Session Information
Session Type: Abstract Submissions (ACR)
Background/Purpose Baricitinib (bari), an oral JAK1/JAK2 signaling inhibitor, was evaluated in a blinded phase 2b study for 12 weeks as a treatment for rheumatoid arthritis (RA) in Japanese patients (pts) on background methotrexate therapy1. Clinical efficacy (ACR20 response) was significantly greater for a combined 4- and 8-mg QD baricitinib group versus placebo (PBO) and safety signals were consistent with previous experience in non-Japanese pts2. Baricitinib’s safety and efficacy during an additional 52 weeks of treatment in Japanese RA pts completing the12 week, PBO-controlled study are reported here.
Methods Pts were randomized (double-blind) to receive PBO or 1-, 2-, 4- or 8-mg baricitinib QD for 12 weeks (Part A; N=145). At 12 weeks, pts receiving PBO or 1- or 2-mg baricitinib were randomized 1:1 to 4- or 8-mg bari QD for an additional 52 weeks (Part B). Pts receiving 4- or 8-mg baricitinib QD during Part A received the same doses in Part B. However, those receiving 8 mg in Part B were dose-reduced to 4 mg bari QD in a blinded fashion, upon approval of a protocol amendment. Pts and investigators remained blinded to Part B treatment assignment. Efficacy and safety were evaluated by ACR response, measures of low disease activity (LDA) and remission, adverse events (AEs), and discontinuation rates.
Results Of 145 pts randomized in Part A, 141 entered Part B and received 4 mg (n=71) or at least one dose of 8 mg (n=70) baricitinib QD (Table). Rates of ACR20 responses at 64 weeks were 66% and 73% for the 4- and 8-mg baricitinib groups, respectively. LDA rates ranged from 48% to 65% and 53% to 70%, respectively, for 4- and 8-mg baricitinib groups. Remission rates ranged from 32% to 56% and 24% to 66% for 4- and 8-mg baricitinib groups, respectively. No deaths occurred during the study. Incidences of serious AEs (SAEs) were 11% and 17% for 4- and 8-mg baricitinib, respectively. Incidences of AEs leading to discontinuation were 21% and 17% for 4- and 8-mg groups. AE incidences leading to study drug interruption occurred for 25% of 4 mg and 43% of the 8 mg baricitinib groups. Treatment-emergent AEs (TEAEs) occurred in over 95% of all pts during Part B. For those pts with TEAEs 74% and 68% were rated as mild and 9% and 12% were rated as severe for the 4- and 8-mg baricitinib groups, respectively. Treatment-emergent (TE) infections occurred in 66% of pts in each group with 3% and 6% of pts experiencing a serious infection for the 4- and 8-mg groups, respectively.
Conclusion In a single-blind 52 week extension of a phase 2b study in Japanese RA patients, efficacy rates observed at 12 weeks1 were well maintained at 64 weeks for patients on either 4- or 8-mg baricitinib QD. Consistent with prior phase 2 data, the benefit: risk profile seen during 64 weeks of treatment in this study continues to support further development of baricitinib for treatment of RA.
1- Y Tanaka et al. Arthr Rheum. 2013;65(S10):S765.
2- P Taylor et al. Ann Rheum Dis. 2013;72(Suppl3):A65-A66.
|
Disease Improvement/Activity Measure at 64 Weeks* % (n) |
Baricitinib 4 mg (N=71) |
Baricitinib 8 mg (N=70) |
|
ACR20 |
66% (47) |
73% (51) |
|
ACR50 |
54% (38) |
61% (43) |
|
ACR70 |
37% (26) |
34% (24) |
|
SDAI ≤ 11.0 LDA |
59% (42) |
66% (46) |
|
SDAI ≤ 3.3 Remission |
38% (27) |
31% (22) |
|
DAS28 ESR ≤3.2 LDA |
48% (34) |
53% (37) |
|
DAS28 ESR < 2.6 Remission |
32% (23) |
33% (23) |
|
DAS28 CRP ≤ 3.2 LDA |
65% (46) |
70% (49) |
|
DAS28 CRP < 2.6 Remission |
55% (39) |
54% (38) |
|
HAQ-DI ≤ 0.5 Remission |
56% (40) |
66% (46) |
|
Boolean Remission |
32% (23) |
24%(17) |
|
Safety Measures Occurring During Weeks 12 to 64 (Part B) % (n) |
|
|
|
Serious Adverse Event |
11% (8) |
17% (12) |
|
Adverse Event (AE) leading to discontinuation |
21% (15) |
17 % (12) |
|
AE leading to study drug interruption |
25% (18) |
43% (30) |
|
Treatment-emergent AEs (TEAEs) |
92% (65) |
99% (69) |
|
*Non-responder imputation used to calculate all values so that all patients discontinuing study during Part B treated as non-responders. |
||
Disclosure:
Y. Tanaka,
Mitsubishi-Tanabe,
5,
Eisai,
5,
Chugai,
5,
Abbott Japan,
5,
Astellas,
5,
Daiichi-Sankyo,
5,
Abbvie,
5,
Janssen Pharmaceutica Product, L.P.,
5,
Pfizer Inc,
5,
Takeda,
5,
AstraZeneca,
5,
Eli Lilly Japan,
5,
GlaxoSmithKline,
5,
Quintiles,
5,
MSD,
5,
Asahi-Kasei,
5,
Bristol-Myers Squibb,
2,
Mitsubishi-Tanabe,
2,
Abbvie,
2,
Chugai,
2,
Astellas,
2,
Daiichi-Sankyo,
2;
K. Emoto,
Eli Lilly Japan,
3;
Z. Cai,
Eli Lilly Japan,
3;
D. E. Schlichting,
Eli Lilly and Company,
1,
Eli Lilly and Company,
3;
T. Rooney,
Eli Lilly and Company,
1,
Eli Lilly and Company,
3;
W. Macias,
Eli Lilly and Company,
3,
Eli Lilly and Company,
1.
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