Session Information
Session Type: Abstract Submissions (ACR)
Background/Purpose: Baricitinib is an oral inhibitor of JAK1/JAK2 being investigated as a treatment for rheumatoid arthritis (RA). In a phase 2b study, baricitinib treatment resulted in significant clinical improvements over 24 wks1. The safety and efficacy findings of baricitinib treatment in RA patients (pts) up to 128 wks are reported here.
Methods: Pts were randomized to placebo (PBO) or 1, 2, 4, or 8 mg baricitinib QD for 12 wks (Part A). Pts assigned to 2, 4, or 8 mg continued assigned treatment and pts assigned to PBO or 1 mg were reassigned to 4 mg QD or 2 mg BID for an additional 12 wks of blinded treatment (Part B). Pts completing Part B were eligible to enter a 52 wk open-label extension (OLE; Wks 24-76, Part C), where pts in the 8 mg group continued to receive 8 mg QD and all other pts received 4 mg QD. During Part C, doses could be escalated to 8 mg QD at 28 or 32 wks at the investigator’s discretion when ≥6 tender and ≥6 swollen joints were present. Pts completing Part C were eligible to enter an additional 52 wk OLE (Wks 76-128, Part D) where pts received 4 mg QD regardless of previous dose.
Results: Of 204 pts at sites participating in Part C, 201 (99%) were treated and 169 (84%) completed 52 wks. Among pts who remained on 4 mg (N=108) in Part C, TEAEs occurred in 63%, SAEs in 16%, infections in 35%, and serious infections in 5%. Among pts who received 8 mg at any time (N=93) in Part C, TEAEs occurred in 68%, SAEs in 13%, infections in 40%, and serious infections in 3%. Of 150 pts at sites participating in Part D, 144 (96%) were treated and 133 (92%) completed an additional 52 wks. Among pts who remained on 4 mg (N=79) in Part D, TEAEs occurred in 53%, SAEs in 6%, infections in 32%, and serious infections in 3%. Among pts who decreased to 4 mg (N=65) in Part D, TEAEs occurred in 55%, SAEs in 6%, infections in 28%, and serious infections in 3%. The exposure-adjusted incidence rates for adverse events for all baricitinib groups in Part D were similar to or lower than those rates observed in Part C (Table 1). No opportunistic infections, tuberculosis cases, or lymphomas were observed through 128 wks. One death due to myocardial infarction occurred in the 8 mg group in Part C. Among all pts combined, the proportions of pts achieving ACR20 or disease improvement at Wk 24 were similar or increased at Wks 76 and 128 (Table 2).
Conclusion: Among pts completing 128 wks of a phase 2b study, clinical improvements observed at Wk 24 were maintained or improved through Wk 128. In addition, safety data collected during the OLE were consistent with previous baricitinib findings1.
1Genovese M, et al. Arth Rheum 2012;64(Suppl 10):S1049-S1050.
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Table 1. Safety Summary |
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|
Weeks 24-76 (Part C) |
Weeks 76-128 (Part D) |
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|
4 mg (N=108) |
8 mg* (N=93) |
All Groups (N=201) |
Remained on 4 mg (N=79) |
Decreased to 4 mg (N=65) |
All Groups (N=144) |
|
|
|
n, (%) |
n, (%) |
IR† |
n, (%) |
n, (%) |
IR† |
|
TEAEs |
68 (63) |
63 (68) |
73.4 |
42 (53) |
36 (55) |
57.6 |
|
SAEs |
17 (16) |
12 (13) |
16.2 |
5 (6) |
3 (6) |
5.9 |
|
Infections |
38 (35) |
37 (40) |
42.6 |
25 (32) |
18 (28) |
31.8 |
|
Serious Infections |
5 (5) |
3 (3) |
4.9 |
2 (3) |
2 (3) |
3.0 |
|
*Randomized to 8 mg in Part A or escalated to 8 mg at Weeks 28 or 32 in Part C. Data after commencing 8 mg †Incidence rate = number of events per 100 patient-years of exposure to treatment |
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Table 2. Disease Improvement |
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n (%) |
Wk 24a (N=201) |
Wk 76b (N=201) |
Wk 128c
(N=144) |
|
ACR20 |
149 (74) |
137 (68) |
101 (70) |
|
CDAI ≤ 2.8 |
34 (17) |
38 (19) |
31 (22) |
|
SDAI ≤ 3.3 |
32 (16) |
38 (19) |
30 (21) |
|
DAS28 ESR < 2.6 |
35 (17) |
44 (22) |
37 (26) |
|
DAS28 ESR ≤ 3.2 |
55 (27) |
69 (34) |
56 (39) |
|
DAS28 CRP < 2.6 |
61 (30) |
76 (38) |
56 (39) |
|
DAS28 CRP ≤ 3.2 |
97 (48) |
100 (50) |
74 (51) |
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aObserved data for pts entering Part C at Wk 24 bNon-response imputed for discontinuing prior to Wk 76, but not for dose-escalation cAmong pts entering Part D, non-response imputed for discontinuing prior to Wk 128 |
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Disclosure:
E. C. Keystone,
Abbott, Amgen, AstraZeneca, Bristol-Myers Squibb, Hoffmann-La Roche, Janssen, Eli Lilly and Company, Novartis, Pfizer, Sanofi-Adventis, UCB ,
2,
Abbott, AstraZeneca, Biotest, Bristol-Myers Squibb, Hoffmann-La Roche, Genetech, Janssen, Eli Lilly and Company, Merck, Pfizer, UCB ,
5;
P. C. Taylor,
Eli Lilly and Company, Pfizer Inc, AstraZeneca,
5;
M. C. Genovese,
Eli Lilly and Company,
2,
Eli Lilly and Company,
5;
D. E. Schlichting,
Eli Lilly and Company,
1,
Eli Lilly and Company,
3;
I. De La Torre,
Eli Lilly and Company,
1,
Eli Lilly and Company,
3;
S. D. Beattie,
Eli Lilly and Company,
1,
Eli Lilly and Company,
3;
T. Rooney,
Eli Lilly and Company,
1,
Eli Lilly and Company,
3.
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