SELECT-NEXT: Study design
A Phase 3 study investigating the efficacy and safety of RINVOQ + csDMARDs compared to placebo + csDMARDs in patients with moderate to severe RA and an inadequate response to csDMARDs1
Permitted background csDMARDs were oral and parenteral MTX, sulfasalazine, hydroxychloroquine, chloroquine, and leflunomide; up to 2 concomitant background csDMARDs were allowed, with the exception of the combination of MTX and leflunomide.
*From Week 12 onward, patients initially randomized to placebo at baseline were switched to RINVOQ 15 mg or upadacitinib 30 mg per prespecified randomization assignment. Patients assigned to RINVOQ 15 mg or upadacitinib 30 mg continued their assigned dose.
Primary
RINVOQ 15 mg + csDMARD(s) and upadacitinib 30 mg + csDMARD(s) vs placebo + csDMARD(s) at Week 12 for DAS28 (CRP) <3.2 (EMA) or ACR20 (FDA)
Safety
Adverse events, serious adverse events, adverse events of special interest (e.g., serious infections, opportunistic infections, MACEs, VTEs, malignancies)
- Patients ≥18 years of age were eligible to participate.
- Diagnosis of RA for ≥3 months fulfilling the 2010 ACR/EULAR classification for RA with active disease (at least 6 swollen joints out of 66, at least 6 tender joints out of 68, and hsCRP of 3 mg/L or more).
- Received csDMARDs for ≥3 months and on a stable dose for ≥4 weeks before study entry.
- Patients must have had an inadequate response to at least 1 prior csDMARD (MTX, sulfasalazine, or leflunomide).
- Patients with prior exposure to at most 1 bDMARD were eligible (up to 20% of total study number of patients) if they had either limited exposure (<3 months) or had to discontinue the bDMARD due to intolerability.
- No prior exposure to a JAK inhibitor or prior inadequate response to bDMARDs.
The approved dose of RINVOQ is 15 mg once daily. Upadacitinib 30 mg QD is not an approved dose.
ACR: American College of Rheumatology; ACR20: improvement of at least 20% in the American College of Rheumatology core criteria; bDMARD: biological disease-modifying antirheumatic drug; csDMARD: conventional synthetic disease-modifying antirheumatic drug; DAS28 (CRP): disease activity score with 28-joint count (C-reactive protein); EMA: European Medicines Agency; EULAR: European League Against Rheumatism; FDA: Food and Drug Administration; hsCRP: high-sensitivity C-reactive protein; JAK: Janus kinase; MACE: major adverse cardiovascular event; MTX: methotrexate; QD: once daily; SF-36: Short-Form 36; VTE: venous thromboembolic event.
RINVOQ: Efficacy with csDMARDS after inadequate response to csDMARDS
SELECT-NEXT: Low disease activity and remission at Week 12 in patients with an inadequate response to csDMARDs (NRI)1,2
*P≤0.001 vs placebo + csDMARD(s)
csDMARD: conventional synthetic disease-modifying anti-rheumatic drug; DAS28 (CRP): disease activity score with 28-joint count (C-reactive protein); NRI: nonresponder imputation.
SELECT-NEXT: Adverse events through 12 weeks of treatment1
*One case of congestive cardiac failure, one cardiovascular procedure.
Safety Information2
References
- Burmester GR, Kremer JM, Van den Bosch F, et al. Safety and efficacy of upadacitinib in patients with rheumatoid arthritis and inadequate response to conventional synthetic disease-modifying anti-rheumatic drugs (SELECT-NEXT): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2018;391(10139):2503-2512. doi:10.1016/S0140-6736(18)31115-2
- RINVOQ [Summary of Product Characteristics]. AbbVie Deutschland GmbH & Co. KG; May 2021.