Modified Juvenile Spondyloarthritis Disease Activity Index in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry.

2023

532-537

04/2023

0315-162X

OBJECTIVE: To validate the Juvenile Spondyloarthritis Disease Activity Index (JSpADA), and modified versions thereof, in a North American cohort of patients with enthesitis-related arthritis (ERA).

METHODS: We utilized the Childhood Arthritis and Rheumatology Research Alliance Registry database ERA cohort to validate the JSpADA and its modifications (JSpADA6-no Schober, no C-reactive protein [CRP]/erythrocyte sedimentation rate [ESR]; JSpADA7-no Schober; and JSpADA7-no CRP/ESR) using the Outcome Measures in Rheumatology principles of face validity, discriminative validity, and responsiveness to change.

RESULTS: There were 51 subjects (64 visits) with complete JSpADA data with a mean age of 13.7 years and disease duration of 30.9 months. Subjects were predominantly White (84.3%), and 56.9% were male and 50% were HLA-B27 positive. The JSpADA showed high correlation with the clinical 10-joint Juvenile Arthritis Disease Activity Score (cJADAS10; = 0.81), moderate-to-high correlation with physician global assessment (PGA; = 0.69), and low-to-fair correlation with Childhood Health Assessment Questionnaire (CHAQ; = 0.22). The modifications of the JSpADA (JSpADA7-no Schober; JSpADA7-no CRP/ESR; and JSpADA6-no Schober, no CRP/ESR) performed similarly with high correlation with cJADAS10 ( = 0.81, 0.79, and 0.80, respectively), moderate-to-high correlation with PGA ( = 0.65, 0.67, 0.64, respectively), and low-to-fair correlation with CHAQ ( = 0.35, 0.34, 0.39, respectively). All modified versions of JSpADA had good responsiveness to change. All versions of JSpADA had excellent discriminative validity.

CONCLUSION: We propose the term for the modification of JSpADA with 6 elements (JSpADA6-no Schober, no CRP/ESR). This shorter disease activity index may improve implementation of JSpADA in both clinical practice and research trials.

10.3899/jrheum.220509

J Rheumatol

36319008

Survey of current practices in the management of anti-TNF failure in juvenile spondyloarthritis.

2022

2022 Apr 20

0392-856X

<p><strong>OBJECTIVES: </strong>To evaluate the current practices in management of patients with juvenile spondyloarthritis (JSpA) who failed anti-tumour necrosis factor agents (anti-TNF).</p>

<p><strong>METHODS: </strong>An online survey was distributed to Childhood Arthritis and Rheumatology Research Alliance (CARRA) members of the JIA workgroup. Data collection included estimated number of JSpA patients who have failed anti-TNF therapy over two-year period, reasons for discontinuing anti-TNF therapy and other medications used afterward. The JSpA population was de ned as the following subtypes: enthesitis-related arthritis, psoriatic arthritis, undifferentiated spondyloarthritis, juvenile ankylosing spondylitis (AS) i.e. meeting modi ed NY criteria for AS before age 16, and reactive arthritis. Findings were summarised using descriptive statistics.</p>

<p><strong>RESULTS: </strong>The survey response rate was 36% (n= 60/169). The majority of participants were paediatric rheumatologists (93%). Many physicians have JSpA patients who failed anti-TNF therapy (63%). The most common reason for changing anti-TNF therapy was secondary non-response (72%). Sacroiliitis was the most important factor considered when assessing response to an anti-TNF agent and the most common reason for primary non-response (45%). When assessing anti-TNF failure for sacroiliitis, many (65%) felt imaging of the sacroiliac joints was the most important aspect in their decision making. The majority try a second anti-TNF agent after initial anti-TNF failure (87%) and switch to another medication class after 2 anti-TNF agents have failed (62%).</p>

<p><strong>CONCLUSIONS: </strong>More than half of paediatric rheumatologists surveyed have at least one JSpA patient who failed anti-TNF therapy. The majority failed because of secondary non-response. Sacroiliitis is an important but challenging aspect to manage for patients with JSpA.</p>

10.55563/clinexprheumatol/gyrtjo

Clin Exp Rheumatol

35485412

Children with enthesitis-related arthritis could benefit from treatments targeted for adults with spondyloarthritis.

2020

2020 Dec 05

2151-4658

<p>This review will summarize clinical, genetic and pathophysiologic characteristics that are shared between children with enthesitis related arthritis (ERA) with axial involvement and adults with non-radiographic, and in some cases radiographic, axial spondyloarthritis (SpA); and between children with ERA and primarily peripheral disease manifestations and adults with peripheral SpA. Due to the differences in classification criteria for children with ERA and adults with axial and peripheral SpA, the FDA granted automatic full waivers of studies in children for new medications for "axial spondyloarthropathies including ankylosing spondylitis" up until July 2020. Thus, although current juvenile idiopathic arthritis (JIA) treatment guidelines recommend the use of biologic disease modifying anti-rheumatic drugs (DMARDs) as part of the early treatment for patients with ERA, none of the FDA-approved therapies for peripheral SpA or non-radiographic axial SpA (certolizumab pegol, ixekizumab, and secukinumab) have been studied or are labelled for use in children with ERA. Considering the similarities between adult spondyloarthritis and ERA in terms of etiology, genetics, pathogenesis and clinical manifestations summarized in this review, medications approved for axial SpA or peripheral SpA should also be studied in children with active ERA involving axial or peripheral joints, respectively, with the intent to achieve labeling for use in children. Considering the current lack of effective FDA-approved therapies for ERA, the FDA should also consider requiring pediatric studies for medications that have already been approved for the treatment of adults with SpA.</p>

10.1002/acr.24529

Arthritis Care Res (Hoboken)

33278336

Juvenile Spondyloarthritis: A Distinct Form of Juvenile Arthritis.

2018

675-690

2018 Aug

1557-8240

<p>Juvenile spondyloarthritis (SpA) is a distinct form of juvenile arthritis characterized by male predominance and adolescent onset. Clinical manifestations include lower extremity and sacroiliac joint arthritis, enthesitis, and subclinical gastrointestinal inflammation. Juvenile SpA is an immune-mediated inflammatory disease long recognized as associated with HLA-B27, which may be related to the microbial environment as suggested by its coexistence with reactive arthritis and psoriasis. Treatment of peripheral arthritis includes nonsteroidal anti-inflammatory drugs, joint injections, and disease-modifying agents, whereas treatment of axial disease may necessitate a tumor necrosis factor inhibitor biologic agent. Fewer than half of children achieve remission off medication 5&nbsp;years after diagnosis.</p>

10.1016/j.pcl.2018.03.006

Pediatr. Clin. North Am.

30031493

American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network 2015 Recommendations for the Treatment of Ankylosing Spondylitis and Nonradiographic Axial Spondyloarthritis.

2016

282-98

2016 Feb

2326-5205

<p><strong>OBJECTIVE: </strong>To provide evidence-based recommendations for the treatment of patients with ankylosing spondylitis (AS) and nonradiographic axial spondyloarthritis (SpA).</p>

<p><strong>METHODS: </strong>A core group led the development of the recommendations, starting with the treatment questions. A literature review group conducted systematic literature reviews of studies that addressed 57 specific treatment questions, based on searches conducted in OVID Medline (1946-2014), PubMed (1966-2014), and the Cochrane Library. We assessed the quality of evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) method. A separate voting group reviewed the evidence and voted on recommendations for each question using the GRADE framework.</p>

<p><strong>RESULTS: </strong>In patients with active AS, the strong recommendations included use of nonsteroidal antiinflammatory drugs (NSAIDs), use of tumor necrosis factor inhibitors (TNFi) when activity persists despite NSAID treatment, not to use systemic glucocorticoids, use of physical therapy, and use of hip arthroplasty for patients with advanced hip arthritis. Among the conditional recommendations was that no particular TNFi was preferred except in patients with concomitant inflammatory bowel disease or recurrent iritis, in whom TNFi monoclonal antibodies should be used. In patients with active nonradiographic axial SpA despite treatment with NSAIDs, we conditionally recommend treatment with TNFi. Other recommendations for patients with nonradiographic axial SpA were based on indirect evidence and were the same as for patients with AS.</p>

<p><strong>CONCLUSION: </strong>These recommendations provide guidance for the management of common clinical questions in AS and nonradiographic axial SpA. Additional research on optimal medication management over time, disease monitoring, and preventive care is needed to help establish best practices in these areas.</p>

10.1002/art.39298

26401991

American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network 2015 Recommendations for the Treatment of Ankylosing Spondylitis and Nonradiographic Axial Spondyloarthritis.

2016

151-66

2016 Feb

2151-4658

OBJECTIVE: To provide evidence-based recommendations for the treatment of patients with ankylosing spondylitis (AS) and nonradiographic axial spondyloarthritis (SpA).

METHODS: A core group led the development of the recommendations, starting with the treatment questions. A literature review group conducted systematic literature reviews of studies that addressed 57 specific treatment questions, based on searches conducted in OVID Medline (1946-2014), PubMed (1966-2014), and the Cochrane Library. We assessed the quality of evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) method. A separate voting group reviewed the evidence and voted on recommendations for each question using the GRADE framework.

RESULTS: In patients with active AS, the strong recommendations included use of nonsteroidal antiinflammatory drugs (NSAIDs), use of tumor necrosis factor inhibitors (TNFi) when activity persists despite NSAID treatment, not to use systemic glucocorticoids, use of physical therapy, and use of hip arthroplasty for patients with advanced hip arthritis. Among the conditional recommendations was that no particular TNFi was preferred except in patients with concomitant inflammatory bowel disease or recurrent iritis, in whom TNFi monoclonal antibodies should be used. In patients with active nonradiographic axial SpA despite treatment with NSAIDs, we conditionally recommend treatment with TNFi. Other recommendations for patients with nonradiographic axial SpA were based on indirect evidence and were the same as for patients with AS.

CONCLUSION: These recommendations provide guidance for the management of common clinical questions in AS and nonradiographic axial SpA. Additional research on optimal medication management over time, disease monitoring, and preventive care is needed to help establish best practices in these areas.

10.1002/acr.22708

Arthritis Care Res (Hoboken)

26401907

Response: Are the Assessment of Spondyloarthritis International Society (ASAS) classification criteria useful in juvenile Spondyloarthritis?

2016

2016 Mar 18

2151-4658

10.1002/acr.22885

Arthritis Care Res (Hoboken)

26991095

Radiography versus magnetic resonance imaging (MRI) in juvenile spondyloarthritis: is the MR image everything?

2014

832-3

2014 May

0315-162X

10.3899/jrheum.140212

J. Rheumatol.

24788462

Childhood Arthritis and Rheumatology Research Alliance consensus treatment plans for new-onset polyarticular juvenile idiopathic arthritis.

2014

1063-72

2014 Jul

2151-4658

<p><strong>OBJECTIVE: </strong>There is no standardized approach to the initial treatment of polyarticular juvenile idiopathic arthritis (JIA) among pediatric rheumatologists. Understanding the comparative effectiveness of the diverse therapeutic options available will result in better health outcomes for polyarticular JIA. The Childhood Arthritis and Rheumatology Research Alliance (CARRA) developed consensus treatment plans (CTPs) for use in clinical practice to facilitate such studies.</p>

<p><strong>METHODS: </strong>A case-based survey was administered to CARRA members to identify the common treatment approaches for new-onset polyarticular JIA. Two face-to-face consensus conferences employed modified nominal group technique to identify treatment strategies, operational case definition, end points, and data elements to be collected. A core workgroup reviewed the relevant literature, refined plans, and developed medication dosing and monitoring recommendations.</p>

<p><strong>RESULTS: </strong>The initial case-based survey identified significant variability among treatment approaches for new-onset polyarticular JIA. We developed 3 CTPs based on treatment strategies for the first 12 months of therapy, as well as case definitions and clinical and laboratory monitoring schedules. The CTPs include a step-up plan (nonbiologic disease-modifying antirheumatic drug [DMARD] followed by a biologic DMARD), an early combination plan (nonbiologic and biologic DMARD combined within a month of treatment initiation), and a biologic only plan. This approach was approved by 96% of the CARRA JIA Research Committee members attending the 2013 CARRA face-to-face meeting.</p>

<p><strong>CONCLUSION: </strong>Three standardized CTPs were developed for new-onset polyarticular JIA. Coupled with data collection at defined intervals, use of these CTPs will enable the study of their comparative effectiveness in an observational setting to optimize initial management of polyarticular JIA.</p>

10.1002/acr.22259

Arthritis Care Res (Hoboken)

24339215

Detection of enthesitis in children with enthesitis-related arthritis: dolorimetry compared to ultrasonography.

2014

218-27

2014 Jan

2326-5205

<p><strong>OBJECTIVE: </strong>To evaluate the distribution of enthesitis and the accuracy of physical examination with a dolorimeter for the detection of enthesitis in children, using ultrasound (US) assessment as the reference standard.</p>

<p><strong>METHODS: </strong>We performed a prospective cross-sectional study of 30 patients with enthesitis-related arthritis (ERA) and 30 control subjects. The following tendon insertion sites were assessed by standardized physical examination with a dolorimeter and US: common extensor on the lateral humeral epicondyle, common flexor on the medial humeral epicondyle, quadriceps at the superior patella, patellar ligament at the inferior patella, Achilles, and plantar fascia at the calcaneus.</p>

<p><strong>RESULTS: </strong>Abnormal findings on US were detected most commonly at the insertion of the quadriceps (30% [18 of 60 sites]), common extensor (12% [7 of 60]), and Achilles (10% [6 of 60]) tendons. The intrarater reliability of US (kappa statistic) was 0.78 (95% confidence interval [95% CI] 0.63-0.93), and the interrater reliability was 0.81 (95% CI 0.67-0.95). Tenderness as detected by standardized dolorimeter examination had poor positive predictive value for US-confirmed enthesitis. In comparison to controls, patients with ERA reported more pain and had lower pain thresholds at every site, including control sites (P &lt; 0.001 for all comparisons). The interrater reliability of dolorimeter examination for detection of enthesitis was low (κ = 0.49 [95% CI 0.33-0.65]).</p>

<p><strong>CONCLUSION: </strong>Compared to US, standardized dolorimeter examination for the detection of enthesitis in children has poor accuracy and reliability. The decreased pain threshold of ERA patients likely contributed to the limited accuracy of the physical examination findings. Further research regarding the utility of US for identifying enthesitis at diagnosis of juvenile idiopathic arthritis, accurately predicting disease progression, and guiding therapeutic decisions is warranted.</p>

10.1002/art.38197

24449586