Overview of the RINVOQ (upadacitinib) RA Phase 3 programme3-9
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MTX-naïve3# | MTX-IR4 | MTX-IR5 | csDMARD-IR6 | Biologic-IR7 | Biologic-IR8 | |
Type of therapy | Mono | Combo | Mono | Combo | Combo | Combo |
Background | ̶ | MTX | ̶ | csDMARDs | csDMARDs | csDMARDs |
Active comparator | MTX | Adalimumab | cMTX | ̶ | ̶ | Abatacept |
Duration of period 1 | 48 weeks | 48 weeks | 14 weeks | 12 weeks | 24 weeks | 24 weeks |
Duration of period 2 | Up to 5 years | Up to 10 years | Up to 5 years | Up to 5 years | Up to 5 years | Up to 5 years |
Sample size | 947 | 1629 | 648 | 661 | 499 | 612 |
Real World Evidence
REFERENCE: 1. Bergman M et al. Adv Ther 2023;40:4493—4503.
REFERENCE: 1. Haaland D et al. Effectiveness of Upadacitinib in Patients With Rheumatoid Arthritis in Canadian Real-World Practice: Interim Results From the CLOSE-UP Post-Marketing Observational Study. Poster presented at ACR 2022 (0298).
REFERENCE: 1. Witte T et al. Clin Exp Rheumatol 2023 Nov 15. Online ahead of print.
REFERENCE: 1. Scheepers L et al. Semin Arthritis Rheum 2024;64:152314.
Clinical trials
Rescue therapy from Weeks 12–24: In patients with <20% improvement in TJC and SJC at 2 consecutive visits, background medications were optimised.
*~25% of patients had previously received a non-MTX csDMARD, primarily hydroxychloroquine or sulfasalazine (8.6% each). Less than 10% of the patients had received MTX prior to study start (≤3 lifetime weekly doses; 6% in the MTX arm, 9.5% in the RINVOQ 15 mg arm.
‡Study drug assignments remain the same in the blinded extension while allowing initiation of, or change in, background RA medication(s) as per local label. RINVOQ is indicated in moderate-severe RA patients who have responded inadequately to, or who are intolerant to, one or more DMARD(s).
The approved dose of RINVOQ is 15 mg QD. Upadacitinib 30 mg is not approved for RA in Australia.
†Assessment at Week 24.
REFERENCE: 1. Van Vollenhoven R et al. Arthritis Rheumatol 2020; 72(10):1607-1620
The study design provided at least 90% power for testing non-inferiority at Week 12 of RINVOQ 15 mg vs adalimumab for DAS28-CRP≤3.2 and ACR50 response rates (non-inferiority margin of 10%). Rescue Criteria: Blinded rescue without washout, from placebo + MTX and adalimumab + MTX to RINVOQ + MTX and from RINVOQ + MTX to adalimumab + MTX, was done if patients had <20% improvement in TJC and SJC at Weeks 14, 18 or 22 or if CDAI >10 at Week 26. All remaining placebo + MTX patients were switched to RINVOQ + MTX at Week 26. Efficacy data up to Week 156 were analysed by originally assigned randomised treatment group (intention-totreat analysis). Binary efficacy endpoints: NRI was applied for rescue, premature discontinuation of study drug, and missing data. Continuous efficacy endpoints: LOCF applied to data observed after rescue, and missing data were not imputed. Analysis of continuous endpoints was conducted using ANCOVA. AO data by treatment sequence were reported without imputation for missing data. Comparisons adjusted for prior bDMARD use. All patients were included in the safety analysis, with assignment of an AE based on drug exposure at the time of event.
REFERENCE: 1. Fleischmann R et al. Arthritis Rheumatol 2019;71(11):1788–800.
At Week 26, patients who did not achieve Clinical Disease Activity Index (CDAI) low disease activity (LDA) (≤10) had background medication(s) adjusted or initiated as rescue.
Upadacitinib 30 mg is not approved for RA in Australia.
*For the primary analysis at Week 14, comparisons of RINVOQ 15 mg and upadacitinib 30 mg vs continued MTX were done by combining data from the two continued MTX groups.
†From Week 14, patients initially randomised to continued MTX at baseline were switched to RINVOQ 15 mg or upadacitinib 30 mg per pre-specified randomisation assignment.
REFERENCE: 1. Smolen JS et al. Lancet 2019;393(10188):2303–11.
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 randomised to placebo at baseline were switched to RINVOQ 15 mg or upadacitinib 30 mg per prespecified randomisation assignment.
The approved dose of RINVOQ is 15 mg once daily. Upadacitinib 30 mg is not approved for RA in Australia.
REFERENCE: 1. Burmester GR et al. Lancet 2018;391(10139):2503–12.
Patients continued stable csDMARD therapy for the first 24 weeks of the study, restricted to oral or parenteral MTX, chloroquine, hydroxychloroquine, sulfasalazine, or leflunomide. Patients could be taking a maximum of 2 background csDMARDs, except the combination of MTX and leflunomide, which was not allowed.
The approved dose of RINVOQ is 15mg once daily. . Upadacitinib 30 mg is not approved for RA in Australia.
*Randomisation was stratified by prior failed bDMARDs (1–2 with same mechanism of action vs ≥3 with the same mechanism of action or at least 2 biologics with different mechanisms of action).
REFERENCE: 1. Genovese MC et al. Lancet 2018;391(10139):2513–24. 2. U.S. National Library of Medicine. A Study to Compare Upadacitinib (ABT-494) to Placebo in Adults With Rheumatoid Arthritis on Stable Dose of Conventional Synthetic Disease-Modifying Antirheumatic Drugs (csDMARDs) With an Inadequate Response or Intolerance to Biologic DMARDs (SELECT-BEYOND). Available at: https://clinicaltrials.gov/ct2/show/NCT02706847 (accessed December 2020).
*Patients assigned to abatacept received abatacept intravenously at Day 1 and Weeks 2, 4, 8, 12, 16, and 20. Abatacept administration to patients was weight based (<60 kg: 500 mg; 60–100 kg: 750 mg; >100 kg: 1000 mg).
†Starting at Week 12, patients who did not have at least a 20% decrease in both the TJC and the SJC as compared with baseline at two consecutive visits were to have background medications adjusted or added.
‡All patients who completed Week 24 were eligible to remain in an open-label, long-term extension period of the trial for up to 5 years, all receiving RINVOQ 15 mg QD.
REFERENCE: 1. Rubbert-Roth A et al. N Engl J Med 2020;383:1511–21.
WARNING: Based on the results from a post-marketing safety study of another JAK inhibitor, RINVOQ should only be used if no suitable treatment alternatives are available in patients: Refer to Product Information. |
PBS Information
RINVOQ: Authority required. Refer to PBS Schedule for full authority information.
Please review the full Product Information (PI) before prescribing, available below.
3. van Vollenhoven R et al. Arthritis Rheumatol 2020;72(10):1607–1620. 4. Fleischmann R, et al. Arthritis Rheumatol 2019;71:1788–800. 5. Smolen JS, et al. Lancet 2019;393:2303–11. 6. Burmester G, et al. Lancet 2018;391:2503–12. 7. Genovese MC, et al. Lancet 2018;391:2513–24. 8. Rubbert-Roth A, et al. N Engl J Med 2020;383:1511–21. 9. RINVOQ Approved Product Information.
#RINVOQ is not approved for the treatment of MTX-naive patients. Upadacitinib 30 mg is not approved for RA in Australia. 25% of patients had exposure to csDMARDs prior to study entry, including 7.5% patients who had received ≤3 weekly doses of MTX.
*SELECT-CHOICE is not a registrational trial.
b/csDMARD, biologic/conventional synthetic DMARD; IR, inadequate responder; (c)MTX, (continued) methotrexate; PBO, placebo; QD, once daily; UPA, upadacitinib.
AU-RNQR-220147. May 2024