Abstract 699:Long-Term Efficacy and Safety of Abatacept through 3 Years of Treatment in Rheumatoid Arthritis Patients in the AIM and ATTAIN Trials
Authors
J. Kremer, R Westhovens, M Luggen, A Russell, R Aranda, J-C Becker, C Joshi, M Gandhi, MC Genovese.
Purpose
To evaluate long-term efficacy and safety of abatacept (ABA) through 3 yrs in the AIM and ATTAIN trials.
Methods
AIM and ATTAIN were randomized, double-blind, placebo-controlled trials of 12 and 6 months’ duration, respectively. Patients received fixed dose of ABA (~10 mg/kg) or PBO. AIM pts continued with background MTX. ATTAIN pts remained on ≥1 DMARD. Patients completing the double blind period were eligible to enroll in the open-label period (fixed dose of ABA ~10 mg/kg every 4 wks plus MTX/DMARDs). As-observed data were used to assess response to treatment (ACR 20, 50 and 70 responses) and disease status (Disease Activity Score 28 [DAS28]-defined remission [DAS28 <2.6, based on C-reactive protein (CRP) levels] and Low Disease Activity State [LDAS (DAS28 ≤3.2)]) in pts originally randomized to ABA. Safety was assessed at each visit.
Results
433 and 219 AIM pts were randomized and treated with ABA or PBO; 378 and 161 of these entered the open-label period, respectively, with 81.6% overall ongoing at 3 years. 258 and 133 ATTAIN pts were randomized and treated with ABA and PBO; 218 and 99 entered the open-lable period, respectively, with 60.9% overall ongoing at 3 years. No unique safety events were observed through 3 years of the AIM and ATTAIN trials, compared with the 12- and 6-month double-blind periods, respectively.
ACR and DAS28 (CRP) responders through 3 years of the AIM and ATTAIN trials |
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Measure of disease activity |
Trial |
Year |
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0.5 |
1 |
1.5 |
2 |
2.5 |
3 |
||
ACR 20 |
AIM |
73.3 (68.8, 77.8) |
82.3 (78.4, 86.2) |
85.0 (81.4, 88.6) |
87.5 (84.2, 90.9) |
83.3 (79.5, 87.1) |
84.8 (81.2, 88.4) |
ATTAIN |
62.0 (55.6, 68.5) |
65.7 (59.3, 72.0) |
70.8 (64.8, 76.9) |
75.6 (69.9, 81.4) |
83.3 (78.4, 88.3) |
97.3 (95.1, 99.4) |
|
ACR 50 |
AIM |
43.7 (38.7, 48.7) |
54.3 (49.3, 59.3) |
61.2 (56.3, 66.1) |
61.2 (56.3, 66.2) |
58.3 (53.3, 63.3) |
63.4 (58.5, 68.3) |
ATTAIN |
24.4 (18.7, 30.1) |
32.3 (26.1, 38.6) |
43.8 (37.2, 50.4) |
45.8 (39.1, 52.4) |
48.1 (41.5, 54.8) |
58.9 (52.4, 65.5) |
|
ACR 70 |
AIM |
22.2 (18.0), 26.4) |
32.4 (27.6, 37.1) |
36.0 (31.1, 40.9) |
38.2 (33.3, 43.1) |
34.7 (29.9, 39.5) |
37.5 (32.6, 42.4) |
ATTAIN |
11.8 (7.5, 16.1) |
18.3 (13.2, 23.5) |
21.6 (16.2, 27.1) |
22.6 (17.0, 28.1) |
20.3 (14.9, 25.6) |
27.4 (21.5, 33.4) |
|
LDAS (DAS28 [CRP] ≤3.2) |
AIM |
31.5 (26.8, 36.2) |
44.1 (39.0, 49.1) |
46.4 (41.3, 51.4) |
51.6 (46.6, 56.7) |
49.5 (44.4, 54.6) |
53.2 (48.1, 58.2) |
ATTAIN |
18.5 (13.4, 23.7) |
24.5 (18.8, 30.2) |
28.4 (22.4, 34.4) |
32.5 (26.2, 38.7) |
37.2 (30.8, 43.6) |
38.9 (32.4, 45.4) |
|
Remission (DAS28 [CRP] <2.6) |
AIM |
16.7 (12.9, 20.5) |
25.4 (21.0, 29.8) |
29.5 (24.8, 34.1) |
28.2 (23.6, 32.7) |
29.4 (24.8, 34.0) |
37.5 (32.6, 42.4) |
ATTAIN |
11.2 (7.0, 15.4) |
14.1 (9.4, 18.7) |
17.3 (12.2, 22.3) |
20.5 (15.2, 25.9) |
19.4 (14.1, 24.6) |
24.1 (18.4, 29.8) |
|
Data are shown as percentages (95% CI) |
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Conclusion
Clinical improvement was sustained in patients treated with abatacept over 3 years in both MTX and TNF-inadequate responders without any new safety signals.
Editorial Comment
These data were as-observed for efficacy endpioints and thus represent a completer analysis that biases toward increasing proportions of responders over time because of discontinuations from lack of efficacy. The numbers of patients at each time point is likely lower, thus accounting for some of the “increases” in response seen over time. There is a high rate of continuation on therapy at 3 years from both studies however suggests that there may not be a significant loss of efficacy over time. However, additional details concerning the numbers of patients at each point are needed as well as the reasons for discontinuation. It is notable that the numbers remaining on therapy at 3 years is higher in the MTX nonresponders (AIM) than in the study of TNF nonresponders (ATTAIN) consistent with a more refractory patient population enrolled in the latter study.
