Session Information
Date: Sunday, November 8, 2015
Session Type: ACR Poster Session A
Session Time: 9:00AM-11:00AM
Background/Purpose: Most clinical trials evaluating anti-TNF agents for treating non-radiographic axial SpA (nr-axSpA) place the primary endpoint at 12 wks, and most formularies require assessment of response 12-16 wks after starting anti-TNF therapy. However, data from the EMBARK study (ClinicalTrials.gov identifier: NCT01258738) suggest the 24-wk time point may be more appropriate for evaluating response to etanercept (ETN). This analysis aimed to compare the baseline (BL) characteristics of patients with early, delayed, and no treatment response.
Methods: Patients had axial SpA per Assessment of SpondyloArthritis international Society (ASAS) criteria without meeting modified NY radiographic criteria; Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score ≥4, disease symptoms for >3 months and <5 yrs, and had failed ≥2 NSAIDs. Patients were randomized to double-blind ETN 50 mg/wk or placebo for 12 wks, then received open-label ETN 50 mg/wk. This analysis includes the open-label modified intent-to-treat (mITT) population that was randomized to ETN. For ASAS20 and ASAS40 response, patients were split into 3 groups: early (12-wk) responders, delayed (24-wk) responders, and non-responders. Observed case (OC) and non-responder imputation (NRI) analyses were performed. Patients with missing data were excluded (OC analysis) or considered non-responders (NRI analysis). Comparison of BL characteristics used one-way analysis of variance with treatment as a factor for continuous variables and Fisher’s exact test or chi-square test for yes/no variables.
Results: 99 patients were in the mITT population, OC analysis. Mean (SD) age was 31.8 (7.8) yrs, 64.7% were male, and duration of disease symptoms was 2.4 (2.0) yrs; 66.7% of patients were human leukocyte antigen B27 (HLA-B27)+ and 83.8% had sacroiliitis on MRI (P=non-significant across response groups for all). For ASAS20 and ASAS40 responses, the OC analysis demonstrated significant BL differences among response groups for the following: CRP, BASDAI, ankylosing spondylitis disease activity score, patient global assessment, total back pain, inflammation, and Spondyloarthritis Research Consortium of Canada (SPARCC) SI joint score (table). Overall, values for BL disease characteristics were higher (more severe) for responders than non-responders, and highest for early responders. No significant BL differences existed in tender/swollen joint count, enthesitis, Maastricht Ankylosing Spondylitis Enthesitis Score, physician global assessment, or prior response to NSAIDs, per ASAS20 or ASAS40 response. NRI analysis results were similar.
Conclusion: Evaluating ASAS20 and ASAS40 results according to early, delayed, and no response demonstrated significant differences in several BL clinical characteristics and SPARCC MRI scores. These results may aid clinicians in treating patients with nr-axSpA.
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Table: Baseline Disease Characteristics of Early and Late Responders and Non-responders |
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Baseline Characteristic |
Week 12 Responders |
Week 24 Responders |
Non-Responders |
P-value* |
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ASAS20 N=55 |
ASAS40 N=35 |
ASAS20 N=16 |
ASAS40 N=15 |
ASAS20 N=28 |
ASAS40 N=49 |
ASAS20 |
ASAS40 |
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|
CRP, mg/L |
8.9 (12.7) |
11.6 (14.7) |
9.3 (10.8) |
3.1 (3.0) |
2.6 (2.6) |
5.3 (7.9) |
0.0182† |
0.0106† |
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CRP, mg/L, median |
4.3 |
5.5 |
3.9 |
2.6 |
1.5 |
2.0 |
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Elevated CRP (>3 mg/L), n (%) |
32 (58.2) |
23 (65.7) |
8 (50.0) |
6 (40.0) |
8 (28.6) |
19 (38.8) |
0.0366 |
0.0427 |
|
BASDAI, 0-10 cm VAS |
6.2 (1.7) |
6.3 (1.6) |
6.3 (1.4) |
6.3 (1.5) |
5.3 (2.0) |
5.5 (1.9) |
0.0382 |
0.0344 |
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BASFI, 0-10 cm VAS |
4.6 (2.3) |
4.9 (2.4) |
3.9 (2.5) |
4.5 (1.7) |
3.7 (2.6) |
3.6 (2.5) |
ns |
0.0152 |
|
ASDAS-CRP |
3.2 (0.9) |
3.5 (0.9) |
3.3 (0.9) |
2.9 (0.7) |
2.4 (0.7) |
2.7 (0.9) |
0.0003 |
0.0001 |
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PtGA, 0-10 cm VAS |
6.4 (1.7) |
6.6 (1.8) |
5.8 (1.8) |
6.1 (1.6) |
4.4 (2.8) |
5.0 (2.5) |
0.0001 |
0.0009 |
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Total back pain, 0-10 cm VAS |
6.0 (2.1) |
6.5 (2.1) |
5.8 (2.2) |
5.8 (1.6) |
4.3 (2.7) |
4.6 (2.6) |
0.0022 |
0.0003 |
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Inflammation,‡ 0-10 cm VAS |
6.5 (2.1) |
6.8 (2.0) |
6.1 (1.8) |
6.5 (2.1) |
4.8 (2.2) |
5.2 (2.1) |
0.0014 |
0.0003 |
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SPARCC MRI SIJ score (0-72) |
10.3 (10.7) |
12.7 (11.4) |
6.1 (5.1) |
7.0 (7.9) |
5.0 (8.8) |
5.2 (7.8) |
0.0168† |
0.0007† |
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SPARCC MRI SIJ score (0-72), median |
6.2 |
8.0 |
4.8 |
4.0 |
2.8 |
3.1 |
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SPARCC MRI 6-DVU spinal score (0-108) |
6.0 (8.8) |
6.7 (9.9) |
2.3 (2.9) |
5.5 (7.2) |
3.5 (3.8) |
3.2 (3.8) |
ns |
0.0258† |
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SPARCC MRI 6-DVU spinal score (0-108), median |
2.0 |
3.0 |
1.5 |
2.0 |
2.3 |
1.5 |
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Values are mean (SD) unless otherwise noted. Observed case analysis, ETN/ETN group. *P-value across early, late, and non-responders; one-way analysis of variance with treatment as factor. †P-value shows significant differences in mean value among the 3 response groups. ‡Inflammation is mean of the 2 morning stiffness-related BASDAI scores. ASDAS-CRP, Ankylosing Spondylitis Disease Activity Score based on C-reactive protein; BASDAI, Bath Ankylosing Spondylitis Disease Activity Index; BASFI, Bath Ankylosing Spondylitis Functional Index; CRP, C-reactive protein; DVU, discovertebral units; MRI, magnetic resonance imaging; ns, non-significant; PtGA, patient global assessment; SIJ, sacroiliac joint; SPARCC, Spondyloarthritis Research Consortium of Canada; VAS, visual analog scale. |
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To cite this abstract in AMA style:
Maksymowych W, Bukowski JF, Marshall L, Szumski A, Jones H. Baseline Characteristics of Early, Delayed, and Non-Responders in a Non-Radiographic Axial Spondyloarthritis Study [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/baseline-characteristics-of-early-delayed-and-non-responders-in-a-non-radiographic-axial-spondyloarthritis-study/. Accessed .« Back to 2015 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/baseline-characteristics-of-early-delayed-and-non-responders-in-a-non-radiographic-axial-spondyloarthritis-study/