Session Information
Session Type: Abstract Submissions
Session Time: 5:30PM-7:00PM
Background/Purpose: Enthesitis-related arthritis (ERA) is a category of juvenile idiopathic arthritis (JIA), with clinical features similar to those of adult spondyloarthritis (SpA). An unmet ERA need is the development of distinct disease activity measures and response criteria. The purpose of this analysis was to assess discriminatory aspects of several JIA and SpA clinical response criteria and disease activity measures for patients (pts) with ERA.
Methods: This post hoc analysis evaluated data from a 12-week (wk), randomized, placebo (PBO)-controlled trial of adalimumab (ADA) in pts 6 – <18 years of age with active ERA despite prior NSAID and DMARD therapy. JIA and SpA clinical response criteria were assessed categorically as the percentage of pts achieving response at wk 12. Continuous disease activity measures were assessed as mean change from baseline to wk 12. Categorical and continuous variables were analyzed by NRI and LOCF, respectively. Differences in categorical variables between ADA and PBO groups were assessed using chi-square values. Continuous variables were assessed for between group differences by Guyatt’s effect size and standardized mean difference (SMD).
Results: At baseline, demographics and disease characteristics in ADA (n=31) and PBO (n=15) were balanced. Most pts were HLA-B27 positive males, with a mean age of 13 years; patients had experienced ~2.5 years of active disease, and exhibited a mean of 8 active joints with arthritis and 8 sites of enthesitis. Of the response criteria evaluated, the ASDAS-CRP disease states, ASDAS major improvement, BASDAI50, and higher levels of ACRPedi response appeared to discriminate best between ADA and PBO groups (Table 1), whereas ACRPedi30 did not discriminate well between treatments. The parent’s assessment of pt’s overall well-being appeared to perform the best of the disease activity measures in discriminating ADA from PBO (Table 2). Physician’s global assessment, parent’s assessment of pt’s pain, BASDAI, ASDAS, and JADAS-10 also appeared to discriminate well.
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Table 1. Discrimination Between Adalimumab and Placebo at Week 12 Using Clinical Response Criteria |
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Clinical Response |
ADA (n=31) |
PBO (n=15) |
Chi Square Value |
P value |
|
ASDAS-CRP ASDAS <1.3 ASDAS ≥1.3 – <2.1 ASDAS ≥2.1 – ≤3.5 ASDAS >3.5 |
52 13 23 13 |
20 20 27 33 |
5.01 |
.17 |
|
BASDAI50 |
61 |
27 |
4.85 |
.057 |
|
ACRPedi30/50/70/90/100 |
71/68/55/42/26 |
60/40/20/13/0 |
0.55/3.21/4.99/3.76/4.69 |
.46/.07/.03/.052/.03 |
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ASDAS major improvement (≥2) |
26 |
0 |
4.69 |
.03 |
|
JADAS-10 MDA (≤2) |
36 |
13 |
2.45 |
.12 |
|
ASDAS clinically important improvement (≥1.1) |
42 |
33 |
0.31 |
.58 |
|
BASDAI improvement ≥2 |
45 |
40 |
0.11 |
.74 |
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ADA and PBO values are percentage of patients. P value is from chi-square. ADA, adalimumab; PBO, placebo; ASDAS, ankylosing spondylitis disease activity score; CRP, C-reactive protein; BASDAI, Bath ankylosing spondylitis disease activity index; ACRPedi American College of Rheumatology pediatric response criteria; JADAS10, 10-joint juvenile arthritis disease activity score; MDA, minimal disease activity. |
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Table 2. Discrimination Between Adalimumab and Placebo at Week 12 Using Disease Activity Measures |
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Outcome Variable |
ADA (n=31) |
PBO (n=15) |
Guyatt’s Effect Size |
SMD |
T-score |
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Parent’s global assessment of patient’s overall well-being, VAS |
-29.2 (29.78) |
-16.5 (10.53) |
-2.77 |
-0.50 |
-1.60 |
|
Parent’s assessment of patient’s pain, VAS |
-32.5 (28.98) |
-19.9 (21.69) |
-1.50 |
-0.47 |
-1.50 |
|
JADAS-10 |
-9.9 (7.30) |
-5.7 (6.90) |
-1.43 |
-0.59 |
-1.87 |
|
Morning stiffness (BASDAI inflammation) |
-3.0 (3.06) |
-1.3 (2.14) |
-1.42 |
-0.60 |
-1.92 |
|
Physician’s global assessment of disease activity, VAS |
-31.4 (24.76) |
-22.1 (23.27) |
-1.35 |
-0.38 |
-1.22 |
|
BASDAI, 0-10 |
-2.5 (2.80) |
-1.4 (2.18) |
-1.17 |
-0.44 |
-1.39 |
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ASDAS-CRP |
-1.0 (1.26) |
-0.6 (0.84) |
-1.15 |
-0.30 |
-0.96 |
|
SPARCC enthesitis index, 0-16 |
-2.6 (3.30) |
-2.4 (2.69) |
-0.98 |
-0.08 |
-0.25 |
|
TJC, 0-72 |
-7.9 (8.25) |
-4.5 (8.97) |
-0.88 |
-0.40 |
-1.28 |
|
Number of sites of enthesitis, 0-35 |
-4.4 (6.20) |
-2.7 (4.98) |
-0.87 |
-0.28 |
-0.88 |
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Number of joints with LOM, 0-66 |
-3.3 (3.89) |
-1.1 (3.77) |
-0.86 |
-0.57 |
-1.81 |
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MASES, 0-13 |
-1.7 (2.61) |
-0.7 (2.28) |
-0.76 |
-0.40 |
-1.28 |
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SJC, 0-68 |
-3.5 (5.61) |
-2.4 (4.66) |
-0.76 |
-0.21 |
-0.67 |
|
AJC, 0-72 |
-4.4 (6.08) |
-2.5 (6.01) |
-0.73 |
-0.32 |
-1.01 |
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Patient’s assessment of total back pain, VAS |
-14.6 (24.18) |
-9.5 (23.89) |
-0.61 |
-0.21 |
-0.65 |
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CHAQ, 0-3 |
-0.2 (0.56) |
-0.1 (0.41) |
-0.60 |
-0.36 |
-1.13 |
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hsCRP, mg/L |
0.4 (16.39) |
-4.8 (23.12) |
0.02 |
0.28 |
0.89 |
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Number of digits with dactylitis, 0-20 |
-0.4 (1.54) |
0.0 (0.00) |
N/A |
-0.28 |
-0.89 |
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ADA and PBO values are mean change from baseline to week 12 (standard deviation). Missing values are imputed using last observation carried forward. Guyatt’s effect size = mean ADA group/PBO standard deviation; SMD = difference between groups/standard deviation for difference between groups. ADA, adalimumab; PBO, placebo; VAS, visual analog scale; JADAS10, 10-joint juvenile arthritis disease activity score; BASDAI, Bath ankylosing spondylitis disease activity index; ASDAS, ankylosing spondylitis disease activity score; CRP, C-reactive protein; SPARCC, spondyloarthritis research consortium of Canada; TJC, tender joint count; LOM, loss of motion; MASES, Maastricht ankylosing spondylitis enthesitis score; SJC, swollen joint count; AJC, active joint count; CHAQ, childhood health assessment questionnaire; hsCRP, high sensitivity C-reactive protein; mg, milligram; L, liter. |
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Conclusion: Of the JIA and SpA assessments, several response criteria and disease activity measures appeared to discriminate active drug from placebo, suggesting candidate efficacy endpoints for future trials of pts with ERA. ACRPedi30, a typical endpoint in polyarticular JIA trials, did not perform well in this cohort, highlighting the differences in manifestations between ERA and polyarticular JIA.
To cite this abstract in AMA style:
Burgos-Vargas R, Horneff G, Tse SML, Quartier P, Unnebrink K, Anderson JK. Performance of Disease Activity Measures in Pediatric Patients With Enthesitis-related Arthritis [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 4). https://acrabstracts.org/abstract/performance-of-disease-activity-measures-in-pediatric-patients-with-enthesitis-related-arthritis/. Accessed .« Back to 2017 Pediatric Rheumatology Symposium
ACR Meeting Abstracts - https://acrabstracts.org/abstract/performance-of-disease-activity-measures-in-pediatric-patients-with-enthesitis-related-arthritis/