Session Information
Session Type: Abstract Submissions (ACR)
Background/Purpose: In a randomized double-blind, placebo-controlled 2-year investigator-initiated trial of patients with early rheumatoid arthritis¹ (RA) we aimed to investigate if additional adalimumab (ADA) for 1 year on top of an aggressive treat-to-target strategy with methotrexate (MTX) and intraarticular (i.a.) corticosteroid reduces structural damage progression assessed by conventional radiography.
Methods: DMARD naïve early RA patients (n=180) were randomized 1:1 to receive i.a. triamcinolone (40 mg/ml) in any swollen joint and MTX (20 mg/wk) for two years in combination with placebo-ADA (MTX+PLA) or MTX+ADA (40 mg eow) during the first year. Oral glucocorticoid was not allowed. After 1 year, PLA/ADA was withdrawn. During year 2, in both treatment arms, ADA (40 mg eow) was only (re)initiated in patients with recurrence of active disease (DAS28CRP>3.2). Radiographic changes in hands, wrists and feet (Joint Space Narrowing (JSN), Erosion (ES) and Total Sharp Score (TSS)) were evaluated at baseline, 1 and 2 years.
Results: Baseline characteristics were similar in the MTX+PLA and MTX+ADA groups: DAS28CRP 5.6 vs. 5.5, p=0.53. After 2 years the median MTX dose in the MTX+PLA/MTX+ADA group was 20/20 mg/wk, p=0.33, and the cumulated i.a. triamcinolone dose 8/6 ml, p=0.15. During the 2ndyear biologics were initiated in 15%/17%, p=0.97. The 1- and 2-year remission rates (DAS28CRP<2.6) in the MTX+PLA/MTX+ADA group were 49%/74% (p=0.0001) and 69%/66% (p=0.79), respectively. ADA reduced erosive progression (ΔES) throughout the study (table). The percentage of patients with erosive disease increased in the MTX+PLA/MTX+ADA group with 12%/2% during year 1 and remained unchanged during year 2. The annual erosive progression (ΔES) and the percentage of patients who progressed were lower in the MTX+ADA group in year 1 (p=0.02/p=0.04) and also in year 2, after ADA withdrawal (p=0.005/p=0.04). After 2 years total ES was borderline lower in the MTX+ADA group (p=0.06). ΔTSS was lower in the ADA+MTX group than in the PLA+MTX group in year 1 (mean 0.27 vs. 1.64, p<0.009) but not in year 2 (0.78 vs. 0.99, p=0.46).
Conclusion: Despite very limited radiographic progression following an aggressive treat-to-target therapeutic strategy applying methotrexate and i.a. glucocorticoid injections into swollen joints during 2 years, radiographic erosive progression was significantly reduced by adding induction therapy with adalimumab during the 1styear. The effect of adalimumab persisted even after its withdrawal.
¹Hørslev-Petersen K et al. Ann Rheum Dis Online First 7 mar 2013
|
MTX+ 1st YR |
MTX+ 1st YR ADA |
P |
MTX+ 1st YR |
MTX+ 1st YR ADA |
P |
MTX+ 1st YR |
MTX+ 1st YR ADA |
P |
|||
|
Baseline |
Year 1 |
Year 2 |
|||||||||
|
ES |
1[0;12]/ 2.23(4.23) |
1[0;8.7]/ 1.92(3.56) |
0.87 |
1[0;15]/ 3.23(5.09) |
1[0;6]/ 2.06(3.49) |
0.17 |
1[0;18]/ 4.02(6.19) |
1[0;10]/ 2.15(3.77) |
0.06 |
||
|
JSN |
1[0;9.4]/ 2.26(3.24) |
2[0;8.8]/ 2.33(2.88) |
0.53 |
2[0;9.5]/ 2.74(3.43) |
2[0;7]/ 2.38(2.78) |
0.69 |
2[0;9.6]/ 2.97(3.86) |
2[0;10.8]/ 3.06(3.66) |
0.80 |
||
|
TSS |
2[0;21]/ 4.48(6.68) |
3[0;14.3]/ 4.28(5.06) |
0.32 |
4[0;22.6]/ 5.94(7.37) |
4[0;14.2]/ 4.46(5.10) |
0.39 |
4[0;28]/ 6.97 (8.61) |
3[0;17.4]/ 5.23(6.03) |
0.36 |
||
|
ES≥1 |
52 % |
54 % |
0.94 |
66 % |
56 % |
0.24 |
66 % |
56 % |
0.21 |
||
|
JSN≥1 |
57 % |
62 % |
0.69 |
63 % |
61 % |
0.97 |
66 % |
67 % |
0.96 |
||
|
TSS≥1 |
72 % |
80 % |
0.28 |
78 % |
79 % |
1.00 |
80 % |
84 % |
0.66 |
||
|
|
|
|
|||||||||
|
Year 0-1 |
Year 1-2 |
Year 0-2 |
|||||||||
|
ΔES |
0[-2;7.5]/ 1.13(3.08) |
0[-2;2]/ 0.12(1.37) |
0.02 |
0[-1;4.6]/ 0.76(2.14) |
0[-1.8;2.8]/ 0.09(1.52) |
0.005 |
0[-2;8]/ 1.90(4.68) |
0[-2;2]/ 0.21(1.49) |
0.008 |
||
|
ΔJSN |
0[-2;3.7]/ 0.52(1.71) |
0[-2;2]/ 0.15(1.34) |
0.08 |
0[-2;3]/ 0.22(1.56) |
0[-0.8;3]/ 0.68(2.31) |
0.13 |
0[-2;5.7]/ 0.74(2.16) |
0[-2;5]/ 0.84(2.65) |
0.86 |
||
|
ΔTSS |
0[-2;8]/ 1.64(3.88) |
0[-2.8;3]/ 0.27(2.01) |
0.009 |
0[-1.6;5.6]/ 0.99(2.71) |
0[-2;5]/ 0.78(2.72) |
0.46 |
0[-2.8;10.8]/ 2.63(5.67) |
0[-2.8;7.8]/ 1.05(3.07) |
0.12 |
||
|
ΔES≥1 |
41 % |
24 % |
0.04 |
36 % |
21 % |
0.04 |
45 % |
28 % |
0.03 |
||
|
DJSN ≥1 |
28 % |
16 % |
0.12 |
20 % |
27 % |
0.36 |
29 % |
29 % |
1.00 |
||
|
ΔTSS≥1 |
48 % |
33 % |
0.07 |
39 % |
40 % |
1.00 |
49 % |
46 % |
0.81 |
||
|
Erosion (ES), Joint Space Narrowing (JSN) and Total Sharp (TSS) scores at baseline, year 1 and 2; and Δ scores 0-1, 1-2 and 0-2 years. Values are median [5%; 95% percentiles]/mean(SD) or percentage. P values are based on Mann-Whitney or Pearson’s chi-square tests. Analysis was by intention-to-treat. ITT with last observation carried forward and completer analyses gave similar results (not shown). |
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Disclosure:
K. Hørslev-Petersen,
UCB,
8;
L. M. Ørnbjerg,
None;
M. L. Hetland,
None;
P. Junker,
None;
J. Pødenphant,
None;
T. Ellingsen,
None;
P. Ahlqvist,
None;
H. M. Lindegaard,
Lilly, MSD, Nordpharma, Roche,
8;
A. Linauskas,
None;
A. Schlemmer,
MSD, UCB,
8;
M. Y. Dam,
None;
I. Hansen,
None;
T. Lottenburger,
None;
A. Jørgensen,
None;
S. B. Krintel,
None;
J. Raun,
None;
C. G. Ammitzbøll,
None;
J. Johansen,
None;
M. Østergaard,
None;
K. Stengaard-Pedersen,
None.
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