scholarly journals Bayesian comparative effectiveness study of four consensus treatment plans for initial management of systemic juvenile idiopathic arthritis: FiRst-Line Options for Systemic juvenile idiopathic arthritis Treatment (FROST)

2018 ◽  
Vol 15 (3) ◽  
pp. 268-277 ◽  
Author(s):  
Peter A Nigrovic ◽  
Timothy Beukelman ◽  
George Tomlinson ◽  
Brian M Feldman ◽  
Laura E Schanberg ◽  
...  
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Systemic Juvenile Idiopathic Arthritis ◽  
Inactive Disease ◽  
First Line ◽  
Rheumatology Research ◽  
Childhood Arthritis ◽  
Patient Reported ◽  
Treatment Plans ◽  
Research Alliance ◽  
New Onset

Background: Systemic juvenile idiopathic arthritis is a rare febrile arthritis of childhood characterized by a potentially severe course, including prolonged glucocorticoid exposure, growth failure, destructive arthritis, and life-threatening macrophage activation syndrome. Early cytokine-blocking biologic therapy may improve long-term outcomes, although some systemic juvenile idiopathic arthritis patients respond well to non-biologic treatment, leaving optimal management undefined. Consequently, treatment of new-onset systemic juvenile idiopathic arthritis by expert clinicians varies widely. Purpose: To describe a pragmatic, observational comparative effectiveness study that takes advantage of diversity in the management of a rare disease: FiRst-Line Options for Systemic juvenile idiopathic arthritis Treatment (FROST), comparing non-biologic and biologic consensus treatment plans for new-onset systemic juvenile idiopathic arthritis within the 60-center Childhood Arthritis and Rheumatology Research Alliance Registry (CARRA). Methods: FiRst-Line Options for Systemic juvenile idiopathic arthritis Treatment (FROST) is a multicenter, prospective, non-randomized study that compares four Childhood Arthritis and Rheumatology Research Alliance (CARRA) consensus treatment plans for new-onset systemic juvenile idiopathic arthritis: (1) glucocorticoids alone, (2) methotrexate, (3) interleukin-1 blockade, and (4) interleukin-6 blockade. Patients consenting to participation in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry are started on one of four Consensus Treatment Plans at the discretion of the treating physician. The outcome of primary interest is clinically inactive disease off glucocorticoids at 9 months, comparing non-biologic (Consensus Treatment Plans 1 + 2) versus biologic (Consensus Treatment Plans 3 + 4) strategies. Bayesian analytic methods will be employed to evaluate response rates, using propensity scoring to balance treatment groups for potential confounding. With 200 patients in a 2:1 ratio of biologic to non-biologic, there is a >90% probability of finding biologic consensus treatment plans more effective if the rate of clinically inactive disease is 30% higher than for non-biologic therapy. Additional outcomes include Patient-Reported Outcomes Measurement Information System measures and other parent-/patient-reported outcomes reported in real time using smartphone technology. Routine operation of the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry will allow assessment of outcomes over at least 10 years. Results: FiRst-Line Options for Systemic juvenile idiopathic arthritis Treatment (FROST) began enrollment in November 2016. Limitations: The observational design may not provide balance in measured and unmeasured confounders. Use of consensus treatment plan (CTP) strategies at frequencies more unbalanced than predicted could reduce the chance of finding differences in efficacy. Conclusion: FiRst-Line Options for Systemic juvenile idiopathic arthritis Treatment (FROST) will provide the first prospective comparison of Childhood Arthritis and Rheumatology Research Alliance’s (CARRA’s) consensus-derived non-biologic versus biologic management strategies in systemic juvenile idiopathic arthritis, performed in a real-world setting wherein each patient receives standard-of-care treatment selected by the treating physician. Outcomes include clinician- and patient-/family-reported outcomes, empowering both physician and patient decision making in new-onset systemic juvenile idiopathic arthritis.

scholarly journals 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 ◽  
Vol 39 (12) ◽  
pp. 2341-2351 ◽  
Author(s):  
PAMELA F. WEISS ◽  
TIMOTHY BEUKELMAN ◽  
LAURA E. SCHANBERG ◽  
YUKIKO KIMURA ◽  
ROBERT A. COLBERT
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Health Status ◽  
Pain Intensity ◽  
Physical Function ◽  
Physician Global Assessment ◽  
Enthesitis Related Arthritis ◽  
Rheumatology Research ◽  
Childhood Arthritis ◽  
Patient Reported ◽  
Research Alliance

Objective.To assess the relative effect of clinical factors and medications on pain intensity, physical function, and health status in juvenile idiopathic arthritis (JIA).Methods.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.Results.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.Conclusion.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.

Biologic Switching among Non-Systemic Juvenile Idiopathic Arthritis Patients: A Cohort Study in the Childhood Arthritis and Rheumatology Research Alliance Registry

2020 ◽  
pp. jrheum.200437
Author(s):  
Melissa L. Mannion ◽  
Fenglong Xie ◽  
Daniel B. Horton ◽  
Sarah Ringold ◽  
Colleen K. Correll ◽  
...  
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Systemic Juvenile Idiopathic Arthritis ◽  
Current Treatment ◽  
Categorical Variables ◽  
Optimal Timing ◽  
Continuous Variables ◽  
Chi Square ◽  
Rheumatology Research ◽  
Childhood Arthritis ◽  
Research Alliance

Objective Biologic medications have significantly improved disease control and outcomes of patients with juvenile idiopathic arthritis (JIA). Current treatment recommendations suggest escalating therapy; including changing biologics if needed, when inactive or low disease activity is not attained. The patterns and reasons for switching biologics in clinical practice in North America are not well described. Methods We used the Childhood Arthritis and Rheumatology Research Alliance Registry and included individuals with JIA if they newly started a biologic after January 1, 2008 and had at least 12 months of subsequent observable time. Subjects with systemic JIA were excluded. We compared characteristics of switchers and non-switchers using chi-square for categorical variables and Wilcoxon rank sum testing for continuous variables and used linear regression for time analysis. Results 1361 eligible children with JIA in the registry started a biologic (94% tumor necrosis factor TNF inhibitors [TNFi]). Median follow-up time was 30 months, and 349 (26%) switched biologics. Among biologic switchers, ineffectiveness/disease flare was the most common reason for switch (202, 58%). The most common documented switch was from etanercept to another TNFi (221, 63%). The median time to switch to a second biologic decreased substantially from 55.2 months in 2008 to 7.2 months in 2016. Conclusion In a multicenter cohort of patients with JIA starting a biologic, one-quarter switched to a second biologic, and the time to switching decreased in recent years. Additional studies should evaluate the outcomes and optimal timing of switching and preferred sequence of biologic use.

The Systemic Juvenile Idiopathic Arthritis Cohort of the Childhood Arthritis and Rheumatology Research Alliance Registry: 2010–2013

2016 ◽  
Vol 43 (9) ◽  
pp. 1755-1762 ◽  
Author(s):  
Ginger Janow ◽  
Laura E. Schanberg ◽  
Soko Setoguchi ◽  
Victor Hasselblad ◽  
Elizabeth D. Mellins ◽  
...  
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Disease Activity ◽  
Disease Duration ◽  
Interleukin 1 ◽  
Systemic Juvenile Idiopathic Arthritis ◽  
Medication Usage ◽  
Rheumatology Research ◽  
Childhood Arthritis ◽  
Systemic Symptoms ◽  
Research Alliance

Objective.We aimed to identify the (1) demographic/clinical characteristics, (2) medication usage trends, (3) variables associated with worse disease activity, and (4) characteristics of patients with persistent chronic arthritis in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Legacy Registry’s systemic juvenile idiopathic arthritis (sJIA) cohort.Methods.Demographics, disease activity measures, and medications at enrollment of patients with sJIA in the CARRA Registry were analyzed using descriptive statistics. Multivariate analyses were conducted to identify associations with increased disease activity. Medication usage frequencies were calculated by year.Results.There were 528 patients with sJIA enrolled in the registry (2010–2013). There were 435 patients who had a complete dataset; of these, 372 met the International League of Associations for Rheumatology criteria and were included in the analysis. At enrollment, median disease duration and joint count were 3.7 years and 0, respectively; 16.4% had a rash and 6.7% had a fever. Twenty-six percent were taking interleukin 1 (IL-1) inhibitors and 29% glucocorticoids. Disease-modifying antirheumatic drugs and tumor necrosis factor inhibitors use decreased, while IL-6 inhibitor use increased between 2010 and 2013. African American patients had worse joint counts (p = 0.003), functional status (p = 0.01), and physician’s global assessment (p = 0.008). Of the 255 subjects with > 2 years of disease duration, 56% had no arthritis or systemic symptoms, while 32% had persistent arthritis only.Conclusion.Most patients in the largest sJIA cohort reported to date had low disease activity. Practice patterns for choice of biologic agents appeared to change over the study period. Nearly one-third had persistent arthritis without systemic symptoms > 2 years after onset. African Americans were associated with worse disease activity. Strategies are needed to improve outcomes in subgroups with poor prognosis.

scholarly journals Childhood Arthritis and Rheumatology Research Alliance Consensus Treatment Plans for Juvenile Idiopathic Arthritis–Associated and Idiopathic Chronic Anterior Uveitis

2019 ◽  
Vol 71 (4) ◽  
pp. 482-491 ◽  
Author(s):  
Sheila T. Angeles‐Han ◽  
Mindy S. Lo ◽  
Lauren A. Henderson ◽  
Melissa A. Lerman ◽  
Leslie Abramson ◽  
...  
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Anterior Uveitis ◽  
Rheumatology Research ◽  
Childhood Arthritis ◽  
Treatment Plans ◽  
Research Alliance

scholarly journals Effect of first-line biologic initiation on glucocorticoid exposure in children hospitalized with new-onset systemic juvenile idiopathic arthritis: emulation of a pragmatic trial using observational data

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Rosemary G. Peterson ◽  
Rui Xiao ◽  
Hannah Katcoff ◽  
Brian T. Fisher ◽  
Pamela F. Weiss
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Biologic Therapy ◽  
Tertiary Care ◽  
Pragmatic Trial ◽  
Systemic Juvenile Idiopathic Arthritis ◽  
Source Population ◽  
First Line ◽  
Eligibility Criteria ◽  
Over Time ◽  
New Onset

Abstract Background Glucocorticoid exposure is a significant driver of morbidity in children with systemic juvenile idiopathic arthritis (sJIA). We determined the effect of early initiation of biologic therapy (IL-1 or IL-6 inhibition) on glucocorticoid exposure in hospitalized patients with new-onset sJIA. Methods We emulated a pragmatic sequence of trials (“pseudo-trials”) of biologic initiation in children (≤ 18 years) hospitalized with new-onset sJIA utilizing retrospective data from an administrative database from 52 tertiary care children’s hospitals from 2008 to 2019. Eligibility window, treatment assignment and start of follow-up between biologic and non-biologic study arms were aligned for each pseudo-trial. Patients in the source population could meet eligibility criteria at several timepoints. Mixed-effects logistic regression was used to determine the effect of biologic initiation on in-hospital glucocorticoid exposure. Results Four hundred sixty-eight children met eligibility criteria, of which 19% received biologic therapy without preceding or concomitant initiation of immunomodulatory medications. This proportion significantly increased over time during the study period (p <  0.01). 1451 trial subjects were included across 4 pseudo-trials with 71 assigned to the biologic arm and 1380 assigned to the non-biologic arm. After adjustment, there was a trend toward decreased odds of glucocorticoid initiation in the biologic arm compared to the non-biologic arm (OR 0.39, 95% CI [0.13, 1.15]). Conclusion Biologic initiation in children hospitalized with new-onset sJIA significantly increased over time and may be associated with reduced glucocorticoid exposure. The increasing use of first-line biologic therapy may lead to clinically relevant reductions in treatment-related adverse effects of glucocorticoid-reliant therapeutic approaches.

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