Table 1.
Summary of phase II and III clinical trials of baricitinib in RA.
| Study (reference) | Population | Baricitinib (bari) | Comparator | Primary endpoint comparing bari at various doses versus placebo (at week 12) | p-value | Key secondary endpoints comparing bari at various doses versus placebo (at week 12) |
p-value |
|---|---|---|---|---|---|---|---|
| Phase II | |||||||
| Greenwald8 | MTX-IR | 4, 7 or 10 mg once daily | Background MTX | ACR 20 (%) 4 mg versus placebo: 52% versus 32% 7 mg versus placebo: 59% versus 32% 10 mg versus placebo: 53% versus 32% |
Abstract form (not available) | ||
| Keystone9,18 | MTX-IR | 1, 2, 4 or 8 mg once daily | Background MTX | ACR 20 (%) 4 mg + 8 mg combined group versus placebo: 76% versus 41% |
p < 0.001 |
ACR 50 and 70 1 mg versus placebo: ACR 50 31% versus 10% ACR 70 12% versus 2% 2 mg versus placebo: ACR 50 17% versus 10% ACR 70 8% versus 2% 4 mg versus placebo: ACR 50 35% versus 10% ACR 70 23% versus 2% 8 mg versus placebo: ACR 50 40% versus 10% ACR 70 20% versus 2% DAS28 < 2.6 1 mg versus placebo: 14% versus 4% 2 mg versus placebo: 15% versus 4% 4 mg versus placebo: 37% versus 4% 8 mg versus placebo: 22% versus 4% |
<0.05 <0.05 NS NS <0.05 <0.05 <0.05 <0.05 <0.05 <0.05 <0.05 <0.05 |
| Phase III | |||||||
| RA-BUILD10 | MTX-IR | 2 mg or 4 mg once daily | Background MTX | ACR 20 (%) 2 mg versus placebo: 66% versus 39% 4 mg versus placebo: 62% versus 39% |
<0.001 <0.001 |
ACR 50 and 70 (%) 2 mg versus placebo: ACR 50 34% versus 13%; ACR 70 18% versus 3% 4 mg versus placebo: ACR 50 33% versus 13%; ACR 70 18% versus 3% DAS28<2.6 (%) 2 mg versus placebo: 11% versus 2% 4 mg versus placebo: 9% versus 2% |
<0.001 <0.001 <0.001 <0.001 <0.001 <0.001 |
| RA-BEACON12 | TNF-IR | 2 mg or 4 mg once daily | Background MTX | ACR 20 (%) 2 mg versus placebo: 49% versus 27% 4 mg versus placebo: 55% versus 27% |
<0.001 <0.001 |
ACR 50 and 70 (%) 2 mg versus placebo: ACR 50 20% versus 8% ACR 70 13% versus 2% 4 mg versus placebo: ACR 50 28% versus 8% ACR 70 11% versus 2% DAS28 < 2.6 (%) 2 mg versus placebo: 6% versus 1% 4 mg versus placebo: 6% versus 1% |
<0.01 <0.001 <0.001 <0.01 <0.01 <0.05 |
| RA-BEGIN14 | Minimal or no DMARD exposure | 4 mg once daily (monotherapy) versus 4 mg once daily + MTX (combo therapy) |
MTX monotherapy | ACR 20% 4 mg monotherapy versus MTX: 77% versus 62% |
<0.01 |
Monotherapy 4 mg versus MTX ACR 50 60% versus 43% ACR 70 42% versus 21% DAS28-CRP < 2.6 (%) 40% versus 24% Combination Therapy 4 mg + MTX versus MTX ACR 50 63% versus 43% ACR 70 40% versus 21% DAS28-CRP<2.6 (%) 40% versus 24% |
<0.05 <0.05 <0.05 <0.05 <0.05 <0.05 |
| RA-BEAM15 | MTX-IR | 4 mg once daily | MTX or ADA |
ACR 20 (%) 4 mg versus placebo: 70% versus 40% |
<0.001 |
ACR 20 (%) Bari versus ADA: 70% versus 60% ACR 50 (%) Bari versus ADA: 45% versus 35% ACR 70 (%) Bari versus ADA: 19% versus 13% Mean change in DAS28-CRP Bari versus ADA: –2.2 versus –1.9 CDAI ⩽ 10 (%) Bari versus ADA: 40% versus 33% SDAI ⩽ 11 (%) Bari versus ADA: 42% versus 35% |
⩽0.05 <0.01 <0.05 <0.01 <0.05 <0.05 |
| RA-BEYOND16 | DMARD-naïve, DMARD-IR, Biologic-IR |
4 mg once daily (continued dose) | Step down bari to 2 mg once daily | CDAI LDA (%) 4 mg versus 2 mg: 93% versus 84% CDAI REM (%) 4 mg versus 2 mg: 39% versus 37% |
<0.05 NS |
Change in DAS28-CRP 4 mg versus 2 mg: 0.70 versus 0.77 |
<0.05 |
ACR 20/50/70, American College of Rheumatology 20%, 50% or 70% response; ADA, adalimumab; Biologic-IR, biologic inadequate response; CDAI, clinical disease activity index; DAS28, disease activity score 28 joints; DAS28-CRP, disease activity score 28 joints using C-reactive protein; DMARD-IR, disease modifying antirheumatic drug inadequate response; LDA, low disease activity; MTX, methotrexate; MTX-IR, methotrexate inadequate response; NS, non-significant; REM, remission; SDAI, simplified disease activity index; TNF-IR, tumor necrosis factor alpha antagonist inadequate response.