Juvenile Spondyloarthritis in the CARRA Registry: High Biologic Use, Low Prevalence of HLA-B27, and Equal Sex Representation in Sacroiliitis.

2020

2020 Dec 16

2151-4658

<p><strong>OBJECTIVE: </strong>To describe characteristics of children with enthesitis-related arthritis (ERA) and juvenile psoriatic arthritis (JPsA) enrolled in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry.</p>

<p><strong>METHODS: </strong>All children with ERA and JPsA were identified. Demographics, clinical characteristics, and treatments were described. Those with and without sacroiliitis were compared. In those with sacroiliitis, the first visit with clinically active sacroiliitis (which came first in 72% of cases) was compared to the first visit without.</p>

<p><strong>RESULTS: </strong>Nine hundred two children with ERA or JPsA were identified. Children with ERA were older at diagnosis (10.8 vs. 8.2 years, p&lt;0.01) and more likely male (56% vs. 38%, p&lt;0.01). Polyarticular involvement was reported in 57% and 72% of those with ERA and JPsA. HLA-B27 was positive in 38% and 12% of those tested with ERA and JPsA. At least one biologic was taken by 72% and 64% of those with ERA and JPsA. Sacroiliitis (diagnosed clinically and/or by imaging) was reported in 28% (40% ERA and 12% JPsA). Of these, 54% were female, 36% were HLA-B27 positive, and 81% took at least one biologic. In children with sacroiliitis, the physician global, parent/patient global, and cJADAS 10 were all significantly worse at the first visit with clinically active sacroiliitis versus the first visit without active sacroiliitis.</p>

<p><strong>CONCLUSION: </strong>In this registry, there are over 900 children with ERA or JPsA. There was high biologic use in this population, especially in those with sacroiliitis. Further, there was equal sex representation in those with sacroiliitis.</p>

10.1002/acr.24537

Arthritis Care Res (Hoboken)

33331139

Comparative Effectiveness of Tumor Necrosis Factor Agents and Disease-modifying Antirheumatic Therapy in Children with Enthesitis-related Arthritis: The First Year after Diagnosis.

2018

107-14

2018 Jan

0315-162X

<p><strong>OBJECTIVE: </strong>To characterize the effect of anti-tumor necrosis factor (TNF) therapy compared to conventional synthetic disease-modifying antirheumatic drugs (csDMARD) in children with enthesitis-related arthritis (ERA) over the first year after diagnosis.</p>

<p><strong>METHODS: </strong>We conducted a multicenter retrospective comparative effectiveness study of children diagnosed with ERA. We estimated the effect of anti-TNF therapy on clinical variables (active joint count, tender entheses count) and patient-reported pain and global assessment of disease activity over the first year after diagnosis using state-of-the-art comparative effectiveness analytic methods.</p>

<p><strong>RESULTS: </strong>During the study period, 217 patients newly diagnosed with ERA had a total of 965 clinic visits the first year after disease diagnosis. Children [median age 11.6 yrs, interquartile range 10-14] were treated with anti-TNF monotherapy (n = 33, 15.2%), csDMARD monotherapy (n = 73, 33.6%), or both (n = 52, 23.9%) in the first year after disease diagnosis. There was a statistically significant improvement in the primary outcome, active joint count, over time in children who received an anti-TNF drug versus those who did not (p = 0.03). Additionally, use of anti-TNF therapy versus no anti-TNF therapy was associated with less patient-reported pain (p &lt; 0.01) and improved disease activity over time as assessed by the clinical Juvenile Arthritis Disease Activity Score (p &lt; 0.01). The magnitude of estimated effect on clinical outcomes was uniformly greater, with the exception of tender entheses count, in children treated with an anti-TNF drug versus a csDMARD.</p>

<p><strong>CONCLUSION: </strong>During the first year after diagnosis, anti-TNF exposure was associated with benefits for several clinically meaningful outcomes in children with enthesitis-related arthritis.</p>

10.3899/jrheum.170251

J. Rheumatol.

28916542

Multicenter inception cohort of enthesitis-related arthritis: variation in disease characteristics and treatment approaches.

2017

84

2017 May 02

1478-6362

<p><strong>BACKGROUND: </strong>Enthesitis-related arthritis (ERA) is a specific subtype of juvenile idiopathic arthritis (JIA) defined according to the International League of Associations for Rheumatology (ILAR) criteria. We aimed to characterize the clinical features and treatment regimens in an inception cohort of children with ERA.</p>

<p><strong>METHODS: </strong>We performed a retrospective, cross-sectional, multicenter cohort study including subjects diagnosed with ERA between 1989 and 2012. Patients all fulfilled the ILAR criteria for ERA within 3&nbsp;months of initial presentation to the rheumatology clinic. Differences in the prevalence of clinical criteria across study sites and by human leukocyte antigen (HLA)-B27 status were assessed using the Wilcoxon rank-sum or chi-square test, as appropriate.</p>

<p><strong>RESULTS: </strong>Two hundred thirty-four children met the inclusion criteria. Their median age at diagnosis was 11.6&nbsp;years, and 59% were HLA-B27-positive. Sixty-nine percent had enthesitis and arthritis at the time of diagnosis. Seventy-eight percent had a pauciarticular onset. The prevalence of all ILAR criteria at diagnosis, except arthritis and acute anterior uveitis, differed significantly across sites (all p &lt; 0.01). Medication use varied significantly across sites for children with peripheral arthritis (p &lt; 0.001), but not for sacroiliitis or enthesitis only. Nonsteroidal anti-inflammatory drugs and disease-modifying antirheumatic drugs were the most commonly prescribed treatments, with anti-TNF agents primarily being initiation for sacroiliitis. HLA-B27 positivity was associated with male sex, higher active joint count, sacroiliitis, and higher disease activity at disease onset.</p>

<p><strong>CONCLUSIONS: </strong>The majority of children had a pauciarticular onset, and several statistically significant clinical differences based on HLA-B27 status were identified. The observed heterogeneity in clinical presentation across sites reflects either true differences in patient populations or differences in how the ILAR criteria are being applied.</p>

10.1186/s13075-017-1297-x

Arthritis Res. Ther.

28464909

Pilot study comparing the Childhood Arthritis & Rheumatology Research Alliance (CARRA) systemic Juvenile Idiopathic Arthritis Consensus Treatment Plans.

2017

23

2017 Apr 11

1546-0096

<p><strong>OBJECTIVES: </strong>To assess the feasibility of studying the comparative effectiveness of the Childhood Arthritis and Rheumatology Research Alliance (CARRA) consensus treatment plans (CTPs) for systemic Juvenile Idiopathic Arthritis (JIA) using an observational registry.</p>

<p><strong>METHODS: </strong>Untreated systemic JIA patients enrolled in the CARRA Registry were begun on one of 4 CTPs chosen by the treating physician and patient/family (glucocorticoid [GC] alone; methotrexate [MTX] ± GC; IL1 inhibitor [IL1i] ± GC; IL6 inhibitor [IL6i] ± GC). The primary outcome of clinical inactive disease (CID) without current GC use was assessed at 9&nbsp;months.</p>

<p><strong>TRIAL REGISTRATION: </strong>clinicaltrials.gov NCT01697254; first registered 9/28/12 (retrospectively enrolled).</p>

<p><strong>RESULTS: </strong>Thirty patients were enrolled at 13 sites; eight patients were started on a non-biologic CTP (2 GC, 6 MTX) and 22 patients on a biologic CTP (12 IL1i, 10 IL6i) at disease onset. Demographic and disease features were similar between CTP groups. CTP choice appeared to segregate by site preference. CID off GC was achieved by 37% (11 of 30) including 11/22 (50%) starting a biologic CTP compared to 0/8 starting a non-biologic CTP (p = 0.014). There were four serious adverse events: two infections, one appendicitis and one macrophage activation syndrome.</p>

<p><strong>CONCLUSIONS: </strong>The CARRA systemic JIA CTP pilot study demonstrated successful implementation of CTPs using the CARRA registry infrastructure. Having demonstrated feasibility, a larger study using CTP response to better determine the relative effectiveness of treatments for new-onset systemic JIA is now underway.</p>

10.1186/s12969-017-0157-1

Pediatr Rheumatol Online J

28399931

2013 update of the 2011 American College of Rheumatology recommendations for treatment of juvenile idiopathic arthritis: recommendations for medical therapy of children with systemic JIA and TB screening among children receiving biologic medications.

2013

2499-512

2013 Oct

1529-0131

10.1002/art.38092

Arthritis Rheum.

24092554

Enthesitis-related arthritis is associated with higher pain intensity and poorer health status in comparison with other categories of juvenile idiopathic arthritis: the Childhood Arthritis and Rheumatology Research Alliance Registry.

2012

2341-51

2012 Dec

0315-162X

<p><strong>OBJECTIVE: </strong>To assess the relative effect of clinical factors and medications on pain intensity, physical function, and health status in juvenile idiopathic arthritis (JIA).</p>

<p><strong>METHODS: </strong>We conducted a retrospective cross-sectional study of data from children with JIA enrolled in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry. We tested whether clinical characteristics of JIA were associated with pain intensity, physical function, and health status using multivariable linear and ordinal logistic regression.</p>

<p><strong>RESULTS: </strong>During the study period, 2571 subjects with JIA enrolled in the CARRA Registry. Ratings of pain intensity, physical function, and health status differed significantly between JIA categories. In comparison to other categories of JIA, subjects with enthesitis-related arthritis (ERA) reported worse pain and function. In multivariable analyses, higher active joint count and current use of nonsteroidal antiinflammatory drugs (NSAID), biologics, or corticosteroids were associated with worse scores on all patient-reported measures. ERA and older age were significantly associated with higher pain intensity and poorer health status. Systemic JIA and uveitis were significantly associated with worse health status. Enthesitis, sacroiliac tenderness, and NSAID use were independently associated with increased pain intensity in ERA. The correlation was low between physician global assessment of disease activity and patient-reported pain intensity, physical function, and health status.</p>

<p><strong>CONCLUSION: </strong>Significant differences in pain intensity, physical function, and health status exist among JIA categories. These results suggest that current treatments may not be equally effective for particular disease characteristics more common in specific JIA categories, such as enthesitis or sacroiliac tenderness in ERA.</p>

10.3899/jrheum.120642

J. Rheumatol.

23070991

Disease-modifying antirheumatic drug use in the treatment of juvenile idiopathic arthritis: a cross-sectional analysis of the CARRA Registry.

2012

1867-74

2012 Sep

0315-162X

<p><strong>OBJECTIVE: </strong>To characterize disease-modifying antirheumatic drug (DMARD) use for children with juvenile idiopathic arthritis (JIA) in the United States and to determine patient factors associated with medication use.</p>

<p><strong>METHODS: </strong>We analyzed cross-sectional baseline enrollment data from the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry from May 2010 through May 2011 for children with JIA. Current and prior medication use was included. We used parsimonious backward stepwise logistic regression models to calculate OR to estimate associations between clinical patient factors and medication use.</p>

<p><strong>RESULTS: </strong>We identified 2748 children with JIA with a median disease duration of 3.9 years from 51 US clinical sites. Overall, 2023 (74%) had ever received a nonbiologic DMARD and 1246 (45%) had ever received a biologic DMARD. Among children without systemic arthritis, methotrexate use was most strongly associated with uveitis (OR 5.2, 95% CI 3.6-7.6), anticitrullinated protein antibodies (OR 4.5, 95% CI 1.7-12), and extended oligoarthritis (OR 4.1, 95% CI 2.5-6.6). Among children without systemic arthritis, biologic DMARD use was most strongly associated with rheumatoid factor (RF)-positive polyarthritis (OR 4.3, 95% CI 2.9-6.6), psoriatic arthritis (PsA; OR 3.0, 95% CI 2.0-4.4), and uveitis (OR 2.8, 95% CI 2.1-3.7). Among children with systemic arthritis, 160 (65%) ever received a biologic DMARD; tumor necrosis factor inhibitor use was associated with polyarthritis (OR 2.5, 95% CI 3.8-16), while interleukin 1 inhibitor use was not.</p>

<p><strong>CONCLUSION: </strong>About three-quarters of all children with JIA in the CARRA Registry received nonbiologic DMARD. Nearly one-half received biologic DMARD, and their use was strongly associated with RF-positive polyarthritis, PsA, uveitis, and systemic arthritis.</p>

10.3899/jrheum.120110

J. Rheumatol.

22859354

Consensus treatment plans for new-onset systemic juvenile idiopathic arthritis.

2012

1001-10

2012 Jul

2151-4658

<p><strong>OBJECTIVE: </strong>There is wide variation in therapeutic approaches to systemic juvenile idiopathic arthritis (JIA) among North American rheumatologists. Understanding the comparative effectiveness of the diverse therapeutic options available for treatment of systemic JIA can result in better health outcomes. The Childhood Arthritis and Rheumatology Research Alliance (CARRA) developed consensus treatment plans and standardized assessment schedules for use in clinical practice to facilitate such studies.</p>

<p><strong>METHODS: </strong>Case-based surveys were administered to CARRA members to identify prevailing treatments for new-onset systemic JIA. A 2-day consensus conference in April 2010 employed modified nominal group technique to formulate preliminary treatment plans and determine important data elements for collection. Followup surveys were employed to refine the plans and assess clinical acceptability.</p>

<p><strong>RESULTS: </strong>The initial case-based survey identified significant variability among current treatment approaches for new-onset systemic JIA, underscoring the utility of standardized plans to evaluate comparative effectiveness. We developed 4 consensus treatment plans for the first 9 months of therapy, as well as case definitions and clinical and laboratory monitoring schedules. The 4 treatment regimens included glucocorticoids only, or therapy with methotrexate, anakinra, or tocilizumab, with or without glucocorticoids. This approach was approved by &gt;78% of the CARRA membership.</p>

<p><strong>CONCLUSION: </strong>Four standardized treatment plans were developed for new-onset systemic JIA. Coupled with data collection at defined intervals, use of these treatment plans will create the opportunity to evaluate comparative effectiveness in an observational setting to optimize initial management of systemic JIA.</p>

10.1002/acr.21625

Arthritis Care Res (Hoboken)

22290637

Development and retrospective validation of the juvenile spondyloarthritis disease activity index.

2014

1775-82

2014 Dec

2151-4658

<p><strong>OBJECTIVE: </strong>To develop and validate the Juvenile Spondyloarthritis Disease Activity Index (JSpADA) for use in clinical practice and research.</p>

<p><strong>METHODS: </strong>Using modified Delphi consensus techniques, 10 items were selected by participants in the international pediatric rheumatology listserv, the Childhood Arthritis and Rheumatology Research Alliance, and the listserv for the pediatric section of the American College of Rheumatology. Validation was performed in a retrospective multicenter cohort of 244 children.</p>

<p><strong>RESULTS: </strong>In total, 106 physicians representing 14 countries completed the initial questionnaire. Completion rates for the subsequent questionnaires were 84%, 75%, and 77% of the original respondents. Ten items exceeded 80% consensus: arthritis, enthesitis, patient pain assessment, inflammatory markers, morning stiffness, clinical sacroiliitis, uveitis, back mobility, and patient and physician assessments of disease activity. After item analysis, 2 items were eliminated (patient and physician assessments of disease activity). Factor analysis identified 3 primary domains that explained 58% of the variance: peripheral disease, axial disease, and uveitis. The Cronbach's α coefficient was 0.66. The JSpADA had high or moderate correlations with the Juvenile Arthritis Disease Activity Score (r = 0.81), patient and physician assessments of disease activity (r = 0.70 and r = 0.66, respectively), and the Childhood Health Assessment Questionnaire (r = 0.56). The JSpADA discriminated well between subjects with active versus inactive disease (P &lt; 0.001) and was responsive to improvement or worsening in disease activity over time (P &lt; 0.001).</p>

<p><strong>CONCLUSION: </strong>Using international input and consensus formation techniques, we developed and validated the first disease activity assessment for juvenile spondyloarthritis. Future studies should validate the JSpADA in a prospective multicenter cohort.</p>

10.1002/acr.22411

Arthritis Care Res (Hoboken)

25047959