Session Information
Session Type: Abstract Submissions (ACR)
Background/Purpose:
We assessed the discriminatory aspects of disease activity measures and response criteria between adalimumab (ADA) and placebo (PBO) in 2 studies of patients (pts) with peripheral spondyloarthritis (pSpA).
Methods:
ABILITY-2 is an ongoing randomized controlled trial of ADA in pts with pSpA fulfilling ASAS peripheral SpA criteria. Primary endpoint was peripheral SpA response criteria (PSpARC)40 at wk 12, defined as ≥40% improvement from baseline (BL) (≥20 mm absolute improvement on a visual analog scale) in Patient Global Assessments of Disease Activity (PGA) and Pain (PGA-pain) and ≥40% improvement in ≥1 of the following: swollen joint (SJC) and tender joint counts (TJC); enthesitis count; or dactylitis count. In an investigator-initiated study (AMC) in the Netherlands, pts fulfilling ESSG and/or AMOR criteria for SpA for ≥3 months but not criteria for ankylosing spondylitis or psoriatic arthritis were randomized to ADA or PBO. Primary endpoint was change in PGA at wk 12. Analyses to determine the discriminatory capacity of disease activity measures between ADA and PBO groups included standardized mean difference (SMD) of the mean change from BL; for categorical response criteria Pearson’s χ2 between treatments were calculated. The higher the SMD and χ2, the higher the discriminatory capacity. Variables evaluated included PGA, PGA-pain, Physician’s Global Assessment of Disease Activity (PhGA), CRP, TJC, SJC, BASDAI, SF-36, HAQ-S, ASDAS, PSpARC40/50/70, ACR20/50/70, ASDAS major improvement/inactive disease, and BASDAI50.
Results:
ABILITY-2 randomized 165 pts (ADA 84, PBO 81); AMC enrolled 40 pts (ADA 20, PBO 20). Among the continuous variables, ASDAS discriminates better than BASDAI or individual measures such as CRP as shown by higher SMD values (Table). For clinical response criteria, PSpARC40, PSpARC50, ASDAS inactive disease and BASDAI50 performed well in differentiating between ADA vs. PBO treatment as shown by the χ2 in the table. ACR20 and ACR50 performed better than ACR70 in differentiating between ADA vs. PBO.
Discrimination between patients on adalimumab vs. placebo at week 12
|
|
ABILITY-2 |
AMC |
||||||||
|
Mean Change from Baseline |
ADA (n) |
PBO (n) |
SMD |
Guyatt’s ES |
ADA (n) |
PBO (n) |
SMD |
Guyatt’s ES |
||
|
ASDAS |
-1.1 (80) |
-0.5 (77) |
-0.63 |
-1.18 |
-1.5 (19) |
-0.6 (19) |
-0.89 |
-1.90 |
||
|
BASDAI |
-2.1 (82) |
-1.0 (80) |
-0.50 |
-0.976 |
-1.9 (19) |
-0.3 (19) |
-0.73 |
-1.26 |
||
|
PGA (0–100 mm VAS) |
-28.0 (81) |
-16.2 (80) |
-0.47 |
-1.14 |
-31.0 (19) |
-5.9 (19) |
-1.12 |
-1.45 |
||
|
PhGA (0–100 mm VAS) |
-32.7 (82) |
-18.2 (81) |
-0.64 |
-1.43 |
-19.8 (19) |
-4.1 (19) |
-0.87 |
-1.21 |
||
|
CRP (mg/L) |
-5.8 (80) |
-2.9 (80) |
-0.18 |
-0.52 |
-5.7 (19) |
4.0 (19) |
-0.53 |
-0.25 |
||
|
SJC 76 |
-3.6 (82) |
-3.1 (81) |
-0.10 |
-0.64 |
-2.5 (19) |
-0.4 (19) |
-0.67 |
-1.40 |
||
|
TJC 78 |
-6.0 (82) |
-1.8 (81) |
-0.50 |
-0.72 |
-1.8 (19) |
1.7 (19) |
-0.45 |
-0.28 |
||
|
n (%) |
ADA |
PBO |
Pearson’s χ2 |
P-value |
ADA |
PBO |
Pearson’s χ2 |
P-value |
||
|
PSpARC40 |
33 (41) |
16 (20) |
8.18 |
0.004 |
7 (37) |
0 (0) |
8.58 |
0.008 |
||
|
PSpARC50 |
29 (36) |
9 (11) |
13.46 |
<0.001 |
6 (32) |
0 (0) |
7.13 |
0.020 |
||
|
PSpARC70 |
19 (24) |
3 (4) |
13.49 |
<0.001 |
3 (16) |
0 (0) |
3.26 |
0.230 |
||
|
ASDAS Major Improvement |
18 (23) |
5 (6) |
8.04 |
0.005 |
5 (26) |
2 (11) |
1.58 |
0.405 |
||
|
ASDAS Inactive Disease |
27 (34) |
12 (15) |
7.2 |
0.007 |
8 (42) |
0 (0) |
10.13 |
0.003 |
||
|
BASDAI50 |
35(43) |
15 (19) |
10.9 |
0.001 |
8 (42) |
1 (5) |
7.13 |
0.019 |
||
|
ACR20 |
47 (57) |
21 (26) |
16.05 |
<0.001 |
9 (47) |
0 (0) |
11.79 |
0.001 |
||
|
ACR50 |
28 (34) |
8 (10) |
13.66 |
<0.001 |
7 (37) |
0 (0) |
8.58 |
0.008 |
||
|
ACR70 |
15 (18) |
2 (3) |
10.75 |
0.001 |
4 (21) |
0 (0) |
4.47 |
0.105 |
||
Observed analyses. SMD: Standardized Mean Difference
Conclusion:
Composite indices (ASDAS and BASDAI) outperformed individual measures (TJC, SJC, CRP) in sensitivity to change and discriminatory properties. The PSpARC response criteria developed for pSpA, as well as ACR20 and ACR50, have good discriminatory ability in patients with pSpA. Although the ASDAS and to some extent BASDAI, which were developed for AS, performed reasonably well in being able to discriminate between active treatment and placebo in patients with peripheral SpA, there may be problems regarding face validity.
Disclosure:
S. Ramiro,
None;
M. C. Turina,
None;
D. L. Baeten,
AbbVie, BMS, Boehringer Ingelheim, Centocor, Janssen, MSD, Novartis, Pfizer, UCB,
2,
AbbVie, BMS, Boehringer Ingelheim, Centocor, Janssen, MSD, Novartis, Pfizer, UCB,
5,
AbbVie, BMS, Boehringer Ingelheim, Centocor, Janssen, MSD, Novartis, Pfizer, UCB,
8;
P. J. Mease,
AbbVie, Amgen, Biogen Idec, Bristol Myers, Celgene, Genentech, Janssen, Lilly, Merck, Novartis, Pfizer, UCB, Vertex,
2,
AbbVie, Amgen, Biogen Idec, Bristol Myers, Celgene, Genentech, Janssen, Lilly, Merck, Novartis, Pfizer, UCB, Vertex,
5,
AbbVie, Amgen, Biogen Idec, Bristol Myers, Celgene, Genentech, Janssen, Lilly, Merck, Novartis, Pfizer, UCB, Vertex,
8;
J. E. Paramarta,
None;
I. H. Song,
AbbVie,
1,
AbbVie,
3;
A. L. Pangan,
AbbVie,
1,
AbbVie,
3;
R. Landewé,
AbbVie, Amgen, BMS, Centocor, GSK, Merck, Novartis, Pfizer, Roche, Schering-Plough, UCB, Wyeth,
5,
Rheumatology Consultancy bv,
4.
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