimmune disease associated with inflammation and destruction of joints and systemic effects, which result in significant impact on patient's quality of life and function.
Sustained remission or low disease activity is the target to achieve in RA management. Ultrasound (US) is an imaging technique potentially helpful at several steps of the disease. A semi-quantitative (0-3) score of synovitis combining B-mode and Power Doppler abnormalities has been developed (GLOESS), and its responsiveness has been demonstrated. Patients Reported Outcomes (PROs) are important parameters in patient perceived health and are increasingly used in clinical practice. Prediction of therapeutic response to biological and targeted synthetic DMARDs remains a challenge for clinician, due to the potential adverse events and the cost of these drugs. To date, only few clinical and biological tools usable in clinical practice have a prognostic value. US or PRO could have added value for this purpose.
Read more
Objectives :
- To determine the predictive added value of the variation of an US score to the variation of the DAS28-CRP (C-Reactive Protein) at 1 month on clinical outcome (low disease activity i.e. DAS28-CRP≤3.2) at 6 months, or on therapeutic response at 3 months (EULAR good or moderate response (DAS)), in RA patients starting a treatment with JAK (Janus Kinase) inhibitors (JAKi).
- To determine the predictive added value of the variation several PROs to the variation of the DAS28-CRP at 1 month on clinical outcome (low disease activity i.e. DAS28-CRP≤3.2) at 6 months, or on therapeutic response at 3 months (EULAR good or moderate response (DAS)), in RA patients starting a treatment with JAKi.
Read the detailed description
Ultrasound (US) is an imaging technique increasingly used in rheumatologic practice. US is a noninvasive, bedside, objective and sensitive tool for visualizing synovial inflammatory joint changes in RA that were not detected by conventional clinical examination. US has added value over clinical management of RA patients and is potentially helpful at several steps of the disease: early diagnosis of early arthritis, evaluation of disease activity, identification of poor prognostic RA, and possibly confirmation of remission status before tapering treatment. The potential role of this technique in the management of RA has been highlighted by the recent EULAR recommendations on how to use imaging in RA clinical practice. Nevertheless, only few studies have evaluated the value of US to predict clinical outcome and therapeutic response. In a Spanish longitudinal study including 42 early RA patients, the number and grade of Power-Doppler ultrasound (PDUS) synovitis were the best parameters correlated with disease activity at following visit. Since 2004, the OMERACT (Outcome Measures in Rheumatology) group has evaluated metric properties of US in RA. A semi-quantitative (0-3) score of synovitis combining B-mode and Power Doppler abnormalities was defined, the PDUS Global OMERACTEULAR Synovitis Score (GLOESS). This score recently demonstrated its responsiveness in a multicentre therapeutic trial of patients starting a treatment by abatacept, as soon as after one week of treatment. However, in this study, variation of this score until 4 months failed to demonstrate a correlation with clinical status or response as measured by DAS28-derived criteria at 6 months, suggesting that these tools evaluate different aspects of disease activity in RA and should be considered complementary in clinical practice, or maybe that DAS28 is not a sufficient stringent composite score. A similar semi-quantitative (0-3) score of tenosynovitis was developed and validated by the OMERACT. On the other hand, no study to date has demonstrated the responsiveness of this tenosynovitis score in RA. However, one study compared intra-muscular glucocorticoid or glucocorticoid administered in soft tissues and demonstrated that peri-tendinous infusions were more efficient at 3 months, both clinically and with US.
Patient-reported outcomes (PROs) are questionnaires used in clinical trials and daily care, with answers directly collected from patients. They allow the evaluation of domains that are often neglected (fatigue, quality of life, subjective disease activity, sleep disorders, etc). PROs are used as multifunctional criteria and therefore can be used as prognostic, therapeutic-evaluation or therapeutic-decision outcomes. Many studies have compared patient self-assessment and evaluation of disease activity by an experienced clinician to determine whether substituting patient assessment of disease activity is possible.
Clinical response during the first 3 months is associated with remission or low disease activity in the long term (6 to 12 months) in some studies. However, the real added value of US (or PRO) to predict medium or long term clinical outcome is not so well-known.
- Conditions
- Rheumatoid Arthritis
- Being tested
- Ultrasound
- Keywords
- JAK Inhibitors, Ultrasound, Patients Reported Outcomes (PROs), Disease activity, Predictors, Therapeutic response
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
UltrasoundOther
An Ultrasound exam (not performed in routine care) will be performed at Baseline, 1, 3 and 6 months for protocol.
All patients will also have CRP dosage (for DAS28 assessment), RAPID-3 and PROs (performed in routine care but analyzed for the study).
| Study group | Role | What they receive |
|---|---|---|
| Active RA patients group | Experimental | 64 active RA patients (DAS28>3,2 AND presence of ≥2 US synovitis with Power-Doppler≥2) with an inadequate response to methotrexate (MTX) starting a treatment with JAKi (tofacitinib ou baricitinib) will be evaluated at baseline, 1, 3 and 6 months in 5 centres.
A clinical joint assessment will be performed and CRP will be tested to calculate DAS28-CRP. Several PROs will be completed: RAPID3, HAQ, pain, and patient global assessment of disease activity on a VAS.
An US exam on 40 joints and 12 tendons will be performed by an independent investigator, looking for synovitis and tenosynovitis with B-Mode and Power Doppler. A Global US score (GLOESS) will be collected at each visit. Receives: Other: Ultrasound |
What is being measured
The primary outcome is the main question the study is designed to answer.
Disease activity
DAS28-CRP evaluated by an ultra-sound-blinded investigator (score calculated with number of painful articulations, synovitis, and C-Reactive Protein ; DAS28 result > 3,2 : moderately active rheumatoid arthritis)
Measured: 6 months
Secondary outcomes (9)
Disease activity
DAS28-CRP evaluated by a blinded investigator
Measured: 1 month
Disease activity
DAS28-CRP evaluated by a blinded investigator
Measured: 3 months
Ultra-sound activity
GLOESS-US evaluated by a blinded investigator
Measured: 1 month
Ultra-sound activity
GLOESS-US evaluated by a blinded investigator
Measured: 3 months
Ultra-sound activity
GLOESS-US evaluated by a blinded investigator
Measured: 6 months
Patient Reported Outcomes: Health assessment (RAPID3)
Health assessment evaluated by RAPID3 questionnaire (Routine Assessment of Patient Index Data 3), a validated questionnaire assessing 3 domains : physical function, pain and disease activity. To calculate RAPID-3 scores, each of the 3 individual measures (Patient Global Activity on a visual analogic scale [VAS], pain [VAS] and function were scored from 0-10 for a total of 30. High scores represent the most altered health state. Cut-off value of disease activity were defined and validated: RAPID3 ≤3: Remission; RAPID3 between 3.1 and 6.0: Low disease activity; RAPID3 between 6,1 and 12: moderate disease activity; RAPID3 >12: high disease activity.
Measured: up to 6 months
Patient Reported Outcomes: Health assessment (HAQ)
Health assessment evaluated by HAQ, a validated Health Assessment Questionnaire disability index for rhumatoid arthritis (score range from 0: no difficulties, to 3: patient disability)
Measured: up to 6 months
Patient Reported Outcomes: pain
Pain evaluated by patient with VAS (visual analog scale) from 0 to 100
Measured: up to 6 months
Patient Reported Outcomes: global health
Disease activity evaluated by patient with VAS (visual analog scale) from 0 to 100
Measured: up to 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Sep 2019
- Study start10 Oct 2019
- Primary completion24 Sep 2024
- Study completion24 Sep 2024
Why it stopped: Slower pace of enrollments
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Rheumatoid ArthritisStudies of the same condition, open and under way.
- More trials run by University Hospital, MontpellierThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 51 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Montpellier
- Sponsor type
- University, hospital or other
- Collaborators
- Centre Hospitalier Universitaire de Nīmes, University Hospital, Clermont-Ferrand, University Hospital, Bordeaux, University Hospital, Toulouse
- Responsible party
- Sponsor
- Investigators
- Gaël MOUTERDE, MD, Principal investigator, University Hospital, Montpellier
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04084223
- Sponsor's protocol ID
- RECHMPL18_0241
- Acronym
- JAKPOT
- Status last verified
- Jan 2025
- First submitted
- 18 Jul 2019
- Last updated
- 10 Jan 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Added Value of Early Collected Ultrasound As Compared to Clinical Evaluation to Predict Definite Clinical Outcome and Therapeutic Response in Rheumatoid Arthritis Patients Treated by JAK Inhibitors
- ClinicalTrials.gov ID
- NCT04084223
- Acronym / sponsor ID
- JAKPOT / RECHMPL18_0241
- Conditions
- Rheumatoid Arthritis
- Keywords
- JAK Inhibitors, Ultrasound, Patients Reported Outcomes (PROs), Disease activity, Predictors, Therapeutic response
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Slower pace of enrollments
- Enrolment
- 51 participants (actual)
- Lead sponsor
- University Hospital, MontpellierUniversity, hospital or other
- Collaborators
- Centre Hospitalier Universitaire de Nīmes, University Hospital, Clermont-Ferrand, University Hospital, Bordeaux, University Hospital, Toulouse
- Study start
- 10 Oct 2019 (actual)
- Primary completion
- 24 Sep 2024 (actual)
- Study completion
- 24 Sep 2024 (actual)
- First posted
- 10 Sep 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Rheumatoid arthritis (RA) is a chronic, progressive autoimmune disease associated with inflammation and destruction of joints and systemic effects, which result in significant impact on patient's quality of life and function.
Sustained remission or low disease activity is the target to achieve in RA management. Ultrasound (US) is an imaging technique potentially helpful at several steps of the disease. A semi-quantitative (0-3) score of synovitis combining B-mode and Power Doppler abnormalities has been developed (GLOESS), and its responsiveness has been demonstrated. Patients Reported Outcomes (PROs) are important parameters in patient perceived health and are increasingly used in clinical practice. Prediction of therapeutic response to biological and targeted synthetic DMARDs remains a challenge for clinician, due to the potential adverse events and the cost of these drugs. To date, only few clinical and biological tools usable in clinical practice have a prognostic value. US or PRO could have added value for this purpose.
Objectives :
- To determine the predictive added value of the variation of an US score to the variation of the DAS28-CRP (C-Reactive Protein) at 1 month on clinical outcome (low disease activity i.e. DAS28-CRP≤3.2) at 6 months, or on therapeutic response at 3 months (EULAR good or moderate response (DAS)), in RA patients starting a treatment with JAK (Janus Kinase) inhibitors (JAKi).
- To determine the predictive added value of the variation several PROs to the variation of the DAS28-CRP at 1 month on clinical outcome (low disease activity i.e. DAS28-CRP≤3.2) at 6 months, or on therapeutic response at 3 months (EULAR good or moderate response (DAS)), in RA patients starting a treatment with JAKi.
Detailed description
Ultrasound (US) is an imaging technique increasingly used in rheumatologic practice. US is a noninvasive, bedside, objective and sensitive tool for visualizing synovial inflammatory joint changes in RA that were not detected by conventional clinical examination. US has added value over clinical management of RA patients and is potentially helpful at several steps of the disease: early diagnosis of early arthritis, evaluation of disease activity, identification of poor prognostic RA, and possibly confirmation of remission status before tapering treatment. The potential role of this technique in the management of RA has been highlighted by the recent EULAR recommendations on how to use imaging in RA clinical practice. Nevertheless, only few studies have evaluated the value of US to predict clinical outcome and therapeutic response. In a Spanish longitudinal study including 42 early RA patients, the number and grade of Power-Doppler ultrasound (PDUS) synovitis were the best parameters correlated with disease activity at following visit. Since 2004, the OMERACT (Outcome Measures in Rheumatology) group has evaluated metric properties of US in RA. A semi-quantitative (0-3) score of synovitis combining B-mode and Power Doppler abnormalities was defined, the PDUS Global OMERACTEULAR Synovitis Score (GLOESS). This score recently demonstrated its responsiveness in a multicentre therapeutic trial of patients starting a treatment by abatacept, as soon as after one week of treatment. However, in this study, variation of this score until 4 months failed to demonstrate a correlation with clinical status or response as measured by DAS28-derived criteria at 6 months, suggesting that these tools evaluate different aspects of disease activity in RA and should be considered complementary in clinical practice, or maybe that DAS28 is not a sufficient stringent composite score. A similar semi-quantitative (0-3) score of tenosynovitis was developed and validated by the OMERACT. On the other hand, no study to date has demonstrated the responsiveness of this tenosynovitis score in RA. However, one study compared intra-muscular glucocorticoid or glucocorticoid administered in soft tissues and demonstrated that peri-tendinous infusions were more efficient at 3 months, both clinically and with US.
Patient-reported outcomes (PROs) are questionnaires used in clinical trials and daily care, with answers directly collected from patients. They allow the evaluation of domains that are often neglected (fatigue, quality of life, subjective disease activity, sleep disorders, etc). PROs are used as multifunctional criteria and therefore can be used as prognostic, therapeutic-evaluation or therapeutic-decision outcomes. Many studies have compared patient self-assessment and evaluation of disease activity by an experienced clinician to determine whether substituting patient assessment of disease activity is possible.
Clinical response during the first 3 months is associated with remission or low disease activity in the long term (6 to 12 months) in some studies. However, the real added value of US (or PRO) to predict medium or long term clinical outcome is not so well-known.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Active RA patients group | Experimental | Other: Ultrasound64 active RA patients (DAS28>3,2 AND presence of ≥2 US synovitis with Power-Doppler≥2) with an inadequate response to methotrexate (MTX) starting a treatment with JAKi (tofacitinib ou baricitinib) will be evaluated at baseline, 1, 3 and 6 months in 5 centres. A clinical joint assessment will be performed and CRP will be tested to calculate DAS28-CRP. Several PROs will be completed: RAPID3, HAQ, pain, and patient global assessment of disease activity on a VAS. An US exam on 40 joints and 12 tendons will be performed by an independent investigator, looking for synovitis and tenosynovitis with B-Mode and Power Doppler. A Global US score (GLOESS) will be collected at each visit. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Patient ≥18 years
- 2010 (American College of Rheumatology) ACR-EULAR classification criteria for RA for ≥3 months
- Inadequate response to MTX (or other csDMARD) for ≥3 months, at stable dosage for ≥1 month
- Active disease defined by DAS28>3,2 AND presence of ≥2 US synovitis with Power-Doppler≥2,
- Starting a treatment with JAKi (baricitinib or tofacitinib),
Key exclusion criteria (6 listed)
- Patient not treated before by MTX (or other csDMARD). Patients with a contraindication or in whom MTX was stopped due to safety issue could be included. Patients treated by MTX will have MTX during the follow-up, others will be treated by JAKi monotherapy,
- Patients with a contraindication to baricitinib or tofacitinib (current infection, recent attenuated vaccine injection, cancer <5 years…) or treated previously with baricitinib or tofacitinib,
- Patients treated by glucocorticoids ≥10 mg/day and unstable dosage for <1 month or with ≥1 glucocorticoids injection <1 month.
- RA with Steinbrocker class IV damage status
- General exclusion criteria (pregnancy, breast feeding…)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| UltrasoundAn Ultrasound exam (not performed in routine care) will be performed at Baseline, 1, 3 and 6 months for protocol. All patients will also have CRP dosage (for DAS28 assessment), RAPID-3 and PROs (performed in routine care but analyzed for the study). | Other | Active RA patients group |
Primary outcome
Disease activity
Time frame: 6 months
DAS28-CRP evaluated by an ultra-sound-blinded investigator (score calculated with number of painful articulations, synovitis, and C-Reactive Protein ; DAS28 result > 3,2 : moderately active rheumatoid arthritis)
9 secondary outcomes
Disease activity
Time frame: 1 month
Disease activity
Time frame: 3 months
Ultra-sound activity
Time frame: 1 month
Ultra-sound activity
Time frame: 3 months
Ultra-sound activity
Time frame: 6 months
Patient Reported Outcomes: Health assessment (RAPID3)
Time frame: up to 6 months
Patient Reported Outcomes: Health assessment (HAQ)
Time frame: up to 6 months
Patient Reported Outcomes: pain
Time frame: up to 6 months
Patient Reported Outcomes: global health
Time frame: up to 6 months
Results and safety
The study was stopped early (reason given: Slower pace of enrollments). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jan 2025.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gaël MOUTERDE, MD principal investigator
University Hospital, Montpellier
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Ultrasound in people with Rheumatoid Arthritis, run by University Hospital, Montpellier at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 10 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was stopped early (reason given: Slower pace of enrollments). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Disease activity (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jan 2025.