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Abstract
Objective
The safety and efficacy of intravenous (IV) abatacept in patients with active RA unresponsive to methotrexate have been demonstrated in short-term (ST) studies in global populations and a ST, Phase III study in a Korean patient population. Abatacept's longterm safety and efficacy profile has been established in open-label global studies with treatment up to 5 years. The objective of this study was to determine the longterm safety and efficacy of abatacept in patients with RA from the ST Korean study.
Methods
This was an open-label longterm extension (LTE) of a Phase III, multicenter, randomized, double-blind, pla-cebo-controlled study in which Korean patients who had received IV abatacept or placebo in the ST trial (169 days) were given the option to receive open-label abatacept to Day 1485 with 84 days' followup (total 1,569 days, ∼4 years).
Results
A total of 105 patients were enrolled in the LTE (86.7% female, median age 49.0 years). Abatacept was generally well tolerated. Adverse events were mostly mild or moderate and no new safety signals were identified. Improvement in disease activity (assessed by ACR response and DAS28 [CRP]), physical function (assessed by KHAQ-DI), and quality of life (assessed by SF-36 score) were maintained in patients initially treated with abatacept or observed in patients who had switched to abatacept after placebo in the ST study.
References
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Figure 1.
Patient disposition and primary reasons for discontinuation over the 1485-day study period: (A) Double-blind ST study; (B) open-label LTE. AE: adverse event, LTE: longterm extension, ST: short-term.
Figure 2.
Response rates over time in all treated patients, by original, double-blind treatment group in the short-term (169 days) and open-label (1569 days) period, according to American College of Rheumatology (ACR) improvement criteria: (A) ACR 20, (B) ACR 50, and (C) ACR 70. As-observed analysis. Note that all patients received open-label abatacept during the LTE. DB: double-blind, LTE: longterm extension, ST: short-term.
Table 1.
Demographics and baseline characteristics of all treated patients in the open-label extension period
| Parameter∗ | ST abatacept (n=53) | ST placebo (n=52) | Total (n=105) |
|---|---|---|---|
| Age in years, mean (SD) | 47.4 (12.4) | 49.2 (10.5) | 48.3 (11.5) |
| Female, n (%) | 45 (84.9) | 46 (88.5) | 91 (86.7) |
| Duration of RA in years, mean (SD) | 9.3 (6.3) | 10.0 (7.0) | 9.6 (6.6) |
| No. of tender joints, mean (SD) | 25.2 (12.9) | 26.3 (16.0) | 25.7 (14.5) |
| No. of swollen joints, mean (SD) | 15.0 (5.3) | 14.1 (4.5) | 14.6 (4.9) |
| DAS28 (CRP), mean (SD) | 5.9 (0.9) | 5.7 (0.8) | 5.8 (0.8) |
| KHAQ-DI, mean (SD) | 1.6 (0.7) | 1.5 (0.6) | 1.6 (0.6) |
Table 2.
Adverse events experienced in all patients treated with abatacept on background methotrexate for an average of approximately 1485 days in the open-label extension period
| Parameter | Patients with events, n (%)(n/N [%])† | Incidence per 100 patient-years (95% CI) |
|---|---|---|
| Deaths | 1 (1.0) | NA |
| SAEs | 41 (39.0) | 14.0 (10.1, 19.0) |
| Related SAEs | 10 (9.5) | NA |
| Discontinuations due to SAEs | 8 (7.6) | NA |
| AEs | 100 (95.2) | NA |
| Related AEs | 45 (42.9) | NA |
| Discontinuations due to AEs | 10 (9.5) | NA |
| AEs of interest | ||
| Infections/Infestations | 75 (71.4) | 44.9 (35.3, 56.3) |
| Malignancy | 5 (4.8) | 1.4 (0.5, 3.3) |
| Autoimmune disorders (pre-specified) | 6 (5.7) | 1.7 (0.6, 3.7) |
| Infusion reactions (pre-specified) | ||
| Acute (≤1 h after start of dosing) | 4 (3.8) | NA |
| Peri-infusional (≤24 h after start of dosing) | 17 (16.2) | NA |
Table 3.
Efficacy responses in all treated patients in the open-label extension period∗
| Parameter | ST abatacept (n=53) | ST placebo (n=52) | ||
|---|---|---|---|---|
| Day 169 | Day 1485 | Day 169 | Day 1485 | |
| ACR response | ||||
| ACR 20, n/N (%) | 36/53 (67.9) | 26/31 (83.9) | 24/52 (46.2) | 30/35 (85.7) |
| ACR 50, n/N (%) | 18/53 (34.0) | 21/31 (67.7) | 9/52 (17.3) | 22/35 (62.9) |
| ACR 70, n/N (%) | 8/53 (15.1) | 12/31 (38.7) | 4/52 (7.7) | 16/35 (45.7) |
| DAS28 (CRP) score | ||||
| LDAS,† n/N (%) | 19/53 (35.8) | 19/31 (61.3) | 7/52 (13.5) | 24/35 (68.6) |
| Remission,‡ n/N (%) | 13/53 (24.5) | 11/31 (35.5) | 5/52 (9.6) | 19/35 (54.3) |
| Mean change (SE) | −2.25 (0.19) | −2.97 (0.23) | −1.26 (0.16) | −3.13 (0.22) |
| KHAQ-DI score | ||||
| KHAQ response,§ n/N (%) | 34/53 (64.2) | 24/31 (77.4) | 22/52 (42.3) | 21/35 (60.0) |
| Mean change (SE) | −0.56 (0.08) | −0.76 (0.14) | −0.28 (0.06) | −0.53 (0.11) |
| SF-36 | ||||
| Physical component score, mean change (SE) | 6.94 (1.19) | 10.34 (1.80) | 1.98 (1.06) | 8.48 (1.57) |
| Mental component score, mean change (SE) | 7.68 (1.64) | 7.93 (2.44) | 5.08 (1.66) | 7.73 (3.34) |
| SDAI score | ||||
| Baseline mean (SD) | 39.35 (12.32) | 39.69 (12.04) | 38.26 (10.93) | 37.01 (11.67) |
| Post-baseline mean (SD) | 16.52 (10.99) | 9.95 (7.50) | 24.18 (14.00) | 7.81 (6.21) |
| Mean change from baseline (SE) | −2.84 (1.87) | −29.74 (2.11) | −14.07 (1.60) | −29.20 (2.21) |
| 95% CI | (−26.58, −19.09) | (−34.06, −25.43) | (−17.28, −10.87) | (−33.70, −24.70) |
| CDAI score | ||||
| Baseline mean (SD) | 36.67 (11.65) | 36.82 (11.19) | 35.99 (10.49) | 34.74 (11.25) |
| Post-baseline mean (SD) | 15.68 (10.40) | 9.04 (7.01) | 22.50 (13.19) | 7.40 (6.08) |
| Mean change from baseline (SE) | −20.99 (1.76) | −27.79 (1.95) | −13.49 (1.46) | −27.34 (2.06) |
| 95% CI | (−24.52, −17.46) | (−31.78, −23.80) | (−16.42, −10.56) | (−31.54, −23.15) |
ACR: American College of Rheumatology, CDAI: Clinical Disease Activity Index, CI: confidence interval, DAS28 (CRP): 28-joint Disease Activity Score (C-reactive protein), KHAQ-DI: Korean Health Assessment Questionnaire Disability Index, LDAS: Low Disease Activity Score, SD: standard deviation, SDAI: Simplified Disease Activity Index, SE: standard error, SF-36: 36-item Short-Form questionnaire, ST: short-term.
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