Table 2.
Main characteristics of the trials included in the phase 3 SELECT program with upadacitinib.
| Inadequate Response to DMARDs | Naïve Patients | |||||
|---|---|---|---|---|---|---|
| NEXT | BEYOND | COMPARE § | CHOICE | MONOTHERAPY | EARLY | |
| Design | 12-wk, M, R, DB | 12-wk, M, R, DB | 26-wk, M, R, DB | 24-wk, M, R, DB | 14-wk, M, R, DB | 48-wk, M, R, DB |
| Population | csDMARD-IR | bDMARD-IR | Methotrexate -IR | bDMARD-IR | Methotrexate -IR | Naïve or limited exposure to methotrexate |
| Background therapy | csDMARD | csDMARD | Methotrexate | csDMARD | Not applicable | Not applicable |
| Upadacitinib arms | 15 mg QD 30 mg QD |
15 mg QD 30 mg QD |
15 mg QD | 15 mg QD | 15 mg QD 30 mg QD |
15 mg QD 30 mg QD |
| Comparator | Placebo | Placebo | Placebo Adalimumab 40 mg/2 wk |
Abatacept | Methotrexate | Methotrexate |
| Type of treatment | Combination | Combination | Combination | Combination | Monotherapy | Monotherapy |
| Sample size | 661 | 499 | 1629 | 612 | 648 | 947 |
| Primary endpoint | ACR20 at wk 12 DAS28-CRP ≤ 3.2 at wk 12 |
ACR20 at wk 12 DAS28-CRP ≤ 3.2 at wk 12 |
ACR20 at wk 12 DAS28-CRP < 2.6 at wk 12 |
∆DAS28-CRP at week 12 (noninferiority) | ACR20 at wk 14 DAS28-CRP ≤ 3.2 at wk 14 |
ACR50 at wk 12 DAS28-CRP < 2.6 at wk 24 |
| Confirmatory endpoints (FDA) | ∆DAS28-CRP ∆HAQ-DI ∆SF-36 PCS DAS28-CRP ≤ 3.2 DAS28-CRP < 2.6 CDAI ≤ 10 ∆Morning stiffness duration ∆FACIT-F |
∆DAS28-CRP ∆HAQ-DI DAS28-CRP ≤ 3.2 ∆SF-36 PCS |
∆DAS28-CRP ∆mTSS ∆HAQ-DI ACR50 | ∆SF-36 PCS DAS28-CRP ≤ 3.2 DAS28-CRP < 2.6 CDAI ≤ 10 ∆FACIT-F ∆Morning stiffness duration ACR50 ¶ ∆HAQ-DI ¶ ∆ Pain ¶ |
∆DAS28-CRP at week 12 (superiority) DAS28-CRP < 2.6 at week 12 (superiority) |
∆DAS28-CRP ∆HAQ-DI ∆SF-36 PCS DAS28-CRP ≤ 3.2 DAS28-CRP < 2.6 ∆Morning stiffness duration |
∆HAQ-DI ∆mTSS † DAS28-CRP ≤ 3.2 DAS28-CRP < 2.6 † ∆SF-36 PCS |
| Confirmatory endpoints (EMA) | ∆DAS28-CRP ∆HAQ-DI ACR20 ∆SF-36 PCS DAS28-CRP < 2.6 CDAI ≤ 10 ∆Morning stiffness duration ∆FACIT |
∆DAS28-CRP ACR20 ∆HAQ-DI ∆SF-36 PCS |
∆mTSS DAS28-CRP ≤ 3.2 ∆DAS28-CRP ∆HAQ-DI ACR20 DAS28-CRP ≤ 3.2 | ∆SF-36 PCS CDAI ≤ 10 ∆Morning stiffness duration ∆FACIT mTSS ≤ 0 ‡ |
∆DAS28-CRP ∆HAQ-DI ∆SF-36 PCS DAS28-CRP ≤ 3.2 DAS28-CRP < 2.6 ∆Morning stiffness duration |
∆DAS28-CRP † ∆HAQ-DI † ACR50 † ∆mTSS † DAS28-CRP ≤ 3.2 † ∆SF-36 PCS † % no radiographic progression: mTSS ≤ 0 † |
|
ACR20—American College of Rheumatology 20% improvement; ACR50—American College of Rheumatology 50% improvement; bDAMRD-IR—inadequate response to biologic disease-modifying antirheumatic drugs; CDAI—clinical disease activity index; csDMARD—conventional synthetic disease-modifying antirheumatic drugs; csDMARD-IR—inadequate response to conventional synthetic disease-modifying antirheumatic drugs; ∆—mean change from baseline; DAS28-CRP—disease activity score in 28 joints using C-reactive protein level; DB—double-blind; DMARDs—disease-modifying antirheumatic drugs; FACIT-F—functional assessment of chronic illness therapy fatigue scale; HAQ-DI—health assessment questionnaire disability index; M—multinational; mTSS—modified total Sharp/van der Heijde score; TX-IR—inadequate response to methotrexate; OD—once daily; R—randomized; SF-36 PCS—36-item short form health survey physical component summary score; wk—week. All endpoints were assessed at week 12 unless stated otherwise. All primary and ranked secondary endpoints were multiplicity controlled and met statistical significance denoted by a p value of ≤0.05. † assessment at week 24; ‡ assessment at week 26; § all comparisons were for upadacitinib + methotrexate vs. placebo + methotrexate, unless indicated as follows, | adalimumab + methotrexate (non-inferiority); ¶ adalimumab + methotrexate (superiority).