Arthritis, Juvenile Idiopathic, Polyarticular Juvenile Rheumatoid Arthritis
Conditions
Keywords
Joint Diseases, Juvenile Arthritis, treatment, biologic therapy, comparative effectiveness
Brief summary
STOP-JIA is a PCORI funded prospective observational study which compared the clinical effectiveness and impact on patient reported outcomes of 3 Childhood Arthritis & Rheumatology Research Alliance (CARRA) consensus derived treatment strategies (CTPs) in new-onset polyarticular JIA (pJIA) patients to answer the critical question of when is the best time to begin biologic medications to achieve the optimal clinical and patient reported outcomes. Because the CARRA Registry will be used for data collection, all patients will be enrolled in the CARRA Registry. The standard of care treatments are chosen by the treating physician and patient/caregiver and are not randomized.
Detailed description
STOP-JIA is a prospective, observational study comparing the clinical effectiveness and impact on patient reported outcomes of 3 different treatment strategies (CTPs) in new onset pJIA patients to answer the critical question of when to start biologic medications. All participants will be enrolled in the CARRA Registry and started on one of the CTPs, which will be decided by the treating physician and patient/caregiver. Subjects will be enrolled at one of 60 participating CARRA sites across the US and Canada. Total anticipated enrollment was 400 and this was completed in 9/19. Specific Aim 1: To compare the clinical effectiveness of different strategies (CTPs) for using biologic medications in achieving clinically inactive disease (CID) at 12 months in new-onset pJIA. Three common strategies that differ in the timing of biologic medication introduction will be compared: 1) Step-Up: disease modifying anti-rheumatic drug (DMARD) monotherapy stepping up by addition of a biologic medication if needed; 2) Early Combination: DMARD plus biologic medication at treatment onset; and 3) Biologic First: biologic medication monotherapy at treatment onset. Hypothesis 1: A significantly higher proportion of children started on a biologic medication at onset (CTP 2 or 3) will achieve CID after 12 months of therapy compared to standard therapy (CTP 1). Specific Aim 2: To compare patient and caregiver reported outcomes between the different strategies. Hypothesis 2: There will be statistically significant differences in patient/caregiver reported outcomes (PROs) between treatment strategies that can inform future patients and providers in selecting optimal treatments. The CARRA Registry will be housed at CARRA's clinical and data coordinating center, Duke Clinical Research Institute (DCRI). The CARRA Registry Protocol documents that the CARRA Registry fulfills all PCOR standards for registries. STOP-JIA will utilize data collection, storage, and management processes, systems requirements, and security processes already established for the CARRA Registry at DCRI. STOP-JIA used Web-based electronic CRFs (eCRFs) developed for the CARRA Registry that are already familiar to site personnel. The eCRF platform, RAVE, is 21CFR part11 compliant and meets regulatory requirements. Database and Web servers are secured by a firewall and through controlled physical access. eCRFs will be monitored for completeness, accuracy, and attention to detail throughout the study by DCRI data and site management teams using processes developed for the CARRA Registry and consistent with DCRI's internal SOPs. Use of electronic data capture will allow for immediate prompts/queries if entered values are out of expected ranges or there are incomplete data fields. The design of the data collection instrument will allow centers to record a planned assessment of a patient was missed and to enter any known reasons for the assessment being missed. DCRI will regularly provide reports detailing data completion metrics to the sites. Stakeholder engagement is also an important aspect of this study, and patients/caregivers as well as other stakeholders are serving as research partners and advisors in this study.
Interventions
None listed
Sponsors
Patient-Centered Outcomes Research Institute
Childhood Arthritis and Rheumatology Research Alliance
Duke Clinical Research Institute
Seattle Children's Hospital
Children's Hospital of Philadelphia
Boston Children's Hospital
The Hospital for Sick Children
University Health Network, Toronto
Hackensack Meridian Health
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
2 Years to 18 Years
Healthy volunteers
No
Inclusion criteria
* Age less than 19 at baseline (if 18 or older, agrees to be followed for at least one year) * Diagnosis of Arthritis per ACR definition. * Arthritis present in one joint for a least six weeks * At least 5 active joints at baseline * Contraception if sexually active (male and female) May have any of the following: * RF+ polyarticular JIA * RF- polyarticular JIA * Extended oligoarticular JIA * Psoriatic JIA * Enthesitis related JIA * Undifferentiated JIA * Psoriasis * Sacroiliitis * Uveitis * Enthesitis * Prior treatments permitted: * NSAIDS * Hydroxychloroquine * Intraocular / topical / intraarticular glucocorticoids * IV or PO steroids if one of the below criteria are met: --If treated ≤ 3 months prior to baseline: treatment cannot exceed 2 weeks --If treated \> 3 months prior to baseline: any treatment course is permitted as long as treatment was completed 90 days prior to baseline * Methotrexate started no more than 1 month prior to the baseline visit * Biologics - received only 1 dose within 1 week of the baseline visit
Exclusion criteria
* Features consistent with systemic JIA * Treatment with any medications for JIA aside from those listed above. * Known inflammatory bowel disease * Known celiac disease * Known Trisomy 21 * History of or current malignancy * Concomitant serious active or recurrent chronic bacterial, fungal or viral infection * Significant organ system disorder limiting use of treatments for pJIA * Live vaccine within a month prior to baseline
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Clinically Inactive Disease (CID) Off Glucocorticoids | 12 months after baseline | This is a provisional criteria which describes a state of complete disease inactivity in Juvenile Idiopathic Arthritis (JIA). We will assess the proportion of patients achieving CID off glucocorticoids in each treatment arm. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Comparison of PROMIS Pain and Mobility Scores Between the 3 Consensus Treatment Plan Groups | 12 months after baseline | The Patient Reported Outcomes Measurement Information System (PROMIS) pain interference and mobility scores will be compared between the 3 CTP groups. Pain interference scores range from 0-100 and higher scores are worse. Mobility scores also range from 0-100 and higher scores are better. |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Step-Up CTP Consensus Treatment Plan where subjects begin non biologic DMARD (methotrexate, sulfasalazine, or leflunomide) stepping up to biologic if not improved by 3 months | 257 |
| Early Combination CTP Consensus Treatment Plan where patients start a DMARD(methotrexate, sulfasalazine, or leflunomide) and biologic treatment within one month of each other. | 100 |
| Biologic Frist CTP Consensus Treatment Plan where patients begin Biologic treatment | 43 |
| Total | 400 |
Baseline characteristics
| Characteristic | Step-Up CTP | Early Combination CTP | Biologic Frist CTP | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 257 Participants | 99 Participants | 43 Participants | 399 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Age, Continuous | 11.07 years | 11.38 years | 12.34 years | 11.28 years |
| Clinical Juvenile Arthritis Disease Activity Score | 17.08 units on a scale STANDARD_DEVIATION 4.55 | 20.18 units on a scale STANDARD_DEVIATION 4.37 | 19.05 units on a scale STANDARD_DEVIATION 4.29 | 18.08 units on a scale STANDARD_DEVIATION 4.67 |
| Race (NIH/OMB) American Indian or Alaska Native | 3 Participants | 0 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) Asian | 15 Participants | 4 Participants | 2 Participants | 21 Participants |
| Race (NIH/OMB) Black or African American | 15 Participants | 5 Participants | 3 Participants | 23 Participants |
| Race (NIH/OMB) More than one race | 9 Participants | 3 Participants | 5 Participants | 17 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 27 Participants | 19 Participants | 6 Participants | 52 Participants |
| Race (NIH/OMB) White | 188 Participants | 68 Participants | 27 Participants | 283 Participants |
| Region of Enrollment Canada | 32 participants | 2 participants | 1 participants | 35 participants |
| Region of Enrollment United States | 225 participants | 98 participants | 42 participants | 365 participants |
| Sex: Female, Male Female | 192 Participants | 75 Participants | 27 Participants | 294 Participants |
| Sex: Female, Male Male | 65 Participants | 25 Participants | 16 Participants | 106 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 257 | 0 / 100 | 0 / 43 |
| other Total, other adverse events | 19 / 257 | 5 / 100 | 1 / 43 |
| serious Total, serious adverse events | 12 / 257 | 3 / 100 | 5 / 43 |
Outcome results
Primary
Percentage of Participants With Clinically Inactive Disease (CID) Off Glucocorticoids
This is a provisional criteria which describes a state of complete disease inactivity in Juvenile Idiopathic Arthritis (JIA). We will assess the proportion of patients achieving CID off glucocorticoids in each treatment arm.
Time frame: 12 months after baseline
Population: Subjects are children and adolescents between the ages of 2 and 18 who are newly diagnosed with a polyarticular form of JIA and treated for 12 months with one of the consensus treatment plans.~328 participants had complete data for the primary CID endpoint at 12 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Step-Up Consensus Treatment Plan (CTP) | Percentage of Participants With Clinically Inactive Disease (CID) Off Glucocorticoids | 32.3 percentage of participants achieving CID |
| Early Combination CTP | Percentage of Participants With Clinically Inactive Disease (CID) Off Glucocorticoids | 37.2 percentage of participants achieving CID |
| Biologic First CTP | Percentage of Participants With Clinically Inactive Disease (CID) Off Glucocorticoids | 24.2 percentage of participants achieving CID |
p-value: >0.0595% CI: [-3.2, 23.8]Propensity weighted regression model
Secondary
Comparison of PROMIS Pain and Mobility Scores Between the 3 Consensus Treatment Plan Groups
The Patient Reported Outcomes Measurement Information System (PROMIS) pain interference and mobility scores will be compared between the 3 CTP groups. Pain interference scores range from 0-100 and higher scores are worse. Mobility scores also range from 0-100 and higher scores are better.
Time frame: 12 months after baseline
Population: Same description as above for the population for the primary outcome
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Step-Up Consensus Treatment Plan (CTP) | Comparison of PROMIS Pain and Mobility Scores Between the 3 Consensus Treatment Plan Groups | Pain Interference | 53.1 score on a scale | Standard Deviation 10 |
| Step-Up Consensus Treatment Plan (CTP) | Comparison of PROMIS Pain and Mobility Scores Between the 3 Consensus Treatment Plan Groups | Mobility | 38.6 score on a scale | Standard Deviation 10.3 |
| Early Combination CTP | Comparison of PROMIS Pain and Mobility Scores Between the 3 Consensus Treatment Plan Groups | Pain Interference | 55.5 score on a scale | Standard Deviation 9.2 |
| Early Combination CTP | Comparison of PROMIS Pain and Mobility Scores Between the 3 Consensus Treatment Plan Groups | Mobility | 35.8 score on a scale | Standard Deviation 9.1 |
| Biologic First CTP | Comparison of PROMIS Pain and Mobility Scores Between the 3 Consensus Treatment Plan Groups | Pain Interference | 55.9 score on a scale | Standard Deviation 9.3 |
| Biologic First CTP | Comparison of PROMIS Pain and Mobility Scores Between the 3 Consensus Treatment Plan Groups | Mobility | 37.5 score on a scale | Standard Deviation 9.1 |
p-value: 0.04Mixed Models Analysis