Clinical trial NCT02593006: Start Time Optimization of Biologics in Polyarticular JIA
Official title: Start Time Optimization of Biologics in Polyarticular JIA
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Polyarticular Juvenile Rheumatoid Arthritis
Arthritis, Juvenile Idiopathic
Keywords: Joint Diseases
Juvenile Arthritis
treatment
biologic therapy
comparative effectiveness
Lead sponsor: Hackensack Meridian Health
Sponsor class: OTHER
Collaborators: name: Patient-Centered Outcomes Research Institute
name: Childhood Arthritis and Rheumatology Research Alliance
name: Duke Clinical Research Institute
name: Seattle Children's Hospital
name: Children's Hospital of Philadelphia
name: Boston Children's Hospital
name: The Hospital for Sick Children
name: University Health Network, Toronto
First posted: 2015-10-30
Enrollment: 400
Sex: ALL
Minimum age (years): 2
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Children with new onset, untreated Poly JIA enrolled in the CARRA Registry.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Percentage of Participants With Clinically Inactive Disease (CID) Off Glucocorticoids
timeFrame: 12 months after baseline
Secondary outcomes:
measure: Comparison of PROMIS Pain and Mobility Scores Between the 3 Consensus Treatment Plan Groups
timeFrame: 12 months after baseline
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Palo Alto
country: United States
facility: Stanford University Medical Center
state: California
city: San Diego
country: United States
facility: Rady Children's Hospital-San Diego
state: California
city: San Francisco
country: United States
facility: University of California at San Francisco Medical Center
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Hartford
country: United States
facility: Connecticut Children's Medical Center
state: Connecticut
city: Gainesville
country: United States
facility: University of Florida Shand's Children's Hospital
state: Florida
city: Atlanta
country: United States
facility: Emory Children's Center
state: Georgia
city: Augusta
country: United States
facility: Georgia Regents University Medical Center
state: Georgia
city: Chicago
country: United States
facility: Ann & Robert H. Lurie Children's Hospital of Chicago
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University School of Medicine
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Louisville
country: United States
facility: University of Louisville School of Medicine
state: Kentucky
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Springfield
country: United States
facility: Baystate Medical Center, High Street Health Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Medical Center
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Kansas City
country: United States
facility: Children's Mercy Hospital
state: Missouri
city: Saint Louis
country: United States
facility: Saint Louis University School of Medicine
state: Missouri
city: Saint Louis
country: United States
facility: Saint Louis Children's Hospital
state: Missouri
city: Hackensack
country: United States
facility: HackensackUniversity Medical Center
state: New Jersey
city: Morristown
country: United States
facility: Goryeb Children's Hospital
state: New Jersey
city: West Orange
country: United States
facility: Pediatric Specialty Center at Saint Barnabas
state: New Jersey
city: Albany
country: United States
facility: Albany Medical College
state: New York
city: Bronx
country: United States
facility: Children's Hospital at Montefiore
state: New York
city: Lake Success
country: United States
facility: Cohen Children's Medical Center of New York
state: New York
city: New York
country: United States
facility: New York University Langone Medical Center
state: New York
city: New York
country: United States
facility: Hospital for Special Surgery
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Charlotte
country: United States
facility: Levine Children's Hospital
state: North Carolina
city: Durham
country: United States
facility: Duke Children's Hospital & Health Center
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Cleveland
country: United States
facility: MetroHealth Medical Center
state: Ohio
city: Cleveland
country: United States
facility: UH Rainbow Babies and Children's Hospital
state: Ohio
city: Cleveland
country: United States
facility: Clevland Clinic Foundation
state: Ohio
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Portland
country: United States
facility: Randall Children's Hospital at Legacy Emanuel
state: Oregon
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Philadelphia
country: United States
facility: St. Christopher's Hospital for Children
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh of UPMC
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina Children's Hospital
state: South Carolina
city: Nashville
country: United States
facility: Monroe Carell Jr. Children's Hospital at Vanderbilt
state: Tennessee
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center Dallas
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine Pediatric Immunology, Allergy and Rheumatology
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah Hospitals and Clinics
state: Utah
city: Burlington
country: United States
facility: University of Vermont Medical Center
state: Vermont
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
city: Madison
country: United States
facility: University of Wisconsin-American Family Children's Hospital
state: Wisconsin
city: Calgary
country: Canada
facility: University of Calgary- Alberta Children's Hospital
state: Alberta
city: Halifax
country: Canada
facility: IWK Health Center
state: Nova Scotia
city: Toronto
country: Canada
facility: The Hospital for Sick Children
state: Ontario
Study officials:
affiliation: Hackensack Meridian Health
name: Yukiko Kimura, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Seattle Children's Hospital
name: Sarah Ringold, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kimura Y, Schanberg LE, Tomlinson GA, Riordan ME, Dennos AC, Del Gaizo V, Murphy KL, Weiss PF, Natter MD, Feldman BM, Ringold S; CARRA STOP-JIA Investigators. Optimizing the Start Time of Biologics in Polyarticular Juvenile Idiopathic Arthritis: A Comparative Effectiveness Study of Childhood Arthritis and Rheumatology Research Alliance Consensus Treatment Plans. Arthritis Rheumatol. 2021 Oct;73(10):1898-1909. doi: 10.1002/art.41888. Epub 2021 Sep 3.
citation: Ong MS, Ringold S, Kimura Y, Schanberg LE, Tomlinson GA, Natter MD; CARRA Registry Investigators. Improved Disease Course Associated With Early Initiation of Biologics in Polyarticular Juvenile Idiopathic Arthritis: Trajectory Analysis of a Childhood Arthritis and Rheumatology Research Alliance Consensus Treatment Plans Study. Arthritis Rheumatol. 2021 Oct;73(10):1910-1920. doi: 10.1002/art.41892. Epub 2021 Aug 27.