Session Information
Session Type: Abstract Submissions (ACR)
Background/Purpose: Baricitinib, an oral inhibitor of JAK1 and JAK2 activity, was investigated as treatment for patients with moderately to severely active RA despite use of conventional disease modifying anti-rheumatic drugs (Phase 2b Study JADA; NCT01185353). Compared to placebo, baricitinib (4 mg or 8 mg once daily (QD)) improved signs, symptoms, and physical function through 12 weeks of treatment with statistically significant effects observed as early as Week 2 of the study. Beneficial responses to baricitinib were maintained or improved through Week 241. The objective of this post-hoc analysis was to determine whether early clinical response to baricitinib at Week 4 for the combined 4 and 8-mg dose groups predicted low disease activity (LDA) or remission at Week 12 and 24.
Methods: In Study JADA, 301 patients were randomized 2:1:1:1:1 to receive placebo or 1, 2, 4, or 8 mg baricitinib QD for 12 weeks, respectively, with the 2, 4, and 8-mg doses continued for an additional 12 weeks. Early clinical response was assessed by a variety of measures including DAS28-ESR (DAS-ESR). Week 12 and 24 outcomes were also assessed by a variety of measures including DAS-ESR LDA (DAS-ESR ≤3.2) or remission (DAS-ESR < 2.6). The association between improvements in clinical response at Week 4 for the combined 4/8-mg dose group (n=97) and Week 12 and 24 outcomes was evaluated based on observed data.
Results: Compared to placebo, baricitinib treatment was associated with rapid decrease in DAS-ESR observed as early as Week 2 (p<0.001 for both 4 and 8-mg dose groups). DAS-ESR LDA and remission rates were similar at Week 12 and Week 24 (35.1% and 35.2% for LDA; 21.6% and 24.2% for remission, respectively) for the combined 4/8-mg dose group. In 16.5% of patients, the decrease in DAS-ESR was <0.6 at Week 4. Among these patients, only 6.3% and 7.1% achieved DAS-ESR LDA at Week 12 and 24, respectively. No patients achieved remission at either time point. Among the 83.5% of patients whose DAS-ESR improved by ≥0.6 at Week 4, 40.7% and 40.3% achieved DAS-ESR LDA and 25.9% and 28.6% achieved DAS-ESR remission at Weeks 12 and 24, respectively (Table). Larger decreases in DAS-ESR at Week 4 were associated with a higher percentage of patients achieving LDA or remission at Weeks 12 and 24.
Conclusion: Baricitinib treatment was associated with a rapid decrease in DAS-ESR with stable DAS-ESR LDA and remission rates observed as early as Week 12 with persistence of benefit through Week 24. A <0.6 decrease in DAS-ESR after 4 weeks of baricitinib treatment was associated with a very low percentage of patients achieving LDA or remission at either Week 12 or Week 24. Larger decreases in DAS-ESR at Week 4 were associated with improved clinical responses. If replicated in Phase 3 studies, a lack of early response to baricitinib may be useful in tailoring therapy to individual patients.
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Low Disease Activity and Remission After 12 and 24 Weeks of 4 or 8 mg Baricitinib Treatment |
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LDA (DAS28-ESR ≤ 3.2) |
Remission (DAS28-ESR < 2.6) |
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Change in DAS-ESR from Baseline to Week 4 |
Week 12 |
Week 24 |
Week 12 |
Week 24 |
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% (Number) of Patients Achieving Clinical Outcome of Interest |
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<0.6 |
6.3% (1/16) |
7.1% (1/14) |
0% (0/16) |
0% (0/14) |
|
<0.8 |
8.7% (2/23) |
14.3% (3/21) |
0% (0/23) |
4.8% (1/21) |
|
<1.0 |
9.4% (3/32) |
16.7% (5/30) |
0% (0/32) |
6.7% (2/30) |
|
<1.2 |
8.3% (3/36) |
17.6% (6/34) |
0% (0/36) |
5.9% (2/34) |
|
|
% (Number) of Patients Achieving Clinical Outcome of Interest |
|||
|
≥0.6 |
40.7% (33/81) |
40.3% (31/77) |
25.9% (21/81) |
28.6% (22/77) |
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≥0.8 |
43.2% (32/74) |
41.4% (29/70) |
28.4% (21/74) |
30.0% (21/70) |
|
≥1.0 |
47.7% (31/65) |
44.3% (27/61) |
32.3% (21/65) |
32.8% (20/61) |
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≥1.2 |
50.8% (31/61) |
45.6% (26/57) |
34.4% (21/61) |
35.1% (20/57) |
- 1. M Genovese et al Arthritis and Rheumatism. 2012;64(10(supp)):S1049.
Disclosure:
E. Keystone,
Abbott Laboratories,
2,
Amgen,
2,
AstraZeneca LP,
2,
Baylis Medical,
2,
Bristol-Myers Squibb,
2,
Hoffmann-La Roche, Inc.,
2,
Janssen Pharmaceutica Product, L.P.,
2,
Eli Lilly and Company,
2,
Novartis Pharmaceutical Corporation,
2,
Pfizer Inc,
2,
Sanofi-Aventis Pharmaceutical,
2,
Ucb,
2,
Abbott Laboratories,
5,
AstraZeneca,
5,
Biotest,
5,
Bristol-Myers Squibb,
5,
Hoffmann-La Roche, Inc.,
5,
Genentech Inc.,
5,
Jannsen inc,
5,
Eli Lilly and Company,
5,
Merck Pharmaceuticals,
5,
Nycomed,
5,
Pfizer Inc,
5,
UCB,
5,
Abbott Laboratories,
9,
AstraZeneca,
9,
Bristol-Myers Squibb Canada,
9,
Hoffmann-La Roche, Inc.,
9,
Janssen Pharmaceutica Product, L.P.,
9,
Pfizer Inc,
9,
UCB,
9,
Amgen,
9;
M. Genovese,
Eli Lilly and Company,
2,
Eli Lilly and Company,
5;
P. Taylor,
Eli Lilly and Company,
5;
B. Zhu,
Eli Lilly and Company,
3,
Eli Lilly and Company,
1;
S. D. Beattie,
Eli Lilly and Company,
1,
Eli Lilly and Company,
3;
S. de Bono,
Eli Lilly and Company,
1,
Eli Lilly and Company,
3;
T. Rooney,
Eli Lilly and Company,
1,
Eli Lilly and Company,
3;
D. E. Schlichting,
Eli Lilly and Company,
1,
Eli Lilly and Company,
3;
W. Macias,
Eli Lilly and Company,
1,
Eli Lilly and Company,
3.
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