Session Information
Session Type: Abstract Submissions (ACR)
Background/Purpose: Functional impairment among patients with rheumatoid arthritis (RA) can be conceptualized as consisting of a reversible component that relates to disease activity (ACT-HAQ) and an irreversible component related to structural damage (DAM-HAQ). We assessed changes in DAM-HAQ and ACT-HAQ in early RA patients receiving different treatment strategies in the OPTIMA trial.
Methods: OPTIMA was a 78-week, phase 4, randomized, controlled trial of adalimumab (ADA) 40 mg every other week + methotrexate (MTX) vs. placebo (PBO)+MTX for 26 wks (period 1) in MTX-naïve patients aged ≥18 yrs with early RA <1 yr in duration. Responders achieving low disease activity (LDA) at both wks 22 and 26 with ADA+MTX were re-randomized to withdraw or continue ADA+MTX; PBO+MTX responders continued PBO+MTX; and inadequate responders (IR) could receive open-label (O-L) ADA+MTX (O-L ADA+MTX) for an additional 52 wks (period 2). HAQ-DI (HAQ) and modified Total Sharp Score (mTSS) were assessed at baseline, wk 26, wk 52, and wk 78. DAM-HAQ was calculated from mTSS, DAM-HAQ = 0.01*mTSS; ACT-HAQ was the difference between HAQ-DI and DAM-HAQ.1
Results: Mean disease activity scores at baseline and wks 26, 52, and 78 are presented in the table. At baseline, HAQ scores were high, indicating substantial functional disability. Since damage was low, ACT-HAQ contributed the vast majority of disability. Baseline DAM-HAQ scores were similar across all treatment groups and remained low throughout the study to wk 78. ACT-HAQ scores improved in patients responding during period 1. HAQ scores also improved in patients not achieving stable LDA during period 1, and continued to improve in period 2. In both ADA+MTX(IR)→O-L ADA+MTX and PBO+MTX(IR)→O-L ADA+MTX groups, although the extent of improvement was less than in the responders in period 1, scores continued to improve in period 2. Of note, although the HAQ score at week 78 was higher in the 2 groups not achieving LDA at weeks 22 and 26, the major contributor was ACT-HAQ, in line with the higher disease activity; DAM-HAQ was comparable across groups and contributed less to the total HAQ.
Conclusion: In these early RA patients, baseline disease activity resulted in substantial functional impairment. Patients who responded to early treatment with either ADA+MTX or PBO+MTX had low ACT-HAQ and DAM-HAQ values at wk 26 that were sustained through week 78. Patients with an inadequate response after 22 and 26 wks of PBO+MTX or ADA+MTX therapy showed significant improvement in HAQ even though not achieving LDA, and further improvement when treated with O-L ADA+MTX. Notably, even among initial inadequate responders, the disability at week 78 mostly consisted of ACT-HAQ, suggesting the potential for further improvement in these patients with further adjustment of treatment regimen.
|
Table. Summary of mean disease activity scores |
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|
|
Na |
Treatment Arm |
Baseline Score |
Week 26 Score |
Week 52 Score |
Week 78 Score |
|
|
Period 1 (Week 0–26) |
Period 2 (Week 27–78) |
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|
HAQ-DIb |
102 |
ADA+MTX(R) |
PBO+MTX |
1.62 |
0.33 |
0.44 |
0.38 |
|
104 |
ADA+MTX(R) |
ADA+MTX |
1.38 |
0.35 |
0.32 |
0.34 |
|
|
255 |
ADA+MTX(IR) |
O-L ADA+MTX |
1.72 |
0.99 |
0.90 |
0.87 |
|
|
112 |
PBO+MTX(R) |
PBO+MTX |
1.36 |
0.29 |
0.30 |
0.39 |
|
|
346 |
PBO+MTX(IR) |
O-L ADA+MTX |
1.66 |
1.07 |
0.76 |
0.74 |
|
|
ACT-HAQb,c,e |
102 |
ADA+MTX(R) |
PBO+MTX |
1.50 |
0.21 |
0.32 |
0.26 |
|
104 |
ADA+MTX(R) |
ADA+MTX |
1.29 |
0.24 |
0.21 |
0.23 |
|
|
255 |
ADA+MTX(IR) |
O-L ADA+MTX |
1.62 |
0.88 |
0.78 |
0.76 |
|
|
112 |
PBO+MTX(R) |
PBO+MTX |
1.28 |
0.20 |
0.21 |
0.29 |
|
|
346 |
PBO+MTX(IR) |
O-L ADA+MTX |
1.54 |
0.94 |
0.63 |
0.61 |
|
|
DAM-HAQd,e |
102 |
ADA+MTX(R) |
PBO+MTX |
0.12 |
0.12 |
0.12 |
0.12 |
|
104 |
ADA+MTX(R) |
ADA+MTX |
0.11 |
0.11 |
0.11 |
0.11 |
|
|
256 |
ADA+MTX(IR) |
O-L ADA+MTX |
0.11 |
0.12 |
0.11 |
0.11 |
|
|
112 |
PBO+MTX(R) |
PBO+MTX |
0.09 |
0.09 |
0.09 |
0.09 |
|
|
347 |
PBO+MTX(IR) |
O-L ADA+MTX |
0.12 |
0.13 |
0.13 |
0.13 |
|
|
mTSSe |
102 |
ADA+MTX(R) |
PBO+MTX |
12.2 |
12.2 |
12.0 |
12.1 |
|
104 |
ADA+MTX(R) |
ADA+MTX |
10.8 |
10.9 |
11.0 |
11.1 |
|
|
256 |
ADA+MTX(IR) |
O-L ADA+MTX |
11.3 |
11.6 |
11.4 |
11.5 |
|
|
112 |
PBO+MTX(R) |
PBO+MTX |
8.9 |
9.2 |
9.4 |
9.4 |
|
|
347 |
PBO+MTX(IR) |
O-L ADA+MTX |
11.7 |
13.0 |
13.1 |
13.2 |
|
|
DAS28b |
99 |
ADA+MTX(R) |
PBO+MTX |
5.90 |
2.19 |
2.44 |
2.37 |
|
104 |
ADA+MTX(R) |
ADA+MTX |
5.70 |
2.04 |
1.96 |
1.99 |
|
|
255 |
ADA+MTX(IR) |
O-L ADA+MTX |
6.21 |
4.15 |
3.56 |
3.51 |
|
|
108 |
PBO+MTX(R) |
PBO+MTX |
5.48 |
2.23 |
2.30 |
2.43 |
|
|
341 |
PBO+MTX(IR) |
O-L ADA+MTX |
6.14 |
4.50 |
3.27 |
3.08 |
|
|
SDAIb |
99 |
ADA+MTX(R) |
PBO+MTX |
41.22 |
4.55 |
6.25 |
5.83 |
|
104 |
ADA+MTX(R) |
ADA+MTX |
39.12 |
3.98 |
3.69 |
3.96 |
|
|
252 |
ADA+MTX(IR) |
O-L ADA+MTX |
46.99 |
21.74 |
15.74 |
15.99 |
|
|
108 |
PBO+MTX(R) |
PBO+MTX |
36.00 |
4.49 |
5.40 |
6.70 |
|
|
341 |
PBO+MTX(IR) |
O-L ADA+MTX |
45.25 |
24.78 |
13.09 |
11.82 |
|
|
aIntent-to-treat patients with at least 1 dose in period 2; bLast observation carried forward; cACT-HAQ = HAQ-DI – DAM-HAQ; dDAM-HAQ = 0.01*mTSS ; eMultiple imputations. ACT-HAQ, disability index related to disease activity; ADA, adalimumab; DAM-HAQ, disability index related to joint damage; DAS28, 28-joint disease activity score with C-reactive protein; HAQ-DI, Health Assessment Questionnaire Disability Index; IR, inadequate responder; mTSS, modified Total Sharp Score; PBO, placebo, R, responder; SDAI, Simplified Disease Activity Index. |
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Reference
Ann Rheum Dis 2010;69:1058–1064.
Disclosure:
J. S. Smolen,
Abbott, Amgen, Astra-Zeneca, BMS, Celgene Centocor-Janssen, Glaxo, Lilly, Pfizer (Wyeth), MSD (Schering-Plough), Novo-Nordisk, Roche, Sandoz, and UCB,
2,
Abbott, Amgen, Astra-Zeneca, BMS, Celgene Centocor-Janssen, Glaxo, Lilly, Pfizer (Wyeth), MSD (Schering-Plough), Novo-Nordisk, Roche, Sandoz, and UCB,
5;
R. Fleischmann,
Abbott, Pfizer, Merck, Roche, UCB, Celgene, Centocor-Jannsen, Amgen, AstraZeneca, BMS, Lilly, and Novartis. ,
2,
Abbott, Pfizer, Merck, Roche, UCB, Celgene, Centocor-Jannsen, Amgen, AstraZeneca, BMS, Lilly, and Novartis. ,
5;
P. Emery,
Abbott, Merck, Pfizer, UCB, Roche, and BMS,
5;
R. F. van Vollenhoven,
Abbott Laboratories,
2,
Bristol-Myers Squibb,
2,
GlaxoSmithKline,
2,
Human Genome Sciences, Inc.,
2,
MSD,
2,
Pfizer Inc,
2,
Roche Pharmaceuticals,
2,
UCB Pharma,
2,
Abbott Laboratories,
5,
Bristol-Myers Squibb,
5,
GlaxoSmithKline,
5,
Human Genome Sciences, Inc.,
5,
MSD,
5,
Pfizer Inc,
5,
Roche Pharmaceuticals,
5,
UCB Pharma,
5;
S. Florentinus,
Abbott Laboratories,
1,
Abbott Laboratories,
3;
F. Faccin,
Abbott Laboratories,
1,
Abbott Laboratories,
3;
S. S. Rathmann,
Abbott Laboratories,
3,
Abbott Laboratories,
1;
H. Kupper,
Abbott Laboratories,
1,
Abbott Laboratories,
3;
A. Kavanaugh,
Abbott, Amgen, Astra-Zeneca, BMS, Celgene, Centocor-Janssen, Pfizer, Roche, and UCB,
2,
Abbott, Amgen, Astra-Zeneca, BMS, Celgene, Centocor-Janssen, Pfizer, Roche, and UCB,
5.
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