A review of upadacitinib in rheumatoid arthritis

Figures & data

Table 1. Summary of the SELECT phase III program.

	SELECT-EARLY [29]	SELECT-NEXT [27]	SELECT-SUNRISE [32]^a	SELECT-MONOTHERAPY [15]	SELECT-COMPARE [30,31]	SELECT-BEYOND [28]	SELECT-CHOICE [NCT03086343]
Population	MTX-naïve	csDMARD-IR	csDMARD-IR	MTX-IR	MTX-IR	bDMARD-IR	bDMARD-IR
Background therapy	—	csDMARDs	csDMARDs	—	MTX	csDMARDs	csDMARDs
Upadacitinib dose(s)	7.5 mg QD^a 15 mg QD 30 mg QD	15 mg QD 30 mg QD	7.5 mg QD 15 mg QD 30 mg QD	15 mg QD 30 mg QD	15 mg QD	15 mg QD 30 mg QD	15 mg QD
Comparator	MTX	Placebo	Placebo	MTX	Placebo Adalimumab	Placebo	Abatacept
Number of patients enrolled	1002	661	197	648	1629	499	657
Primary endpoint	ACR20^b/50^c at week 12; DAS28-CRP <2.6^c, mTSS change from BL^b at week 24	ACR20^c, DAS28-CRP ≤3.2^d at week 12	ACR20 at week 12	ACR20^c, DAS28-CRP ≤3.2^d at week 14	ACR20^c, DAS28-CRP <2.6^d at week 12	ACR20^c, DAS28-CRP ≤3.2^d at week 12	Change in DAS28-CRP (non-inferiority) at week 12

^a Japanese patients only. ^bPrimary endpoint for the Pharmaceuticals and Medical Devices Agency. ^cPrimary endpoint for the Food and Drug Administration. ^dPrimary endpoint for the European Medicines Agency.

ACR20/50: 20%/50% improvement in American College of Rheumatology criteria; bDMARD: biologic disease-modifying anti-rheumatic drug; BL: baseline; csDMARD: conventional synthetic disease-modifying anti-rheumatic drug; DAS28-CRP: 28-joint Disease Activity Score with C-reactive protein; IR: inadequate response; mTSS: modified Total Sharp Score; MTX: methotrexate; QD: once daily.

Figure 1. Event rates of serious AEs, AEs of special interest, and deaths in the global upadacitinib SELECT phase III program (reproduced with permission from Cohen et al. [33]). ^aPBO pooled (12–14 weeks): n = 1042. ^bMTX pooled (mean exposure of 36 weeks): n = 530, includes patients on MTX monotherapy censored at time of switch/addition of upadacitinib. ^cADA 40 mg EOW (mean exposure of 42 weeks): n = 579. ^dUpadacitinib 15 mg pooled (mean exposure of 53 weeks): n = 2630. ^eUpadacitinib 30 mg pooled (mean exposure of 59 weeks): n = 1204. ^fDeaths included non-treatment-emergent deaths (3 on upadacitinib 15 mg, 3 on upadacitinib 30 mg, and 1 on ADA). ^gMACE was defined as CV death, non-fatal MI, and non-fatal stroke. ^hVTE was defined as deep vein thrombosis and pulmonary embolism. ADA: adalimumab; AE: adverse event; CI: confidence interval; CV: cardiovascular; E: events; EOW: every other week; MACE: major adverse cardiovascular events; MI: myocardial infarction; MTX: methotrexate; NMSC: non-melanoma skin cancer; PBO: placebo; PYs: patient-years; UPA: upadacitinib; VTE: venous thromboembolic event.

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